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Session Listing


Tuesday, November 6

4:00 PM–4:30 PM

SESSION 1 – ASHG Presidential Address: The Scientist as a Citizen of the World

Hall D, Lower Level North, Moscone Center

Mary-Claire King
2012 President
Univ. of Washington

One of the most fulfilling features of our lives as scientists is to act as citizens of the world. We both take this citizenship for granted and take its responsibilities seriously. In one generation, this role has evolved dramatically, as scientists travel far more widely and as modern communication tools enable us to remain in contact with our colleagues worldwide. In my presidential address, I will specify some elements of the scientific life that lead naturally to world citizenship. Then I will focus in particular on how the intellectual structure of human genetics enables us to be particularly effective world citizens. I will also discuss migration as a force in our lives, as well as in human evolution, and will try to define the concept of "home" for a scientist. Finally, I will suggest that scientific goals are both practical and idealistic, and that we should celebrate both.


Tuesday, November 6

4:30 PM–6:30 PM

SESSION 2 – Plenary Abstract Presentations

Hall D, Lower Level North, Moscone Center

Moderator: Joel N. Hirschhorn, 2012 Program Committee Chair
Boston Children's Hosp., Harvard Med. Sch. and Broad Inst.

1/4:30 A novel molecular and functional mechanism predisposing to ototoxicity. B. Wollnik, E. Pohl, N. Offenhäuser, A. Uzumcu, F. J. Kersten, A. K. Rzadzinska, O. Uyguner, B. Lorente, G. Nürnberg, M. Emiroglu, H. Kayserili, I. del Castillo, P. Nürnberg, T. Moser, C. Kubisch, K. P. Steel, P. P. Di Fiore, H. Kremer, Y. Li.

2/4:50 Genome-wide comparison of genetic and epigenetic regulatory mechanisms in primates. Y. Gilad, A. Pai, R. Pique-Regi, C. Cain, J. Degner, N. Lewellen, K. Michelini, J. Pritchard.

3/5:10 Multidisciplinary and translational task force for neonatal genomics. E. E. Davis, A. Sabo, N. C. Oien, S. H. Katsanis, H. Cope, K. Sheets, A. Sadeghpour, K. McDonald, M. Kousi, J. R. Willer, J. Kim, S. Dugan-Rocha, D. M. Muzny, A. Ashley-Koch, E. Hauser, M. Hauser, J. Sun, J. Kurtzberg, A. Murtha, B. Boyd, W. B. Gallentine, R. Goldberg, M. T. McDonald, R. A. Gibbs, M. Angrist, C. M. Cotten, N. Katsanis.

4/5:30 Genome-wide identification and functional analysis of distant-acting craniofacial enhancers. C. Attanasio, Y. Zhu, M. J. Blow, A. S. Nord, V. Afzal, B. Hallgrimsson, D. FitzPatrick, H. Morrison, E. M. Rubin, L. A. Pennacchio, A. Visel.

5/5:50 Translational cis-regulation of gene expression in human genome: The effect of human single nucleotide polymorphisms. Q. Li, A. Makri, Y. Lu, L. Marchand, R. Grabs, M. Rousseau, H. Ounissi-Benkalha1, H. Qu, C. Polychronakos.

6/6:10 Lessons learned from the NHLBI-Exome Sequencing Project. S. M. Leal on behalf of NHLBI Exome Sequencing Project.

The Opening Mixer and Trainee-Mixer-within-a-Mixer will follow the plenary session at the Marriott Marquis Hotel, Yerba Buena Ballroom.


Wednesday, November 7

8:00 AM–10:00 AM

Concurrent Invited Session I (3-10)

SESSION 3 – Implementing Next-Generation Sequencing as a Clinical Test

Hall D, Lower Level North, Moscone Center

Moderators: Nazneen Aziz, Col. of American Pathologists, Lexington, MA
  Ira Lubin, Ctr. for Dis. Control and Prevent.

Next-generation sequencing (NGS) is used widely in clinical research for the discovery of disease-associated genes and the clinical community is beginning to embrace this technology for diagnostic testing. The rapid evolution of NGS technologies presents significant opportunities and challenges for researchers and clinicians for improving health outcomes; particularly with respect to an increased emphasis on personalized and preventive medicine. Adoption of NGS in the clinical laboratory setting requires the adoption of many processes and procedures, such as, the analytic and clinical validation of the test, CLIA/CAP certification, standards for reference materials for proficiency testing, and questions regarding reimbursement and informed consent. This session will initially review the state of NGS in the clinical setting today and what is anticipated in the near future. This will be followed by consideration for what is practically needed for clinical adoption of NGS such as regulatory and professional standards, development, availability, and access to reference materials, and the laboratory professional’s role for ensuring high quality test results that are useful for informing clinical decision making. This session will be informative and practical for the researcher and laboratorians who are considering launching NGS as a clinical test.


8:00 AM   Challenges of introducing NGS in the clinical laboratory. S. Richards. Oregon Hlth. & Sci. Univ.

8:15 AM   Addressing the fundamentals: NGS validation and implementation in a clinical setting. M. Hegde. Emory Univ.

8:45 AM   Proficiency testing, quality control and development of reference material for NGS clinical testing. E. Lyon. Univ. of Utah Sch. of Med.

9:00 AM   Development of accreditation standards for laboratories offering NGS as a clinical test. N. Aziz. Col. of American Pathologists, Lexington, MA.

9:30 AM   Lessons from the clinic—What’s next? H. Jacob. Med. Col. of Wisconsin.

Wednesday, November 7

8:00 AM–10:00 AM

Concurrent Invited Session I (3-10)

SESSION 4 – Assessing the Pathogenicity of Genetic Variants: Translating in Vitro and in Silico Advances to the Clinic

Gateway Ballroom 103, Lower Level South, Moscone Center

Moderators: Marc S. Greenblatt, Univ. of Vermont
  Sean V. Tavtigian, Univ. of Utah

Interpreting which genetic variants are pathogenic and which are not remains a critical challenge in the genetics of hereditary cancer syndromes and other inherited disorders. Genetic testing for disorders such as Lynch syndrome (caused by mutations in DNA mismatch repair genes) and hereditary breast-ovarian cancer (BRCA1, BRCA2 genes) often identifies a ‘Variant of Uncertain Significance’ (VUS). As DNA sequencing capacity increases at a furious pace, there is an ever greater need to have effective methods to analyze these data. There is a consensus in the field of genetic testing that proper classification of variants requires the integration of multiple types of data. Some lines of evidence are familiar to clinicians (e.g., segregation of an allele with disease, detailed phenotype), and others are less familiar (e.g., in vitro protein functional assays, in silico algorithms based on gene sequence or protein structure). Ideally, integration can be done in a quantitative way, such as Bayesian probabilistic analysis, but qualitative data may be used if quantitative measurements are not possible. This session will 1) explore recent advances in applying and integrating statistical, laboratory, and computational methods in the classification of missense, splice site, and other genetic variants, and 2) report on international collaborations that are using these methods to classify variants in mismatch repair, BRCA, and other genes and disseminating validated conclusions to the cancer genetics community.


8:00 AM   Innovative in vitro and in vivo assays to investigate the function of mismatch repair gene variants in Lynch syndrome. N. de Wind. Leiden Univ. Med. Ctr., Netherlands.

8:30 AM   Analysis of splicing abnormalities to define pathogenic variants in cancer susceptibility genes. A. B. Spurdle. Queensland Inst. of Med. Res., Australia.

9:00 AM   Integrating in silico with in vitro, statistical, and phenotype data to classify missense variants: A paradigm that is ready for translation to the clinic. S. V. Tavtigian. Univ. of Utah.

9:20 AM   CAGI: The Critical Assessment of Genome Interpretation, a community experiment to evaluate phenotype prediction. S. E. Brenner. Univ. of California, Berkeley.

9:40 AM   International collaborations to establish standards for classifying genetic variants and to disseminate results. M. S. Greenblatt. Univ. of Vermont.

Wednesday, November 7

8:00 AM–10:00 AM

Concurrent Invited Session I (3-10)

SESSION 5 – Gene Regulatory Change: The Engine of Human Evolution?

Room 135, Lower Level North, Moscone Center

Moderators: James P. Noonan, Yale Univ. Sch. of Med.
  Nadav Ahituv, UCSF

What makes us human? Classic human traits, such as language and sophisticated tool use, are the result of physical changes during human evolution, including increased brain complexity and altered limb morphology. This session will focus on efforts to identify evolutionary changes in gene regulation that produced uniquely human phenotypes. Speakers will describe novel approaches that are empowering research in this emerging field, and the insights that are being gained. Topics to be discussed include: 1) Computational identification of putative gene regulatory elements that changed extensively during human evolution; 2) The role of repetitive elements in generating novel regulatory functions; 3) Human-specific loss of developmental regulatory elements; 4) New methods to link phenotypic and genotypic variation across closely related species, and the implications for understanding human-specific biology and disease; and 5) Identifying human-specific developmental regulatory changes by direct comparisons of enhancer function and gene expression in embryonic human and nonhuman primate tissues using functional genomics. The session will illustrate how the synthesis of diverse computational and experimental approaches is beginning to reveal the genetic basis of unique human biology.


8:00 AM   Chromatin profiling of human embryonic tissues identifies regulatory elements with human-specific developmental functions. J. P. Noonan. Yale Univ. Sch. of Med.

8:25 AM   Many human accelerated regions are developmental enhancers. K. S. Pollard. UCSF.

8:50 AM   Linking human and mammalian genotypes to phenotype. G. Bejerano. Stanford Univ.

9:15 AM   The role of repetitive elements in driving human and mammalian genome regulation. D. Odom. Cancer Research UK, Cambridge, U.K.

9:40 AM   Evidence of regulatory turnover in the human lineage revealed by comparing mammalian constraint, human diversity, and biochemical activity. M. Kellis. MIT.

Wednesday, November 7

8:00 AM–10:00 AM

Concurrent Invited Session I (3-10)

SESSION 6 – Insights into Human Demography and Selection from Full Genome Sequencing

Room 134, Lower Level North, Moscone Center

Moderators: Jeffrey M. Kidd, Univ. of Michigan
  Carlos D. Bustamante, Stanford Univ.

Next-generation sequencing allows geneticists to directly test the extent and pattern of natural selection in the human genome. These new genomic data address previous concerns of ascertainment bias and accurate identification of causal alleles. Recently, population geneticists have proposed multiple, strong positive sweeps related to diet and immune defense, pervasive negative selection in and nearby genes, and adaptation by allele frequency shifts from standing variation. The proportion of the human genome attributable to these different patterns is currently under intense debate. Furthermore, selection is operating on the background of complex human demography, such as long-range continental migrations and population-specific bottlenecks. This symposium aims to provide diverse viewpoints on the different modes of selection operating on the human genome and a discussion of how demographic processes may have constrained evolution in both recent and ancient human history.


8:00 AM   The effect of out-of-Africa migrations on the distribution of deleterious alleles in diverse human genomes. B. M. Henn. Stanford Univ.

8:30 AM   Genetic adaptations to new environments in humans. A. Di Rienzo. Univ. of Chicago.

9:00 AM   Insights into selective sweeps and diversity from thousands of sequenced genomes. R. Hernandez. UCSF.

9:30 AM   A genomic view of the demographic and adaptive history of African pygmies. L. Quintana-Murci. Inst. Pasteur, Paris, France.

Wednesday, November 7

8:00 AM–10:00 AM

Concurrent Invited Session I (3-10)

SESSION 7 – Age-Related Macular Degeneration—GWAS and Beyond: Guiding Light for the Complex Neurodegenerative Diseases

Gateway Ballroom 104, Lower Level South, Moscone Center

Moderators: Anand Swaroop, NEI/NIH
  Hemin Chin, NEI/NIH

AMD is a complex multi-factorial neurodegenerative disease that is a major cause of visual impairment in the elderly. Genetic linkage and genome-wide association studies (GWAS) have been immensely successful in identifying genetic susceptibility loci in AMD and in providing insights into cellular pathways underlying pathogenesis of the disease . Numerous groups worldwide have validated the strong association of variants at CFH and ARMS2/HTRA1 loci with AMD risk, and genome-wide association studies have suggested the involvement of complement, extracellular matrix, angiogenesis and HDL cholesterol pathways. This session will discuss the current progress to carry out comprehensive genetic analyses of AMD, highlighting experimental approaches that may be applicable to other complex traits and multigenic diseases. The speakers in this session will provide the current status of meta-analysis of AMD-GWAS, targeted resequencing, and whole exome sequencing efforts to discover or search for rare causal variants and functional pathways, and diagnostic/therapeutic implications of genetic variants. Additionally, we will discuss the relevance of AMD genetics for other complex neurodegenerative diseases and the future of genetic studies.


8:00 AM   The bigger the better: Searching for novel loci for age-related macular degeneration in a large consortium effort. I. Heid. Regensburg Univ. Med. Ctr., Germany.

8:30 AM   From genetic association to causal alleles by resequencing and exome arrays: The stage after GWAS. G. Abecasis. Univ. of Michigan.

9:00 AM   The Pathways of AMD: Synergy between Eye Pathology and Genetics. C. Curcio. Univ. of Alabama.

9:30 AM   An updated recipe for Mendel’s pea soup. M. A. Pericak-Vance. Univ. of Miami Miller Sch. of Med.

Wednesday, November 7

8:00 AM–10:00 AM

Concurrent Invited Session I (3-10)

SESSION 8 – "Yes Virginia, Family Studies Really Are Useful for Complex Traits in the Next-Generation Sequencing Era" (session in honor of Dr. Robert Elston's contributions to human genetics in the year of his 80th birthday)

Room 124, Lower Level North, Moscone Center

Moderators: Michael A. Province, Washington Univ. in St. Louis
  Francoise Clerget-Darpoux, INSERM U781, Univ. Paris V, France.

The pros and cons of family designs as NGS targets in dissecting complex traits are presented. In the linkage era, family studies were ubiquitous, but they were largely neglected in the GWAS era, which concentrated mostly on unrelated subjects. But as attention now moves from the common to the rare variants that can only be completely interrogated through sequencing, it is useful to at least consider whether the designs that were optimal for GWAS remain so for NGS studies. Pedigrees seem to have at least some advantages over studies of unrelateds for studying rare variation. First, it may be easier to distinguish true rare variant calls from sequence errors in family designs than it is in unrelated cohorts, since there is the added dimension of pedigree consistency information, especially for low coverage. Second, a key statistical challenge to analyzing the phenotype/genotype correlation with rare variants, is finding enough copies of any one variant allele with which to make inferences (hence the various collapsing or burden tests, which combine multiple nearby rare variants into a single test). For any given very rare allele, sampling additional unrelateds is an inefficient strategy to find more copies of that allele, whereas family members of allele carriers are much more likely to be allele carriers themselves. On the other hand, a disadvantage of family designs is that there is a smaller diversity of founder mutations, so less of the overall population of alleles is measured per individual. This session emphasizes the results of real sequencing studies in pedigrees as well as simulation results to delineate the areas in which family designs offer advantages and where they offer disadvantages over sequencing unrelated subjects, such as case-control designs.


8:00 AM   Whole genome sequencing in large pedigrees for the identification of human QTLs. J. Blangero. Texas Biomed. Res. Inst., Austin.

8:30 AM   Linkage and association information should be considered as complementary and not redundant. F. Clerget-Darpoux. INSERM U781, Univ. Paris V, France.

9:00 AM   Power to find rare causal variants in pedigrees. M. A. Province. Washington Univ. in St. Louis.

9:30 AM   Whither human genetics? R. C. Elston. Case Western Reserve Univ.

Wednesday, November 7

8:00 AM–10:00 AM

Concurrent Invited Session I (3-10)

SESSION 9 – Surveying Customer Responses to Personal Genetic Services

Room 132, Lower Level North, Moscone Center

Moderator: J. Scott Roberts, Univ. of Michigan

This session will feature presentation of empirical data on the responses of personal genome testing consumers to their individual genomic information. Dr. David Kaufman of Johns Hopkins University will discuss publicly available interpretations of individual whole genome sequence data in light of his Center's prior work on direct-to-consumer (DTC) testing and return of individual genetic research results. Dr. Cinnamon Bloss of the Scripps Genomic Health Initiative (SGHI) will present new long-term follow-up data from the SGHI, including data related to DTC pharmacogenomic testing and genetic ancestry testing. Dr. Sandra Lee of Stanford University will describe an anthropological study of how the public integrates information on population genetic variation in their interpretation of individualized genetic risk information for disease and drug response. The session will conclude with a panel discussion moderated by Dr. Scott Roberts of the University of Michigan, joint PI (with Dr. Robert Green at Brigham and Women’s Hospital) of the Impact of Personal Genomics (PGen) Study. The PGen Study is a longitudinal survey study examining consumers’ response to personal genome testing, including their motivations and expectations, risk perceptions, health behaviors and intentions. Two personal genomics companies, 23andMe and Pathway Genomics, are collaborators on the PGen Study, and the closing panel will feature a discussion that includes company representatives Dr. Joanna Mountain and Dr. Tanya Moreno. In this discussion, panelists and audience members will share their perspectives on the potential benefits and risks involved in research partnerships between academicians and personal genomics companies.


8:00 AM   Interpretomics: Using studies of DTC testing and the return of research results to shape the interpretation of personal whole genomic sequence data. D. Kaufman. Genet. and Publ. Policy Ctr., Johns Hopkins Univ.

8:30 AM   Impact of DTC genomic testing at long-term follow-up. C. S. Bloss. Scripps Translational Sci. Inst. and Scripps Hlth.

9:00 AM   Rendering population differences meaningful: A study of consumer interpretation of genetic diversity. S. S-J. Lee. Stanford Univ. Med. Sch.

9:30 AM   The role of personal genomic testing companies in research: A panel discussion featuring industry and academic perspectives. J. Mountain1, T. Moreno2, J. S. Roberts3. 1) 23andMe Inc., Mountain View, CA; 2) Genomics Corp., San Diego; 3) Univ. of Michigan.

Wednesday, November 7

8:00 AM–10:00 AM

Concurrent Invited Session I (3-10)

SESSION 10 – Metabolism, Metals, and Neurodegeneration: Toward Enhanced Understanding of Disease Mechanisms and Rational Therapeutics

Room 130, Lower Level North, Moscone Center

Moderators: Stephen G. Kaler, NICHD/NIH
  Susan J. Hayflick, Oregon Hlth. & Sci. Univ.

This session will focus on the expanding knowledge concerning the influence of inborn errors of metabolism and disorders of trace metal homeostasis on neurodegeneration. Increasing numbers of clinical phenotypes and molecular defects are now associated with disordered metabolism in the central and peripheral nervous systems. These include Alzheimer and Parkinson diseases, Menkes and Wilson diseases, ATP7A-related distal motor neuropathy, acetyl CoA transporter 1-related hypocupremia, pantothenate kinase-associated neurodegeneration, infantile neuroaxonal dystrophy, dystonia-parkinsonism, Friedreich ataxia, hemochromatosis, and iron sulfur cluster scaffold myopathy. Expert speakers will discuss and review translational research advances relevant to these conditions, as well as emerging data on disease mechanisms, pathophysiology, and potential novel remedies.


8:00 AM   Neurodegeneration with brain iron accumulation. S. J. Hayflick. Oregon Hlth. & Sci. Univ.

8:30 AM   Friedreich ataxia and diseases of iron sulfur cluster assembly. T. A. Rouault. NICHD/NIH.

9:00 AM   Neurodegeneration and disorders of copper transport. S. G. Kaler. NICHD/NIH.

9:30 AM   Exploring the link between glucocerebrosidase mutations and Parkinson disease. E. Sidransky. NHGRI/NIH.

Wednesday, November 7

10:30 AM–12:45 PM

Concurrent Platform (abstract-driven) Session A (11-19)

SESSION 11 – Genetics of Autism Spectrum Disorders

Hall D, Lower Level North, Moscone Center

Moderators: Fuki M. Hisama, Univ. of Washington
  Dan E. Arking, Johns Hopkins Sch. of Med.

7/10:30 Genetic epidemiology of autism spectrum disorder in a cohort of over 11,000 affected sibships and half-sibships: Evidence of genetic and maternal environmental effects. N. Risch, T. J. Hoffmann, M. Anderson, L. A. Croen, J. Grether, G. Windham.

8/10:45 Identifying inherited autism mutations using whole exome sequencing. T. W. Yu, M. H. Chahrour, M. E. Coulter, S. Jiralerspong, K. Okamura-Ikeda, K. Schmitz-Abe, G. H. Mochida, J. N. Partlow, R. S. Hill, M. Al-Saffar, N. M. Mukaddes, A. Hashmi, S. Balkhy, G. G. Gascon, O. Oner, S. Al-Saad, T. Ben-Omran, L. Al-Gazali, V. Eapen, C. Stevens, S. Gabriel, K. Markianos, H. Taniguchi, N. E. Braverman, E. M. Morrow, C. A. Walsh.

9/11:00 Identical by descent filtering in extended families reveals novel autism genes detected by exome sequencing. H. N. Cukier, N. D. Dueker, S. H. Slifer, J. M. Lee, P. L. Whitehead, E. Lalanne, N. Leyva, I. Konidari, R. C. Gentry, W. F. Hulme, D. Van Booven, D. J. Hedges, V. Mayo, S. S. Ramsook, B. A. Barrionuevo, J. M. Jaworski, M. A. Schmidt, J. L. Haines, M. L. Cuccaro, J. R. Gilbert, M. A. Pericak-Vance.

10/11:15 The discovery and validation of genes recurrently disrupted in autism spectrum disorders. B. J. O'Roak, L. Vives, A. Kumar, I. B. Stanaway, J. Egertson, E. Turner, C. Lee, G. L. Carvil, I. G. Phelps, D. R. O'Day, W. Fu, J. Hiatt, B. Martin, N. Krumm, B. P. Coe, R. Levy, E. Borenstein, D. A. Nickerson, H. C. Mefford, D. Doherty, J. M. Akey, R. Bernier, E. E. Eichler, J. A. Shendure.

11/11:30 Rare complete human knockouts: Population distribution and significant role in autism spectrum disorders. E. T. Lim, M. J. Daly, ARRA Autism Sequencing Consortium.

12/11:45 Exome-based discovery of CNVs in simplex autism families. N. Krumm, B. Nelson, S. Girirajan, M. Dennis, C. Baker, M. Malig, NHLBI Exome Sequencing Project, A. Quinlan, D. A. Nickerson, E. E. Eichler.

13/12:00 Delta catenin (CTNND2): Genetics and function of a novel autism gene. T. Turner, E. Oh, Y. Liu, M. X. Sosa, S. Sanders, K. Sharma, D. Moreno-De-Luca, T. Plona, K. Pike, D. Soppet, M. W. Smith, M. State, S. W. Cheung, C. Lese Martin, R. Huganir, E. Cook, N. Katsanis, A. Chakravarti.

14/12:15 Novel hotspots of recurrent copy number variation associated with autism spectrum disorder. S. Girirajan, M. Y. Dennis, C. Baker, M. M. Malig, B. P. Coe, C. D. Campbell, K. Mark, T. Vu, C. Alkan, Z. Cheng, R. Bernier, E. E. Eichler.

15/12:30 Cluster analysis defines subgroups of phenotypic expression for autism spectrum disorders. O. J. Veatch, B. Yaspan, N. Schnetz-Boutaud, M. A. Pericak-Vance, J. L. Haines.

Wednesday, November 7

10:30 AM–12:45 PM

Concurrent Platform (abstract-driven) Session A (11-19)

SESSION 12 – New Methods for Big Data

Gateway Ballroom 103, Lower Level South, Moscone Center

Moderators: Elizabeth Marchani, Univ. of Washington
  Rita Cantor-Chiu, UCLA Sch. of Med.

16/10:30 The detection, structure and uses of haplotype identity in population genetic data. D. Xifara, I. Mathieson, G. McVean.

17/10:45 Inferring and sequencing the founding bottleneck of Ashkenazim. I. Pe'er, S. Carmi, S. Mukherjee, N. Parlamee, M. Bowen, K. Hui, V. Joseph, P. F. Palamara, L. Ozelius, I. Peter, A. Darvasi, K. Offit, H. Ostrer, J. Cho, L. Clark, G. Atzmon, T. Lencz, Ashkenazi Genome Consortium.

18/11:00 Statistical methods for association test of rare variants using summarized data without individual-subject information. Q. Zhang, I. Borecki, M. A. Province.

19/11:15 Testing for rare variant associations in the presence of missing data. P. Livermore Auer, S. Leal, G. Wang, NHLBI Exome Sequencing Project.

20/11:30 Quantitative trait locus analysis for next-generation sequencing with the functional linear models. M. Xiong, L. Luo, Y. Zhu.

21/11:45 A rapid and powerful method for protein-protein interaction- and pathway-based association analysis in genome-wide association studies. M. Li, S. Kwan, H. Gui, P. Sham.

22/12:00 Statistics for X-chromosome association. U. Ozbek, D. E. Weeks, W. Chen, J. Shaffer, S. M. Purcell, E. Feingold.

23/12:15 Joint association analysis of pleiotropy SNPs using GWAS summary statistics. R. M. Salem, J. N. Hirschhorn.

24/12:30 Multivariate regression-based analysis of relative abundance data in metagenomics. O. Libiger, N. J. Schork.

Wednesday, November 7

10:30 AM–12:45 PM

Concurrent Platform (abstract-driven) Session A (11-19)

SESSION 13 – Cancer Genetics I: Rare Variants

Room 135, Lower Level North, Moscone Center

Moderators: Ellen L. Goode, Mayo Clin. Col. of Med.
  John D. McPherson, Ontario Inst. for Cancer Res., Canada

25/10:30 Exome sequencing of more than 6,700 samples and the study of genetic susceptibility to common cancer. A. Kiezun, A. McKenna, G. Kryukov, G. Getz.

26/10:45 Exome sequencing of families severely affected with breast cancer suggests eight new candidate genes: ATR, BAP1, CHEK1, GEN1, KANK4, OBSL1, RAD51B and TP53BP1. C. H. Spurrell, A. M. Thornton, M. K. Lee, S. Casadei, S. Ng, T. Walsh, J. Shendure, M.-C. King.

27/11:00 Rare variants in XRCC2 as breast cancer susceptibility alleles. F. S. Hilbers, M. C. Völker-Albert, W. W. Wiegant, M. P. G. Vreeswijk, N. Hoogerbrugge, J. C. Oosterwijk, J. M. Collee, M. C. Southey, P. Peterlongo, P. Radice, F. J. Couch, K. Offit, I. G. Campbell, J. Benitez, C. J. van Asperen, H. van Attikum, P. Devilee.

28/11:15 HOXB13 is a susceptibility gene for prostate cancer: Results from the International Consortium for Prostate Cancer Genetics. K. Cooney, W. Isaacs, J. Xu, E. Lange, L. Lu, S. Zheng, Z. Wong, L. Cannon-Albright, J. Stanford, E. A. Ostrander, C. Maier, J. Schleutker, D. Schaid, S. Thibodeau, G. Cancel-Tassin, F. Wiklund, R. Eeles, D. Easton, A. Wittemore, G. Giles, W. Catalona, D. Mandal, W. Foulkes, J. Carpten, D. Seminara on behalf of International Consortium for Prostate Cancer Genetics.

29/11:30 Parkinson disease and melanoma: A common genetic pathway linked to PARKIN inactivation. H. Hu, N. Dumaz, S. Lesage, L. Michel, V. Descamps, S. Mourah, C. Lebbé, N. Basset-Seguin, M. Bagot, A. Bensussan, L. Deschamps, M.-T. Leccia, A. Tsalamlal, P. Sivaramakrishna Rachakonda, S. Klebe, K. Rajive, C. Kannengiesser, A. Couvelard, B. Grandchamp, L. Thomas, A. Brice, N. Soufir.

30/11:45 Exome sequencing in families at high risk for lymphoid malignancies. L. R. Goldin, M. L. McMaster, M. Rotunno, K. B. Jacobs, L. Burdette, M. Malasky, A. Hutchinson, M. Cullen, J. Boland, M. Yeager, M. A. Tucker, S. J. Chanock, N. E. Caporaso.

31/12:00 Rare allelic forms of PRDM9 associated with childhood leukemia. J. Hussin, D. Sinnett, F. Casals, Y. Idaghdour, V. Bruat, V. Saillour, J.-C. Grenier, J. Healy, T. de Malliard, J.-F. Spinella, M. Lariviere, S. Busche, G. Gibson, A. Andersson, L. Holmfeldt, J. Ma, L. Wei, J. Zhang, G. Andelfinger, J. R. Downing, C. M. Mullighan, P. Awadalla.

32/12:15 De novo mutation of the TGF beta family in early-onset ovarian cancer. I. Tournier, F. Charbonnier, S. Coutant, K. Walton, R. Marlin, M. Vezain, J. Tinat, E. Angot, R. Sesboué, J.-C. Sabourin, D. Vaur, C. Harrison, T. Frebourg.

33/12:30 Somatic activating mutations in PIK3CA cause progressive segmental overgrowth. M. J. Lindhurst, V. E. R. Parker, F. Payne, J. C. Sapp, S. Rudge, J. Harris, A. M. Witkowski, Q. Zhang, M. P. Groeneveld, C. E. Scott, A. Daly, S. M. Huson, L. L. Tosi, M. L. Cunningham, T. N. Darling, J. Geer, Z. Gucev, P. A. Kreiger, V. R. Sutton, M. M. Thacker, C. Tziotzios, A. K. Dixon, T. Helliwell, S. O'Rahilly, D. B. Savage, M. J. O. Wakelam, R. K. Semple, I. Barroso, L. G. Biesecker.

Wednesday, November 7

10:30 AM–12:45 PM

Concurrent Platform (abstract-driven) Session A (11-19)

SESSION 14 – Quantitation and Measurement of Regulatory Oversight by the Cell

Room 134, Lower Level North, Moscone Center

Moderators: Richard M. Myers, HudsonAlpha Inst. for Biotechnol., Huntsville, AL
  Jeffrey C. Barrett, Wellcome Trust Sanger Inst. UK

34/10:30 ChipEnrich: Gene set enrichment testing for ChIP-seq data. R. P. Welch, C. Lee, L. J. Scott, R. A. Smith, P. Imbriano, M. A. Sartor.

35/10:45 Enhanced exome sequencing to capture genome-wide common variants. I. C. R. M. Kolder, K. I. Morley, E. Birney, I. Dunham, J. C. Barrett.

36/11:00 Complete HIV-1 genomes from sequencing single molecules: Simple and complex samples. M. P. S. Brown, M. Schaefer, Y. Gao, W. Kilembe, S. Allen, E. Hunter, E. E. Paxinos.

37/11:15 DeTCT pipeline: A software pipeline for the analysis of transcript count data. J. A. Morris, J. E. Collins, I. Sealy, N. Wali, E. Busch-Netwich, R. White, D. L. Stemple, J. C. Barrett.

38/11:30 Fast genome-wide QTL association mapping with pedigrees. H. Zhou, E. M. Sobel, K. Lange.

39/11:45 Discovering SNPs regulating human gene expression using allele specific expression from RNA-seq data. E. Eskin, E. Kang, B. Han, A. J. Lusis, L. Martin, S. Shiffman.

40/12:00 Association of genetic variation affecting exon skipping to disease susceptibility. Y. Lee, H. Im, W. Hernandez, N. J. Cox.

41/12:15 Haplotype-based variant detection and interpretation enables the population-scale analysis of multi-nucleotide sequence variants. E. Garrison, J. A. Rosenfeld, D. MacArthur, Y. Xue, Z. Iqbal, S. Balasubramanian, L. Habegger, R. Poplin, M. A. DePristo, G. Marth, M. B. Gerstein, C. Tyler-Smith, 1000 Genomes Project.

42/12:30 eQTL analysis identifies novel associations between genotype and gene expression in the human intestine. B. Kabakchiev, NIDDK IBD Genetics Consortium, M. S. Silverberg.

Wednesday, November 7

10:30 AM–12:45 PM

Concurrent Platform (abstract-driven) Session A (11-19)

SESSION 15 – New Loci for Obesity, Diabetes, and Related Traits

Gateway Ballroom 104, Lower Level South, Moscone Center

Moderators: Jose Florez, Massachusetts Gen. Hosp.
  Richa Saxena, Massachusetts Gen. Hosp.

43/10:30 A genome-wide association analysis of early-onset severe obesity: The SCOOP project. E. Wheeler, N. Huang, E. Bochukova, S. Lindsay, J. Keogh, R. J. F. Loos, N. J. Wareham, S. O'Rahilly, M. Hurles, I. Barroso, I. S. Farooqi.

44/10:45 Mapping obesity traits using an integrated ‘omics’ approach in adipose tissue from female twins. A. K. Hedman, J. K. Sandling, E. Grundberg, K. S. Small, E. Meduri, S. Keildson, A. Nica, A. Buil, J. T. Bell, J. Nisbet, M. Sekowska, A. Wilk, A. Barrett, N. Hassanali, T.-P. Yang, D. Glass, S.-Y. Shin, L. Parts, N. Soranzo, R. Durbin, K. Ahmadi, K. T. Zondervan, C. M. Lindgren, T. D. Spector, E. T. Dermitzakis, M. I. McCarthy, P. Deloukas for MuTHER Consortium.

45/11:00 Whole exome sequencing identifies candidate causal genes for severe insulin resistance. F. Payne, A. Daly, W. Bottomley, E. Raffan, E. Goncalves Serra, A. Thompson, D. B. Savage, R. K. Semple, S. O'Rahilly, I. Barroso, UK10K Consortium.

46/11:15 Exome analysis in 8,232 Finnish men identifies novel loci and low-frequency variants for insulin processing and secretion. J. R. Huyghe, A. U. Jackson, M. P. Fogarty, A. Stančáková, H. M. Stringham, M. L. Buchkovich, C. Fuchsberger, J. Paananen, P. S. Chines, T. M. Teslovich, J. M. Romm, H. Ling, I. McMullen, R. Ingersoll, E. W. Pugh, K. F. Doheny, J. Kuusisto, L. J. Scott, F. S. Collins, G. R. Abecasis, R. M. Watanabe, M. Boehnke, M. Laakso, K. L. Mohlke.

47/11:30 Global genomic and transcriptomic variation in human pancreatic islets reveals novel loci associated with type 2 diabetes and related traits. J. Fadista, P. Vikman, I. Mollet, E. O. Laakso, U. Krus, O. Hansson, L. Groop.

48/11:45 Identification of a novel genome-wide significant association with type 2 diabetes risk in Mexican and Mexican Americans. A. L. Williams, H. García-Ortiz, M. J. Gómez-Vázquez, C. A. Haiman, A. Huerta-Chagoya, A. K. Manning, C. Márquez-Luna, H. Moreno-Macías for SIGMA Type 2 Diabetes Consortium.

49/12:00 Discovery and fine-mapping of type 2 diabetes susceptibility loci through trans-ethnic meta-analysis. A. Mahajan, J. E. Below, W. Zhang, M. J. Go, E. Parra, A. P. Morris, AGEN-T2D, DIAGRAM, MA-T2D and SA-T2D Consortia.

50/12:15 TCF7L2 genetic variation is associated with impaired incretin effect and lower glucagon. B. Chamarthi, K. R. Littleton, V. Kaur, L. Chen, A. K. Manning, M. K. Thomas, M. S. Hudson, J. C. Florez.

51/12:30 Novel locus including FGF21 is associated with dietary macronutrient intake. A. Y. Chu, T. Workalemahu, N. P. Paynter, L. M. Rose, F. Giulianini, CHARGE Nutrition Working Group, Q. Qi, G. C. Curhan, E. B. Rimm, D. J. Hunter, L. R. Pasquale, P. M. Ridker, F. B. Hu, D. I. Chasman, L. Qi on behalf of DietGen Consortium.

Wednesday, November 7

10:30 AM–12:45 PM

Concurrent Platform (abstract-driven) Session A (11-19)

SESSION 16 – Neuromuscular Disease and Deafness

Room 124, Lower Level North, Moscone Center

Moderators: Anthony Antonellis, Univ. of Michigan
  Thomas Glover, Univ. of Michigan

52/10:30 The TRK-fused gene is mutated in hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P). H. Ishiura, W. Sako, M. Yoshida, T. Kawarai, O. Tanabe, J. Goto, Y. Takahashi, H. Date, J. Mitsui, B. Ahsan, Y. Ichikawa, A. Iwata, H. Yoshino, Y. Izumi, K. Fujita, K. Maeda, S. Goto, H. Koizumi, R. Morigaki, M. Ikemura, N. Yamauchi, S. Murayama, G. Nicholson, H. Ito, G. Sobue, M. Nakagawa, R. Kaji, S. Tsuji.

53/10:45 Mutation in the autophagy-related TECPR2 gene causes hereditary spastic paraparesis. D. Oz-Levi, B. Ben-Zeev, E. Ruzzo, Y. Hitomi, A. Gelman, K. Pelak, Y. Anikster, H. Reznik-Wolf, I. Bar-Joseph, T. Olender, A. Alkelai, M. Weiss, E. Ben-Asher, D. Ge, K. Shianna, Z. Elazar, D. Goldstein, E. Pras, D. Lancet.

54/11:00 Spinal muscular atrophy associated with progressive myoclonic epilepsy is caused by mutations in ASAH1. J. Melki, J. Zhou, M. Tawk, F. D. Tiziano, J. Veillet, M. Bayés, F. Nolent, V. Garcia, S. Servidei, E. Bertini, F. Castro-Giner, Y. Renda, S. Carpentier, N. Andrieu-Abadie, I. Gut, T. Levade, H. Topaloglu.

55/11:15 Genetic variants in chromatin modifying genes cause D4Z4 hypomethylation, DUX4 expression, and contraction-independent facioscapulohumeral muscular dystrophy (FSHD2). D. G. Miller, R. J. L. F. Lemmers, L. M. Petek, J. Balog, P. J. van der Vliet, G. J. Block, J. W. Lim, G. N. Filippova, A. M. Amell, G. W. E. Santen, B. Bakker, M. J. Bamshad, S. J. Tapscott, R. Tawil, S. M. van der Maarel.

56/11:30 Unexpected extension of the phenotype spectrum associated with SMAD3 mutations in aneurysms-osteoarthritis syndrome. M. Aubart, D. Gobert, N. Hanna, C. Muti, J. Roume, V. Cusin, B. Grandchamp, L. Gouya, D. Detains, G. Jondeau, C. Boileau.

57/11:45 Whole-exome sequencing for autosomal recessive non-syndromic deafness: 93% of known genes covered and OTOGL and SLITRK6 are novel genes. M. Tekin, O. Diaz-Horta, D. Duman, J. Foster II, A. Sirmaci, M. Gonzalez, N. Mahdieh, M. Bonyadi, F. B. Cengiz, R. Ulloa, S. Zuchner, S. Blanton.

58/12:00 Whole exome sequencing and more to unravel the genetics and genotype-phenotype correlations for deafness. H. Kremer, M. Schraders, C. Zazo Seco, J. Oostrik, I. Feenstra, A. M. M. Oonk, E. van Beelen, M. van Bers, K. Neveling, J. A. Veltman, R. J. C. Admiraal, H. P. M. Kunst, R. J. E. Pennings, E. H. Hoefsloot.

59/12:15 A mutation in Ca2+ binding protein 2, expressed in cochlear inner hair cells, causes autosomal recessive hearing impairment. I. Schrauwen, S. Helfmann, A. Inagaki, F. Wolk, M. A. Tabatabaiefar, M. M. Picher, M. Sommen, C. Zazo Seco, H. Kremer, A. Dheedene, C. Claes, E. Fransen, M. A. Chaleshtori, P. Coucke, A. Lee, T. Moser, G. Van Camp.

60/12:30 Comprehensive diagnosis for hearing loss using personal genomics: The first 100 cases. E. Shearer, E. A. Black-Ziegelbein, M. S. Hildebrand, A. P. DeLuca, R. W. Eppsteiner, S. E. Scherer, T. E. Scheetz, T. L. Casavant, R. J. H. Smith.

Wednesday, November 7

10:30 AM–12:45 PM

Concurrent Platform (abstract-driven) Session A (11-19)

SESSION 17 – Chromosomes and Disease

Room 132, Lower Level North, Moscone Center

Moderators: Christa Lese Martin, Emory Univ.
  Blake Ballif, Signature Genomics, Spokane, WA

61/10:30 Characterization of de novo copy-number variations in two subjects with a constitutional “CNV mutator” phenotype. P. Liu, K. Walter, K. Writzl, V. Gelowani, S. Lindsay, C. M. B. Carvalho, M. Withers, J. Wiszniewska, A. Patel, B. Rautenstrauss, M. Hurles, J. R. Lupski.

62/10:45 Associations between gene expression and phenotypes in 16p11.2 rearrangements. E. Migliavacca, K. Mannik, F. Zufferey, N. D. Beckmann, L. Harewood, A. Mace, Z. Kutalik, L. Hippolyte, A. Maillard, V. Siffredi, R. M. Witwicki, G. Didelot, S. Jacquemont, S. Bergmann, J. S. Beckmann, 16p11.2 European Consortium Collaborators.

63/11:00 De novo triplication can arise from a duplication of the 17p12 region and confers a severe Charcot-Marie-Tooth, type 1A phenotype. V. Gelowani, P. Liu, F. Zhang, S. B. Shachar, S. D. Batish, E. Roney, V. Drory, A. Orr-Urtreger, J. R. Lupski.

64/11:15 A long, non-coding RNA from the Prader-Willi critical region forms a subnuclear cloud and recruits transcriptional activating complexes to the Snord116 locus in postnatal neurons. W. T. Powell, R. Coulson, F. Crary, S. Wong, D. H. Yasui, J. M. LaSalle.

65/11:30 Molecular analysis of patients whose clinical features overlap the 22q11.2 deletion syndrome. S. Saitta, T. Busse, D. McDonald-McGinn, E. Zackai, S. Woyciechowski, J. Garbarini, E. Goldmuntz, C. Van Ravenswaaij, L. Hoefsloot, B. Emanuel, D. Driscoll.

66/11:45 Mouse model implicates GNB3copy number in a novel childhood obesity syndrome. I. S. Goldlust, K. E. Hermetz, L. M. Catalano, R. A. Cozad, R. T. Barfield, K. N. Conneely, J. G. Mulle, S. Dharamrup, M. Hegde, K. Kim, B. Angle, A. Colley, A. E. Webb, E. C. Thorland, J. Ellison, J. Rosenfeld, B. C. Ballif, L. G. Shaffer, L. A. Demmer, Unique Rare Chromosome Support, M. K. Rudd.

67/12:00 Modeling neurogenesis impairment in Down syndrome using induced pluripotent stem cells from monozygotic twins discordant for trisomy 21. Y. Hibaoui, I. Grad, S. R. Sailani, A. Letourneau, S. Dahoun, S. Gimelli, M. F. Pelte, F. Béna, S. E. Antonarakis, A. Feki.

68/12:15 Discovery and interpretation of balanced chromosomal aberrations in neurodevelopmental abnormalities and prenatal diagnostics. M. E. Talkowski, V. Pillalamarri, I. Blumenthal, C. Hanscom, Z. Ordulu, J. Rosenfeld, L. G. Shaffer, J. F. Gusella, C. C. Morton.

69/12:30 Predisposition of acrocentric short arm fusions due to nuclear location, nucleolar disorganization, and telomere-induced DNA damage. K. M. Stimpson, L. L. Sullivan, S. Chen, B. A. Sullivan.

Wednesday, November 7

10:30 AM–12:45 PM

Concurrent Platform (abstract-driven) Session A (11-19)

SESSION 18 – Prenatal and Perinatal Genetics

Room 130, Lower Level North, Moscone Center

Moderators: Natalie Blagowidow, Harvey Inst. for Human Genet., Baltimore
  David Chitayat, Mount Sinai Hosp., Toronto, Canada

70/10:30 Lessons learned from next-gen cytogenetics: Whole genome sequence-based prenatal diagnosis of apparently balanced de novo chromosome rearrangements. Z. Ordulu, M. Talkowski, V. Pillalamarri, S. Pereira, I. Blumenthal, C. Hanscom, A. M. Lindgren, N. Hussain, S. Connolly, L. E. Wilkins-Haug, J. F. Gusella, C. C. Morton.

71/10:45 The use of chromosome microarray analysis as a first-line test in pregnancies with a priori low risk for detection of submicroscopic chromosomal abnormalities. F. Fiorentino, S. Napoletano, C. Caiazzo, M. Sessa, S. Bono, L. Spizzichino, S. Michiorri, A. Gordon, A. Nuccitelli, G. Rizzo, M. Baldi.

72/11:00 The challenge of preconceptional, preimplantation, and prenatal genetic diagnoses of mitochondrial DNA disorders. J. Steffann, S. Monnot, N. Gigarel, P. Vachin, E. Herzog, P. Burlet, N. Frydman, A. Benachi, G. Chalouhi, Y. Ville, R. Frydman, A.-S. Lebre, A. Rotig, D. C. Samuels, C. Elie, A. Munnich, J.-P. Bonnefont.

73/11:15 The incidence and spectrum of genomic imbalance in products of conception: New insights from SNP microarray analysis of 2,400 miscarriage specimens. B. Levy, S. Sigurjonsson, B. J. Pettersen, M. K. Maisenbacher, Z. P. Demko, R. Lathi, R. Tao, V. Aggarwal, M. Rabinowitz.

74/11:30 Noninvasive whole-genome sequencing of a human fetus. J. O. Kitzman, M. W. Snyder, M. Ventura, A. P. Lewis, R. Qiu, L. E. Simmons, H. S. Gammill, C. E. Rubens, D. A. Santillan, M. K. Santillan, J. C. Murray, H. K. Tabor, M. J. Bamshad, E. E. Eichler, J. A. Shendure.

75/11:45 Spina bifida risk is conferred by multiple polymorphisms in folate one-carbon pathway genes. D. Gilbert, K. Lazaruk, J. Stein, J. Hardin, J. Witte, G. Shaw, E. Lammer, N. Marini, J. Rine.

76/12:00 Bioinformatics approach for identifying the genetic contributions to preeclampsia. A. Uzun, I. Kurihara, J. Tavormina, R. Cabezas, A. Laliberte, A. Dewan, E. Triche, J. Padbury.

77/12:15 Antenatal spectrum of CHARGE syndrome in 40 fetuses with CHD7 mutations. M. Legendre, M. Gonzales, G. Goudefroye, F. Bilan, P. Parisot, M. J. Perez, M. Bonnière, B. Bessières, J. Martinovic, A.-L. Delezoide, F. Jossic, C. Fallet-Bianco, M. Bucourt, J. Tantau, P. Loget, L. Loeuillet, N. Laurent, B. Leroy, H. Salhi, C. Rouleau, F. Guimiot, C. Chelin, A. Bazin, C. Alby, A. Kitzis, Y. Ville, F. Encha-Razavi, B. Gilbert-Dussardier, M. Vekemans, T. Attié-Bitach, SOFFOET.

78/12:30 Genetic normalization of day-3 embryos: Results from two independent preimplantation genetic screening laboratories. P. Brezina, E. Littman, Y. Sun, V. Phan, R. Anchan, A. Barker, M. Hughes, G. R. Cutting, W. G. Kearns.

Wednesday, November 7

10:30 AM–12:45 PM

Concurrent Platform (abstract-driven) Session A (11-19)

SESSION 19 – Vascular and Congenital Heart Disease

Room 123, Lower Level North, Moscone Center

Moderators: Amy Roberts, Children's Hosp. Boston
  Bart L. Loeys, Univ. of Antwerp., Belgium

79/10:30 Heterozygous germline mutations in a prototypical TGFβ repressor cause Shprintzen-Goldberg syndrome with aortic aneurysm. A. J. Doyle, J. J. Doyle, M. E. Lindsay, S. L. Bessling, N. Huso, D. Schepers, L. Gillis, G. Mortier, L. Van Laer, D. W. Mohr, M. J. Caulfield, A. F. Scott, C. J. Curry, B. Loeys, A. S. McCallion, H. C. Dietz.

80/10:45 Loss-of-function mutations in TGFB2 cause Loeys-Dietz syndrome: Towards solving the TGFβ paradox in aortic aneurysmal disease. B. Loeys, M. E. Lindsay, D. Schepers, N. Ajit Bolar, J. Doyle, E. Gallo, J. Fert-Bober, M. J. E. Kempers, E. Fishman, Y. Chen, L. Myers, D. Bjeda, G. Oswald, B. M. Anderlid, M. Y. Yang, E. M. H. F. Bongers, J. Timmermans, A. C. Braverman, N. Canham, G. R. Mortier, H. G. Brunner, P. H. Byers, J. Van Eyk, L. Van Laer, H. Dietz.

81/11:00 Genetic dissection of aortic disease in the Marfan syndrome. F. Ramirez, L. Carta, M. Del Solar, M. Lindsay, H. Dietz, J. R. Cook.

82/11:15 Bicuspid aortic valve, aortic coarctation and patent ductus associated with MATR3 disruption in human and mouse. F. Quintero-Rivera, Q. J. Xi, K. M. Keppler-Noreuil, J. H. Lee, A. W. Higgins, R. Anchan, A. E. Roberts, G. A. P. Bruns, R. Berezney, B. D. Gelb, R. V. Lacro, D. J. Harris, A. Kamp, I. P. Moskowitz, W. Lu, C. C. Morton, J. F. Gusella, R. L. Maas.

83/11:30 Identification of the cause of blue rubber bleb nevus syndrome. J. Soblet, N. Limaye, M. Cordisco, A. Dompmartin, O. Enjolras, S. Holden, A. D. Irvine, C. Labrèze, A. Lanoel, P. N. Rieu, S. Syed, C. J. van der Vleuten, R. Watson, S. J. Fishman, J. B. Mulliken, L. M. Boon, M. Vikkula.

84/11:45 Identifying genetic determinants of congenital heart defect in Down syndrome. M. R. Sailani, P. Makrythanasis, S. Deutsch, A. Valsesia, E. Migliavacca, F. Santoni, A. Sharp, C. Serra-Juhe, S. Vicari, R. Rabionet, Y. Grattau, G. Dembour, A. Megarbane, R. Touraine, S. Kitsiou, H. Fryssira, C. Chatzisevastou-Loukidou, E. Kanavakis, G. Merla, L. Perez-Jurado, X. Estivill, J. Delabar, S. E. Antonarakis.

85/12:00 Transcriptome-wide decreased variation in gene expression of Down syndrome fibroblasts: Selection or canalization? K. Popadin, A. Letourneau, F. Santoni, S. E. Antonarakis.

86/12:15 Mutations in OLFML2B within the QT interval associated region 1q23.3 disturb cardiac repolarization, predispose to Long-QT syndrome and to sudden infant death syndrome. A. Pfeufer, C. Congiu, Z. Schäfer, H. Prucha, M. Vennemann, I. Sinicina, N. Strutz-Seebohm, H. Kartmann, M. Schell, E. Kremmer, E. R. Behr, N. H. Bishopric, R. J. Myerburg, L. Crotti, P. J. Schwartz, A. A. Hicks, P. P. Pramstaller, W. Rottbauer, S. Kääb, T. Meitinger, M. Näbauer, M. Cohen, M. Donner, D. T. Mage, H. W. Mewes, T. Bajanowski, G. Seebohm, M. Ueffing, C. J. Gloeckner.

87/12:30 The impact of inherited genetic variants associated with lipid profile, hypertension, and coronary artery disease on the risk of intracranial and abdominal aortic aneurysms. F. N. G. van 't Hof, Y. M. Ruigrok, A. F. Baas, L. A. L. M. Kiemeney, S. H. Vermeulen, A. G. Uitterlinden, F. Rivadeneira, A. Hofman, G. J. E. Rinkel, P. I. W. de Bakker.

Wednesday, November 7

4:30 PM–6:30 PM

SESSION 20 – Invited Presidential Symposium: Gene Discovery and Patent Law: Present Experience in the U.S. and in Europe

Hall D, Lower Level North, Moscone Center

With the present extraordinary pace of gene discovery, the question of who, if anyone, owns newly discovered genes will be critical to research and practice in human genetics. This issue was before the U.S. Supreme Court and remanded to the Federal Circuit Court of Appeals as Association for Molecular Pathology et al. v. Myriad Genetics, No. 11-725 where the decision was affirmed. In order to understand the many legal issues represented by this case, the role of this case in the larger context of legal issues in genetics, and the consequences of the decision on this case for research and services in human genetics, we have asked a panel of experts to educate us.

Hank Greely, Professor of Law and Director of the Center for Law and Biosciences at Stanford University, will moderate the panel and present an overview of issues on which genetics and the law have come in contact in the U.S.

Mark Lemley, Professor of Law and Director of the Program in Law, Science, and Technology at Stanford University, will describe the meaning of patents in the context of intellectual property in general and gene discovery in particular.

Lori Andrews, Professor of Law at IIT Chicago-Kent College of Law and Fellow of the Hastings Institution, will describe the issues of the Myriad case and the roles of lawyers, practitioners and advocates in the evolution of the case.

Gert Matthijs, Professor and Head of the Laboratory for Molecular Diagnostics at the Center for Human Genetics at University of Leuven, Belgium, will discuss the challenge to gene patenting brought to the European Patent Office by European human geneticists, the consequences for genetics services of the 2008 EPO decisions, and the present issues of gene patents in Europe.

We intend these presentations to be educational rather than confrontational. Each speaker will present both their own views and alternative, opposing points of view. Our goal is to understand the complexity of these issues from the legal perspective. Considerable time after the presentations will be devoted to answering questions from the audience. We hope ASHG members will enjoy looking at these questions from a different angle and will find this perspective useful in their future research.


Thursday, November 8

8:00 AM–10:00 AM

Concurrent Invited Session II (21-28)

SESSION 21 – Mendelian Randomization: Using Genetic Variants to Inform Causality in Observational Epidemiology

Room 135, Lower Level North, Moscone Center

Moderators: David M. Evans, Univ. of Bristol, U.K.
  Lyle J. Palmer, Univ. of Ontario, Canada

A central problem in classical observational epidemiology concerns whether an association between a medically relevant exposure and a disease outcome reflects a causal relationship, or whether the purported association is a spurious result of latent confounding, bias or reverse causality. For example, does an inverse correlation between red wine drinking and heart disease, mean that red wine prevents heart attacks? The gold standard in proving whether an association reflects a causal relationship is the randomized controlled trial (RCT), in which participants are randomly assigned into groups that differ on average only in terms of their treatment (exposure) effect. However, RCTs are typically expensive, of long duration and in some cases, ethically or practically infeasible to implement. Mendelian randomization is a relatively new methodology that uses genetic variants that have been robustly associated with medically relevant exposures from genetic association studies (e.g. genetic variants related to BMI, smoking, alcohol etc.) to determine whether these exposures are truly causally related to disease outcomes. This session describes the principles behind Mendelian randomization, explains how Mendelian randomization can be used in epidemiological and gene expression studies to assess causality, describes its assumptions and limitations, and finally discusses extensions and promising alternatives to the method.


8:00 AM   Mendelian randomization: Overcoming the limitations. G. D. Smith. Univ. of Bristol, U.K.

8:30 AM   Utilizing multiple variants to improve Mendelian randomization studies. B. Pierce. Univ. of Chicago.

9:00 AM   Application of Mendelian randomization analyses in prospective studies from Denmark. A. Tybjærg-Hansen. Univ. of Copenhagen, Denmark.

9:30 AM   Mendelian randomization for HDL levels and implications for clinical risk prediction. B. F. Voight. Univ. of Pennsylvania Sch. of Med.

Thursday, November 8

8:00 AM–10:00 AM

Concurrent Invited Session II (21-28)

SESSION 22 – Common and Rare CNVs: Genesis, Patterns of Variations and Human Diseases

Hall D, Lower Level North, Moscone Center

Moderators: Chack Yung Yu, Nationwide Children's Hosp. and The Ohio State Univ.
  Edward J. Hollox, Univ. of Leicester, U.K.

Copy number variation (CNV) is a part of human genomic variation. There are two types of CNVs. The first type is common CNVs that occur at regions with complex genomic structures and engage genes involving in gene-environment interactions. The diversity of common CNVs both in terms of copy number and sequence variation is remarkable, yet because of their complex and challenging nature, they are under-studied. The second type is de novo or recent CNVs involving deletions and duplications of genomic DNA fragments that are rare individually but moderately frequent collectively, particularly among subjects with developmental, neurologic and psychiatric disorders. This session will highlight the complexity of common CNVs and discuss their roles in immune-mediated and cognitive diseases. In addition, the session will feature mechanistic studies to understand the generation of CNVs, and illustrate techniques for the detection and quantification of common and rare CNVs.


8:00 AM   CNVs engaged in immune complex handling and autoimmune diseases: Complement C4 and immunoglobulin Fc-gamma receptors. C. Y. Yu. Nationwide Children’s Hosp. and The Ohio State Univ.

8:30 AM   Human lineage-specific CNVs: DUF1220 domain copy number linked to cognitive disease and brain evolution. J. M. Sikela. Univ. of Colorado Sch. of Med., Aurora.

8:55 AM   TAR: A mixed genomic disorder caused by a low-frequency regulatory SNP combined with a 1q21.1 microdeletion. W. H. Ouwehand. Cambridge Univ. and Wellcome Trust Sanger Inst., Cambridge, U.K.

9:20 AM   Genetic and environmental risk factors for de novo CNVs. T. W. Glover. Univ. of Michigan.

9:40 AM   Frequency estimation of low-level somatic mosaicism for pathogenic CNVs. P. T. Stankiewicz. Baylor Col. of Med.

Thursday, November 8

8:00 AM–10:00 AM

Concurrent Invited Session II (21-28)

SESSION 23 – Advancing Gene Therapy to the Clinic: Molecular Medicines Come of Age

Gateway Ballroom 104, Lower Level South, Moscone Center

Moderator: Beverly Davidson, Univ. of Iowa

The first evidence for uptake and expression of exogenous DNA in mammalian cells occurred in the 60s and 70s, and in 1980 the first experiment was performed in which patients were given plasmid DNA expressing protein lacking in their blood cells. Over the next 25 years researchers focused on improved vector development and better delivery modalities, along with more appropriate clinical trial design, to improve the chances to positively impact disease course in patients with genetic diseases. In this symposium we will present exciting advances in gene therapy for the eye (Jean Bennett), the liver (Kathy High), blood disorders (Maria-Gracia Roncolo), the leukodystrophies (Nathalie Cartier), and lysosomal storage diseases affecting the brain (Beverly Davidson). Data presented will span from preclinical studies in animal models to advanced clinical trials in affected individuals using several vector platforms.


8:00 AM   Safety and efficacy of AAV-mediated gene transfer to liver for severe hemophilia B. K. High. Children’s Hosp. of Philadelphia.

8:25 AM   Safety and efficacy after AAV2 re-administration in subjects with congenital blindness due to RPE65 mutations. J. Bennett. Univ. of Pennsylvania.

8:45 AM   Advancing gene therapy for ADA-SCID and beyond. M-G. Roncarolo. Univ. Vita-Salute San Raffaele., Milan, Italy.

9:10 AM   Gene therapy for the leukodystrophies. N. Cartier. Saint Vincent de Paul Hosp., Paris, France.

9:30 AM   AAV gene therapy for childhood onset neurological disease caused by lysosomal enzyme deficiencies. B. Davidson. Univ. of Iowa.

Thursday, November 8

8:00 AM–10:00 AM

Concurrent Invited Session II (21-28)

SESSION 24 – RNA Splicing in Human Development, Diseases and Natural Variation

Room 124, Lower Level North, Moscone Center

Moderators: David E. Symer, The Ohio State Univ. Comprehen. Cancer Ctr.
  Richard A. Padgett, Lerner Res. Inst., Cleveland

RNA splicing has been identified and studied for decades, but its roles in normal human biology and in contributing to human diseases have not been fully described to date. The presentations in this session will address the latest breakthroughs in understanding how RNA splicing and processing contribute to human development, diseases including various cancers and neurodegeneration, and natural variation. Also discussed will be the development of animal models of aberrant RNA splicing, and optimization of the latest technologies of RNA-seq and bioinformatics analysis of RNA splicing variation.


8:00 AM   Functional consequences of minor spliceosomal snRNA mutations in human development and natural variation. D. E. Symer. The Ohio State Univ. Comprehen. Cancer Ctr.

8:25 AM   Multicopy snRNA genes and neurodegeneration. S. L. Ackerman. HHMI/The Jackson Lab., Bar Harbor, ME.

8:50 AM   Understanding the chemical mechanisms and biological implications of splicing reactions. R. A. Padgett. Lerner Res. Inst., Cleveland.

9:15 AM   Overlaying RNA maps onto human disease. R. B. Darnell. HHMI and Rockefeller Univ.

9:40 AM   "Seq-ing" the Myotonic Dystrophy Transcriptome. E. Wang. MIT.

Thursday, November 8

8:00 AM–10:00 AM

Concurrent Invited Session II (21-28)

SESSION 25 – Genomic Medicine: ELSI Goes Mainstream

Room 132, Lower Level North, Moscone Center

Moderators: Wylie Burke, Univ. of Washington
  James P. Evans, Univ. of North Carolina at Chapel Hill

Next-generation sequencing of the human genome has the potential to predict disease risk, identify disease causation, and refine therapeutic interventions. As research-based sequencing moves into clinical practice, however, a number of ethical and social questions will enter mainstream practice, and will need to be addressed in a practical manner to inform best practices. For example, how do key stakeholders (patients, providers, researchers, and the public) view the risks and benefits of genome sequencing, and how can benefits be optimized and risks mitigated? How do we address children’s rights as well as other family members’ rights with respect to potentially shared information learned from sequencing individuals? Empirical data can contribute to a better understanding of these issues; but what kinds of data are most relevant and how can they be used to inform practice and policy? How do we navigate the increasingly blurred line between research and clinical care? These issues will be discussed and empirical data presented by a panel of experts investigating the ethical and social issues of genome sequencing in a variety of research and patient populations.


8:00 AM   Views of patients, parents of patients, and clinicians toward whole genome sequencing for clinical care management. A. A. Lemke. Med. Col. of Wisconsin.

8:30 AM   My46: An innovative web-based approach to managing and returning results from exome and whole genome sequencing. H. K. Tabor. Seattle Children’s Hosp.

9:00 AM   Returning "actionable" results to family members in a pancreatic cancer biobank: Views of probands and family members. B. Koenig. Sch. of Nursing, UCSF.

9:20 AM   Approaches and attitudes on return of WGS/WES results. K. Ormond. Stanford Univ.

9:40 AM   Next steps in development of best practices for use of genome sequencing in clinical care. . A. McGuire. Baylor Col. of Med.

Thursday, November 8

8:00 AM–10:00 AM

Concurrent Invited Session II (21-28)

SESSION 26 – Model Organism Genetics, Human Biology and Human Disease

Gateway Ballroom 103, Lower Level South, Moscone Center

Moderators: Phil Hieter, Univ. of British Columbia
  Hal Dietz, Johns Hopkins Univ. Sch. of Med.

Yeast, worms, flies, zebrafish, and mice are key ‘model’ organisms that offer powerful experimental approaches for the study of biological processes relevant to human biology and disease. The genome sequencing projects of the 1990s reemphasized the striking extent to which all organisms are built from the same genes, and highlighted the enormous value of model experimental organisms for the study of evolutionarily conserved gene function. Few, if any, processes at the gene level are known to be unique to humans. Indeed, key aspects of most human disorders can be modeled in experimentally tractable organisms through the analysis of orthologous genes and pathways, using the genetic, biochemical and cell biological toolboxes that have been developed in each model organism. This symposium will accent the current relevance of model organism studies for the understanding, diagnosis, and treatment of human disease, and anticipate the future role of model organisms in human disease research. We chose to highlight a diverse set of biological processes and experimental systems to make the point that the principles of cross species analysis of basic gene function extend to the study of all human disorders.


8:00 AM   Budding yeast: Lessons from yeast applied to the study of human genetic diseases of protein traffic. R. Schekman. Univ. of California, Berkeley.

8:30 AM   The nematode worm: Mechanisms regulating aging in worms and man. C. Kenyon. UCSF.

9:00 AM   The zebrafish: Zebrafish heart development and function. D. Stainier. Max Planck Inst. for Heart and Lung Res., Bad Nauheim, Germany.

9:30 AM   The laboratory mouse: Mouse models of glaucoma and retinal ganglion cell loss. S. John. HHMI/The Jackson Lab., Bar Harbor, ME.

Thursday, November 8

8:00 AM–10:00 AM

Concurrent Invited Session II (21-28)

SESSION 27 – Next-Generation Sequencing in Isolated Populations: Opportunities for Accelerated Gene Discovery in Complex Traits

Room 134, Lower Level North, Moscone Center

Moderators: William K. Scott, Univ. of Miami
  Jeffrey R. O'Connell, Univ. of Maryland Baltimore

This session will present recent developments in the application of whole-exome or whole-genome sequencing (collectively ‘next-generation sequencing’ or NGS) in samples from genetically isolated populations. Such populations have long been the focus of gene discovery efforts for complex traits because of the hypothesized reduction in the genetic complexity of the trait, and the enrichment of rare alleles. Prior genome-wide linkage efforts could detect large genomic regions potentially harboring rare alleles, while genome-wide association efforts could detect smaller areas with more common alleles. NGS allows the direct examination of both common and rare alleles and can be analyzed in both frameworks. Characterisics of isolated population may facilitate the blending of NGS with these prior approaches, by deep sequencing a small number of individuals to use as a reference panel for imputation within pedigrees or on the population level, by ‘filtering’ detected variants against pedigree relationships (or kinship estimates) in individuals with the trait. However, since the structure of the population must be taken into account, application of existing reference panels or methods for these analyses must be done carefully. The speakers for this session will discuss approaches to using NGS data for gene discovery for complex traits in isolated populations, reviewing methodologic approaches specific to such studies and illustrating their use in data sets drawn from such populations.


8:00 AM   Using low-pass whole genome sequencing to create a reference population for genome imputation in an isolated population: Examples from the SardiNIA study. S. Sanna. Cittadella Univ. di Monserrato, Italy.

8:30 AM   Fine-mapping linkage of age-related traits using whole-exome sequencing in a midwestern Amish population sample. W. K. Scott. Univ. of Miami.

9:00 AM   The many-of-few: The power of genetic isolates for discovery and function of rare variants. J. R. O'Connell. Univ. of Maryland Baltimore.

9:30 AM   Studying rare variants in the Genetic Research in Isolated Populations program. C. van Duijn. Erasmus Med. Ctr. Rotterdam, Netherlands.

Thursday, November 8

8:00 AM–10:00 AM

Concurrent Invited Session II (21-28)

SESSION 28 – Transforming Medical Student Education in Genetics and Genomics: How Do We Improve Health and Individualize Care through Medical School Genetic and Genomic Curricula?

Room 130, Lower Level North, Moscone Center

Moderators: Joann N. Bodurtha, Johns Hopkins Univ.
  Joan Scott, NCHPEG, Lutherville, MD

This session will provide national perspectives on integrating genetics and genomics in medical student education. Controversies, ranging from the marketing of curriculum change to addressing personal genotyping, and lessons learned will be emphasized. Challenges in 4-year integration, evaluation, ethical issues and competing priorities will be included. Drs. Valle, Burke, and Potocki will describe 3 different models of curriculum development and delivery. Drs. Demmer and Salari will provide contrasting experiences in introducing personal genotyping by students into the curriculum.


8:00 AM   Genes to Society—3 years of implementation. D. Valle. Johns Hopkins Univ.

8:30 AM   The Vermont Integrated Curriculum: The UVM experience. L. Burke. Univ. of Vermont Col. of Med.

8:55 AM   Effecting change: Building a genetics curriculum that supports the physicians of tomorrow. L. Potocki. Baylor Col. of Med.

9:20 AM   Lessons learned from the introduction of personalized genotyping into a medical school curriculum. L. Demmer. Carolinas Medical Center.

9:40 AM   Personal genotyping in a medical school curriculum on genomics and personalized medicine. K. Salari. Stanford Univ. Sch. of Med.

Thursday, November 8

10:30 AM–12:45 PM

Concurrent Platform (abstract-driven) Session B (29-37)

SESSION 29 – Next-Generation Sequencing: Methods and Applications

Hall D, Lower Level North, Moscone Center

Moderators: John S. Witte, UCSF
  Priya Duggal, Johns Hopkins Bloomberg Sch of Publ. Hlth.

88/10:30 The value of population-specific reference panels for genotype imputation in the age of whole-genome sequencing. C. Fuchsberger, B. Howie, M. Laakso, M. Boehnke, G. Abecasis on behalf of Genetics of Type-2 Diabetes Consortium.

89/10:45 Fast and accurate 1000 Genomes imputation using summary statistics or low-coverage sequencing data. B. Pasaniuc, N. Zaitlen, G. Bhatia, A. Gusev, N. Patterson, A. L. Price.

90/11:00 Accurate haplotype estimation using phase informative sequencing reads. O. Delaneau, J.-F. Zagury, J. Marchini.

91/11:15 An LD-based method for genotype calling and phasing using low-coverage sequencing reads and a haplotype scaffold. A. Menelaou, J. Marchini.

92/11:30 Mixed functional linear model for sequence-based quantitative trait association studies unifying population and family study designs. M. Cao, Y. Zhu, M. Xiong.

93/11:45 Rare variant extensions of the transmission disequilibrium test detects associations with autism exome sequence data. Z. He, B. O'Road, J. Smith, G. Wang, M. Kan, S. Hooker, B. Li, N. Krumm, D. Nickerson, E. Eichler, S. Leal.

94/12:00 Methods for noninvasive prenatal determination of fetal genomes. M. W. Snyder, J. O. Kitzman, M. Ventura, A. P. Lewis, R. Qiu, L. E. Simmons, H. S. Gammill, C. E. Rubens, D. A. Santillan, M. K. Santillan, J. C. Murray, H. K. Tabor, M. J. Bamshad, E. E. Eichler, J. A. Shendure.

95/12:15 Associating complex traits with rare variants identified by NGS: Improving power by a position-dependent kernel approach. U. Bodenhofer, S. Hochreiter.

96/12:30 The Kaiser Permanente/UCSF Genetic Epidemiology Research Study on Adult Health and Aging: Demographic and behavioral influences on telomeres and relationship with all-cause mortality. C. Schaefer, S. Sciortino, M. Kvale, K. Lapham, J. Lin, D. Ranatunga, S. Rowell, M. Sadler, S. Miles, W. McGuire, D. Ludwig, L. Walter, I. Listerman, S. Van Den Eeden, R. Whitmer, C. Quesenberry, N. Risch, E. Blackburn.

Thursday, November 8

10:30 AM–12:45 PM

Concurrent Platform (abstract-driven) Session B (29-37)

SESSION 30 – Genetics and Intellectual Disability

Gateway Ballroom 103, Lower Level South, Moscone Center

Moderators: Roger Reeves, Johns Hopkins Univ.
  Heidi Rehm, Harvard Univ.

97/10:30 Diagnostic exome sequencing in patients with intellectual disability of unknown cause. J. de Ligt, M. H. Willemsen, B. W. M. van Bon, T. Kleefstra, H. G. Yntema, T. Kroes, A. T. Vulto-van Silfhout, D. A. Koolen, P. de Vries, C. Gilissen, A. Hoischen, H. Scheffer, B. B. A. de Vries, H. G. Brunner, J. A. Veltman, L. E. L. M. Vissers.

98/10:45 C-terminal deletions of the AUTS2 locus cause distinct syndromic features and cognitive impairment. E. Voorhoeve, G. Beunders, C. Golzio, L. Pardo, J. Rosenfeld, M. Talkowski, I. Simonic, A. Lionel, S. Vergult, R. Pyatt, J. van de Kamp, A. Nieuwint, M. Weiss, P. Rizzu, D. Posthuma, L. Verwer, H. Meijers-Heijboer, B. Menten, G. Mortier, S. Scherer, E. Eichler, S. Girirajan, N. Katsanis, A. Groffen, E. Sistermans.

99/11:00 Autism traits in the RASopathies. I. Corbin, G. Desachy, K. Rauen, L. Weiss.

100/11:15 Identification of novel recessive mutations in genes for intellectual disability. B. De Vries, J. H. M. Schuurs-Hoeijmakers, A. T. Vulto-van Silfhout, L. E. L. M. Vissers, J. de Ligt, C. Gilissen, I. van de Vondervoort, M. T. Greally, C. W. Ockeloen, M. H. Willemsen, E. M. Bongers, G. Hira, J. Y. Hehir-Kwa, R. Pfundt, T. Kleefstra, K. Neveling, S. Reinateo, A. Vitello, P. Failla, D. Greco, M. Fichera, O. Galesi, B. W. M. van Bon, J. A. Veltman, C. Romano, M. A. Willemsen, H. G. Brunner, H. van Bokhoven, A. P. M. de Brouwer.

101/11:30 Causal de novo SNVs, indels and CNVs in children with undiagnosed developmental disorders. M. Hurles, M. van Kogelenberg, K. Morley, T. Fitzgerald, S. Gerety, A. Tivey, S. Gribble, S. Al-Turki, S. Clayton, C. Wright, J. Barrett, H. Firth, D. FitzPatrick, N. Carter on behalf of DDD Project.

102/11:45 Making headway with the molecular and clinical definition of rare genetic disorders with intellectual disability. M. H. Willemsen, W. M. Wissink-Lindhout, L. E. L. M. Vissers, A. P. M. de Brouwer, J. H. M. Rensen, N. de Leeuw, R. Pfundt, H. G. Yntema, J. de Ligt, J. A. Veltman, H. G. Brunner, H. M. J. Lantman - de Valk, B. C. J. Hamel, H. van Bokhoven, T. Kleefstra.

103/12:00 MBD5 dosage affects multiple neurodevelopmental pathways in common with other genetic syndromes. S. V. Mullegama, J. A. Rosenfeld, C. Orellana, B. W. M. van Bon, E. A. Repnikova, L. Brick, L. Dupuis, D. J. Stavropoulos, D. L. Thrush, J. G. Foster, K. Manickam, A. Lin, J. C. Hodge, M. E. Talkowski, J. F. Gusella, S. Schwartz, S. Aradhya, R. E. Pyatt, B. B. A. de Vries, R. Mendoza-Londono, L. G. Shaffer, S. H. Elsea.

104/12:15 Exome sequencing in X-linked intellectual disability family assess the role of the KIAA2022 gene in the etiology of intellectual disability. M. Rio, S. Mouton, AC. Mazery, C. Bole-Feysot, P. Nitschke, N. Bahi-Buisson, A. Munnich, L. Colleaux.

105/12:30 Biallelic mutations of a ubiquitin-ligase-encoding gene cause an Ohdo-like intellectual disability syndrome. G. Borck, B. Dallapiccola, R. Ramirez-Solis, A. Segref, H. Thiele, A. Edwards, M. J. Arends, X. Miro, J. K. White, J. Desir, M. Abramowicz, M. L. Dentici, K. Hofmann, A. Har-Zahav, E. Ryder, N. A. Karp, N. J. Ingham, G. Nuernberg, S. Abdelhak, M. Pasmanik-Chor, O. Konen, R. I. Kelley, M. Shohat, P. Nuernberg, J. Flint, K. P. Steel, T. Hoppe, C. Kubisch, D. J. Adams, L. Basel-Vanagaite.

Thursday, November 8

10:30 AM–12:45 PM

Concurrent Platform (abstract-driven) Session B (29-37)

SESSION 31 – GWAS from Head to Toe

Room 135, Lower Level North, Moscone Center

Moderators: Erik Ingelsson, Karolinska Inst., Sweden
  Nora Franceschini, Univ. of North Carolina at Chapel Hill

106/10:30 Androgenetic alopecia: Identification of four new genetic risk loci and evidence for the contribution of WNT-signaling to its etiology. S. Heilmann, A. K. Kiefer, N. Kluck, D. Drichel, A. M. Hillmer, C. Herold, J. Y. Tung, N. Eriksson, S. Redler, R. C. Betz, R. Li, H. Stefansson, D. R. Nyholt, K. Song, S. H. Vermeulen, S. Kanoni, G. Dedoussis, N. G. Martin, L. A. Kiemeney, V. Mooser, K. Stefansson, J. B. Richards, T. Becker, F. F. Brockschmidt, D. Hinds, M. M. Nöthen.

107/10:45 A polymorphism in human estrogen-related receptor beta is associated with early indications of hearing loss from acoustic overload in young adult musicians. V. C. Henrich, S. L. Phillips, S. J. Richter, S. Teglas, R. Morehouse.

108/11:00 Dissection of polygenic variation for human height into individual variants, specific loci and biological pathways from a GWAS meta-analysis of 250,000 individuals. T. Esko, A. R. Wood, S. Vedantam, J. Yang, S. Gustaffsson, S. I. Berndt, J. Karjalainen, H. M. Kang, A. E. Locke, A. Scherag, D. C. Croteau-Chonka, F. Day, R. Magi, T. Ferreira, J. Randall, T. W. Winkler, T. Fall, Z. Kutalik, T. Workalemahu, G. Abecasis, M. E. Goddard, L. Franke, R. J. F. Loos, M. N. Weedon, E. Ingelsson, P. M. Visscher, J. N. Hirschhorn, T. M. Frayling, GIANT Consortium.

109/11:15 Genome-wide association studies meta-analysis for fracture risk points to loci related to hormonal and neurological pathways: The GEFOS Consortium. L. Oei, H. F. Zheng, E. E. Ntzani, C. M. Nielson, U. Styrkarsdottir, P. M. Ridker, K. K. Tsilidis, K. Estrada, A. Enneman, A. Vernon-Smith, R. D. Jackson, S. Trompet, T. Lehtimäki, S. Kaptoge, T. B. Harris, J. Eriksson, N. Amin, A. Metspalu, P. C. Sham, E. Evangelou, J. P. A. Ioannidis, G. Thorleifsson, A. G. Uitterlinden, S. A. Cummings, T. Spector, D. P. Kiel, D. Chasman, E. Orwoll, J. B. Richards, F. Rivadeneira, GEFOS Consortium.

110/11:30 Genetic landscape of the red blood cell. J. C. Chambers, P. van der Harst, W. Zhang, I. Mateo Leach, J. Sehmi, N. Verweij, D. S. Paul, A. Rendon, U. Elling, H. Allayee, A. Radhakrishnan, J. S. Beckmann, G. V. Dedoussis, P. Deloukas, A. A. Hicks, S. Sanna, M. Uda, J. Penninger, C. Gieger, J. S. Kooner, W. Ouwehand, N. Soranzo, HaemGen RBC Consortium.

111/11:45 Discovery and fine-mapping of serum protein loci through trans-ethnic meta-analysis. A. P. Morris, Y. Okada, F. J. A. van Rooij, B. P. Prins, M. F. Feitosa, M. Karakas, J. Felix, B. Z. Alizadeh, L. A. Cupples, J. R. B. Perry, N. Franceschini, CHARGE Consortium Protein Working Group.

112/12:00 The Kaiser Permanente/UCSF Genetic Epidemiology Research Study on Adult Health and Aging: A genome-wide association study of telomere length in a multi-ethnic cohort of 100,000 subjects. M. Kvale, K. Lapham, T. Hoffmann, S. Sciortino, L. Walter, Y. Banda, I. Listerman, J. Lin, S. Hesselson, P. Kwok, E. Blackburn, C. Schaefer, N. Risch.

113/12:15 Heritability of the variation in aging in two longitudinal family cohort studies: SardiNIA/Progenia Study and Framingham Heart Study. J. Bragg-Gresham, S. Sanna, C. Sidore, A. Mulas, F. Busonero, A. Maschio, M. Urru, F. Reinier, R. Berutti, M. Marcelli, R. Cusano, M. Oppo, D. Pitzalis, M. Zoledziewska, A. Angius, C. Jones, A. Cao, M. Uda, S. Kardia, D. Schlessinger, F. Cucca, G. Abecasis.

114/12:30 Over 250 novel associations with human morphological traits. N. Eriksson, C. B. Do, J. Y. Tung, A. K. Kiefer, D. A. Hinds, J. L. Mountain, U. Francke.

Thursday, November 8

10:30 AM–12:45 PM

Concurrent Platform (abstract-driven) Session B (29-37)

SESSION 32 – Cardiovascular Genetics: GWAS and Beyond

Room 134, Lower Level North, Moscone Center

Moderators: Cristen J. Willer, Univ. of Michigan
  Panagiotis Deloukas, Wellcome Trust Sanger Inst., U.K.

115/10:30 Coronary artery disease loci identified in over 190,000 individuals implicate lipid metabolism and inflammation as key causal pathways: Evidence for independent signals in many of the risk loci. S. Kanoni, C. Willenborg, M. Farrall, T. L. Assimes, J. R. Thompson, E. Ingelsson, D. Saleheen, J. Erdmann, M. P. Reilly, R. Collins, S. Kathiresan, A. Hamsten, U. Thorsteinsdottir, J. S. Kooner, J. Danesh, C. N. A. Palmer, R. Roberts, H. Watkins, H. Schunkert, N. J. Samani, P. Deloukas for CARDIoGRAMplusC4D Consortium.

116/10:45 Genome-wide association study in Han Chinese identifies four new susceptibility loci for coronary artery disease. D. Gu, X. Lu, L. Wang, S. Chen, J. Huang, H. Li, X. Yang, Y. Hao, China Atherosclerosis Genetics Consortium.

117/11:00 Discovery of 63 novel loci and refinement of known loci associated with lipid levels. C. Willer, G. R. Abecasis, M. Boehnke, L. A. Cupples, P. Deloukas, P. W. Franks, S. Gustafsson, E. Ingelsson, S. Kathiresan, K. L. Mohlke, G. M. Peloso, S. S. Rich, S. Ripatti, M. Sandhu, E. M. Schmidt, S. Sengupta, Global Lipids Genetics Consortium.

118/11:15 The Kaiser Permanente/UCSF Genetic Epidemiology Research Study on Adult Health and Aging: Genome-wide association study of plasma HDL and LDL and treatment response in over 100,000 subjects. T. J. Hoffmann, M. N. Kvale, Y. Banda, S. E. Hesselson, L. Walter, S. Sciortino, D. K. Ranatunga, D. Ludwig, C. Iribarren, R. Grant, P. Kwok, C. Schaefer, N. Risch.

119/11:30 Genome-wide screen with 1000 Genomes imputed data identifies 19 new lipid loci and new variants with stronger effects in previously known loci. I. Surakka, A.-P. Sarin, R. Mägi, M. Horikoshi, S. Wiltshire, T. Esko, T. Ferreira, L. Marullo, G. Thorleifsson, A. Mahajan, S. Hägg, A. Isaacs, M. Beekman, J. S. Ried, T. W. Winkler, C. P. Nelson, C. Willenborg, A. Morris, M. I. McCarthy, I. Prokopenko, S. Ripatti for ENGAGE Consortium.

120/11:45 Rare coding variation and risk for myocardial infarction: an exome chip study of ~6,000 cases and controls. R. Do on behalf of NHLBI Exome Sequencing Project - Early Onset Myocardial Infarction.

121/12:00 High exome mutational burden in 58 African Americans with persistent extreme blood pressure. K.-D. H. Nguyen, A. C. Morrison, A. Li, R. Gibbs, E. Boerwinkle, A. Chakravarti.

122/12:15 Chipping a hole-in-one from the FAIRE way: Use of post-GWAS fine-mapping genotyping arrays for functional variant discovery. A. J. P. Smith, F. Drenos, P. Howard, C. Giambartolomei, P. J. Talmud, V. Plagnol, S. E. Humphries.

123/12:30 Strong association of one carbon metabolism genes with stroke and change in post-methionine load homocysteine levels in the Framingham Heart and Vitamin Intervention for Stroke Prevention studies. S. R. Williams, Q. Yang, F. Chen, X. Liu, K. Keen, P. Jacques, W. M. Chen, G. Weinstein, F. C. Hsu, A. Beiser, L. Wang, K. F. Doheny, P. A. Wolf, M. Zilka, J. Selhub, B. B. Worrall, S. Seshadri, M. M. Sale, Genomics and Randomized Trials Network (GARNET).

Thursday, November 8

10:30 AM–12:45 PM

Concurrent Platform (abstract-driven) Session B (29-37)

SESSION 33 – Clinical Genetics: Mutations, Mutations and Syndromes

Gateway Ballroom 104, Lower Level South, Moscone Center

Moderators: Nathaniel Robin, Univ. of Alabama at Birmingham
  Anne Slavotinek, UCSF

124/10:30 Baraitser-Winter syndrome: Delineation of the phenotypicspectrum in a large series of molecularly defined patients. A. Verloes, O. A. Abdul-Rahman, J. Allanson, J. F. Atkin, M. Baraitser, H. Brunner, N. Chassaing, K. Devriendt, V. Drouin, A. Fry, J. P. Fryns, F. Giuliano, K. W. Gripp, D. Lacombe, A. Lin, G. Mancini, M. Marble, M. Nezarati, M. Nowaczyk, S. Osimani, M. Rossi, C. Rusu, Y. Sznajer, C. Van Ravenswaaij, J. Masliah, J. B. Rivière, B. W. M. van Bon, A. Hoischen, W. Dobyns, D. Pilz.

125/10:45 Three novel mutations in MED12 cause Ohdo syndrome Maat-Kievit-Brunner type. A. T. Vulto-van Silfhout, A. Hoischen, B. W. M. van Bon, W. M. Nillesen, C. Gilissen, F. Gao, J. M. Spaeth, B. C. Hamel, T. Kleefstra, M. A. A. P. Willemsen, H. van Bokhoven, H. G. Yntema, B. B. A. de Vries, H. G. Brunner, T. G. Boyer, A. P. M. de Brouwer.

126/11:00 Heterogeneity of mutational mechanisms and modes of inheritance in auriculo-condylar syndrome. C. Gordon, A. Vuillot, A. Omarjee, S. Park, J. Horst, R. McGowan, E. Tobias, S. García-Miñaúr, M. Bitner, L. Jakobsen, P. Kroisel, A. Stewart, R. Palmer, A. Munnich, M. Holder, A. Lin, A. Henderson, L. Basel-Vanagaite, E. Gerkes, L. Wilson, M. Cunningham, S. Marlin, S. Lyonnet, J. Amiel.

127/11:15 Genetic heterogeneity of Myhre syndrome. C. Le Goff, C. Michot, C. Mahaut, A. Abhyankar, W. Le Goff, V. Serre, A. Afenjar, A. Brooks, N. Brunetti-Pierri, P. Campeau, A. Destrée, M. di Rocco, D. Donnai, R. Hennekam, D. Heron, S. Jacquemont, S. Mansour, S. Marlin, R. McGowan, H. Murphy, M. Simon, I. Stolte- Dijkstra, J. Tolmie, R. Touraine, N. Van der Aa, T. Van Essen, A. Verloes, J. L. Casanova, A. Munnich, V. Cormier-Daire.

128/11:30 Seven novel families with ADCL favor clinical and molecular homogeneity. C. Bodemer, B. Callewaert, M. Kempers, E. Bourrat, M. Renard, O. Vanakker, F. Malfait, J. De Backer, P. J. Coucke, S. Hadj-Rabia, A. De Paepe.

129/11:45 Comprehensive clinical and molecular analysis of 12 families with type I recessive cutis laxa. B. Callewaert, C.-T. Su, T. Van Damme, P. Vlummens, F. Malfait, O. Vanakker, B. Schulz, M. Mac Neal, E. C. Davis, J. G. H. Lee, A. Salhi, S. Unger, K. Heimdal, S. De Almeida, U. Kornak, H. Gaspard, J. L. Bresson, K. Prescott, M. E. Gosendi, S. Mansour, G. E. Pierard, S. Madan-Khetarpal, F. C. Sciurba, S. Symoens, P. J. Coucke, L. Van Maldergem, Z. Urban, A. De Paepe.

130/12:00 M694V mutation in Armenian-Americans: A ten-year retrospective study of MEFV mutations testing for familial Mediterranean fever at UCLA. F. S. Ong, H. Vakil, Y. Xue, K. H. Shah, J. Z. Kuo, K. E. Bernstein, D. L. Rimoin, J. I. Rotter, J. L. Deignan, K. Das, W. W. Grody.

131/12:15 Clinical features of individuals with Floating-Harbor syndrome due to mutations in SRCAP. S. M. Nikkel, A. Dauber, R. L. Hood, M. Feingold, M. Connolly, M. J. M. Nowaczyk, S. M. White, A. Afenjar, F. Brancati, I. Cordeiro, A. Destrée, F. Forzano, E. M. Honey, D. Héron, C. M. Jacob, S. G. Kant, U. Kini, E. Kirk, E. Lemos Silveira-Lucas, L. Silveira Lucas, L. Audi Delaney, B. Santos da Cunha, V. Mericq, K. Pope, S. Price, J. M. Wit, D. E. Bulman, K. M. Boycott, FORGE Canada Consortium.

132/12:30 A prospective natural history study of DICER1-related familial pleuropulmonary blastoma syndrome shows incomplete penetrance, pleiotropy and variable expressivity. D. R. Stewart, L. Doros, G. Glenn, A. Bauer, G. Williams, A. Carr, J. Ivanovich, R. Kase, L. Harney, K. A. Schultz, C. P. Kratz, L. P. Dehner, D. A. Hill, Y. Messinger.

Thursday, November 8

10:30 AM–12:45 PM

Concurrent Platform (abstract-driven) Session B (29-37)

SESSION 34 – Cancer Genetics II: Clinical Translation

Room 124, Lower Level North, Moscone Center

Moderators: Robert Pilarski, The Ohio State Univ.
  Stephen Thibodeau, Mayo Clin.

133/10:30 Clinical implementation of a cancer care model based on comprehensive molecular profiling of tumor-normal pairs. J. C. Taylor, K. Kaur, S. Henderson, E. Domingo, A. Cutts, J. Woods, C. Motley, B. Dougherty, M. Middleton, B. Hassan, Y. Wang, E. Beasley, M. Naley, I. Tomlinson, A. Schuh, TSB LifeTech Consortium.

134/10:45 Clinical implementation of single nucleotide polymorphism microarrays in pediatric cancer and non-malignant hematologic disorders. X. Lu, Y. Zhao, S. Gurusiddappa, C. Lau, J. Shohet, P. Rao, K. Rabin, S. E. Plon.

135/11:00 A prospective clinical trial to evaluate DNA sequencing as a diagnostic tool to guide cancer therapy. A. M. K. Brown, P. L. Bedard, B. Tran, J. Dancey, E. Winquist, S. J. Hotte, G. Goss, S. Welch, T. Zhang, L. Stein, V. Ferretti, S. Watt, W. Jiao, K. Ng, P. Shaw, B. G. Neel, T. J. Hudson, J. D. McPherson, S. Kamel-Reid, L. Siu.

136/11:15 Whole genome sequencing of a highly aggressive melanoma identified BRAF L597 mutants associated with sensitivity to MEK inhibitors. Z. Zhao, K. B. Dahlman, J. Xia, H. Hutchinson, C. Ng, D. Hucks, P. Jia, M. Atefi, Z. Su, S. Branch, P. Lyle, D. J. Hicks, V. Bozon, J. A. Glaspy, J. L. Netterville, C. L. Vnencak-Jones, J. Sosman, A. Ribas, W. Pao.

137/11:30 Identification of novel mechanisms of drug resistance in BRCA1-deficient cancer by exome and RNA sequencing. K. K. Dhillon, T. Taniguchi.

138/11:45 BRCA1 and BRCA2 mutational spectrum in a normal population: Implications for clinical diagnostics and incidental findings. E. Ruark, K. W. Lau, A. Renwick, E. Ramsay, F. Zhang, S. Seal, N. Rahman.

139/12:00 Targeted re-sequencing of 10 ovarian cancer candidate genes in 2,240 cases and 355 controls. H. Song, M. Cieck, J. Cunningham, B. Fridley, E. Dicks, P. Harrington, S. Ramus, S. Gayther, E. Goode, P. Pharoah.

140/12:15 Enhanced detection of low-level mosaic mutations in RB1 gene in sporadic unilateral RB by ion torrent semiconductor sequencing: Risk of second cancer. Z. Chen, S. Walther, K. Moran, D. Gerhart, T. Ganguly, A. Ganguly.

141/12:30 Risk of colorectal cancer for monoallelic and biallelic MUTYH mutation carriers. A. K. Win, S. P. Cleary, J. G. Dowty, D. D. Buchanan, J. P. Young, N. M. Lindor, R. W. Haile, P. A. Newcomb, L. Marchand, J. L. Hopper, S. Gallinger, M. A. Jenkins, Colon Cancer Family Registry.

Thursday, November 8

10:30 AM–12:45 PM

Concurrent Platform (abstract-driven) Session B (29-37)

SESSION 35 – Ethical, Legal, Social and Policy Issues

Room 132, Lower Level North, Moscone Center

Moderators: Maureen Smith, Northwestern Univ.
  Neil Lamb, HudsonAlpha Inst. for Biotechnol., Huntsville, AL

142/10:30 Newborn screening for cystic fibrosis: Preliminary results on the false positive experience. C. J. Barg, F. A. Miller, R. Z. Hayeems, P. Durie, J. C. Carroll, P. Chakraborty, B. K. Potter, Y. Bombard, K. Tam, L. Taylor, E. Kerr, C. Davies, J. Milburn, F. Ratjen, A. Guttmann.

143/10:45 Conflicting views on newborn and infant genetic screening: Perspectives of relatives of children with genetic conditions causing developmental delay and parents of healthy children. S. A. Metcalfe, A. D. Archibald, A. L. Atkinson, C. Hickerton, S. Lawton, B. J. McClaren, S. H. Wong.

144/11:00 Do research participants really want to know? The Seattle Colorectal Cancer Family Registry experience on the return of research genetic test results. M. Laurino, D. Fisher, W. Grady, P. Newcomb.

145/11:15 The student-athletes’ knowledge of sickle cell trait and the impact of mandatory genetic testing. N. Lovick, L. Mar, M. Treadwell, J. Youngblom, C. Hartshorne.

146/11:30 Impact of direct-to-consumer pharmacogenomic testing. C. S. Bloss, N. J. Schork, E. J. Topol.

147/11:45 Impact of genomic risk for type 2 diabetes on health behaviors. S. B. Haga, W. Barry, R. Mills, J. Sullivan, H. F. Willard, L. P. Svetkey, G. S. Ginsburg.

148/12:00 African American attitudes toward exome and whole genome sequencing. J. Yu, J. Crouch, S. M. Jamal, H. K. Tabor, M. J. Bamshad.

149/12:15 Personalized health literacy in the age of personalized medicine: Results from a deliberative public engagement exercise. B. J. Wilson, J. C. Carroll, S. G. Nicholls, S. M. Craigie, H. Etchegary, D. Castle, B. K. Potter, J. Little, L. Lemyre on behalf of Emerging Team in Genomics in Screening.

150/12:30 Dynamics, definitions and discrepancies: Public perspectives on the systematic collection and use of family health history in routine health care. H. Etchegary, B. J. Wilson, S. M. Craigie, S. G. Nicholls, D. Castle, J. C. Carroll, J. Allanson, B. K. Potter, P. Chakraborty on behalf of CIHR Emerging Team in Genomics in Screening.

Thursday, November 8

10:30 AM–12:45 PM

Concurrent Platform (abstract-driven) Session B (29-37)

SESSION 36 – Chipping Away at Autoimmune Disease

Room 130, Lower Level North, Moscone Center

Moderators: Judy H. Cho, Yale Univ.
  Soumya Raychaudhuri, Brigham and Women's Hosp.

151/10:30 Immunochip: Redefining the genetic architecture of multiple sclerosis. J. McCauley, International Multiple Sclerosis Genetics Consortium.

152/10:45 Dense genotyping of candidate genes indentifies 16 new susceptibility loci in ankylosing spondylitis. A. Cortes, P. C. Robinson, P. Leo, D. M. David, M. A. Brown, International Genetics of Ankylosing Spondylitis and Wellcome Trust Case Control Consortia.

153/11:00 Dense fine-mapping study identifies novel disease loci and implicates coding and non-coding variation in primary biliary cirrhosis risk. J. Z. Liu, M. A. Almarri, D. J. Gaffney, G. F. Mells, L. Jostins, H. J. Cordell, S. Ducker, D. Day, M. A. Heneghan, J. M. Neuberger, P. T. Donaldson, A. Bathgate, A. Burroughs, M. Davies, D. E. Jones, G. J. Alexander, J. C. Barrett, R. N. Sandford, C. A. Anderson, UK PBC Consortium and Wellcome Trust Case Control Consortium 3.

154/11:15 Fifteen novel psoriasis susceptibility loci: Disease-specific signals highlight the role of innate immunity. L. C. Tsoi, S. L. Spain, J. Knight, E. Ellinghaus, P. E. Stuart, F. Capon, J. Ding, Y. Li, T. Tejasvi, J. E. Gudjonsson, H. M. Kang, A. M. Bowcock, U. Mrowietz, S. Koks, T. Esko, J. J. Voorhees, M. Weichenthal, P. Rahman, D. Gladman, C. E. M. Griffiths, A. Reis, J. Kere, R. P. Nair, A. Franke, J. N. W. N. Barker, G. R. Abecasis, J. T. Elder, R. C. Trembath, Genetic Analysis of Psoriasis Consortium, Wellcome Trust Case Control Consortium 2.

155/11:30 MHC fine-mapping in celiac disease reveals structural basis of HLA-gluten interaction. J. Gutierrez-Achury, G. Trynka, K. A. Hunt, J. Romanos, D. van Heel, C. Wijmenga, P. I. W. de Bakker.

156/11:45 Host-microbe interactions shape genetic risk for inflammatory bowel disease. J. Barrett, International IBD Genetics Consortium.

157/12:00 Sequencing-based and multiplatform genome-wide association study for multiple sclerosis and type 1 diabetes in Sardinians. I. Zara, E. Porcu, M. Zoledziewska, M. Pitzalis, M. Valentini, A. Mulas, F. Busonero, R. Atzeni, M. Oppo, F. Reinier, R. Berutti, R. Pilu, F. Deidda, C. Sidore, R. Piras, A. Loi, S. Sanna, E. Cocco, F. Poddie, G. Farina, G. Rosati, L. Lianas, G. Cuccuru, G. Zanetti, A. Angius, M. G. Marrosu, C. M. Jones, G. R. Abecasis, S. Sanna, F. Cucca.

158/12:15 Admixture mapping for asthma in Latinos identifies additional heritable risk factors from genome-wide meta-analysis data. C. R. Gignoux, D. G. Torgerson, J. M. Galanter, L. A. Roth, C. Eng, D. Hu, S. Huntsman, R. D. Hernandez, R. A. Mathias, S. Sen, K. C. Barnes, E. G. Burchard.

159/12:30 Deep exome sequencing of psoriasis identified new association signals contribute by INDELs, CNVs and rare SNPs. X. Jin, H. Tang, H. Jiang, D. Cao, H. Shao, Q. Li, J. Shen, L. Song, Y. Shi, J. Mei, X. Yang, L. Coin, Y. Li, X. Zhang, J. Wang.

Thursday, November 8

10:30 AM–12:45 PM

Concurrent Platform (abstract-driven) Session B (29-37)

SESSION 37 – Metabolic Disease Discoveries

Room 123, Lower Level North, Moscone Center

Moderators: Kimberly Chapman, Children's Natl. Med. Ctr.
  Hans Andersson, Tulane Univ. Med. Ctr.

160/10:30 Mutations in DDHD2 cause recessive spastic paraplegia with intellectual disability, thin corpus callosum and periventricular white matter hyperintensities. A. P. M. de Brouwer, J. H. M. Schuurs-Hoeijmakers, E. J. Kamsteeg, S. Ben-Salem, S. T. de Bot, I. van de Vondervoort, S. Vermeer, J. Schwartzentruber, B. R. Ali, S. A. Al-Yahyaee, S. Tariq, T. Pramathan, R. Bayoumi, B. P. van de Warrenburg, W. M. van den Akker, C. Gilissen, J. A. Veltman, I. M. Janssen, A. T. Vulto-van Silfhout, S. van der Velde-Visser, A. Diekstra, C. E. Erasmus, M. A. Willemsen, L. E. L. M. Vissers, H. van Bokhoven, R. A. Wevers, L. Al-Gazali, M. T. Geraghty, B. B. A. de Vries.

161/10:45 Lipidomics of Gaucher disease: Substrate composition and nature is dependent on tissue/region and acid β-glucosidase mutations: Phenotypic implications. Y. Sun, W. Zhang, Y. Xu, B. Quinn, N. Dasgupta, B. Liou, K. D. R. Setchell, G. A. Grabowski.

162/11:00 Sterol precursors induce Niemann-Pick C disease phenotypes in Smith-Lemli-Opitz syndrome causing defective LDL-cholesterol utilization that is corrected by imino-sugars. C. A. Wassif, E. Lloyd-Evans, L. J. Haslett, I. M. Williams, C. L. Toth, F. D. Porter, F. M. Platt.

163/11:15 Glucose kinetics in subjects with MELAS syndrome: Interim results. L. Emrick, A. El-Hattab, J. Hsu, F. Jarhoor, F. Scaglia, W. Craigen.

164/11:30 Phenylbutyrate therapy for pyruvate dehydrogenase complex deficiency. R. Ferriero, E. Lamantea, P. W. Stacpoole, L. Bonafè, B. Lee, M. Zeviani, N. Brunetti-Pierri.

165/11:45 Etiologies for neurocognitive delays in argininosuccinic aciduria. A. Erez, S. Nagamani, P. Campeau, O. Shchelochkov, J. Kho, K. Bissig, Q. Sun, N. Bryan, S. Cederbaum, B. Lee.

166/12:00 Enzyme substitution therapy for phenylketonuria delivered orally using a genetically modified probiotic: Proof of principle. J. Christodoulou, N. Al-Hafid, X.-Z. Tong, K. Carpenter, V. Wiley, S. Cunniingham, I. E. Alexander.

167/12:15 A new inborn error of manganese metabolism caused by mutations in SLC30A10, a newly identified human manganese transporter. K. Tuschl, P. T. Clayton, S. M. Gospe, Jr., S. Gulab, S. Ibrahim, P. Singhi, R. T. Ribeiro, M. S. Zaki, M. Luz del Rosario, S. Dyack, V. Price, R. A. Wevers, P. B. Mills.

168/12:30 Combined methylmalonic acidemia and homocystinuria, cblC type: A prospective clinical protocol focusing on neurologic and neurodevelopmental parameters in a cohort of pre-school children diagnosed on expanded newborn screening. J. D. Weisfeld-Adams, H. A. Bender, A. M. Akerstedt, E. Miles-Mason, T. P. Naidich, S. Lipson, T. Bottiglieri, S. P. Young, G. A. Diaz.

Thursday, November 8

4:30 PM–6:45 PM

Concurrent Platform (abstract-driven) Session C (38-46)

SESSION 38 – A Sequencing Jamboree: Exomes to Genomes

Hall D, Lower Level North, Moscone Center

Moderators: Nancy Cox, Univ. of Chicago
  Orli Bahcall, Nature Genetics

169/4:30 Whole-exome sequencing of 10,000 type 2 diabetes cases and controls from five major ancestry groups. T. M. Teslovich, A. P. Morris, P. Fontanillas, M. A. Rivas, X. Sim, J. Flannick, N. Burtt, H. Chen, A. G. Day-Williams, A. Mahajan, G. Atzmon, P. Cingolani, L. Moutsianas, H. M. Highland, T2D-GENES Consortium.

170/4:45 Rare and low frequency coding variants are associated with LDL cholesterol levels: Findings from the NHLBI Exome Sequencing Project. L. A. Lange, Y. Hu, C. Xue, Z. Tang, C. Bizon, E. M. Lange, J. D. Smith, E. H. Turner, G. Jun, H.-M. Kang, K. P. Li, G. M. Peloso, C. L. Wassel, A. P. Reiner, E. Boerwinkle, B. M. Psaty, C. J. O'Donnell, S. Kathiresan, K. E. North, D. Lin, G. P. Jarvik, L. A. Cupples, C. Kooperberg, J. G. Wilson, D. A. Nickerson, G. R. Abecasis, S. S. Rich, R. P. Tracy, C. J. Willer on behalf of NHLBI Exome Sequencing Project.

171/5:00 Exome sequencing of extreme phenotypes identifies DCTN4 and CAV2 as modifiers of chronic Pseudomonas aeruginosa infection in cystic fibrosis. M. J. Emond, T. Louie, J. Emerson, S. McNamara, W. Zhao, R. A. Mathias, M. R. Knowles, F. A. Wright, M. J. Reider, H. K. Tabor, D. A. Nickerson, K. C. Barnes, R. L. Gibson, M. J. Bamshad.

172/5:15 A high resolution study of type 2 diabetes genetic architecture through whole-genome sequencing of 2850 European individuals: The GoT2D Study. J. Flannick, C. Fuchsberger, K. J. Gaulton, N. P. Burtt, H. M. Kang, C. Hartl, R. D. Pearson, GoT2D Consortium.

173/5:30 Mapping quantitative traits with integrated whole exome/genome/array panel in individuals of European descent. X. Sim, M. A. Rivas, A. K. Manning, A. E. Locke, C. M. Lindgren, GoT2D Consortium.

174/5:45 Whole genome sequence analyses describe the genetic architecture of complex traits: The Cohorts for Heart and Aging Research in Genetic Epidemiology Consortium. A. C. Morrison, A. Voorman, A. D. Johnson, X. Liu, J. Yu, A. Li, D. Muzny, F. Yu, K. Rice, G. Zhu, G. Heiss, C. J. O'Donnell, B. Psaty, L. A. Cupples, R. Gibbs, E. Boerwinkle.

175/6:00 Genome sequencing and analysis in autism spectrum disorder. S. Walker, A. Prasad, L. Lau, B. Thiruvahindrapuram, B. Fernandez, R. Yuen, C. R. Marshall, E. Fombonne, W. Roberts, L. Zwaigenbaum, P. Szatmari, S. W. Scherer.

176/6:15 Deep whole genome sequencing in pedigrees illuminates the contribution of low frequency and private mutations to the genetic architecture of metabolic quantitative traits. A. K. Manning, A. R. Wood, P. Fontanillas, G. Jun, P. Cingolani, M. Almeida, C. Fuchsberger, T. D. Dyer, M. Rivas, K. Gaulton, J. Maller, J. Curran, J. Grunstad, T. W. Blackwell, T. M. Teslovich, D. M. Lehman, R. Grossman, J. Laramie, S. E. Lincoln, M. Boehnke, M. I. McCarthy, T. M. Frayling, R. Sladek, R. Duggirala, J. Blangero, G. Abecasis, D. Altshuler, T2D-GENES.

177/6:30 Whole genome sequencing of 2100 individuals in the founder Sardinian population. C. Sidore, S. Sanna, A. Kwong, H. M. Kang, R. Cusano, M. Pitzalis, M. Zoledziewska, A. Maschio, F. Busonero, M. Lobina, A. Angius, R. Lyons, B. Terrier, C. Brennan, R. Atzeni, A. Mulas, M. Dei, M. G. Piras, S. Lai, F. Reinier, R. Berutti, C. Jones, M. Marcelli, M. Urru, M. Oppo, D. Schlessinger, G. Abecasis, F. Cucca.

Thursday, November 8

4:30 PM–6:45 PM

Concurrent Platform (abstract-driven) Session C (38-46)

SESSION 39 – Admixture and Demography

Gateway Ballroom 103, Lower Level South, Moscone Center

Moderators: Katarzyna Bryc, Harvard Univ.
  John Novembre, UCLA

178/4:30 Differential relatedness of African Americans to populations within West Africa. K. Bryc, A. Williams, N. Patterson, S. Musani, M. Sale, W. Chen, J. Divers, M. Ng, D. W. Bowden, J. G. Wilson, D. Reich.

179/4:45 Fine scale population genetic structure of African Americans. E. Y. Durand, M. Macpherson, B. T. Naughton, J. Mountain, C. B. Do.

180/5:00 A model-based approach for analysis of spatial structure in genetic data. W. Yang, J. Novembre, E. Eskin, E. Halperin.

181/5:15 People of the British Isles: An analysis of the genetic contributions of European populations to a UK control population. S. Leslie, B. Winney, G. Hellenthal, S. Myers, P. Donnelly, W. Bodmer.

182/5:30 The applicability of the Balding-Nichols model to a dataset of over 100,000 Brazilian individuals. R. V. Rohlfs, A. Bhaskar, V. R. C. Aguiar, K. Lohmueller, A. M. Castro, A. C. S. Ferreira, F. S. V. Malta, Y. Song, I. D. Louro, R. Nielsen.

183/5:45 Rare genetic variants in deep sequencing of neutral regions from a homogeneous population refine models of recent explosive human population growth. A. Keinan, E. Gazave, A. Coventry, S. Gottipati, D. Chang, L. Ma, D. Muzny, E. Boerwinkle, C. Sing, R. Gibbs, A. Clark.

184/6:00 Estimating human population sizes using the coalescent with recombination. S. Sheehan, K. Harris, Y. S. Song.

185/6:15 Reconstructing historical contributions to modern gene pools using the sequentially Markovian coalescent conditional sampling distribution. A. Platt, J. Novembre.

186/6:30 On the Sardinian ancestry of the Tyrolean Iceman. M. Sikora, M. Carpenter, A. Moreno-Estrada, B. M. Henn, P. A. Underhill, I. Zara, M. Pitzalis, C. Sidore, F. Reinier, M. Marcelli, A. Angius, C. Jones, T. T. Harkins, A. Keller, A. Zink, G. Abecasis, S. Sanna, F. Cucca, C. D. Bustamante.

Thursday, November 8

4:30 PM–6:45 PM

Concurrent Platform (abstract-driven) Session C (38-46)

SESSION 40 – Analysis of Multilocus Systems

Room 135, Lower Level North, Moscone Center

Moderators: Brendan Keating, Univ. of Pennsylvania
  Laura Almasy, Texas Biomed. Res. Inst., San Antonio

187/4:30 Gene-based epistasis analysis in genome-wide association studies. L. Ma, A. Brautbar, E. Boerwinkle, C. F. Sing, A. G. Clark, A. Keinan.

188/4:45 Building human phenotype networks from shared genetic risk variants. C. Darabos, K. Desai, M. Giacobini, M. Lupien, J. H. Moore.

189/5:00 Incorporating network dynamics to prioritize genes through genome-wide association studies. L. Hou, M. Chen, C. K. Zhang, J. Cho, H. Zhao.

190/5:15 Large-scale multi-phenotype meta-analysis evaluates pleiotropic effects at FADS1 and GIPR loci. V. Lagou, R. Mägi, K. Fischer, M. Akerlund, I. Surakka, M. Kaakinen, J. S. Ried, A. Mahajan, M. Horikoshi, L. Marullo, K. Strauch, C. Gieger, S. Ripatti, A. P. Morris, V. Lyssenko, I. Prokopenko for ENGAGE (European Network for Genetic and Genomic Epidemiology) Consortium.

191/5:30 Building and assessing protein-protein interaction networks from genome-wide association results in cancer. L. T. Hiraki, A. D. Joshi, S. Lindstrom, A. T. Chan, S. Chanock, P. Kraft.

192/5:45 A smoothed functional principal component analysis for pathway analysis with next-generation sequencing data. J. Zhao, Y. Zhu, E. Boerwinkle, M. Xiong.

193/6:00 Variants in exons and in transcription factors affect gene expression in trans. A. Kreimer, I. Pe'er.

194/6:15 The continuation of theory by other means: ForSim as a forward simulator for improved understanding of the genetic architecture of complex traits and its evolution. K. M. Weiss, J. H. Lee, J. D. Terwilliger, B. W. Lambert.

195/6:30 Incorporating phylogenetic conservation and pedigree information in tests of rare-variant association. H. Hu, C. D. Huff, H. Coon, S. Guthery, S. V. Tavtigian, J. C. Roach, Z. Kronenberg, J. Xing, A. F. A. Smit, G. Glusman, A. K. Holloway, V. Garg, B. Moore, R. Hubley, W. S. Watkins, H. Li, S. Z. Montsaroff, D. E. Abbott, L. E. Hood, K. S. Pollard, D. J. Galas, D. Srivastava, M. G. Reese, L. B. Jorde, M. Yandell.

Thursday, November 8

4:30 PM–6:45 PM

Concurrent Platform (abstract-driven) Session C (38-46)

SESSION 41 – Genes Underlying Neurological Disease

Room 134, Lower Level North, Moscone Center

Moderators: Stylianos Antonarakis, Univ. of Geneva Med. Sch.
  Laurie Ozelius, Mount Sinai Med. Sch.

196/4:30 TMTC4: A novel candidate gene for callosal development. L. Fernandez, J. Li, M. Wakahiro, E. Rider, T. Bartman, E. Sherr.

197/4:45 CLK2 missense mutation in a family with pontocerebellar hypoplasia type 7. V. R. C. Eggens, Y. Namavar, M. A. Haagmans, K. Fluiter, E. J. Bradley, P. G. Barth, B. T. Poll-The, F. Baas.

198/5:00 Missense mutations in ITPR1 cause autosomal dominant congenital nonprogressive spinocerebellar ataxia. J. Warman Chardon, L. Huang, M. Carter, K. Friend, T. Dudding, J. Schwartzentruber, R. Zou, P. Schofield, S. Douglas, D. Bulman, K. Boycott.

199/5:15 Vps37A causes a novel form of complex hereditary spastic paraparesis. T. Falik-Zaccai, Y. Zivony-Elboum, W. Westbroek, D. Savitzki, Y. Shoval, Y. Anikster, A. Waters, R. Kleta.

200/5:30 Genome-wide association study identifies two novel susceptibility loci for musician’s dystonia. K. Lohmann, A. Schmidt, A. Schillert, S. Winkler, K. Siegesmund, H.-C. Jabusch, M. Kasten, J. L. Groen, C. Hemmelmann, J. Hagenah, J. Graf, N. Brüggemann, A. Grünewald, F. Baas, A. Münchau, K. E. Zeuner, S. Schreiber, G. Deuschl, M. A. J. de Koning-Tijssen, E. Altenmüller, A. Ziegler, C. Klein.

201/5:45 Autosomal recessive axonal neuropathy with neuromyotonia: A novel disease entity caused by mutations in HINT1. J. Baets, M. Zimon, L. Almeida-Souza, J. Nikodinovic, Y. Parman, E. Battaloglu, V. Guergueltcheva, I. Tournev, M. Auer-Grumbach, T. Müller, P. Van Damme, W. N. Löscher, N. Barisic, Z. Mitrovic, S. C. Previtali, H. Topaloglu, G. Bernert, A. Beleza-Meireles, S. Todorovic, B. Ishpekova, K. Peeters, A. F. Hahn, S. Züchner, V. Timmerman, V. Milic Rasic, A. R. Janecke, A. Jordanova, P. De Jonghe.

202/6:00 De novo gain of function KCNT1 channel mutations cause seizures and developmental delay in malignant migrating partial seizures of infancy. G. Barcia, M. R. Fleming, A. Deligniere, V. Gazula, M. R. Brown, M. Langouet, H. Chen, J. Kronengold, A. Abhyankar, R. Cilio, P. Nitschke, A. Kaminska, N. Boddaert, J. L. Casanova, I. Desguerre, A. Munnich, O. Dulac, L. K. Kaczmarek, L. Colleaux, R. Nabbout.

203/6:15 Investigating the genetic etiology of familial epilepsies using next-generation sequencing. E. K. Ruzzo, E. L. Heinzen, R. Wedel, K. V. Shianna, I. E. Scheffer, S. F. Berkovic, R. Ottman, D. B. Goldstein.

204/6:30 Autoregulation of the DYT6-gene THAP1. A. Erogullari, P. Seibler, D. Braunholz, A. Grünewald, R. Depping, J. Eckhold, A. Rakovic, T. Lohnau, G. Gillessen-Kaesbach, C. Klein, K. Lohmann, F. J. Kaiser.

Thursday, November 8

4:30 PM–6:45 PM

Concurrent Platform (abstract-driven) Session C (38-46)

SESSION 42 – Cancer Genetics III: Common Variants

Gateway Ballroom 104, Lower Level South, Moscone Center

Moderators: Kathleen Cooney, Univ. of Michigan
  Meredith Yeager, NCI/NIH

205/4:30 Identification of 23 novel prostate cancer susceptibility loci using a custom array (the iCOGS) in an international consortium, PRACTICAL. R. Eeles, A. Amin Al Olama, S. Benlloch, E. Saunders, D. Leongamornlert, M. Tymrakiewicz, M. Ghoussaini, C. Luccarini, J. Dennis, S. Jugurnauth-Little, T. Dadaev, PROTECT Group, G. Giles, G. Severi, F. Wiklund, H. Gronberg, C. Haiman, F. Schumacher, B. Henderson, L. Le Marchand, S. Lindstrom, P. Kraft, D. Hunter, S. Gapstur, S. Chanock, S. Berndt, PRACTICAL Consortium, Z. Kote-Jarai, D. Easton.

206/4:45 Large-scale genotyping identifies more than 40 novel breast cancer susceptibility loci. K. Michailidou, P. Hall, A. Gonzalez-Neira, M. Ghoussaini, J. Dennis, R. L. Milne, M. K. Schmidt, J. Chang-Claude, S. E. Bojesen, M. K. Humphreys, Q. Wang, M. Garcia-Closas, P. D. P. Pharoah, G. Chenevix-Trench, A. M. Dunning, J. Benitez, D. F. Easton, Breast Cancer Association Consortium.

207/5:00 Genome-wide association study in BRCA1 mutation carriers identifies novel loci associated with breast and ovarian cancer risk. A. C. Antoniou, X. Wang, L. McGuffog, A. Lee, M. M. Guedet, K. B. Kuchenbaecker, P. Soucy, J. Simard, K. Offit, D. F. Easton, G. Chenevix-Trench, F. J. Couch, Consortium of Investigators of Modifiers of BRCA1/2.

208/5:15 Identification of the first locus to modify breast cancer risk specifically in BRCA2 mutation carriers. K. Kuchenbaecker, M. Gaudet, J. Vijai, R. Klein, T. Kirchhoff, L. McGuffog, D. Barrowdale, A. Dunning, A. Lee, P. Hall, F. Couch, J. Simard, D. Altshuler, D. Easton, G. Chenevix-Trench, A. Antoniou, K. Offit, Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) Collaborators.

209/5:30 Fine-scale mapping and functional analysis of the breast cancer 11q13 (CCND1) locus. M. Ghoussaini, K. B. Meyer, S. Edwards, J. D. French, K. Michailidou, S. Ahmed, S. Khan, M. J. Maranian, C. S. Healey, P. D. P. Pharoah, H. Nevanlinna, M. A. Brown, G. Chenevix-Trench, D. F. Easton, A. M. Dunning, BCAC.

210/5:45 Three independent loci within the TERT-CLPTM1L locus associated with telomere length and risk of breast and ovarian cancer. G. Chenevix-Trench, S. E. Bojesen, K. A. Pooley, S. Johnatty, J. Beesley, K. Michailidou, J. Tyrer, S. L. Edwards, H. C. Shen, K. Lawrenson, H. Pickett, M. Stutz, C. Smart, J. French, P. L. Mai, M. H. Greene, S. Gayther, R. Reddel, P. D. P. Pharoah, E. L. Goode, A. Berchuk, D. F. Easton, A. C. Antoniou, A. M. Dunning on behalf of CIMBA, OCAC and BCAC.

211/6:00 Statistical fine mapping of regions containing melanoma susceptibility genes identified through genome-wide association studies. J. H. Barrett, J. C. Taylor, M. Brossard, A. M. Goldstein, P. A. Kanetsky, E. M. Gillanders, J. A. Newton Bishop, D. T. Bishop, F. Demenais, M. M. Iles, GenoMEL Consortium.

212/6:15 Combining expression phenotypes with high density imputation to identify melanoma risk genes. M. H. Law, G. W. Montgomery, K. M. Brown, A. E. Cust, N. G. Martin, G. J. Mann, N. K. Hayward, S. MacGregor, Q-MEGA and AMFS Investigators.

213/6:30 Meta-analysis identifies four new loci for testicular germ cell tumor. C. C. Chung, Z. Wang, P. A. Kanetsky, C. Turnbull, K. McGlynn, R. L. Erickson, M. H. Greene, M. A. T. Hildebrandt, R. I. Skotheim, C. Kratz, M. B. Cook, F. Schumacher, R. Koster, M. Yeager, K. B. Jacobs, S. M. Schwartz, D. T. Bishop, H. K. Gjessing, V. Cortessis, N. Rahman, X. Wu, S. J. Chanock, K. L. Nathanson.

Thursday, November 8

4:30 PM–6:45 PM

Concurrent Platform (abstract-driven) Session C (38-46)

SESSION 43 – Genetics of Craniofacial and Musculoskeletal Disorders

Room 124, Lower Level North, Moscone Center

Moderators: Irini Manoli, NHGRI/NIH
  Siddharth Prakash, Univ. of Texas Hlth. Sci. Ctr. at Houston

214/4:30 Next-generation sequencing detects mutations in ISPD as a common cause of Walker-Warburg syndrome with defective glycosylation of α-dystroglycan. T. Roscioli, E.-J. Kamsteeg, K. Buysse, I. Maystadt, J. van Reeuwijk, C. van den Elzen, E. van Beusekom, M. Riemersma, R. Pfundt, L. E. L. M. Vissers, M. Schraders, M. F. Buckley, H. G. Brunner, H. Zhou, J. A. Veltman, C. Gilissen, G. M. S. Mancini, M. A. Willemsen, D. Petković Ramadža, D. Chitayat, C. Bennett, E. Sheridan, E. A. J. Peeters, G. M. B. Tan-Sindhunata, H. Kayserili, O. Abd El-Fattah El-Hashash, D. L. Stemple, D. J. Lefeber, Y.-Y. Lin, H. van Bokhoven.

215/4:45 The identification of a novel gene identified by exome sequencing reveals the upstream components of the RAS/MAPK signaling pathway involved in Noonan syndrome. H. Yntema, W. Nillesen, J. Paardekooper Overman, M. Bonetti, J. de Ligt, H. Venselaar, M. Tartaglia, S. G. M. Frints, L. E. L. M. Vissers, J. den Hertog, I. van der Burgt.

216/5:00 DYNC2H1 mutations are commonly found in Jeune asphyxating thoracic dysplasia (JATD) without extraskeletal features while IFT140 mutations cause JATD with renal involvement. M. Schmidts, H. H. Arts, Z. Yap, E. M. H. F. Boengers, D. Anthony, M. M. Oud, S. Al-Turki, L. Duijkers, J. Stalker, J. B. Yntema, A. Hoischen, R. Bogdanovic, A. Peco-Antic, C. Gillisen, H. Kayserili, I. Veltman, A. Kutkowska, E. J. Kamsteeg, R. C. M. Hennekam, P. Scambler, P. L. Beales, UK10K Consortium, N. V. A. M. Knoers, R. Roepman, H. M. Mitchison.

217/5:15 Dominant missense mutations in ABCC9 cause Cantú syndrome. G. van Haaften, M. Harakalova, J. J. T. van Harssel, P. Terhal, S. van Lieshout, K. Duran, I. Renkens, D. J. Amor, L. C. Wilson, E. P. Kirk, C. L. S. Turner, D. Shears, S. García-Miñaúr, M. M. Lees, A. Ross, H. Venselaar, G. Vriend, H. Takanari, M. B. Rook, M. A. G. van der Heyden, M. E. Swinkels, I. J. Scurr, S. F. Smithson, N. V. Knoers, J. J. van der Smagt, I. J. Nijman, W. P. Kloosterman, M. M. van Haelst, E. Cuppen.

218/5:30 Reduced dosage of ERF causes complex craniosynostosis in humans and mice, and links ERK1/2 signaling to regulation of osteogenesis. S. R. F. Twigg, I. Paraki, S. J. McGowan, M. Allegra, A. L. Fenwick, V. P. Sharma, E. Vorgia, A. Zaragkoulias, E. Sadighi Akha, S. J. Knight, H. Lord, T. Lester, L. Izatt, A. K. Lampe, S. N. Mohammed, F. J. Stewart, A. Verloes, L. C. Wilson, D. Johnson, S. A. Wall, P. Hammond, J. Hughes, S. Taylor, G. Mavrothalassitis, A. O. M. Wilkie.

219/5:45 Mutations in the multidomain protein MEGF8 identify a new subtype of Carpenter syndrome associated with defective lateralization. D. L. Lloyd, S. R. Twigg, N. Elcioglu, D. Jenkins, C. D. O. Cooper, N. Akarsu, E. Taskiran, N. Al-Sannaa, A. Annagür, G. Gillessen-Kaesbach, I. Stefanova, S. J. L. Knight, J. A. Goodship, B. Keavney, P. L. Beales, O. Gileadi, S. McGowan, A. O. M. Wilkie.

220/6:00 Increased frequency of FBN1 variants in adolescent idiopathic scoliosis. J. G. Buchan, D. A. Alvarado, M. C. Willing, M. B. Dobbs, C. A. Gurnett.

221/6:15 Exome sequencing in idiopathic scoliosis reveals rare variants in VANGL, a planar cell polarity gene involved in axial development. S. Sharma, J. A. Herring, X. Gao, D. Zhang, C. Wise.

222/6:30 Recessive mutations in FKBP10, a PPIase known to cause type XI OI, extend the phenotype to a congenital contracture syndrome (Kuskokwim disease), and cause diminished collagen cross-linking in matrix. A. M. Barnes, M. Weis, W. A. Cabral, E. Makareeva, E. L. Mertz, W. Paton, G. Duncan, C. Trujillo, S. Leikin, D. R. Eyre, S. J. Bale, J. C. Marini.

Thursday, November 8

4:30 PM–6:45 PM

Concurrent Platform (abstract-driven) Session C (38-46)

SESSION 44 – Tools for Phenotype Analysis

Room 132, Lower Level North, Moscone Center

Moderators: Donna Maglott, NCBI/NIH
  Gregory E. Crawford, Duke Univ.

223/4:30 PRIMUS: Pedigree Reconstruction and Identification of the Maximum Unrelated Set. J. Staples, D. Nickerson, J. Below.

224/4:45 Pharmacogenoinformatics: Novel approach of in silico drug designing based on genetic variation of MDR1 gene involved in statin resistance. A. Munshi, M. Sai Babu, A. Venkateswara Rao, A. Jyothy.

225/5:00 A general, integrated variant prioritization method for rapid determination of disease causing mutations from next-generation sequencing data. B. D. O'Fallon, W. Wooderchak-Donahue, P. Bayrak-Toydemir.

226/5:15 Visually integrating and exploring high throughput phenome-wide association (PheWAS) results using PheWAS-view and PhenoGram. S. A. Pendergrass, S. Dudek, D. C. Crawford, M. D. Ritchie.

227/5:30 PhenoDB: A new web-based tool for the collection, storage and analysis of phenotypic features. A. Hamosh, J. Hoover-Fong, V. R. Sutton, N. Sobreira, C. Boehm, F. Schiettecatte, D. Valle.

228/5:45 A novel metabolomics analysis workflow provides new biological insights into the genetic basis of human metabolic variation. H. Dharuri, P. Henneman, D. O. Mook-Kanamori, K. Suhre, K. Willems van Dijk, P. A. C. 't Hoen.

229/6:00 Integration of large-scale gene annotation, electronic medical records, and incidence data to produce phenotype-specific posterior probabilities to aid interpretation of genome-wide variant data. I. M. Campbell, S. W. Cheung, A. Patel, S. R. Lalani, P. Stankiewicz, M. B. Ramocki, J. R. Lupski, C. A. Shaw.

230/6:15 The Kaiser Permanente/UCSF Genetic Epidemiology Research Study on Adult Health and Aging: CREX, computerized methodology to identify health conditions using the EMR for GWAS. S. Sciortino, L. Walter, D. Ranatunga, L. Shen, D. Ludwig, J. Kay, L. Sakoda, N. Risch, C. Schaefer.

231/6:30 An informatics approach to analyzing the incidentalome. M. C. Adams, J. S. Berg, N. Nassar, C. Bizon, K. Lee, C. P. Schmitt, K. C. Wilhelmsen, J. P. Evans.

Thursday, November 8

4:30 PM–6:45 PM

Concurrent Platform (abstract-driven) Session C (38-46)

SESSION 45 – Therapy of Genetic Disorders

Room 130, Lower Level North, Moscone Center

Moderators: Cynthia J.R. Curry, UCSF
  Brunhilde Wirth, Univ. of Cologne, Germany

232/4:30 Pathogenic exon-trapping by SVA retrotransposon and rescue in Fukuyama muscular dystrophy. M. Taniguchi, K. Kobayashi, M. Kanagawa, C. C. Yu, T. Oda, A. Kuga, H. Kurahashi, H. O. Akmen, S. DiMauro, T. Yokota, S. Takeda, T. Toda.

233/4:45 Hematopoietic stem cell transplantation for adolescent and adult onset cerebral X-linked adrenoleukodystrophy. T. Matsukawa, T. Yamamoto, S. Seo, K. Kumano, M. Ichikawa, Y. Takahashi, H. Ishiura, J. Mitsui, M. Tanaka, J. Goto, M. Kurokawa, S. Tsuji.

234/5:00 Treating Pelizaeus-Merzbacher disease with clinically applicable compounds, curcumin and chloroquine: Preclinical studies. K. Inoue, T. Morimura, Y. Numata, L.-H. Yu, L. Gotoh, R. Yamamoto, N. Inoue, B. Antalfy, K. Deguchi, H. Osaka, Y. Goto.

235/5:15 Systemic L-threo-dihydroxyphenylserine corrects neurochemical abnormalities in a mouse model of Menkes disease. S. Kaler, A. Donsante, P. Sullivan, D. Goldstein, C. Holmes.

236/5:30 Response to VPA therapy in SMA patients is concordant from blood to neurons and influenced by CD36. B. Wirth, L. Heesen, I. Hölker, T. Bauer, J. Schreml, K. Zimmermann, M. Thoenes, M. Walter, J. Dimos, M. Peitz, O. Brüstle, R. Heller, L. Garbes.

237/5:45 Melatonin, a new biomarker reflecting brain serotonin metabolism in individuals with phenylketonuria: Evaluation of large neutral amino acid therapy by a randomized, double-blind crossover study. S. Yano, K. Moseley, C. Azen.

238/6:00 Beyond cholesterol: Antioxidant treatment for patients with Smith-Lemli-Opitz syndrome. E. Elias, R. Braverman, S. Tong.

239/6:15 Positive effects of short course androgen therapy on the neurodevelopmental outcome in boys with 47, XXY syndrome at 36 and 72 months of age. C. Samango-Sprouse, E. Stapleton, T. Sadeghin, F. Mitchell, T. Dixon, M. Kingery, A. Gropman.

240/6:30 A mechanism and treatment strategy for pregnancy-associated aortic dissection in Marfan syndrome. J. P. Habashi, N. Huso, D. Bedja, G. Rykiel, J. J. Doyle, H. C. Dietz.

Thursday, November 8

4:30 PM–6:45 PM

Concurrent Platform (abstract-driven) Session C (38-46)

SESSION 46 – Pharmacogenetics: From Discovery to Implementation

Room 123, Lower Level North, Moscone Center

Moderators: Toni Pollin, Univ. of Maryland Sch. of Med.
  Edward Ramos, NHGRI/NIH

241/4:30 Pharmacogenomics, ancestry and clinical decision making for global populations. E. Ramos, A. Doumatey, H. Huang, D. Shriner, G. Chen, S. Callier, J. Zhou, A. Adeyemo, H. Mcleod, C. Rotimi.

242/4:45 Cell line profiling in oncology (CELLO) as a discovery platform for systematic identification of genetic and genomic biomarkers of drug sensitivity. J. Zhong, H. Niu, J. Cai, S. Middleton, H. Bian, J. Hakenberg, C. Saisanit, F. Birzele, W. Berkofsky-Fessler, J. Rosinski, N. Sanapareddy, Z. Albertyn, B. Chen, S. Bader, G. Chen, M. Xia, L. Vassilev, A. Belousov, L. Essioux.

243/5:00 Screening of the TPMT gene before thiopurine treatment results in a lower leucopenia occurrence in patient with inflammatory bowel disease. M. J. H. Coenen, C. J. van Marrewijk, L. J. J. Derijks, S. H. Vermeulen, O. H. Klungel, A. L. M. Verbeek, H. Scheffer, B. Franke, H. J. Guchelaar, D. J. de Jong, TOPIC Study.

244/5:15 PGRNseq: A new sequencing-based platform for high-throughput pharmacogenomic implementation and discovery. A. S. Gordon, J. D. Smith, Q. Xiang, M. L. Metzker, R. A. Gibbs, E. R. Mardis, D. A. Nickerson, R. S. Fulton, S. E. Scherer.

245/5:30 Genetic variation in the GRK4 gene associates with susceptibility to hypertension and response to angiotensin receptor blockade. M. White, Z. Wang, H. Sanada, M. Yoneda, S. M. Williams, J. Bartlett, L. Gordon, S. Chen, L. Asico, C. Escano, V. Villar, C. Zeng, L. Wong, J. Jones, R. Felder, G. Eisner, P. Jose.

246/5:45 Genome-wide discovery of drug-dependent human liver enhancers. R. P. Smith, K. M. Morrissey, X. Sun, T. J. Hoffman, K. M. Giacomini, N. Ahituv.

247/6:00 Genome-wide association study of vancomycin pharmacokinetics using a de-identified biorepository. S. L. Van Driest, T. L. McGregor, Z. Lu, S. Vear, C. B. Creech, P. J. Kannankeril, K. B. Brothers, A. Potts, E. Bowton, J. T. Delaney, Y. Bradford, S. Wilson, L. Olson, D. C. Crawford, B. Saville, D. M. Roden, J. C. Denny.

248/6:15 Integrating multiple levels of phenotypic information to map genetic determinants of glucocorticoid sensitivity. J. Maranville, S. Baxter, D. Witonsky, A. Di Rienzo.

249/6:30 Common and rare genetic variation in maturity-onset diabetes of the young genes influence response to interventions for diabetes prevention. L. Billings, l. Tipton, A. Warner, J. McAteer, A. Shuldiner, D. Ehrmann, A. Manning, D. Dabelea, P. Franks, S. Kahn, T. Pollin, W. Knowler, D. Altshuler, K. Jablonski, J. Florez.

Friday, November 9

8:00 AM–10:15 AM

Concurrent Platform (abstract-driven) Session D (47-55)

SESSION 47 – Structural and Regulatory Genomic Variation

Hall D, Lower Level North, Moscone Center

Moderators: Mike Lovett, Washington Univ. in St. Louis
  Douglas Mortlock, Vanderbilt Univ Sch Med

250/8:00 Germline mosaicism does not explain the maternal age effect on trisomy. R. Rowsey, B. Murdoch, P. Hunt, C. Dickerson, T. Woodruff, T. Hassold.

251/8:15 Female meiosis II errors prevalence and their impact on human embryo viability. A. Kuliev, Z. Zlatopolsky, I. Kirillova, J. Cieslak-Janzen.

252/8:30 A population isolate reveals enriched recessive deleterious variants underlying neurodevelopmental traits. O. Pietiläinen, J. Suvisaari, W. Hennah, V. Leppä, T. Paunio, M. Torniainen, S. Ripatti, S. Ala-Mello, K. Rehnström, A. Tuulio-Henriksson, T. Varilo, J. Tallila, K. Kristiansson, M. Isohanni, J. Kaprio, J. Eriksson, M. Jarvelin, R. Durbin, J. Lonnqvist, M. Hurles, H. Stefansson, N. Freimer, M. Daly, A. Palotie.

253/8:45 The role of trans-acting factors on recombination in oocytes with nondisjoined chromosomes 21. C. D. Middlebrooks, N. Mukhopadhyay, S. W. Tinker, E. G. Allen, L. J. H. Bean, F. Begum, R. Chowdhury, V. Cheung, E. Feingold, S. L. Sherman.

254/9:00 Large-scale function-based enhancer discovery. D. E. Dickel, Y. Zhu, A. S. Nord, J. A. Akiyama, A. Visel, L. A. Pennacchio.

255/9:15 A single enhancer on human chromosome 11 directly controls >1,000 promoters and distal regulatory elements genome-wide. J. A. Stamatoyannopoulos, H. Wang, G. J. Cost, H. Quh, Y. Santago, J. Belton, R. McCord, S. Orlando, S. Neph, L. Zhang, T. Canfield, E. Giste, R. Sandstrom, R. S. Hansen, R. E. Thurman, P. D. Gregory, J. Dekker, F. D. Urnov.

256/9:30 Identification of trait- and disease-relevant genetic polymorphisms in microRNA target sites. S. Busche, B. Ge, T. Kwan, K. Wong, S.-H. Chen, M. Georges, D. Ginzinger, T. Pastinen.

257/9:45 Mapping functional p53 response elements and their variants in human genome. X. Wang, M. R. Campbell, V. G. Cheung, D. A. Bell.

258/10:00 A SNP associated with skin cancer and pigmentation disrupts a melanocyte enhancer in an intron of IRF4. D. U. Gorkin, S. K. Loftus, D. Lee, M. A. Beer, W. J. Pavan, A. S. McCallion.

Friday, November 9

8:00 AM–10:15 AM

Concurrent Platform (abstract-driven) Session D (47-55)

SESSION 48 – Neuropsychiatric Disorders

Gateway Ballroom 103, Lower Level South, Moscone Center

Moderators: Dimitrios Avramopoulos, Johns Hopkins Univ.
  Tatiana Foroud, Indiana Univ. Sch. of Med.

259/8:00 Genetic and functional abnormalities of the melatonin biosynthesis pathway in patients with bipolar disorder. S. Jamain, B. Etain, A. Dumaine, F. Bellivier, C. Pagan, L. Francelle, H. Goubran-Botros, S. Moreno, J. Deshommes, K. Moustafa, K. Le Dudal, F. Mathieu, C. Henry, J. P. Kahn, J. M. Launay, T. W. Mühleisen, S. Cichon, T. Bourgeron, M. Leboyer.

260/8:15 Massively-parallel sequencing of the brain transcriptome reveals differential expression of novel genes in bipolar disorder. N. Akula, J. Barb, X. Jiang, J. Wendland, K. Choi, S. Sen, B. K. Lipska, J. E. Kleinman, H. C. Bravo, D. T. Chen, P. J. Munson, F. J. McMahon.

261/8:30 Rare and common gain-of-function alleles of the serotonin transporter gene, SLC6A4, associated with Tourette disorder. P. R. Moya, J. R. Wendland, A. M. Andrews, L. M. Rubenstein, K. R. Timpano, G. A. Heiman, J. A. Tischfield, R. A. King, S. Rammamoorthy, F. J. McMahon, D. L. Murphy.

262/8:45 GLRB is the third major gene-of-effect in hyperekplexia or startle disease. S. K. Chung, A. Bode, C. A. Hunt, A. Derrick, T. D. Cushion, S. Wood, C. Drew, O. W. Howells, R. H. Thomas, J. G. Mullins, J. Lynch, M. I. Rees.

263/9:00 Functional analysis of rare chimeric genes in schizophrenia. C. Rippey, C. Remmers, M. Cahill, A. Nord, T. Walsh, M. Lee, M. Gasperini, P. Penzes, J. McClellan, M.-C. King.

264/9:15 Excess homozygosity in the major histocompatibility complex in schizophrenia. S. Mukherjee, S. Guha, M. Ikeda, N. Iwata, A. K. Malhotra, I. Pe'er, A. Darvasi, T. Lencz.

265/9:30 Significant risk of new mutations for Huntington disease: CAG-size specific risk estimates of intermediate allele repeat instability. A. Semaka, C. Kay, C. Doty, J. A. Collins, M. R. Hayden.

266/9:45 Mutations in AKT3 lead to hemimegalencephaly. A. Poduri, G. D. Evrony, X. Cai, P. C. Elhosary, R. Beroukhim, M. K. Lehtinen, L. B. Hills, E. L. Heinzen, A. Hill, R. S. Hill, B. J. Barry, B. F. D. Bourgeois, J. J. Riviello, A. J. Barkovich, P. M. Black, J. Madsen, K. L. Ligon, C. A. Walsh.

267/10:00 De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly. J. Lee, M. Huynh, G. Mathern, J. Gleeson.

Friday, November 9

8:00 AM–10:15 AM

Concurrent Platform (abstract-driven) Session D (47-55)

SESSION 49 – Common Variants, Rare Variants, and Everything in-Between

Room 135, Lower Level North, Moscone Center

Moderators: Joan E. Bailey-Wilson, NIH/NHGRI
  Rasika Mathias, Johns Hopkins Univ. Sch. of Med.

268/8:00 Minimal differences in single nucleotide variation calls between blood- and cell line-derived DNA from the same individuals. C. M. Schafer, N. G. Campbell, G. Cai, J. S. Sutcliffe, J. D. Buxbaum, K. Roeder, ARRA Autism Sequencing Consortium.

269/8:15 The impact of genetic variation on diabetes-related quantitative traits from whole exome sequences: The T2D-GENES Consortium. H. M. Highland, X. Sim, A. Manning, M. Rivas, G. Atzmon, S. Choi, B. K. Cornes, J. Dupuis, J. C. Florez, P. Fontanillas, T. Frayling, E. R. Gamazon, I.-S. Huh, H. K. Im, J. Kim, Y. J. Kim, C. M. Lindgren, A. E. Locke, J. B. Meigs, A. P. Morris, N. Palmer, I. Prokopenko, T. M. Teslovich, T2D-GENES Consortium.

270/8:30 Whole-exome sequencing in multiplex families identifies novel rare variants in multiple sclerosis. A. H. Beecham, J. L. McCauley, A. Hadjixenofontos, P. L. Whitehead, I. Konidari, A. Aviram, Y. Pasco, S. L. Hauser, J. R. Oksenberg, D. J. Hedges, J. M. Vance, J. L. Haines, M. A. Pericak-Vance.

271/8:45 A Mendelian randomization study on vitamin D status and blood pressure: A meta-analysis in up to 89,042 individuals. K. S. Vimaleswaran, D. J. Berry, A. Cavadino, M. R. Järvelin, E. Hyppönen, D-CarDia Collaboration.

272/9:00 APOE modulates the relationship among triglycerides, cholesterol, and CHD through pleiotropy and gene-gene interactions. T. J. Maxwell, C. M. Ballantyne, J. M. Cheverud, C. S. Guild, C. E. Ndumele, E. Boerwinkle.

273/9:15 Statistical inference of tissue-consistent and tissue-specific eQTLs. T. Flutre, X. Wen, J. Pritchard, M. Stephens.

274/9:30 Estimates of penetrance for common pathogenic copy number variations. J. A. Rosenfeld, B. P. Coe, E. E. Eichler, H. Cuckle, L. G. Shaffer.

275/9:45 Combining Illumina gene expression microarrays from different tissues: Methodological aspects. K. Heim, C. Schurmann, A. Schillert, C. Müller, T. Zeller, C. Herder, J. Kruppa, T. Illig, G. Homuth, K. Strauch, A. Peters, H. Wallaschofski, M. Dörr, T. Meitinger, P. S. Wild, S. Blankenberg, U. Völker, M. Roden, A. Teumer, H. Prokisch, A. Ziegler on behalf of MetaXpress Consortium.

276/10:00 A DNA variant caller adapted to assess mitochondrial DNA variation in lymphocytes from 1,000 Sardinians. J. Ding, C. Sidore, O. Meirelles, M. K. Trost, F. Busonero, R. Nagaraja, F. Cucca, G. R. Abecasis, D. Schlessinger.

Friday, November 9

8:00 AM–10:15 AM

Concurrent Platform (abstract-driven) Session D (47-55)

SESSION 50 – Population Genetics Genome-Wide

Room 134, Lower Level North, Moscone Center

Moderators: Melissa A. Wilson Sayres, Univ. of California, Berkeley
  Sarah Tishkoff, Univ. of Pennsylvania

277/8:00 Direct measure of human somatic base-substitution mutation rate in monozygotic twins. J. B. Richards, R. Li, A. Montpetit, T. D. Spector, C. Polychronakos.

278/8:15 Estimating human mutation rate using autozygosity in a founder population. C. D. Campbell, J. X. Chong, M. Malig, A. Ko, B. L. Dumont, L. Han, L. Vives, B. J. O'Roak, P. H. Sudmant, M. Abney, C. Ober, E. E. Eichler.

279/8:30 The myth of random mating: Evidence of ancestry-related assortative mating across 3 generations in Framingham, MA. R. Sebro, G. Peloso, J. Dupuis, N. Risch.

280/8:45 Combined analysis of loss-of-function variants in protein-coding genes from over 16,000 individuals. D. G. MacArthur, M. Lek, K. Shakir, S. Balasubramanian, E. Lim, B. M. Neale, L. Habegger, S. Gabriel, P. Sullivan, S. Kathiresan, M. I. McCarthy, M. Boehnke, S. Purcell, S. A. McCarroll, M. B. Gerstein, D. Altshuler, M. A. DePristo, M. J. Daly.

281/9:00 Abundant selection explains low diversity on human Y chromosomes. M. Wilson Sayres, K. Lohmueller, R. Nielsen.

282/9:15 The genomic geography of close relatives across Europe. P. Ralph, G. Coop.

283/9:30 Evolutionary history and adaptation inferred from whole-genome sequences of diverse African hunter-gatherers. J. Lachance, B. Vernot, C. Elbers, B. Ferwerda, A. Froment, J. Bodo, G. Lema, W. Fu, T. Nyambo, T. Rebbeck, K. Zhang, J. Akey, S. Tishkoff.

284/9:45 Mapping the human genome's missing pieces using population admixture. G. Genovese, R. E. Handsaker, H. Li, N. Altemose, A. M. Lindgren, K. Chambert, B. Pasaniuc, A. Price, D. Reich, C. C. Morton, M. R. Pollak, J. G. Wilson, S. A. McCarroll.

285/10:00 When ancestry runs deep: Trans-species polymorphisms in apes. L. Segurel, E. Leffler, Z. Gao, S. Pfeifer, A. Auton, O. Venn, L. Stevison, A. Venkat, J. L. Kelley, J. Kidd, C. Bustamante, R. Bontrop, M. Hammer, J. Wall, P. Donnelly, G. McVean, M. Przeworski.

Friday, November 9

8:00 AM–10:15 AM

Concurrent Platform (abstract-driven) Session D (47-55)

SESSION 51 – Endless Forms Most Beautiful: Variant Discovery in Genomic Data

Gateway Ballroom 104, Lower Level South, Moscone Center

Moderators: Terry Furey, Univ. of North Carolina at Chapel Hill
  Deanna Church, NCBI/NIH

286/8:00 Dark matter of the diseasome: Annotating personal genomes for gene regulatory disease risk alleles. G. Bejerano.

287/8:15 Causal mutation discovery using next-generation sequencing data: Development and application of a pipeline to reduce false positive calls and to map regions of shared homozygosity and IBD. S. Gulsuner, T. Walsh, A. C. Watts, M. K. Lee, T. Ozcelik, M.-C. King.

288/8:30 A new framework for large-scale genomic variant discovery and validation using pooled sequencing data. G. del Angel, M. Carneiro, E. Banks, R. Poplin, C. Hartl, M. A. DePristo.

289/8:45 Discovery of genomic variants from RNA-sequencing data. R. Piskol, G. Ramaswami, J. B. Li.

290/9:00 zCall: A rare variant caller for array-based genotyping. J. I. Goldstein, A. Crenshaw, J. Carey, G. Grant, J. Maguire, M. Fromer, C. O'Dushlaine, J. L. Moran, K. Chambert, C. Stevens, P. Sklar, C. Hultman, S. Purcell, S. McCarroll, P. F. Sullivan, M. J. Daly, B. M. Neale, Swedish Schizophrenia Consortium, ARRA Autism Sequencing Consortium.

291/9:15 Copy number detection and variant classification in the DDD project. T. W. Fitzgerald, K. I. Morley, M. van Kogelenberg, E. Bragin, P. Vijayarangakannan, A. Tivey, S. Clayton, S. Gribble, C. Wright, D. FitzPatrick, H. Firth, J. Barrett, N. Carter, M. Hurles.

292/9:30 Removal of mapping biases in sequence-based functional data improves regulatory element identification at heterozygous variants. M. Buchkovich, K. L. Mohlke, T. S. Furey.

293/9:45 SNP discovery in diverse human populations by rapid, very-low-cost next-generation sequencing of reduced representation libraries. T. F. Cooke, M. C. Yee, M. Muzzio, R. Bell, O. E. Cornejo, C. D. Bustamante, E. E. Kenny.

294/10:00 HIBAG -- HLA genotype imputation with attribute bagging. X. Zheng, J. Shen, C. Cox, J. Wakefield, M. Ehm, M. Nelson, B. Weir.

Friday, November 9

8:00 AM–10:15 AM

Concurrent Platform (abstract-driven) Session D (47-55)

SESSION 52 – Clinical Genetics: Complex Mechanisms and Exome-Discovery

Room 124, Lower Level North, Moscone Center

Moderators: Michael Gambello, Emory Univ.
  Antonie D. Kline, Harvey Inst. for Human Genet., Baltimore

295/8:00 Systematic identification of causal mutations in Mendelian disorders using exome sequence data. M. Lek, N. F. Clarke, L. B. Waddell, B. Thomas, M. A. DePristo, M. J. Daly, K. N. North, D. G. MacArthur.

296/8:15 Exome sequencing of a large cohort of patients with congenital digestive system disorders. M. Yourshaw, S. F. Nelson, M. G. Martín.

297/8:30 Novel defect in kinetochore assembly causes short stature and microcephaly of postnatal onset. C. Y. Hung, J. E. Dallman, O. Rittinger, J. W. Bauer, M. Tekin, O. A. Bodamer.

298/8:45 Mutations in PIGO, a member of the GPI anchor synthesis pathway, cause hyperphosphatasia with mental retardation syndrome. P. M. Krawitz, Y. Murakami, J. Hecht, U. Krüger, S. E. Holder, G. R. Mortier, B. Chiaie, E. Baere, M. D. Thompson, T. Roscioli, S. Kielbasa, T. Kinoshita, S. Mundlos, P. N. Robinson, D. Horn.

299/9:00 The 600 kb deletion syndrome at 16p11.2 leads to energy imbalance and neuropsychiatric disorders. S. Jacquemont, F. Zufferey, E. H. Sherr, N. D. Beckmann, E. Hanson, A. Maillard, L. Hippolyte, A. Mace, C. Ferrari, Z. Kutalik, J. Andrieux, R. Bernier, S. Bouquillon, B. Delobel, W. Andrew-Faucett, R. P. Goin-Kochel, L. Harewood, S. Lebon, D. H. Ledbetter, C. Lese-Martin, K. Mannick, D. Martinet, M. B. Ramocki, S. J. Spence, K. Steinmann, J. Tjernagel, J. E. Spiro, A. Reymond, W. Chung, J. S. Beckmann on behalf of Simons VIP Consortium, and 16p11.2 European Consortium.

300/9:15 Ras/MAPK dysregulation caused by MEK2 haploinsufficiency: A novel mechanism for a RASopathy phenotype. M. J. M. Nowaczyk, B. Thompson, S. Zeesman, U. Moog, P. A. Sanchez-Lara, R. Falk, P. Magoulas, L. Brueton, S. M. Ahmudavalli, J. H. Fong, D. Batista, K. Rauen.

301/9:30 Analysis of ESP5400 exomes for results of clinical utility in genes for conditions tested as part of newborn screening programs and age-related macular degeneration. H. K. Tabor, S. M. Jamal, J. H. Yu, A. S. Gordon, W. S. Post, A. D. Johnson, T. A. Graubert, D. A. Nickerson, P. L. Auer, M. J. Bamshad on behalf of NHLBI Personal Genomics Project Team and NHLBI Exome Sequencing Project.

302/9:45 High congenital malformation rates in a Chornobyl ionizing radiation impacted population isolate in Ukraine. W. Wertelecki, L. Yevtushok, N. Zymak-Zakutnia, S. Lachenko.

303/10:00 Somatic mosaicism is responsible for congenital melanocytic naevus syndrome, and underpins the associated risk of melanoma. V. A. Kinsler, A. C. Thomas, N. W. Bulstrode, S. Abu-Amero, K. McKenzie, E. Chanudet, P. Stanier, E. Healy, N. J. Sebire, G. E. Moore.

Friday, November 9

8:00 AM–10:15 AM

Concurrent Platform (abstract-driven) Session D (47-55)

SESSION 53 – From SNP to Function in Complex Traits

Room 132, Lower Level North, Moscone Center

Moderators: Praveen Sethupathy, Univ. of North Carolina at Chapel Hill
  Aravinda Chakravarti, McKusick-Nathans Inst. of Genet. Med., Baltimore

304/8:00 The type 2 diabetes risk allele of rs11603334 increases ARAP1 promoter activity and is associated with increased ARAP1 mRNA in pancreatic islets. J. R. Kulzer, M. L. Stitzel, M. A. Morken, F. S. Collins, K. L. Mohlke.

305/8:15 NOS1AP is the major genetic electrocardiographic QT-interval regulator. A. Kapoor, R. B. Sekar, V. Pihur, M. K. Halushka, G. F. Tomaselli, A. Chakravarti.

306/8:30 A regulatory polymorphism in Csk, a Lyp binding partner, associates with systemic lupus erythematosus and affects B cell signaling, maturation and activation. N. Manjarrez-Orduño, E. Marasco, S. A. Chung, M. S. Katz, J. F. Kiridly, K. R. Simpfendorfer, J. Freudenberg, D. H. Ballard, E. Nashi, T. J. Hopkins, D. S. Cunninghame Graham, A. T. Lee, M. J. H. Coenen, B. Franke, D. S. Swinkels, R. Graham, R. P. Kimberly, P. M. Gaffney, T. J. Vyse, T. W. Behrens, L. A. Criswell, B. Diamond, P. K. Gregersen.

307/8:45 ITGAM coding variant, rs1143679 (R77H) that is associated with systemic lupus erythematosus (SLE) susceptibility affects its own expression in monocytes and ligand binding activities in SLE patients. A. K. Maiti, X. Kim-Howard, P. Motghare, J. M. Anaya, L. Loogers, S. K. Nath.

308/9:00 Loss-of-function of semaphorins 3C and 3D in Hirschsprung disease. Q. Jiang, K. P. Kilambi, T. Heanue, M. X. Sosa, Q. Wang, J. J. Gray, A. L. Kolodkin, D. D. Ginty, A. Chakravarti.

309/9:15 Functional assessment of human coding polymorphisms affecting skin pigmentation using zebrafish. Z. Tsetskhladze, V. Canfield, K. Ang, S. Wentzel, K. Reid, A. Berg, S. Johnson, K. Kawakami, K. Cheng.

310/9:30 Dosage effects of 169 Chr21 genes on early development events in zebrafish. S. Edie, N. Zaghloul, D. Klinedinst, J. Lebron, N. Katsanis, R. Reeves.

311/9:45 Two birds, one stone: Epistasis profiling of many single-nucleotide variants in a human gene. O. Zill, J. Kitzman, J. Shendure, S. Fields.

312/10:00 Discovery and replication of pathway-based trans-eQTL associations. L. Wiley, W. Bush.

Friday, November 9

8:00 AM–10:15 AM

Concurrent Platform (abstract-driven) Session D (47-55)

SESSION 54 – Genetic Counseling and Clinical Testing

Room 130, Lower Level North, Moscone Center

Moderators: Susan Hahn, Univ. of Miami, Hussman Inst. for Human Genomics
  Andrew Faucett, Geisinger Hlth. Syst., Danville, PA

313/8:00 Utilization of chromosomal microarrays in pediatrics. A. H. Seeley, C. E. Keegan, C. S. Remmert, B. A. Tarini.

314/8:15 Maximizing detection and minimizing noise: The first report of large scale whole exome sequencing data interpretation in a clinical laboratory. F. Xia, J. Beuten, M. Bainbridge, Z. Niu, M. Vatta, M. R. Bekheirnia, R. E. Person, M. Hardison, J. G. Reid, D. P. Sexton, A. C. Hawes, P. A. Pham, M. Wang, N. Saada, W. Liu, H. Sun, M. Scheel, Y. Ding, A. Roy, J. Wiszniewska, A. Willis, D. M. Muzny, S. E. Plon, J. R. Lupski, A. L. Beaudet, R. A. Gibbs, C. M. Eng, Y. Yang.

315/8:30 Efficient detection of causative mutations for rare diseases: Rethinking clinical practice. H. Lee, J. Deignan, T. Toy, B. Harry, M. Yourshaw, P. Taylor, S. Webb, N. Dorrani, K. Das, F. Quintero, S. Kantarci, D. A. Wong, W. W. Grody, E. Vilain, S. F. Nelson.

316/8:45 Intentions to receive individual results from whole-genome sequencing among participants in the ClinSeq™ study. B. B. Biesecker, F. M. Facio, H. Eidem, T. Fisher, S. Brooks, A. Linn, K. A. Kaphingst, L. G. Biesecker.

317/9:00 Changes to control perceptions following disclosure of APOE-coronary artery disease associations during genetic susceptibility testing for Alzheimer’s disease: Findings from the REVEAL Study. K. Christensen, J. S. Roberts, W. R. Uhlmann, P. J. Whitehouse, T. O. Obisesan, D. L. Bhatt, L. A. Cupples, R. C. Green.

318/9:15 Decreased prediction ability of common genetic variants on breast cancer risk with age: Possible underlying models and impact on risk prediction. H. Aschard, S. Lindstrom, P. Kraft.

319/9:30 Large-sample size, comprehensive catalog of variants and advanced machine learning technique boost risk prediction for inflammatory bowel disease. Z. Wei, W. Wang, J. Bradfield, E. Frackelton, C. Kim, F. Mentch, R. Baldassano, H. Hakonarson, International IBD Genetics Consortium.

320/9:45 A comparison of risk estimates for complex diseases: Navigenics SNP-based testing and family history assessment. L. Aiyar, C. Shuman, R. Hayeems, L. Velsher, S. Wodak, D. Chitayat, J. Davies.

321/10:00 Web-based case conferencing: An effective source of cancer genetics training for community-based clinicians. K. Blazer, J. Weitzel.

Friday, November 9

8:00 AM–10:15 AM

Concurrent Platform (abstract-driven) Session D (47-55)

SESSION 55 – Mitochondrial Disorders and Ciliopathies

Room 123, Lower Level North, Moscone Center

Moderators: Catherine E. Keegan, Univ. of Michigan
  Mitzi Murray, Univ. of Washington

322/8:00 Combination of modern and traditional techniques identify MCKD1 causal frameshift variants within the MUC1 VNTR. A. Kirby, A. Gnirke, D. Jaffe, V. Barešová, N. Pochet, B. Blumenstiel, C. Ye, D. Aird, C. Stevens, J. Robinson, M. Calibi, I. Gat-Viks, E. Kelliher, R. Daza, M. DeFelice, H. Hůlková, J. Sovová, C. Antignac, M. Guttman, R. Handsaker, K. Lindblad-Toh, S. Gabriel, P. S. Hart, A. Regev, C. Nusbaum, S. Kmoch, A. Bleyer, E. Lander, M. Daly.

323/8:15 ARL13B, INPP5E, PDE6D and CEP164 form a functional network involved in Joubert syndrome and nephronophthisis. S. Seo, M. C. Humbert, K. Weihbrecht, C. C. Searby, Y. Li, R. M. Pope, V. C. Sheffield.

324/8:30 Mainzer-Saldino syndrome is a ciliopathy caused by mutations in the IFT140 gene. I. Perrault, S. Saunier, S. Hanein, E. Filhol, A. Bizet, F. Collins, M. Salih, S. Gerber, N. Delphin, E. Silva, V. Baudouin, M. Oud, N. Shannon, M. Le Merrer, O. Roche, C. Pietrement, C. Bole-Feysot, P. Nitschke, M. Zahrate, P. Beales, H. Arts, A. Munnich, J. Kaplan, C. Antignac, V. Cormier-Daire, J.-M. Rozet.

325/8:45 Mutations in ALDH1B1, which encodes a mitochondrial protein belonging to the aldehyde dehydrogenase family, result in hepatic failure and mitochondrial respiratory chain deficiency. S. Salhi, V. Serre, M. Beinat, P. Nitschke, O. Bernard, A. Slama, A. Munnich, A. Rotig.

326/9:00 Targeted exome sequencing of 102 patients with clinical evidence of mitochondrial disease. D. S. Lieber, S. E. Calvo, K. Shanahan, N. G. Slate, S. Liu, S. G. Hershman, N. B. Gold, B. A. Chapman, M. Borowsky, D. R. Thorburn, G. T. Berry, J. D. Schmahmann, D. M. Mueller, K. B. Sims, V. K. Mootha.

327/9:15 Genetic diagnosis of mitochondrial disorders by whole-exome sequencing. C. J. Carroll, V. Brilhante, P. Isohanni, R. Pöyhönen, L. Euro, U. Richter, T. Lahtinen, A. Götz, H. Almusa, P. Ellonen, H. Pihko, B. Battersby, H. Tyynismaa, A. Suomalainen.

328/9:30 Constitutive activation of STIM1 causes tubular aggregate myopathy. J. Laporte, F. Chevessier, A. Maues de Paula, C. Koch, S. Attarian, C. Feger, D. Hantaï, P. Laforêt, K. Ghorab, J. M. Vallat, M. Fardeau, D. Figarella-Branger, J. Pouget, M. Koch, C. Ebel, N. Levy, B. Eymard, M. Bartoli, J. Bohm.

329/9:45 Mutation in PNPT1 gene, which encodes a mitochondrial polyribonucleotide nucleotidyltransferase, causes encephalopathy with choreo-athetotic movements. V. Vedrenne, A. Gowher, P. De Lonlay, P. Nitschke, V. Serre, N. Boddaert, C. Altuzarra, A. M. Mager-Heckel, F. Chretien, N. Entelis, I. Tarassov, A. Munnich, A. Rotig.

330/10:00 Comprehensive analysis of 101 nuclear genes for molecular diagnosis of mitochondrial disorders. R. Bai, J. Higgs, S. F. Suchy, S. Buchholz, D. Arjona, B. Boggs, C. Chinault, N. Smaoui, S. Benhamed, J. Compton, Y. Shevchenko, G. Richard, S. Bale, F. D. Kendall, S. Parikh, A. L. Gropman, W. Chung, A. Goldstein, S. E. Palmer, J. A. Panzer, S. W. Yum, M. J. Falk.

Friday, November 9

10:30 AM–11:15 AM

SESSION 56 – Gruber Genetics Prize Award Presentation and Rosalind Franklin Young Investigator Award Announcement

Hall D, Lower Level North, Moscone Center

The Genetics Prize is awarded annually by The Gruber Foundation. The Genetics Prize is presented to a leading scientist, or up to three, in recognition of groundbreaking contributions to any realm of genetics research. The recipient will be presented with a gold medal and a $500,000 unrestricted cash award.


Douglas Wallace, PhD
Ctr. of Mitochondrial and Epigenomic Med., Children's Hosp. of Philadelphia
Prof. of Pathol. and Lab. Med., Univ. of Pennsylvania

The 2012 Genetics Prize of The Gruber Foundation will be presented to pioneering geneticist Douglas C. Wallace for the discovery of mutations in the mitochondrial genome and their impact on human health and disease.

Dr. Wallace will deliver a lecture entitled, "A Bioenergetic Perspective on Origins, Health, and Disease".

Life is the interplay between structure (anatomy), energy (vital force), and the information to encode the structural and energetic systems. Classical Western biomedical thought has taken an anatomical perspective on disease and a Mendelian perspective on genetics. However, these perspectives are proving increasingly inadequate to explain the biological and genetic basis of complex diseases, cancer, and aging. To augment this classical perspective, we need to consider the bioenergetics of the eukarotic cell which is centered on the symbiotic bacterium known as the mitochondrion. The mitochondrion has its own DNA, the mitochondrial DNA (mtDNA), which encodes the core cellular energy genes. Mutations in the mtDNA have been found to cause the full range of complex disease phenotypes, the thousands of mtDNAs per cell provides an alternative explanation for quantitative genetic traits, and the analysis of mtDNA variation in human populations has offered new insights into ancient ancestral migrations and adaptation to alternative environments. The causal role of bioenergetic changes in complex disease has been validated by the introduction of mtDNA mutations into mice which then manifest common complex disease phenotypes. The recognition of the dichotomy between anatomical-chromosomal genes and bioenergetic-mtDNA genes has generated new insights into the molecular genetic basis of human health and disease, offered a new perspective on the neutralist-selectionist debate, and provided an explanation for the force that drives the evolution of complex biological forms.

The Gruber Genetics Prize has been presented annually since 2001. Laureates are: Rudolf Jaenisch, H. Robert Horvitz, David Botstein, Mary-Claire King, Robert H. Waterston, Elizabeth H. Blackburn, Maynard V. Olson, Allan C. Spradling, Janet Davison Rowley, Gerald Fink, Ronald Davis.

Nominations for the 2013 Prize are currently open. The deadline is December 15, 2012. For further information see

ROSALIND FRANKLIN YOUNG INVESTIGATOR AWARDS:Every three years, The Gruber Foundation presents the Rosalind Franklin Young Investigator Awards to two young women geneticists. One award is for research in genetics of humans and other mammals, and one award is for research in genetics of other model organisms. The awards are for career development and are $75,000 over three years. Winners of the Rosalind Franklin Award are in their first three years in an independent faculty level position in any area of genetics. The winners are selected by a committee of women geneticists, including former winners of the award. The recipients of the 2013-2015 Rosalind Franklin Young Investigator Awards are:

Valerie Horsley, PhD, Assistant Professor of Molecular, Cellular, and Developmental Biology at Yale University, for her studies of the epithelial stem cell niche delineated by mouse genetic models;


Mary Gehring, PhD, Member of the Whitehead Institute and Assistant Professor of Biology at MIT, for her studies of imprinting and epigenetic regulation in Arabidopsis.

Other finalists were Genevieve Konopka, PhD, Assistant Professor of Neuroscience at UT Southwestern and Avital Rodal, PhD, Assistant Professor of Biology at Brandeis University.


Friday, November 9

11:15 AM–11:45 AM

SESSION 57 – ASHG William Allan Award Presentation

Hall D, Lower Level North, Moscone Center

The William Allan Award is presented annually by ASHG to recognize substantial and far-reaching scientific contributions to human and medical genetics, carried out over a lifetime of scientific inquiry and productivity.

Tayfun Özcelik
Bilkent Univ., Ankara, Turkey


Uta Francke, MD
Prof. Em., Stanford Univ. Med. Ctr.

Dr. Francke was chosen for her outstanding and tireless contributions to human and medical genetics fields, for her major impact on the study of many human disorders, for the breadth and depth of her applications of chromosomal analyses and molecular studies, and for her innovative uses of mouse models for understanding human genetic disease. The award recognizes her seminal work which extends back to the early days of medical and human genetics and includes more than 500 peer-reviewed publications.

Among Francke's exemplary achievements are advances in understanding Charcot-Marie-Tooth, Marfan, Rett, Prader-Willi, Williams, and Wiskott-Aldrich syndromes, which have had a major impact on the studying and treatment of these disorders. In essence, her lifetime of scientific discoveries and numerous contributions to the field over the decades have been far-reaching and have made a significant impact on advancing both basic and clinical human genetics. Dr. Francke has been one of the most respected scientists in the genetics community and is a stellar example of a tireless scientist, always seeking answers to important questions that interested her.

Past Recipients: John Opitz (2011); Jurg Ott (2010); Hunt Willard (2009); Haig Kazazian (2008); Arthur Beaudet (2007); Dorothy Warburton (2006); Francis Collins (2005); Louis Kunkel (2004); David Weatherall (2003); Albert de La Chapelle (2002); Charles Epstein (2001); Stephen Warren (1999); Bert Vogelstein (1998); Philip Leder (1997); Robert Elston (1996); Kurt Hirschhorn (1995); Douglas Wallace (1994); Antonio Cao & Michael Kaback (1993); Alec Jeffreys (1992); Janet Rowley & Alfred Knudson (1991); Kary Mullis (1990); David Bostein & Ray White (1989); T. Caspersson (1988); L. L. Cavalli-Sforza (1987); Mary Lyon (1986); Joseph Goldstein & Michael Brown (1985); Y.W. Kan (1984); Frank Ruddle (1983); Elizabeth Neufield (1982); Patricia Jacobs (1981); Walter Bodmer (1980); F. Clarke Fraser (1979); Charles Scriver (1978); Victor McKusick (1977); Philip Levin and A.S. Wiener (1975); Curt Stern (1974); Barton Childs (1973); Arno Motulsky (1970); Jerome Lejeune (1969); Harry Harris (1968); Vernon Ingram (1967); James Neel (1965); Newton Morton (1962).


Friday, November 9

11:45 AM–12:45 PM

SESSION 58 – ASHG Membership and Business Meeting

Hall D, Lower Level North, Moscone Center

Reports highlighting current Society business will be presented. This is an opportunity for members to learn about recent ASHG activities and to provide suggestions to leaders. There will be a moment of silence for those members and colleagues we have lost in 2012. Discussion from the floor is encouraged.


Friday, November 9

4:30 PM–6:45 PM

Concurrent Platform (abstract-driven) Session E (59-67)

SESSION 59 – Genome Structure and Variation

Hall D, Lower Level North, Moscone Center

Moderators: John Moran, Univ. of Michigan Med. Sch.
  Ryan Mills, Univ. of Michigan Med. Sch.

331/4:30 A map of human genetic variation: Update from the 1000 Genomes Project. F. Yu, 1000 Genomes Consortium.

332/4:45 Towards a whole genome map of heritable copy number variation. S. Aradhya, L. Matyakhina, D. Pineda Alvarez, D. Riethmaier, A. Fuller, G. Richard, J. Meck.

333/5:00 Charting the population-scale landscape of short tandem repeat variation in humans. M. Gymrek, J. Chen, C. O'Dushlaine, M. Daly, D. Reich, Y. Erlich.

334/5:15 Whole-genome sequencing analysis of iPSC lines uncovers lineage-manifested CNVs. A. E. Urban, A. Abyzov, D. Palejev, L. Rosenberg-Belmaker, Y. Zhang, J. Mariani, L. Tomasini, A. Ferrandino, A. Szekely, M. Wilson, M. Haney, E. Grigorenko, A. Huttner, S. Weissman, M. Gerstein, F. Vaccarino.

335/5:30 SNP markers identify areas with restricted recombination suggesting structural variation across the human genome is widespread. P. G. Hysi, B. Tamraz, A. Nag, C. Venturini, J. S. Rahi, T. D. Spector, C. J. Hammond.

336/5:45 Mapping the L1 interactome reveals RISC-associated helicase MOV10 as a potent inhibitor of retrotransposition. J. Goodier, L. Cheung, H. H. Kazazian.

337/6:00 FoSTeS/MMBIR replicative repair mechanisms are error prone: High frequency of nucleotide variation at the breakpoint junctions. C. M. B. Carvalho, M. B. Ramocki, D. Pehlivan, P. Fang, L. M. Franco, J. W. Belmont, P. J. Hastings, J. R. Lupski.

338/6:15 Telomere position effect in patients with subtelomeric deletions. J. Gerfen, M. K. Rudd, H. Mason-Suares.

339/6:30 De novo CNV formation in mouse embryonic stem cells occurs in the absence of Xrcc4-dependent nonhomologous end joining. M. F. Arlt, S. Rajendran, S. R. Birkeland, K. M. McSweeney, T. E. Wilson, T. W. Glover.

Friday, November 9

4:30 PM–6:45 PM

Concurrent Platform (abstract-driven) Session E (59-67)

SESSION 60 – Advances in Neurodegenerative Disease

Gateway Ballroom 103, Lower Level South, Moscone Center

Moderators: Jeff Vance, Univ. of Miami
  Tricia Thornton-Wells, Vanderbilt Univ.

340/4:30 A genome-wide association study for cerebrospinal fluid tau and amyloid beta 42 identify new candidate variants implicated in Alzheimer's disease. J. S. K. Kauwe, C. Cruchaga, O. Harari, K. Mayo, S. Bertelsen, M. Bailey, D. McKean, P. G. Ridge, T. J. Maxwell, E. Peskind, D. Galasko, A. M. Goate, ADGC, ADNI, GERAD.

341/4:45 Analysis of whole transcriptome specific to the temporal pole of late-onset Alzheimer’s disease. C. E. Humphries, M. A. Kohli, P. W. Whitehead, W. F. Hulme, L. Nathanson, D. C. Mash, M. A. Pericak-Vance, J. R. Gilbert.

342/5:00 Rare variants from high-density exome genotyping in late-onset Alzheimer’s disease: Update from Alzheimer’s Disease Genetics Consortium. L.-S. Wang, A. C. Naj, C. Cruchaga, S. Mukherjee, C.-F. Lin, O. Valladares, L. B. Cantwell, R. Graham, T. Behrens, P. K. Crane, A. M. Goate, M. A. Pericak-Vance, G. D. Schellenberg, Alzheimer’s Disease Genetics Consortium.

343/5:15 Common variants in ABCA7 and GRIN3B, HMHA1 and SBNO2, are associated with late-onset Alzheimer’s disease in African Americans. C. Reitz, G. Jun, J. Buros, B. Vardarajan, L.-S. Wang, J. D. Buxbaum, E. B. Larson, N. Graff-Radford, D. Evans, N. Ertekin-Taner, M. Logue, C. T. Baldwin, R. C. Green, L. L. Barnes, L. B. Cantwell, M. D. Fallin, J. Manly, K. L. Lunetta, M. I. Kamboh, D. A. Bennett, K. Hall, A. M. Goate, G. S. Byrd, W. A. Kukull, T. M. Foroud, J. L. Haines, M. A. Pericak-Vance, L. A. Farrer, G. Schellenberg, R. Mayeux, ADGC Consortium.

344/5:30 Genome-wide association analyses of onset age in late-onset Alzheimer disease demonstrate no strong effect outside of the APOE region. A. C. Naj, Y. S. Park, R. Rajbhandary, K. L. Hamilton, G. W. Beecham, E. R. Martin, R. Mayeux, J. L. Haines, L. A. Farrer, G. D. Schellenberg, M. A. Pericak-Vance, Alzheimer's Disease Genetics Consortium.

345/5:45 Identification by exome analysis of the molecular bases of familial idiopathic basal ganglia calcification not related to SLC20A2 mutation. G. Nicolas, C. Pottier, D. Maltête, S. Coutant, A. Rovelet-Lecrux, S. Legallic, Y. Vaschalde, L. Guyant-Maréchal, J. Augustin, O. Martinaud, L. Defebvre, P. Krystkowiak, J. Pariente, I. Le Ber, T. Frebourg, D. Hannequin, D. Campion.

346/6:00 Mutations in DNAJ cause autosomal dominant Parkinson disease in the Mennonite community. C. Vilarino-Guell, A. Rajput, S. Appel-Cresswell, B. Shah, I. Yu, C. Thompson, C. Szu Tu, J. Trinh, M. Encarnacion, D. W. Dickson, A. J. Stoessl, M. L. Rajput, M. J. Farrer, A. H. Rajput.

347/6:15 C9ORF72 repeat expansion is a risk factor for Parkinson disease. K. Nuytemans, G. Bademci, M. M. Kohli, G. Beecham, V. Inchausti, A. Dressen, L. Wang, J. I. Young, F. Nahab, C. Singer, E. R. Martin, J. R. Gilbert, M. Benatar, J. L. Haines, W. K. Scott, S. Zuchner, M. A. Pericak-Vance, J. M. Vance.

348/6:30 Age-dependent penetrance of ALS+/-FTD due to C9orf72 hexanucleotide intronic repeat expansion mutations. B. N. Smith, S. Topp, J. Barnwell, A. Al-Chalabi, J. Kirby, P. J. Shaw, H. Pall, K. E. Morrison, V. de Jong, F. Bass, C. E. Shaw, C. M. Lewis.

Friday, November 9

4:30 PM–6:45 PM

Concurrent Platform (abstract-driven) Session E (59-67)

SESSION 61 – Missing Heritability, Interactions and Sequencing

Room 135, Lower Level North, Moscone Center

Moderators: Dana Crawford, Vanderbilt Univ.
  Alkes Price, Harvard Sch. of Publ. Hlth.

349/4:30 Empirical and theoretical studies on genetic variance of rare variants for complex traits using whole genome sequencing in the CHARGE Consortium. C. Zhu, A. Morrison, J. Reid, C. J. O’Donnell, B. Psaty, L. A. Cupples, R. Gibbs, E. Boerwinkle, X. Liu.

350/4:45 Leveraging admixture analysis to resolve missing and cross-population heritability in GWAS. N. Zaitlen, A. Gusev, B. Pasaniuc, G. Bhatia, S. Pollack, A. Tandon, E. Stahl, R. Do, B. Vilhjalmsson, E. Akylbekova, A. Cupples, M. Fornage, L. Kao, L. Lange, S. Musani, G. Papanicolaou, J. Rotter, I. Ruczinksi, D. Siscovick, X. Zhu, S. McCarroll, G. Lettre, J. Hirschhorn, N. Patterson, D. Reich, J. Wilson, S. Kathiresan, A. Price, CARe Analysis Core.

351/5:00 Applying a quantitative genetics test of evolutionary neutrality to finger ridge-count, a classical model trait in humans. S. E. Medland, P. M. Visscher, G. W. Montgomery, D. M. Evans, N. G. Martin.

352/5:15 Does common variation contribute to the shared genetic basis for schizophrenia and autism? P. H. Lee, S. Ripke, S. Santangelo, M. Daly, Psychiatric GWAS Consortium - Schizophrenia & Autism Working Group.

353/5:30 Ultrafast genome-wide interaction scan on case-control data implicates epistatic calcium channels in bipolar disorder. S. Prabhu, I. Pe'er.

354/5:45 Computational challenges in the analysis of low coverage sequence data in thousands of individuals. Y. Luo, L. Jostins, C. A. Anderson, J. C. Barrett, UK10K, UKIBDGC.

355/6:00 Sparse sequencing of 6,000 cases and 6,000 controls from Chinese women for genome-wide association study of major depression. X. Gan, R. Mott, J. Flint, CONVERGE Consortium.

356/6:15 Deep targeted sequencing of 12 breast cancer loci in 4,700 women across four different ethnicities. P. Kraft, S. Lindstrom, B. Chapman, G. Chen, C. Chen, O. Hofman, D. Mirel, C. Haiman.

357/6:30 Population stratification of human disease-associated SNPs, and their relevance to human disease networks. S. M. Raj, G. E. Hoffman, A. G. Clark.

Friday, November 9

4:30 PM–6:45 PM

Concurrent Platform (abstract-driven) Session E (59-67)

SESSION 62 – Exome Sequencing Uncovers Etiology of Mendelian Disease

Room 134, Lower Level North, Moscone Center

Moderators: Cheryl Maslen, Oregon Hlth. & Sci. Univ.
  Jun Z. Li, Univ of Michigan

358/4:30 Loss of function mutations in known human disease genes in 572 exomes. J. Johnston, K. Lewis, D. Ng, S. Gonsalves, J. Mullikin, L. G. Biesecker.

359/4:45 The problem of multiple plausible molecular diagnoses in next-generation sequencing data: The NIH Undiagnosed Diseases Program experience. D. Adams, C. Boerkoel, K. Fuentes-Fajardo, P. Cherukuri, M. Sincan, C. Toro, C. Tifft, W. Gahl, T. Markello.

360/5:00 Exome sequencing to identify the cause of Mendelian diseases. J. Lupski, C. Gonzaga-Jauregui, W. Wiszniewski, D. Pehlivan, E. Karaca, A. Stray-Pedersen, S. Jhangiani, J. Reid, D. Muzny, R. A. Gibbs, Baylor-Hopkins Center for Mendelian Genomics.

361/5:15 Domain-specific mutations in CDKN1C cause two disorders with opposing phenotypes: The undergrowth disorder IMAGe syndrome or the overgrowth disorder Beckwith-Wiedemann syndrome. V. Arboleda, H. Lee, R. Parnaik, A. Fleming, A. Banerjee, B. Ferraz-de-Souza, E. Delot, I. A. Rodriguez-Fernandez, D. Braslavsky, I. Bergadá, E. C. Dell’Angelica, S. F. Nelson, J. A. Martinez-Agosto, J. C. Achermann, E. Vilain.

362/5:30 SCID newborn screening and exome sequencing identifies ataxia telangiectasia and low T cells early in life. J. M. Mallott, A. Kwan, J. Church, D. Gonzalez, S. Rana, U. Sunderam, R. Srinivasan, S. E. Brenner, L. F. Tang, F. Lorey, J. Puck.

363/5:45 Identification of a new melanocyte differentiation gene underlying human autosomal recessive albinism. K. Grønskov, C. M. Dooley, E. Østergaard, R. N. Kelsh, L. Hansen, M. P. Levesque, K. Vilhelmsen, D. Stemple, T. Rosenberg.

364/6:00 Exome sequencing results in 230 patients with severe developmental disorders in the DDD project. M. van Kogelenberg, K. Morley, T. Fitzgerald, S. Gerety, A. Tivey, S. Al-Turki, S. Clayton, C. Wright, J. Barrett, H. Firth, D. FitzPatrick, N. Carter, M. Hurles on behalf of DDD Project.

365/6:15 Genetic etiology of isolated congenital asplenia. A. Bolze, L. Abel, A. Puel, N. Trede, L. Selleri, J.-L. Casanova.

366/6:30 Whole genome sequencing in two brothers with heterotaxy reveals BCL9L as a novel gene associated with autosomal recessive heterotaxy (HTX6). C. J. Saunders, N. A. Miller, S. E. Soden, E. Farrow, D. L. Dinwiddie, N. P. Safina, S. Humphray, P. Saffrey, Z. Kingsbury, J. C. Weir, J. Betley, R. J. Grocock, J. E. Petrikin, K. P. Hall, S. F. Kingsmore.

Friday, November 9

4:30 PM–6:45 PM

Concurrent Platform (abstract-driven) Session E (59-67)

SESSION 63 – Transcriptional Regulation, Variation and Complexity

Gateway Ballroom 104, Lower Level South, Moscone Center

Moderators: Barbara Stranger, Brigham and Women’s Hosp., Harvard Med. Sch
  Ross Hardison, Penn State

367/4:30 The complete GENCODE human annotation: New insights into the functionality of transcriptional complexity. J. M. Mudge, A. Frankish, GENCODE Consortium, T. Hubbard, J. L. Harrow.

368/4:45 Genetic analyses in the Genotype-Tissue Expression (GTEx) project. K. Ardlie, N. Cox, D. DeLuca, E. Dermitzakis, B. Foster, G. Getz, R. Guigo, S. Jewell, D. Koller, J. Liu, J. Londsdale, D. Mash, M. McCarthy, M. Moser, D. L. Nicolae, A. Nobel, J. Pritchard, I. Rusyn, J. Thomas, W. Winckler, F. Wright, J. Zhu, GTEx Consortium.

369/5:00 Characterizing the genetic basis of transcriptome diversity in a large RNA sequencing study. A. Battle, S. Mostafavi, X. Zhu, S. B. Montgomery, J. B. Potash, M. M. Weissman, C. Haudenschild, C. McCormick, R. Mei, A. E. Urban, D. F. Levinson, D. Koller.

370/5:15 Genetic and molecular basis of RNA-DNA sequence differences in humans. V. G. Cheung, A. Bruzel, L. McDaniel, A. L. Richards, J. M. Toung, I. X. Wang.

371/5:30 Characterizing gene expression variation across seven diverse human populations. A. R. Martin, H. A. Costa, J. M. Kidd, B. M. Henn, M. C. Yee, F. Grubert, S. B. Montgomery, H. M. Cann, M. P. Snyder, C. D. Bustamante.

372/5:45 Comparative eQTL analyses within and between seven tissue types suggest mechanisms underlying cell type specificity of eQTLs. B. Engelhardt, C. Brown.

373/6:00 Identification of novel genetic determinants of induced innate immune responses and context specific eQTL in human primary monocytes. B. P. Fairfax, S. Makino, J. C. Knight.

374/6:15 Gene-level and exon-level expression QTL signals in the UK Brain Expression Consortium dataset. M. E. Weale, A. Ramasamy, D. Trabzuni, R. Walker, C. Smith, M. Ryten, J. Hardy, UK Brain Expression Consortium.

375/6:30 First complete haplotype of the human immunoglobulin heavy chain locus from a single individual and characterization of novel allelic and structural variation. K. Meltz Steinberg, C. T. Watson, J. Huddleston, P. H. Sudmant, R. L. Warren, M. Malig, J. Schein, A. J. Willsey, J. B. Joy, J. K. Scott, T. Graves, R. K. Wilson, R. A. Holt, F. Breden, E. E. Eichler.

Friday, November 9

4:30 PM–6:45 PM

Concurrent Platform (abstract-driven) Session E (59-67)

SESSION 64 – Epigenetics

Room 124, Lower Level North, Moscone Center

Moderators: Bernd Wollnik, Univ of Cologne, Germany
  Beth A. Sullivan, Duke Univ.

376/4:30 The epitranscriptome reveals novel mechanisms of RNA regulation and spatiotemporal dynamics. C. E. Mason, K. Meyer, Y. Saletore, P. Zumbo, O. Elemento, S. Jaffrey.

377/4:45 Epigenome-wide profiling of circulating DNA in colorectal cancer. R. Cortese, Y. Li, A. Kwan, B. Zanke, Z. Zhang, A. Petronis.

378/5:00 Alterations in genomically imprinted miRNA and snoRNA clusters in a mouse model of fetal alcohol spectrum disorders. B. I. Laufer, K. Mantha, M. L. Kleiber, E. J. Diehl, S. M. F. Addison, S. M. Singh.

379/5:15 KDM6A escapes X inactivation and controls expression of reproduction-related homeobox genes in female ES cells and ovary: Deficiency may explain embryonic and ovarian failure in Turner. C. M. Disteche, J. B. Berletch, X. Deng, D. Nguyen.

380/5:30 Genome-wide scan of DNA methylation in the aging brain and its relation to Alzheimer’s disease. P. L. De Jager, G. Srivastava, M. L. Eaton, L. E. Chibnik, B. Keenan, N. Taner, A. Myers, B. Bernstein, A. Meissner, M. Kellis, D. A. Bennett.

381/5:45 RNA-mediated transcriptional silencing in Friedreich ataxia. Y. K. Chutake, A. M. Castro, S. I. Bidichandani.

382/6:00 P53 regulates 5-hydroxymethylcytosine-mediated epigenetic landscape through GADD45A. Y. Li, Y. Zhu, K. Szulwach, L. Lin, C. Street, H. Wu, D. Chen, P. Jin.

383/6:15 Maps of open chromatin highlight cell type-specific patterns of regulatory sequence variation at hematological trait loci. C. A. Albers, D. S. Paul, A. Rendon, K. Voss, J. Stephens, P. van der Harst, J. C. Chambers, N. Soranzo, W. H. Ouwehand, P. Deloukas, HaemGen Consortium.

384/6:30 Functional epialleles at an endogenous human centromere. B. A. Sullivan, K. A. Maloney, L. L. Sullivan, E. D. Strome, J. Matheny.

Friday, November 9

4:30 PM–6:45 PM

Concurrent Platform (abstract-driven) Session E (59-67)

SESSION 65 – Advances in Ocular Genetics

Room 132, Lower Level North, Moscone Center

Moderators: Erica Davis, Duke Univ. Med. Ctr
  Arupa Ganguly, Univ. of Pennsylvania

385/4:30 Rare insertion polymorphisms identified by exome sequencing may be associated with age-related macular degeneration. L. Farrer, J. Kozubek, M. Schu, J. Farrell, M. Morrison, K. Mayne, D. Morgan, R. Robinson, A. Swaroop, D. Schaumberg, K.-H. Park, E. E. Tsironi, G. Silvestri, I.-K.. Kim, R. Chen, C. Huff, G. Jun, M. deAngelis.

386/4:45 The role of SIX6 in primary open-angle glaucoma. M. Ulmer, B. Whigham, D. Parker, X. Qin, N. Katsanis, Y. Liu, A. Ashley-Koch, R. R. Allingham, M. Hauser, NEIGHBOR Consortium Investigators.

387/5:00 Topical ocular sodium 4-phenylbutyrate rescues glaucoma in a mouse model of primary open angle glaucoma. G. S. Zode, K. E. Bugge, E. M. Stone, V. C. Sheffield.

388/5:15 Meta-analysis of GWAS on corneal thickness identifies a total of 27 associated loci, including six risk loci for eye disease keratoconus. S. Macgregor on behalf of CCT Consortium.

389/5:30 Mouse models reveal an essential role for RERE in eye development. B. Kim, Z. Yu, O. Shchelochkov, M. Justice, B. Lee, D. Scott.

390/5:45 Mutations in the nuclear NAD synthesizing enzyme NMNAT1 cause autosomal recessive Leber congenital amaurosis with early-onset severe macular atrophy and optic atrophy. J. Rozet, I. Perrault, S. Hanein, X. Zanlonghi, V. Serre, M. Nicouleau, S. Defoort-Delhemmes, N. Delphin, L. Fares-Taie, S. Gerber, O. Xerri, C. Edelson, A. Goldenberg, A. Duncombe, G. Le Meur, C. Hamel, E. Silva, P. Nitschke, P. Calvas, A. Munnich, O. Roche, H. Dollfus, J. Kaplan.

391/6:00 RNA-DNA differences in miRNA transcriptome of retina and retinoblastoma. A. Ganguly, J. Leipzig, J. Richards, J. Purrazzella, T. Ganguly.

392/6:15 Knock-in of human KIAA0649P into the mouse Rb1 locus: Modeling the mechanism of imprinted RB1 expression in humans. L. Steenpass, D. Kanber, M. Hiber, K. Buiting, D. Lohmann, B. Horsthemke.

393/6:30 Gene therapy provides long-term visual function in a pre-clinical model of retinitis pigmentosa. K. J. Wert, R. J. Davis, S. H. Tsang.

Friday, November 9

4:30 PM–6:45 PM

Concurrent Platform (abstract-driven) Session E (59-67)

SESSION 66 – Cancer Genetics: Somatic Variants

Room 130, Lower Level North, Moscone Center

Moderators: Charis Eng, Cleveland Clinic
  Jennelle Hodge, Mayo Clin.

394/4:30 The genomic landscape of childhood pre-B acute lymphoblastic leukemia. J. Spinella, R. Vidal, J. Healy, V. Saillour, E. Bareke, C. Richer, S. Busche, B. Ge, T. Pastinen, D. Sinnett.

395/4:45 Genomic analysis of serial chronic lymphocytic leukemia samples suggests that epigenetic changes, rather than clonal evolution, drive progression of disease. E. N. Smith, C. DeBoever, L. Rassenti, E. Ghia, S. Rozenzhak, P. Shepard, H. Alakus, O. Harismendy, C. Barrett, T. J. Kipps, K. A. Frazer.

396/5:00 Whole-genome sequencing of liver cancers identifies etiological influences on mutation patterns and recurrent mutations in chromatin regulators. A. Fujimoto, Y. Totoki, T. Abe, K. A. Boroevich, F. Hosoda, H. H. Nguyen, M. Aoki, N. Hosono, M. Kubo, F. Miya, Y. Arai, H. Takahashi, T. Shirakihara, M. Nagasaki, T. Shibuya, K. Nakano, K. Watanabe-Makino, H. Tanaka, H. Nakamura, K. Chayama, N. Kamatani, S. Miyano, H. Nakagama, Y. Nakamura, T. Tsunoda, T. Shibata, H. Nakagawa.

397/5:15 Breast cancer evolution revealed by deep whole-genome sequencing of early neoplasias and their concurrent carcinomas. A. Sidow, D. Kashef-Haghighi, D. Newburger, Z. Weng, T. Sweeney, S. Batzoglou, R. West.

398/5:30 Intra-tumor genetic heterogeneity in cancer tissues: The key to assessing its significance is the distribution profile of gene variants not just their presence in tumors. B. Gottlieb, C. Alvarado, C. Wang, B. Gharizadeh, F. Babrzadeh, L. K. Britel, M. Trifiro.

399/5:45 Next -generation sequencing and chromosomal microarray analysis provide novel insight into the genomic landscape of metastatic breast cancer. M. Li, Y. Wen, E. Fang, Y. Li, P. Chen, G. Douglas, C. Carmack, K. Osborne.

400/6:00 The 3D topographic mapping of genetic variations in treatment of naïve advanced ovarian cancer. E. Cuppen, M. de Pagter, M. Hoogstraat, G. Cirkel, J. Kreeftmeijer, C. Lee, E. Levandowsky, T. Guy, K. Duran, R. 't Slot, T. Jonges, S. van Lieshout, M. Lolkema, R. Zweemer, M. Koudijs, I. Nijman, E. Voest, T. Harkins, W. Kloosterman.

401/6:15 Transcriptome sequence analysis of human colorectal cancer samples to reveal functional attributes. H. Ongen, T. F. Orntoft, B. Oster, L. Romano, A. Planchon, C. L. Andersen, E. T. Dermitzakis.

402/6:30 Regulatory regions are somatic mutation cold spots in cancer genomes. S. Sunyaev, P. Polak, M. S. Lawrence, R. E. Thurman, N. Stoletzki, P. Stojanov, E. Rynes, L. A. Garraway, S. Mirkin, G. Getz, J. A. Stamatoyannopoulos.

Friday, November 9

4:30 PM–6:45 PM

Concurrent Platform (abstract-driven) Session E (59-67)

SESSION 67 – Developmental Insights into Human Malformations

Room 123, Lower Level North, Moscone Center

Moderators: Lucy Osborne, Univ. of Toronto, Canada
  Rhona Schreck, Cedars-Sinai Med Ctr.

403/4:30 TECTONIC3 mutations cause orofaciodigital syndrome type IV (Mohr-Majewski). S. Thomas, M. Legendre, S. Saunier, B. Bessières, C. Alby, M. Bonnière, A. Toutain, L. Loeuillet, K. Szymanska, F. Jossic, D. Gaillard, M. Tahar Yacoubi, S. Mougou-Zerelli, A. David, M.-A. Barthez, Y. Ville, C. Bole-Feysot, P. Nitschke, A. Munnich, C. A. Johnson, F. Encha-Razavi, V. Cormier-Daire, C. Thauvin-Robinet, M. Vekemans, T. Attié-Bitach.

404/4:45 Abnormal development of NG2+PDGFRα+ neural progenitor cells causes neonatal hydrocephalus in a ciliopathy mouse model. C. S. Carter, T. W. Vogel, Q. Zhang, T. O. Moninger, D. R. Thedens, K. M. Keppler-Noreuil, D. Y. Nishimura, C. C. Searby, K. Bugge, V. C. Sheffield.

405/5:00 Malformation of the brain cortex, as the only expression of a ciliopathy, results from mutation in human Rotatin. G. M. S. Mancini, F. W. Verheijen.

406/5:15 Whole exome resequencing identifies mutations in LRRC6 as a novel single-gene cause of primary cliary dyskinesia. M. Chaki, H. Y. Gee, E. A. Otto, K. Diaz, T. W. Hurd, J. Halbritter, S. J. Allen, M. B. Zariwala, M. R. Knowles, F. Hildebrandt.

407/5:30 Temporally and spatially resolved catalogues of in vivo forebrain enhancers. A. S. Nord, L. Taher, J. Akiyama, M. J. Blow, A. Holt, R. Hosseini, S. Phouanenavong, I. Plajzer-Frick, M. Shoukry, V. Afzal, E. M. Rubin, I. Ovcharenko, J. L. R. Rubenstein, L. A. Pennacchio, A. Visel.

408/5:45 SRY regulation of the RET gene suggests a potential role of the Y-chromosome gene in sexual dimorphism in Hirschsprung disease. Y. Li, Z. L. Tabatabai, M.-M. Garcia-Barceló, P. K. H. Tam, Y.-F. C. Lau.

409/6:00 MAP3K1 mutations in 46,XY DGDs alter crosstalk in downstream signal transduction pathways to cause abnormal human gonadal development. J. Loke, A. Pearlman, H. Ostrer.

410/6:15 Soft tissue aspects of the Williams-Beuren syndrome facial phenotype can be attributed to GTF2IRD1. S. J. Palmer, C. P. Canales, P. Carmona-Mora, P. Kaur, P. W. Gunning, E. C. Hardeman.

411/6:30 Notch gain of function inhibits chondrocyte differentiation via Rbpj-dependent suppression. S. Chen, J. Tao, Y. Bae, M. Jiang, T. Bertin, Y. Chen, T. Yang, B. Lee.

Saturday, November 10

8:00 AM–8:20 AM

SESSION 68 – ASHG Award for Excellence in Human Genetics Education

Hall D, Lower Level North, Moscone Center

The ASHG Award for Excellence in Human Genetics Education was established to recognize those who have made significant contributions of exceptional quality and great importance to human genetics education.

Kay Davies, Univ. of Oxford


Alan E. H. Emery, MD, PhD, DSc
Em. Prof. of Human Genetics, Univ. of Edinburgh
Hon. Fellow, Green Templeton Col., Univ. of Oxford

Professor Emery is being recognized for his distinguished work in education through lecturing, mentoring, establishment of programs, and for his writings, which include over 400 peer-reviewed articles and 26 books on all aspects of human and medical genetics (as well as poetry and the relationship between Medicine and Art). Indeed, Professor Emery has been one of the most prolific authors of important genetics texts in the world.

His books have covered all aspects of medical genetics, prenatal diagnosis, genetic counseling, statistics, molecular genetics, and historical perspectives. His texts including Elements of Medical Genetics (general), Methodology in Medical Genetics (statistics), Introduction to Recombinant DNA (molecular genetics) and Principles and Practice of Medical Genetics with David Rimoin (medical), remain among the most important texts in their fields. One of his textbooks has been republished in twelve editions and translated into seven languages. Professor Emery was the first to describe a form of muscular dystrophy now referred to as Emery-Dreifuss Muscular Dystrophy (EDMD or EMD) and the defective protein Emerin is named after him.

Among his many accolades, Professor Emery is a fellow or honorary fellow in ten different societies, including the Royal Society of Medicine and the Royal Society of Arts. Emery has also received many awards, including the Lifetime Achievement Award from the World Federation of Neurology and the Cockcroft Medal from the University of Manchester, plus several honorary degrees. For many in the field of human genetics, Professor Emery is simply known as "the expert."

Past Recipients: Giovanni Romeo (2011); Thomas Gelehrter (2010); Bruce Korf (2009); John Carey, Lynn Jorde & Louisa Stark (2008); Robert Elston (2007); Roberta Pagon (2006); Joseph McInerney (2005); Robert Gorlin (2004); Joan Marks (2003); Kurt Hirschhorn (2002); Charles Scriver (2001); F. Clarke Fraser (2000); Arno Motulsky (1999); C.C. Li (1998); Victor McKusick (1997); Barton Childs (1996); Margaret Thompson (1995).


Saturday, November 10

8:20 AM–8:40 AM

SESSION 69 – ASHG Victor A. McKusick Leadership Award Presentation

Hall D, Lower Level North, Moscone Center

ASHG established this prestigious award in honor of Dr. Victor A. McKusick and his inspiring contributions to the human genetics field. The McKusick Leadership Award is presented to an individual whose professional achievements have fostered and enriched the development of the field of human genetics. Recipients of this award exemplify the enduring leadership and vision required to ensure that the field of human genetics will flourish and successfully assimilate into the broader context of science, medicine, and health.

Joann A. Boughman, Univ. Syst. of Maryland


Francis S. Collins, MD, PhD
Director, National Institutes of Health

Dr. Collins has been named as the 2012 winner in recognition of his extensive achievements in genetics research, his efforts to advance health science and technology through policy and education, and his stellar leadership of the genetics community in mapping the human genome. The revolution that was dreamed of at the start of the Human Genome Project is currently being realized. Today's medical geneticists, genetic counselors, and other health professionals are increasingly able to identify and test genes associated with both single-gene and complex disease. Today's medical researchers are increasingly able to investigate treatments and therapies for diseases with genetic causes. These medical and scientific advances would not have been possible without Dr. Collin's leadership and dedication to studying the molecular genetics of diseases, for the benefit of health and medicine.

During the completion of the NIH-based Human Genome Project, Dr. Collins served as the Director of the National Human Genome Research Institute. However, prior to taking on that leadership role, he had already contributed much to human genetics. He took part in the identification of the gene for cystic fibrosis in 1989, the gene for neurofibromatosis in 1990, and the gene for Huntington's disease in 1993. His laboratory is known for its past and continuing focus on the function of genes involved in breast cancer, diabetes, Hutchinson-Gilford progeria syndrome, and many other conditions. In 2008, Dr. Collins stepped down from the NHGRI, and less than a year later, he was chosen by President Obama to serve as the director of the National Institutes of Health.

Dr. Collins has received many awards for his achievements in science and technology, including the Presidential Medal of Freedom in November 2007, the National Medal of Science in 2009, and election into the Institute of Medicine and the National Academy of Sciences.

Dr. Collins has also made "singing for science" an emphasis of his professional career. His efforts in education and outreach are commended by many. These efforts include, among many others, creating clinical partnerships with four historically black colleges and universities to develop clinical research degrees and conduct treatment trials among minority patients, and establishing the National Center for Advancing Translational Sciences to enhance the process of translating scientific discoveries into new drugs, diagnostics, and devices. Dr. Collins continues to play a vital role in the advancement of genetics and medical research and the improvement of health and medicine.

Past Recipients: Leon E. Rosenberg (2011); Charles J. Epstein (2010); Arno G. Motulsky (2009); Victor A. McKusick (2008); Walter Nance (2007); David Rimoin (2006).


Saturday, November 10

8:40 AM–8:45 AM

SESSION 70 – AJHG C.W. Cotterman Awards Announcement

Hall D, Lower Level North, Moscone Center

Presenter: David L. Nelson, Editor, The American Journal of Human Genetics
Baylor Coll. of Med

Each September, the editorial board of The American Journal of Human Genetics selects two articles published in the journal in the previous year that best represent outstanding scientific contributions to the field of human genetics. Two Cotterman Awards are given annually . Monetary awards of $1,000 and a certificate will be presented to the recipients for the top two papers published in the Journal during the previous year on which the first author was either a pre- or post- doctoral trainee and an ASHG member.


Saturday, November 10

8:45 AM–8:55 AM

SESSION 71 – ASHG Charles J. Epstein Trainee Awards for Excellence in Human Genetics Research: Announcement of Winners

Hall D, Lower Level North, Moscone Center

Presenter: C. E. Pearson, Awards Committee Chair
Hosp. for Sick Children

ASHG honors excellence in research conducted by predoctoral and postdoctoral trainees, including genetic counseling trainees, through merit-based awards that recognize highly competitive abstracts submitted for the Annual Meeting. These awards were renamed in 2012 to honor the late Dr. Charles Epstein.

60 Semifinalists were selected based on abstract score and awarded complimentary registration plus $750 each. Of those semifinalists, 18 finalists (selected by the Awards Committee) received an additional $250. The finalists' presentations were reviewed by the ASHG Awards Committee and volunteer judges during the Annual Meeting.

Six winners announced today will receive an additional $1000 each.

Members of the Awards Committee are Christopher Pearson, Chair; Goncalo Abecasis, Georgia Dunston, Maximilian Muenke, Pragna Patel, Sharon Plon.


Saturday, November 10

8:55 AM–9:20 AM

SESSION 72 – ASHG Curt Stern Award Presentation

Hall D, Lower Level North, Moscone Center

The Curt Stern Award is given annually by ASHG in recognition of major scientific achievement in human genetics that has occurred in the last 10 years. The work could be a single discovery or a series of contributions on similar or related topics. This Award honors the memory of Dr. Curt Stern (1902-1981), an outstanding pioneer in human genetics who served as ASHG president in 1956.

Evan Eichler, Univ. of Washington


Jay A. Shendure, MD, PhD
Assoc. Prof., Dept. of Genome Sciences
Univ. of Washington

Dr. Shendure was selected for his outstanding contributions to the broad development and application of exome sequencing and its truly revolutionary effects on human genetics, as well as for the development of methods for high-throughput functional analysis of non-coding areas of DNA. This work has been - and will continue to be - of great impact to human disease gene discovery and understanding in clinical genetics. Importantly, these contributions have permitted individual (particularly small) clinical and laboratory groups to make significant contributions to our understanding of disease. Most recently, Dr. Shendure and colleagues non-invasively sequenced the whole genome of a fetus, using DNA from the blood of the mother and the saliva of the father. This work will lead to major changes in prenatal diagnosis as the field moves toward non-invasive yet comprehensive testing. Dr. Shendure is one of the most promising young scientists in our genetics community. He will certainly continue to lead the way in developing techniques that will have great impact on patients.

Past Recipients: David Altshuler (2011); Vivian Cheung (2010); David Haussler and James Kent (2009); Evan Eichler (2008); Jeffrey Murray (2007); Hal Dietz (2006); Patrick Brown (2005); Neil Risch (2004); David Page (2003); James Lupski (2002); Daniel Pinkel and Joe Gray (2001).


Saturday, November 10

9:40 AM–11:40 AM

Concurrent Invited Session III (73-80)

SESSION 73 – Returning Results from Large-Scale Sequencing: Where the Rubber Meets the Road

Gateway Ballroom 103, Lower Level South, Moscone Center

Moderators: Leslie G. Biesecker, NHGRI/NIH
  Robert C. Green, Brigham and Women’s Hosp.

Medicine is on the brink of a revolution, as large-scale medical sequencing (LSMS) is now available for patient care, marking the dawn of genomic medicine. LSMS may be used in patients with a family history or symptoms of a disease for diagnosis or to predict future health risks for prevention and surveillance. Developing standards and procedures for the use of LSMS in clinical medicine is critical and there is a need for empiric data to determine how to interpret, analyze, and return results. A critical question is how to handle secondary findings from LSMS. Speakers in this session will share their pioneering research initiatives that explore the translation of LSMS into meaningful clinical information and the delivery to patients. The speakers will report on a range of studies, including patients ascertained with diseases, healthy volunteers, adults, and children, research versus clinical, and rare versus common disease. All of the speakers will focus on results, and not just opinions, to inform the practice of genomic medicine and future research studies on the return of results. Dr. Biesecker will introduce the session and present ClinSeq, a large cohort LSMS study with return of results to subjects. Dr. Green will present the results of two efforts to formulate consensus on return of incidental findings in LSMS. Dr. Kingsmore will present experience with neonatal and pediatric diagnosis by LSMS. Finally, Dr. Veltman will present the results of a pilot using LSMS to diagnose genetically heterogeneous diseases with required return of all medically relevant results.


9:40 AM   ClinSeq: A pilot study of large-scale medical sequencing in research and implications for clinical genomic medicine. L. G. Biesecker. NHGRI/NIH.

10:10 AM   Expert concordance and discordance for return of incidental findings from whole genome sequencing. R. C. Green. Brigham and Women’s Hosp.

10:40 AM   Using next-generation sequencing for carrier testing for severe childhood recessive diseases. C. Saunders. Dept. of Pediatrics.

11:10 AM   Diagnostic implementation of exome sequencing: Results from 500 patients. J. Veltman. Genomic Disorders Nijmegen, Netherlands.

Saturday, November 10

9:40 AM–11:40 AM

Concurrent Invited Session III (73-80)

SESSION 74 – Genomic Approaches to Mendelian Disorders

Hall D, Lower Level North, Moscone Center

Moderators: Jay Shendure, Univ. of Washington
  David Valle, Johns Hopkins Univ. Sch. of Med.

Although the gene(s) underlying approximately 3,000 Mendelian disorders are known, there are thousands of well-defined or suspected Mendelian disorders for which the genetic basis remains unknown. The past three years have been witness to an explosion of interest in applying new technologies such as exome and genome sequencing to identify the genetic basis of Mendelian disorders that have proven intractable to conventional strategies. In this session, we will describe the progress as well as current challenges facing efforts to scale and accelerate the application of next-generation technologies to Mendelian disorders, e.g. the U.S.-based Mendelian Genome Centers as well as related international efforts. Topics that will be explored include primary research results from leading groups in this field; advances and ongoing challenges in phenotype curation, sequencing technology, and data analysis; and the broader implications of these efforts for biology and medicine.


9:40 AM   Genomic approaches to Mendelian disorders. D. Valle. Johns Hopkins Univ. Sch. of Med.

9:55 AM   FORGE Canada: A nation-wide effort to understand the genomics of childhood disorders. K. Boycott. Children’s Hosp. of Eastern Ontario, Canada.

10:10 AM   Current challenges in exome or genome-based analysis of Mendelian disorders. J. Shendure. Univ. of Washington.

10:40 AM   Lessons from 500 diagnostic exomes. H. G. Brunner. Radboud Univ. Nijmegen Med. Ctr., Netherlands.

11:10 AM   Genes, genomes and the future of medicine. R. Lifton. Yale Univ.

Saturday, November 10

9:40 AM–11:40 AM

Concurrent Invited Session III (73-80)

SESSION 75 – Emerging Applications of Identity by Descent Segment Detection

Gateway Ballroom 104, Lower Level South, Moscone Center

Moderators: Sharon R. Browning, Univ. of Washington
  Brian L. Browning, Univ. of Washington

Identity by descent (IBD) is fundamental to genetics and has diverse applications. Recently developed statistical methods and genome-wide SNP data have made it possible to detect haplotypes shared identically by descent between individuals with common ancestry up to 25-50 generations ago. With sequence data, shared haplotypes from even more distant ancestry can be detected. Patterns of IBD segment sharing within and between populations reveal important population demographic features including recent effective population size and migration patterns. IBD segment sharing is directly relevant to disease gene mapping and estimation of heritability. Individuals who share a genetic basis for a trait are more likely to have IBD sharing compared to randomly chosen individuals, and this forms the basis for IBD mapping and heritability estimation. Analysis of data from extended pedigrees was extremely difficult with standard linkage approaches, but is now possible using approaches based on detected IBD segments. Detected IBD can be present across pedigrees, which enhances power to detect association with the trait. Further, in population samples there is potential to utilize detected IBD segments to improve power to detect association when multiple variants within a gene influence the trait. IBD segments can also be used to greatly improve haplotype phase estimates, which is critical to understanding the functional consequence of genetic variation. IBD-based long-range phasing has previously been shown to be effective in isolated populations such as Iceland, but recent advances have extended its application to large outbred populations. In this session, we explore these exciting new developments.


9:40 AM   Identity by descent within and between pedigrees. E. A. Thompson. Univ. of Washington.

10:10 AM   Length distributions of identity by descent reveal fine-scale demographic history. I. Pe'er. Columbia Univ.

10:40 AM   Using high resolution identity by descent: From detecting selection to explaining trait variability. M. Abney. Univ. of Chicago.

11:10 AM   Extending the limits of IBD segment detection with sequence data and new statistical methods. B. L. Browning. Univ. of Washington.

Saturday, November 10

9:40 AM–11:40 AM

Concurrent Invited Session III (73-80)

SESSION 76 – The Functional Consequences of microRNA Dysregulation in Human Disease

Room 134, Lower Level North, Moscone Center

Moderators: Cheryl L. Thompson, Case Western Reserve Univ.
  Ahmad Khalil, Case Western Reserve Univ.

MicroRNAs (miRNAs) are an evolutionarily conserved class of small non-coding RNAs that have been shown to regulate the expression levels of numerous protein-coding genes. Although integral to animal biology, their role in human disease has only recently been studied. Previously, numerous miRNAs have been demonstrated to be dysregulated in multiple diseases, including cancer, cardiovascular disease, neurological disease and many others. However, the exact functions and mechanisms of these miRNAs in human diseases are yet to be fully elucidated. A number of recent studies have now begun to shed light on the role of miRNAs in disease, providing insights into mechanisms for imitation and progression of disease as well as targets for preventive and therapeutic intervention. In this session we have assembled a group of world leaders in the field of miRNA and human diseases. The speakers will discuss their latest research on miRNAs, which will cover a range of topics from targets of miRNAs, animal models of miRNA action as well as the role of circulating miRNAs in diagnostics.


9:40 AM   OncomiR-1 in cancer and development: A tale of mice and men. A. Ventura. Sloan-Kettering Inst.

10:10 AM   microRNA reprogramming in cancer: Mechanisms and consequences. J. Mendell. Univ. of Texas Southwestern Med. Ctr.

10:40 AM   Exploring circulating miRNAs as blood-based diagnostic biomarkers. M. Shapero. Affymetrix, Santa Clara, CA.

11:10 AM   Circulating microRNAs in obesity and postmenopausal breast cancer. C. L. Thompson. Case Western Reserve Univ.

Saturday, November 10

9:40 AM–11:40 AM

Concurrent Invited Session III (73-80)

SESSION 77 – Centralizing the Deposition and Curation of Human Mutations

Room 132, Lower Level North, Moscone Center

Moderators: Robert L. Nussbaum, UCSF
  David H. Ledbetter, Geisinger Hlth. Syst., Danville, PA

Hundreds of thousands of disease-causing variants have been identified in patients with disease, yet only a small fraction of that data, and the interpretation of it, is accessible to researchers and clinicians. The centralization of data on human genomic variation is a critical step in accelerating advances within the field of genomic medicine. Such centralization of variant data will not only enable more efficient approaches to data analysis, but will also ensure the use of a uniform set of standards across the many communities contributing data and intending to use the resources for research and clinical applications. This session will highlight groups that have recently joined efforts to solve this challenge and create a free and useful human genomic mutation database for the community.


9:40 AM   Improving the accuracy of variant identification. D. Church. NLM/NIH.

10:10 AM   The ISCA Consortium: Standardization and sharing of structural variation data. C. L. Martin. Emory Univ. Sch. of Med.

10:40 AM   Introducing ClinVar. D. Maglott. NCBI, NLM/NIH.

11:10 AM   Community involvement in centralized mutation curation. H. L. Rehm. Harvard Med. Sch.

Saturday, November 10

9:40 AM–11:40 AM

Concurrent Invited Session III (73-80)

SESSION 78 – Stem Cells and Personalized Medicine

Room 135, Lower Level North, Moscone Center

Moderator: Stephen H. Tsang, Columbia Univ.

Speakers will discuss applications of patient-specific and disease-specific stem cell lines, including disease modeling, drug screening, and regenerative medicine. Panelists will bring experience in clinical genetics, genetic manipulation in stem cells, and disease modeling. The FDA has recently approved phase I/II clinical trials to investigate the safety and efficacy of embryonic stem cell-based retinal cell transplantation, but such therapy requires immunosuppression. Patient-specific stem cells may offer an alternative to embryonic stem cells that will skirt the need for immunosuppressive therapy as well as the social and political ramifications of embryonic stem cell research, but their utility even extends far beyond such groundbreaking advances.


9:40 AM   Stem cells and personalized medicine in retinal degenerations. S. H. Tsang. Columbia Univ.

10:10 AM   Direct reprogramming to generate patient-specific stem cells and neurons. M. Wernig. Stanford Sch. of Med.

10:40 AM   A chemical approach to controlling cell fate. S. Ding. UCSF.

11:10 AM   Patient-specific stem cells and cardiovascular genetics. B. Conklin. UCSF.

Saturday, November 10

9:40 AM–11:40 AM

Concurrent Invited Session III (73-80)

SESSION 79 – Should Noninvasive Prenatal Diagnosis Augment or Replace Current Prenatal Screening and Diagnosis?

Room 124, Lower Level North, Moscone Center

Moderators: Mark E. Nunes, Kaiser Permanente, San Diego
  Mildred K. Cho, Stanford Univ.

The discovery of circulating cell-free fetal nucleic acid (cffDNA) in maternal blood plasma in 1997 allowed for the development of noninvasive prenatal diagnosis (NIPD) offered commercially in a medical setting in North America beginning in October 2011. From the initial discovery, ethical issues were raised in that the method could most easily be validated seeking circulating Y chromosome transcripts. The method subsequently has been validated for fetal Rh typing and fetal aneuploidy, but the next-generation sequencing methods used to analyze cffDNA allow any Mendelian trait or disorder with a known gene to be detected by the method. This technology convergence, coupled with the test being offered at 10-weeks gestation, could provide a level of access and choice in women’s reproductive decision making unprecedented since the introduction of oral contraception. We will briefly introduce the topic, and then debate the ethical, legal, and social issues of broadening the scope and availability of NIPD. The technique will be placed in the context of the history of seeking fetal markers and cells in maternal circulation. The ethical context will be outlined, with competing issues of autonomy and societal interest. The legal context, within the current debate surrounding reproductive freedom, will be discussed. The possible impact on society and medical practice will be described.


9:40 AM   Lessons from the clinical introduction of noninvasive prenatal diagnosis: How we got here. A. T. Bombard. Sequenom Inc., San Diego.

10:05 AM   Cell-free fetal DNA in prenatal diagnosis: Where we are going? D. Bianchi. Tufts Univ., Boston.

10:30 AM   Academia and industry in the development of noninvasive prenatal diagnosis. M. K. Cho. Stanford Univ.

10:55 AM   Ethical and policy implications of early noninvasive prenatal diagnosis. J. S. King. UC Hastings Col. of the Law, San Francisco.

11:20 AM   Discussion. M. E. Nunes. Kaiser Permanente, San Diego.

Saturday, November 10

9:40 AM–11:40 AM

Concurrent Invited Session III (73-80)

SESSION 80 – Selection Signatures and the Genetics of Autoimmunity and Infectious Diseases

Room 130, Lower Level North, Moscone Center

Moderators: Judy H. Cho, Yale Univ.
  Richard A. Spritz, Univ. of Colorado Denver Anschutz Med. Campus

The overlap of autoimmune and infectious disease loci is one of the seminal findings of the GWAS era. The presence of a relatively limited and recurring number of major autoimmune and infectious disease-associated genes and pathways may well correspond with functional networks that evolved in response to historically significant infectious pathogens. It may be speculated that the plethora of common functional polymorphisms identified through GWAS in autoimmune diseases evolved through positive selection; in subsequent eras and environmental conditions, these once beneficial polymorphisms confer increased susceptibility to autoimmunity. Support for this concept is provided by the observation that uncommon, often highly penetrant, mutations in overlapping genes and pathways are associated in infectious diseases such as severe mycobacterial infections. Predictive functional networks may be optimized by integration of complementary data sources, notably selection signatures. Novel approaches of identifying signatures of positive selection at single and multiple loci will require integration of genetic association data with biologic data that optimally models relevant selection conditions.


9:40 AM   The genetics of autoimmunity. J. H. Cho. Yale Univ.

9.55 AM   The genetics of autoimmunity. R. A. Spritz. Univ. of Colorado Denver.

10:10 AM   Selection signatures and mechanisms of host-microbe interactions. P. Sabeti. Harvard Univ.

10:40 AM   Interactions of HLA class I with killer-cell immunoglobulin-like receptors: Influences on human disease. P. Parham. Stanford Univ.

11:10 AM   Toward a genetic theory of infectious diseases. J.-L. Casanova. Rockefeller Univ.

Saturday, November 10

12:00 NOON–1:00 PM

SESSION 81 – Closing Plenary: Human Genetics 2012 and Beyond: Present Progress and Future Frontiers

Hall D, Lower Level North, Moscone Center

Moderator: Joel N. Hirschhorn, 2012 Program Committee Chair
Boston Children's Hosp., Harvard Med. Sch. and Broad Inst.

Presenter: Chris Gunter, HudsonAlpha Inst. for Biotechnol.

Han Brunner, Radboud Univ. Nijmegen
Jay Shendure, Univ. of Washington
Dian Donnai, Univ. of Manchester
Lynn Jorde, Univ. of Utah
Hal Dietz, Johns Hopkins Univ.

An outstanding panel of expert human geneticists with varying perspectives will make will make brief presentations and then participate in a wide-ranging discussion on the most exciting advances and important upcoming challenges in their areas of human genetics.Topics will be driven by questions from the panelists and the audience, but will include many of the following perspectives:

  • The importance of education for the public, scientists, and clinicians

  • The impact of new technology on human genetics and genomics

  • Advances that define biological mechanisms

  • Challenges of interpretation of exome and genome sequencing

  • Translation of advances into clinical care

During the course of the 62nd Annual Meeting, registrants are encouraged to post their thoughts on scientific or clinical advances they have heard about at the meeting, and on upcoming important challenges in human genetics, via ASHG's social media outlets (Twitter, Facebook).

Twitter: use hashtag #ASHG2012

You can also address your comments through Twitter directly to Chris Gunter, @girlscientist, during the meeting.

Posts by meeting participants will be followed and summarized at the beginning of the session by Chris Gunter, 2012 Program Committee Member.

After the brief presentations by the panelists, there will be opportunities for audience members to ask questions of one or more panel members.

At the conclusion of the session, the moderator will provide a brief summary, and the meeting will be adjourned by the 2012 President, Mary-Claire King.




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