Navigation Menu is only visible when JavaScript is enabled

Tuesday, October 22

4:30 PM–5:00 PM

SESSION 1 – ASHG Presidential Address: Just Another President's Speech (BUT It's All About You)

Hall B2, Level 0 (Lower Level), Convention Center

Presenter: Jeff Murray, ASHG 2013 President, University of Iowa

Although our society turned 65 this year it is far from ready for retirement. Our members have led the way as changes in knowledge, technology, policy and education have challenged our mission over the last seven decades. Genetics has never been more central than it is today to the national and international conversations surrounding science and its application in health, law and teaching. But we must ever focus our commitment to being a part of the solution to the changes that confront us. Having an engaged and active membership who create a strategic vision for our future can ensure that we increase in relevance and utility for ASHG in particular and for advancing the good of society in general.


Tuesday, October 22

5:00 PM–7:00 PM

SESSION 2 – Plenary Abstract Presentations

Hall B2, Level 0 (Lower Level), Convention Center

Moderator: Andrew G. Clark, Cornell Univ.

1/5:00 Whole exome sequencing of 94 matched brain metastases and paired primary tumors reveals patterns of clonal evolution and selection of driver mutations. S. L. Carter, P. K. Brastianos, S. Santagata, A. Taylor-Weiner, P. Horowitz, K. Ligon, J. Seaone, E. Martinez-Saez, J. Tabernero, D. Cahill, S. Paek, I. Dunn, B. Johnson, M. Rabin, N.U. Lin, R. Jones, P. Hummelen, A. Stemmer-Rachamimov, D.L. Louis, T.T. Batchelor, J. Baselga, R. Beroukhim, G. Getz, W.C. Hahn.

2/5:20 Pathogenic de novo SNVs, indels and CNVs in 1,000 children with undiagnosed developmental disorders. M. Hurles, M. van Kogelenberg, T. Fitzgerald, W. D. Jones, D. King, P. Vijayarangakannan, S. Gerety, K. Morley, S. Gribble, D. Barrett, K. Ambridge, N. Krishnappa, E. Prigmore, D. Rajan, T. Bayzetinova, S. Al-Turki, A. Tivey, S. Clayton, R. Miller, P. Jones, N. Carter, C. Wright, J. Barrett, D. FitzPatrick, H. Firth, DDD Study.

3/5:40 Chromatin loops and CNVs: The complex spatial organization of the 16p11.2 locus. M. N. Loviglio, M. Leleu, N. Ghedolf, E. Migliavacca, K. Männik, J. S. Beckmann, S. Jacquemont, J. Rougemont, A. Reymond.

4/6:00 Fine-mapping GWAS followed by genome editing identifies an essential erythroid enhancer at the HbF-associated BCL11A locus. D. E. Bauer, S. Lessard, S. C. Kamran, J. Xu, Y. Fujiwara, C. Lin, Z. Shao, M. C. Canver, E. C. Smith, L. Pinello, P. J. Sabo, J. Vierstra, R. A. Voit, G. C. Yuan, M. H. Porteus, J. A. Stamatoyannopoulos, G. Lettre, S. H. Orkin.

5/6:20 Translating dosage compensation to Trisomy 21: A novel approach to Down syndrome. J. B. Lawrence, J. Jiang, Y. Jing, C. J. Cost, J. Chiang, H. J. Kolpa, A. M. Cotton, D. M. Carone, B. R. Carone, D. A. Shivak, M. Byron, P. D. Gregory, C. J. Brown, F. D. Urnov, L. L. Hall.

6/6:40 Insights into population history from a high coverage Neandertal genome. D. Reich, Neandertal Genome Consortium.

Wednesday, October 23

8:00 AM–10:00 AM

Concurrent Invited Session I (3-9)

SESSION 3 – A Renaissance in Gene Therapy: New Tools and Clinical Trials

Room 253, Level 2, Convention Center

Moderators: Stephen Kaler, NICHD/NIH
  Luk H. Vandenberghe, Harvard Med. Sch.

This session will focus on expanding knowledge and experience in the field of therapeutic gene transfer, with a focus on monogenetic disorders. Advances in somatic gene transfer have led to a renaissance in the field, in large part due to recent success in early clinical trials for hemophilia and inherited blinding diseases. This session will provide an update on recent improvements in the development of adeno-associated viral and lentiviral vector systems. Speakers will discuss preclinical and clinical advances that these novel technologies have enabled. Emerging data on the clinical application of viral gene therapy, as well as the contribution of this approach to understanding of disease mechanism and pathophysiology will be highlighted.


8:00 AM   Adeno-associated viral vectors for gene therapy: Virus, vector, nanoparticle. L. H. Vandenberghe. Harvard Med. Sch.

8:30 AM   Gene therapy for metabolic CNS disorders. R. G. Crystal. Weill Cornell Med. Col.

9:00 AM   Brain-directed AAV gene therapy. S. Kaler. NICHD/NIH.

9:30 AM   Lentiviral-mediated gene therapy for human disease: Extensive genetic engineering of hematopoiesis with therapeutic benefit in metachromatic leukodystrophy patients after lentiviral hematopoietic stem cell gene therapy. L. Naldini. San Raffaele Telethon Inst. for Gene Therapy, Milan.

Wednesday, October 23

8:00 AM–10:00 AM

Concurrent Invited Session I (3-9)

SESSION 4 – DNA Damage Response Network Defects and Cancer Predisposition: Where One Plus One Does Not Equal Two

Room 210, Level 2, Convention Center

Moderators: Marc Tischkowitz, Univ. of Cambridge
  William D. Foulkes, McGill Univ.

Ataxia-telangiectasia (A-T) and Fanconi Anemia (FA) are important DNA damage response network syndromes whose genes exhibit different clinical phenotypes in the mono-allelic and bi-allelic mutated state. In 2002, D’Andrea and colleagues made the pivotal discovery that biallelic mutations in FANCD1/BRCA2 are a cause of FA. Since then two other genes (FANCJ/BRIP1, FANCN/PALB2) have been shown to cause FA and hereditary breast cancer in a similar manner while a fourth gene, RAD51C/FANCO causes an FA-like phenotype and hereditary ovarian cancer. Genes in the FA/BRCA pathway predispose to a number of other malignancies including prostate cancer (BRCA2), pancreatic cancer (BRCA2&PALB2) and pediatric brain tumors, Wilms tumors, leukemias (all seen in FA). Interestingly, bi-allelic mutations in a fifth gene, BRCA1 (a FANCJ/BRIP1 binding partner), have recently been shown to cause an inherited ovarian cancer syndrome distinct from FA. The proteins encoded by these genes act downstream of the core FA complex and study of their interactions has given insight into key mechanisms underlying cancer predisposition. However, many questions remain e.g. why is FA due to biallelic BRCA2/PALB2 mutations more severe compared to other FA complementation groups? How can we explain the different cancer spectrum and penetrance caused by mono-allelic mutations in these genes? What can we learn about the role of FA and ATM in carcinogenesis and mediating sensitivity to chemotherapy agents? Using the ATM/FA/BRCA molecular crossroads as a starting point, this session will focus on clinical, epidemiological, functional and therapeutic aspects to provide a detailed overview and attempt to answer these questions.


8:00 AM   The molecular crossroads of ataxia telangiectasia, Fanconi anemia and hereditary breast/ovarian cancer. M. Tischkowitz. Univ. of Cambridge.

8:30 AM   Characterizing cancer risks in carriers with mutations in the FA/BRCA and ATM genes. A. C. Antoniou. Univ. of Cambridge.

9:00 AM   Ataxia-telangiectasia: From phenotype to biology, and onto treatment strategies. Y. Shiloh. Sackler Sch. of Med., Tel Aviv.

9:30 AM   Targeting the FA/BRCA pathway in cancer therapy. A. D. D'Andrea. Dana-Farber Cancer Inst.

Wednesday, October 23

8:00 AM–10:00 AM

Concurrent Invited Session I (3-9)

SESSION 5 – Does the Increasingly Blurry Distinction between Research and Clinical Care Create an Obligation to Actively Search for Secondary Findings in Genomic Research or Otherwise Change the Relationship between Researchers and Participants?

Grand Ballroom East, Level 3, Convention Center

Moderators: Benjamin E. Berkman, NHGRI/NIH
  Stacy Gray, Dana Farber Cancer Inst.

The rise of next-gen sequencing has raised questions about how best to negotiate the management of large quantities of uncertain human DNA sequence information in ways that reconcile the demands and expectations of researchers, clinicians, regulators and patients/participants. Particularly acute is the debate about what responsibilities, if any, researchers have to disclose secondary findings. Assuming there is some obligation to disclose certain incidental findings that are inadvertently discovered in the course of research, is there a positive obligation to search for these findings? And if so does this obligation extend beyond identifying risks for “actionable” severe or life-threatening diseases? The standard view has been that researchers are not obligated to fulfill a clinical role of actively searching for incidental findings, but this assumption seems to be relatively unexamined. An argument for a duty to look finds support in the fact that genomic researchers are often in a unique position to help their participants through application of the knowledge, abilities and resources they hold as scientists and/or physicians. On the other hand, with finite resources and legal constraints, there is often a tension between the research agenda and provision of ancillary care to participants. The “duty to look” question is arguably synecdochic: given the potential of whole-genome/whole-exome sequencing to uncover clinically relevant variants, is the research-clinical distinction still viable in a human genomic context? And should the heterogeneous wishes of research participants and patients be taken into consideration? This session will explore both the narrow issue of whether there is a duty to look for secondary genomic findings as well as the broader questions of how large-scale sequencing results should be governed, the a priori obligations researchers have (and don't have) to participants, and the epistemology of research versus medicine in a genomic age that is both blurrier and more transparent.


8:00 AM   Why researchers do not have a duty to look for incidental findings. E. W. Clayton. Vanderbilt Law Sch.

8:30 AM   Appropriately - but narrowly - defining a researcher's obligations to look for incidental findings. J. P. Evans. Univ. of North Carolina at Chapel Hill.

9:00 AM   Neither duty nor prohibition: Using private ordering to transcend 'one-size-fits-all' in large-scale sequencing of human beings. M. N. Meyer. Harvard Law Sch.

9:30 AM   What we've got here is failure to communicate: The growing disconnect between 20th-century research protections and individual agency in an age of whole-genome sequencing. M. Angrist. Duke Inst. for Genome Sciences & Policy.

Wednesday, October 23

8:00 AM–10:00 AM

Concurrent Invited Session I (3-9)

SESSION 6 – Evidence-Based Genetic Counseling for Clinical Genome Sequencing

Grand Ballroom West, Level 3, Convention Center

Moderators: Shelin Adam, Univ. of British Columbia
  Myra Roche, Univ. of North Carolina at Chapel Hill

The current standard of care in providing clinical genetic counseling continues to rely on face-to-face encounters, occurring at specific times and places, usually prior to, and/or following, genetic testing. Yet there is little empirical evidence to demonstrate that this model is an optimal one for enhancing informed decision-making and communicating genetic test results; two critical goals of genetic counseling. Attempts to study the effectiveness of this traditional model have often focused on recall of quantitative information such as recurrence risk, which is disappointingly poor. However, aside from knowledge, other factors have also been suggested as important outcomes. Furthermore, serious doubts have been raised about the appropriateness of the current model and its ability to be scaled up to the volume, complexity and potential implications of clinical sequencing. Alternative models such as e-learning platforms are now beginning to be used for both education and counseling. Such computer-based systems can be designed to present flexibility in literacy level, prior knowledge of genomics and interest level, have the advantage of accessibility at locations, times and circumstances that are most convenient for the family, and provide information that is consistent with current science. However, are we sacrificing effectiveness for practicality and cost? This session will summarize the current counseling model as well as alternative, multi-media options for providing genetic counseling for genome sequencing. We will discuss the need for more evidence, and provide examples of validated methods that can be used to gather robust outcome data regarding the effectiveness of genetic counseling.


8:00 AM   Evidence-based genomic counseling for 21st century medicine. M. J. Khoury. Ctrs. for Dis. Control and Prevent.

8:30 AM   Measuring patient benefits from genetic counseling and testing interventions: Is patient empowerment a useful outcome? M. McAllister. Cardiff Univ.

9:00 AM   Can an e-learning platform provide adequate genetic counseling? P. Birch. Univ. of British Columbia.

9:30 AM   Online genetic education and counseling — Lessons from a direct-access genotyping service. U. Francke. 23andMe Inc., Mountain View, CA.

Wednesday, October 23

8:00 AM–10:00 AM

Concurrent Invited Session I (3-9)

SESSION 7 – Functional Interpretation of Genomes Using Biological Networks

Room 205, Level 2, Convention Center

Moderator: Kasper Lage, Massachusetts Gen. Hosp.

The recent explosion in genome-wide association studies, exome sequencing projects, and epigenetic data sets, have revealed many genetic variants likely to be involved in disease processes, but the composition and function of the molecular systems they affect remain largely obscure. This limits our progress towards biological understanding and therapeutic intervention. Computational analyses that systematically integrate biological networks (i.e., networks in which genes are connected if they are functionally associated in some experimental system) with genetic data have emerged as a powerful approach to functionally interpret large genomic data sets by enabling the identification of de novo pathways perturbed in disease. This session will highlight algorithms, statistics, and web portals being developed in this area, and exemplify how different network-based methods have been used to analyze common and rare genetic variants, as well as epigenetic data sets. We will introduce specific methods being developed and applied by leaders in the field, which will enable the audience to use these tools in their work. Furthermore, we will exemplify how draft molecular systems involved in immunological, metabolic, muscular, cardiovascular, and psychiatric disorders have been elucidated by coupling genetic data and biological networks through rigorous statistical frameworks.


8:00 AM   Integrating biological networks and genetics to reverse engineer molecular systems driving diseases. K. Lage. Massachusetts Gen. Hosp.

8:30 AM   Cell-type specificity of gene networks to understand disease biology. S. Raychaudhuri. Brigham and Women's Hosp.

9:00 AM   Using networks, functional genomics resources and signals of selection to understand hundreds of complex disease loci. J. Barrett. Wellcome Trust Sanger Inst., Hinxton, U.K.

9:30 AM   Network-based association models for exome-sequencing data. S. Purcell. Mount Sinai Sch. of Med.

Wednesday, October 23

8:00 AM–10:00 AM

Concurrent Invited Session I (3-9)

SESSION 8 – Insights from Large Scale Sequencing

Hall B2, Level 0 (Lower Level), Convention Center

Moderators: Goncalo R. Abecasis, Univ. of Michigan Sch. of Publ. Hlth.
  Gabor Marth, Boston Col.

Large-scale genomic sequencing studies are fueling rapid advances in many areas of human genetics. Many of the opportunities (such as our ability to conveniently access rare and even private variants in many individuals) and challenges (such as the large volumes of data that must be managed) are shared across many areas of application. It is also clear that different fields have elected to focus on quite different strategies for data generation, ranging from deep whole genome sequencing, to deep targeted sequencing of exomes or even smaller regions, to shallow whole genome sequencing. Approaches to data analysis also vary, including both analysis based on mapping (where interpretation is guided by the reference genome) and emerging assembly-based analytical approaches (where interpretation might eventually become independent of the reference). In this session, we will compare and contrast advances in studies of Mendelian disorders, cancer sequencing, complex trait analysis, genome informatics and population genetics and discuss how they are deploying sequencing-based approaches, examples of success for each area, and challenges and opportunities for the future. The goal of this set of presentations is to show how different people can look at the same interesting, new data and come up with very different (and valuable) interpretations.


8:00 AM   Mechanistic and clinical advances from sequencing cancer patients. N. Rahman. Inst. of Cancer Res., Sutton, U.K.

8:30 AM   Accelerating Mendelian genetics. D. Nickerson. Univ. of Washington Sch. of Med.

9:00 AM   Whole genome mapping, assembly and analysis. H. Li. Broad Inst. of Harvard and MIT.

9:30 AM   Population genetic insights from 10,000s of human samples. J. Novembre. Univ. of Chicago.

Wednesday, October 23

8:00 AM–10:00 AM

Concurrent Invited Session I (3-9)

SESSION 9 – Population-Based Animal Models for Discovery of Complex Traits

Room 258, Level 2, Convention Center

Moderators: John French, NIEHS/NIH, Research Triangle Park
  Kimberly McAllister, NIEHS/NIH, Research Triangle Park

Understanding human gene by environment interactions is difficult due to uncontrolled individual differences in host susceptibility to individual variation in multiple stressors (chemicals, infections, etc.) over a lifetime. Appropriate experimental models can be used to identify morbidity and disease for epidemiology research or confirm observations from epidemiology under controlled conditions with multiple variables. Over the past decade, members of the complex traits community have led the development of new and powerful mouse resources for quantitative genetics. These new mouse populations are designed to model human genetic diversity with approximately 45 million segregating SNPs, CNV, and structural variants. The Collaborative Cross (CC) is a population of advanced intercross recombinant inbred lines (AIRILs) created from a randomized eight-way intercross of inbred strains and subsequently inbred to fix each genetically diverse genome. Selected generations of breeders from the CC AIRILs were then used to create the diversity outbred (DO) mice. The CC AIRILs and the DO mice are critical tools for mapping and validating candidate genes identified from QTLs using molecular biology and reverse genetics approaches. New research results will be presented in this session that demonstrate a discovery approach that can facilitate identification of genetic or epigenetic variants associated with factors that interact to determine phenotypic outcome to environmental and genetic variations at the population level. Experimental and quantitative genetic approaches will likely enable the identification of genetic variants that contribute to differential responses in humans to environmental exposures and thus corroborate genetic epidemiology and provide new targets for human investigation.


8:00 AM   High-resolution genetic mapping using the mouse collaborative cross and diversity outbred populations. G. Churchill. The Jackson Lab.

8:30 AM   Genomic characterization of house dust mite-induced allergic airway disease in mice. S. Kelada. Univ. of North Carolina at Chapel Hill.

9:00 AM   Host genetics and modulation of the gut microbiome as a means to understanding metabolic function. A. Benson. Univ. of Nebraska-Lincoln.

9:30 AM   Mapping susceptibility QTLs for gene-environment interactions and environmental toxicity. J. French. NIEHS/NIH, Research Triangle Park.

Wednesday, October 23

2:00 PM–4:15 PM

Concurrent Platform (abstract-driven) Session A (10-18)

SESSION 10 – Which Comes First: The Sequence or the Biology?

Hall B2, Level 0 (Lower Level), Convention Center

Moderators: Maja Bucan, Univ. of Pennsylvania
  Melissa Wilson Sayres, Univ. of California, Berkeley

7/2:00 Annotation of pseudogenous gene segments by massively parallel sequencing of rearranged lymphocyte receptor loci. R. O. Emerson, A. M. Sherwood, H. S. Robins, C. S. Carlson, M. J. Rieder.

8/2:15 High throughput sequence analysis of the TCR repertoire in glioma-associated immune dysregulation. B. Grinshpun, J. Sims, Y. Feng, P. Canoll, P. Sims, J. Bruce, Y. Shen.

9/2:30 Extraction and analysis of clinical traits of multiple sclerosis using electronic medical records. M. F. Davis, S. Sriram, W. S. Bush, J. C. Denny, J. L. Haines.

10/2:45 Haplotype of CpG-related SNPs is associated with DNA methylation pattern. Y. Ma, C. E. Smith, Y. C. Lee, L. D. Parnell, C. Q. Lai, J. M. Ordovas.

11/3:00 Comprehensive blood group prediction using whole genome sequencing data from The MedSeq Project. W. J. Lane, I. Leshchiner, S. Boehler, J. M. Uy, M. Aguad, R. Smeland-Wagman, R. C. Green, H. L. Rehm, R. M. Kaufman, L. E. Silberstein, for The MedSeq Project.

12/3:15 pVAAST: A new method for family-based rare variant association testing. C. D. Huff, H. Hu, H. Coon, S. Guthery, S. Tavtigian, J. C. Roach, Z. Kronenberg, J. Xing, G. Glusman, V. Garg, B. Moore, L. E. Hood, K. S. Pollard, D. J. Galas, D. Srivastava, M. G. Reese, L. B. Jorde, M. Yandell.

13/3:30 Functional genomic confounds of transgenic integration and methods for their delineation. J. C. Jacobsen, C. Chiang, C. Ernst, A. J. Morton, C. Hanscom, S. J. Reid, R. G. Snell, M. E. MacDonald, J. F. Gusella, M. E. Talkowski.

14/3:45 Improved exome prioritization of disease genes through cross species phenotype comparison. D. Smedley, S. Köhler, A. Oellrich, K. Wang, C. Mungall, S. E. Lewis, S. Bauer, D. Seelow, P. Krawitz, C. Gilissen, M. Haendel, P. Robinson, Sanger Mouse Genetics Project.

15/4:00 Phased allele-specific expression analysis in integrated whole exome and mRNA sequencing study in a family with non-random X chromosome inactivation. S. Szelinger, V. Narayanan, J. J. Corneveaux, I. Schrauwen, A. L. Siniard, A. A. Kurdoglu, I. Malenica, K. M. Ramsey, M. J. Huentelman, D. W. Craig.

Wednesday, October 23

2:00 PM–4:15 PM

Concurrent Platform (abstract-driven) Session A (10-18)

SESSION 11 – The Shifting Landscape of Genetic Testing: Approaches and Success Stories

Grand Ballroom East, Level 3, Convention Center

Moderators: Catherine E. Keegan, Univ. of Michigan
  Stephanie Bielas, Univ. of Michigan

16/2:00 The utility of the traditional medical genetics diagnostic evaluation in the context of next-generation sequencing for undiagnosed genetic disorders. V. Shashi, A. McConkie-Rosell, B. Rosell, K. Schoch, K. Vellore, M. McDonald, Y.-H. Jiang, P.-X. Xie, A. Need, D. Goldstein.

17/2:15 The National Institutes of Health Undiagnosed Diseases Program: The first four years. D. R. Adams, C. F. Boerkoel, R. Godfrey, G. Golas, C. Groden, A. Gropman, D. Landis, T. C. Markello, M. Nehrebecky, T. Pierson, M. Sincan, C. J. Tifft, C. Toro, C. Wahl, L. Wolfe, W. A. Gahl.

18/2:30 First year experience of clinical exome sequencing for rare disease diagnosis at UCLA. H. Lee, J. L. Deignan, N. Dorrani, F. Quintero-Rivera, S. Kantarci, K. Das, T. Toy, S. Strom, R. Baxter, T. Hambuch, Y. Xue, L. Li, C. Louie, D. Cherukuri, E. Lin, B. Harry, M. Yourshaw, M. Fox, C. Palmer, D. Wong, B. L. Fogel, W. W. Grody, E. Vilain, S. F. Nelson.

19/2:45 Clinical utility of the first one thousand clinical whole exome sequencing tests: Molecular diagnostic rate, changes in medical management, and the impact of incidental findings. C. Eng, D. Muzny, J. Reid, M. Bainbridge, A. Willis, M. Landsverk, J. Beuten, M. Leduc, P. Ward, A. Braxton, M. Hardison, Z. Niu, R. Person, F. Xia, M. Bekheirnia, J. Scull, S. Wen, J. Zhang, A. Hawes, C. Buhay, Y. Ding, M. Scheel, N. Saada, W. Liu, J. Ma, J. Chandarana, L. Dolores-Freiberg, W. Alcaraz, H. Cui, M. Walkiewicz, E. Boerwinkle, S. Plon, J. Lupski, A. Beaudet, R. Gibbs, Y. Yang.

20/3:00 Discordant karyotype results among non-invasive prenatal screening positive cases. K. W. Choy, K. Y. Kwok, E. T. Lau, M. H. Tang, A. Pursley, J. Smith, S. W. Cheung, T. Y. Leung, A. Petal.

21/3:15 Genetic testing for mitochondrial disorders in the next-generation sequencing era: Targeted multiplex PCR gene panel or capture-based WES? R. Bai, N. Smaoui, E. Haverfield, J. Higgs, S. F. Suchy, D. Arjona, K. Retterer, A. Shanmugham, F. D. Kendall, S. Parikh, A. L. Gropman, R. Haas, A. Goldstein, J. Panzer, S. Yum, M. J. Falk, R. P. Saneto, G. M. Enns, W. K. Chung, S. Bale, G. Richard.

22/3:30 Comparison of results between karyotyping and microarray testing in postnatal and prenatal specimens: Karyotyping is not dead yet. D. Warburton, V. Jobanputra, V. Aggarwal, A. Sobrino, M. Macera, O. Nahum, B. Levy.

23/3:45 Parental studies of 2,248 chromosomal microarray analysis cases: Role of parental studies in facilitating the interpretation of copy number variants. W. Bi, J. Pham, J. Denham, E. Roney, A. N. Pursley, P. Stankiewicz, A. Breman, S. Lalani, J. Smith, C. Bacino, A. Patel, S. W. Cheung.

24/4:00 Rapid and cost-effective whole exome sequencing for clinical diagnosis and personalized medicine. D. Muzny, M. Wang, C. Buhay, Y. Han, H. Dinh, C. Kovar, H. Doddapanei, M. Bainbridge, J. Reid, E. Boerwinkle, R. Gibbs.

Wednesday, October 23

2:00 PM–4:15 PM

Concurrent Platform (abstract-driven) Session A (10-18)

SESSION 12 – Methods in Statistical Genetics

Grand Ballroom West, Level 3, Convention Center

Moderators: L. Adrienne Cupples, Boston Univ. Sch of Publ. Hlth
  Ingrid B. Borecki, Washington Univ. Sch. of Med.

25/2:00 Prioritizing sequence variants using statistical evidence: Not all measures are alike. W. Li, L. Strug, D. Pal.

26/2:15 Mixed model association methods: Advantages and pitfalls. A. Price, J. Yang, N. A. Zaitlen, M. E. Goddard, P. M. Visscher.

27/2:30 Assessing multivariate gene-metabolome associations using Bayesian reduced rank regression. P. Marttinen, M. Pirinen, A.-P. Sarin, J. Gillberg, J. Kettunen, I. Surakka, A. J. Kangas, P. Soininen, T. Lehtimäki, M. Ala-Korpela, O. T. Raitakari, M.-R. Järvelin, S. Ripatti, S. Kaski.

28/2:45 Characterizing shared pathogenetics from genome-wide association studies via principal component analysis. A. Keinan, D. Chang.

29/3:00 Power studies for the “extreme versus control” design for exome sequencing studies and identification of a variant of TMC6 as a deleterious modifier for age of onset of chronic Pseudomonas infection in children with cystic fibrosis. M. J. Emond, T. Louie, J. Emerson, R. A. Mathias, M. R. Knowles, D. A. Nickerson, H. K. Tabor, K. C. Barnes, R. L. Gibson, M. J. Bamshad, NHLBI Exome Sequencing Project, Lung GO.

30/3:15 A novel statistical framework for using ‘out of study’ control groups in association studies with next-generation data. A. Derkach, T. Chiang, L. Addis, S. Dobbins, I. Tomlinson, R. Houlston, D. K. Pal, J. Gong, L. J. Strug.

31/3:30 Using coalescent-based modeling for large-scale fine mapping of complex trait loci using sequencing data in large-scale case-control studies. Z. Geng, P. Scheet, S. Zöllner.

32/3:45 Quantifying and partitioning variation due to genetic effects and population stratification using within-family prediction analysis. J. Yang.

33/4:00 Meta-imputation: A simple and flexible method to combine multiple reference panels for imputing genetic variants. P. K. Albers, G. R. Abecasis, M. I. McCarthy, K. J. Gaulton.

Wednesday, October 23

2:00 PM–4:15 PM

Concurrent Platform (abstract-driven) Session A (10-18)

SESSION 13 – Genetic Variation in Gene Expression

Room 210, Level 2, Convention Center

Moderators: Cisca Wijmenga, Univ. of Groningen
  Barbara Stranger, Univ. of Chicago

34/2:00 Epistasis is widespread in the genetic control of transcription in humans. J. Powell, G. Hemani, K. Shakhbazov, A. Henders, A. McRae, N. Martin, G. Montgomery, P. Visscher.

35/2:15 Low-pass whole-genome sequencing in Europeans identifies 1325 SNPs and indels associated with cis gene expression of which 4% are independent low frequency-large effect associations. A. R. Wood, M. A. Tuke, H. Yaghootkar, D. Pasko, H. Lin, C. S. Xu, D. G. Hernandez, M. A. Nalls, J. R. Gibbs, L. Qibin, S. Juan, A. Murray, D. Melzer, M. N. Weedon, A. B. Singleton, L. Ferrucci, T. M. Frayling.

36/2:30 Deep whole-genome sequencing in pedigrees to quantify the contribution of private variants to type 2 diabetes and related metabolic traits. G. Jun, M. Almeida, A. Manning, T. Teslovich, A. Wood, M. Zawistowski, S. Won, C. Fuchsberger, S. Feng, K. Gaulton, P. Cingolani, T. Frayling, G. Abecasis, J. Blangero, T2D-GENES Consortium.

37/2:45 Inflammatory bowel disease-associated genetic variants preferentially alter gene expression in neutrophil granulocytes. H. Westra, D. Arends, T. Esko, M. J. Peters, R. Weersma, A. Metspalu, A. G. Uitterlinden, J. van Meurs, R. Jansen, L. Franke.

38/3:00 Multi-tissue eQTL and pathway analysis of genome-wide genetic association data helps uncover tissue-specific processes of complex disease. A. V. Segrè, E. R. Gamazon, D. S. DeLuca, Y. Meng, L. D. Ward, T. Lappalainen, T. Flutre, X. Wen, E. T. Dermitzakis, M. Kellis, D. L. Nicolae, N. Cox, D. G. MacArthur, K. Ardlie, G. Getz, GTEx Consortium.

39/3:15 High-resolution functional analysis of eQTLs in multiple tissues. X. Wen, R. Pique-Regi, T. Flutre, G. Moyerbrailean, F. Luca.

40/3:30 Network QTLs: A new methodology for multi-tissue eQTL discovery. B. Iriarte, M. Kellis, L. Ward, GTEx Consortium.

41/3:45 Identification and characteristics of common genetic variants controlling transcript isoform variation in the Framingham Heart Study. X. Zhang, R. Joehanes, T. Huan, P. Munson, A. Johnson, D. Levy, C. O’Donnell.

42/4:00 Identification of a Sjögren’s syndrome-associated variant that influences OAS1 isoform switching. H. Li, J. A. Ice, J. A. Kelly, I. Adrianto, S. B. Glenn, K. S. Hefner, E. Vista, D. U. Stone, R. Gopalakrishnan, G. D. Houston, D. M. Lewis, M. Rohrer, P. Hughes, J. B. Harley, C. G. Montgomery, J. Chodosh, J. A. Lessard, J. Anaya, B. M. Segal, N. L. Rhodus, L. Radfar, R. H. Scofield, C. J. Lessard, K. L. Sivils.

Wednesday, October 23

2:00 PM–4:15 PM

Concurrent Platform (abstract-driven) Session A (10-18)

SESSION 14 – Cancer Epidemiology: New Loci and Methods

Room 205, Level 2, Convention Center

Moderators: Sharon Savage, NCI/NIH
  Antonis C. Antoniou, Univ. of Cambridge

43/2:00 Heritability and familial risk of cancer: An update from the Nordic Twin Registry of Cancer. L. A. Mucci, J. Kaprio, J. Harris, K. Czene, P. Kraft, T. Scheike, R. Graff, I. Brandt, N. Holmes, D. Havelick, M. Hartman, K. Penney, E. Pukkala, G. Parmigiani, A. Skytthe, H. O. Adami, J. Hjelmborg, Nordic Twin Study of Cancer (NorTwinCan).

44/2:15 A comprehensive genetic analysis of common cancer risk through the development of the Oncochip. C. I. Amos, A. C. Antoniou, A. Berchuck, G. Chenevix-Trench, F. J. Couch, R. A. Eeles, L. J. Esserman, S. A. Gayther, C. L. Goh, D. E. Goldgar, S. B. Gruber, C. A. Haiman, P. Hall, D. J. Hunter, Z. Kote-Jarai, P. K. Lepage, S. Lindstrom, J. McKay, R. L. Milne, U. Peters, P. D. Pharoah, C. M. Phelan, F. R. Schumacher, T. A. Sellers, J. Simard, Z. Wang, D. Seminara, S. J. Chanock, D. F. Easton, B. E. Henderson.

45/2:30 Detection of large clonal mosaic events in existing genome-wide association study data. M. Machiela, W. Zhou, M. Yeager, K. Jacobs, S. Berndt, Q. Lan, N. Rothman, S. Savage, P. Taylor, N. Caporaso, I. DeVivo, R. Hoover, M. Tucker, S. Chanock.

46/2:45 Most common 'sporadic' cancers have a substantial germline genetic component. S. Macgregor, W. E. Ek, Y. Lu, D. Whiteman, T. L. Vaughan, A. B. Spurdle, D. F. Easton, P. D. Pharoah, D. J. Thompson, A. M. Dunning, A. K. Hayward, G. Chenevix-Trench, Q-MEGA and AMFS Investigators, ANECS-SEARCH, UKOPS-SEARCH, BEACON Consortium.

47/3:00 Meta-analysis of genome-wide association studies in 125,000 women identifies fourteen new breast cancer susceptibility loci. K. Michailidou, P. Hall, P. Kraft, D. F. Easton, Breast Cancer Association Consortium, DRIVE.

48/3:15 Identification of seven new ovarian cancer susceptibility loci: Risk of ovarian cancer in the general population and in BRCA1 and BRCA2 carriers. K. Kuchenbaecker, J. Tyrer, F. J. Couch, S. A. Gayther, P. P. Pharoah, S. J. Ramus, A. C. Antoniou, G. Chenevix-Trench, CIMBA and OCAC.

49/3:30 Breast cancer risk and survival at the 2q35 locus are mediated through chromatin looping and regulation of IGFBP5 expression. M. Ghoussaini, S. L. Edwards, J. D. French, K. Michailidou, S. Nord, J. Dennis, Q. Guo, M. K. Schmidt, K. Hillman, S. Kaufmann, E. Dicks, S. Ahmed, M. Maranian, C. S. Healey, C. Baynes, C. Luccarini, M. Bolla, J. Wang, V. N. Kristensen, P. D. P. Pharoah, G. Chenevix-Trench, D. F. Easton, A. M. Dunning, Breast Cancer Association Consortium.

50/3:45 Expression quantitative trait loci analysis in breast cancer tumor and normal adjacent FFPE specimens from the Nurses’ Health Study. A. Quiroz-Zarate, B. J. Harshfield, N. Knoblauch, S. Christe, R. Hu, D. J. Hunter, A. H. Beck, R. M. Tamimi, J. Quackenbush, A. Hazra, U19/GAME-ON DRIVE Consortium.

51/4:00 Finding genes in animal models of histiocytic sarcoma. E. A. Ostrander, J. L. Rowell, G. R. Rutteman, H. G. Parker.

Wednesday, October 23

2:00 PM–4:15 PM

Concurrent Platform (abstract-driven) Session A (10-18)

SESSION 15 – Psychiatric Disease: GWAS to Genes

Room 253, Level 2, Convention Center

Moderators: Brian O'Roak, Univ. of Washington
  Joseph D. Buxbaum, Mount Sinai Sch. of Med.

52/2:00 Using brain molecular QTLs to identify novel risk genes shared by multiple psychiatric diseases. C. Liu, C. Zhang, C. Chen, J. A. Badner, N. Alliey-Rodriguez, E. S. Gershon, E. R. Gamazon, N. J. Cox, TSAICG, IOCDF-GC.

53/2:15 Functional enrichment analysis on genome-wide epistasis patterns reveals pathway interactions in bipolar disorder. S. Prabhu, N. Clinger, B. Burnett, I. Pe'er.

54/2:30 Role of the Wnt signaling pathway in bipolar disorder susceptibility: Gene-set analysis of SNP-BMI interaction effects. M. A. Simonson, S. J. Winham, G. D. Jenkins, A. Cuellar Barboza, M. H. Jang, S. McElroy, M. A. F. Frye, J. M. Biernacka.

55/2:45 A novel variant in the HERG3 voltage-gated potassium ion channel gene (KCNH7) is associated with bipolar spectrum disorder among the Old Order Amish. A. R. Benkert, E. G. Puffenberger, S. Markx, S. M. Paul, R. N. Jinks, B. Georgi, T. Hoshi, A. McDonald, M. B. First, W. Liu, A. Heaps, Y. Tian, A. Chakravarti, D. H. Morton, M. Bucan, K. A. Strauss.

56/3:00 Exome sequencing in sporadic cases of schizophrenia and functional studies identify 21 putative candidate genes for schizophrenia and establish the RGS12 gene as a strong candidate. M. Guipponi, F. Santoni, V. Setola, E. Oestreich, C. Gehrig, M. Rotharmel, M. Cuenca, O. Guilin, D. Dikeos, G. Papadimitriou, A. Méary, F. Schürhoff, S. Jamain, M. Leboyer, D. Rujescu, A. Pulver, S. Moy, D. Campion, A. Malafosse, D. Siderovski, S. E. Antonarakis.

57/3:15 Rare duplications in RB1CC1 are associated with schizophrenia in large datasets from Europe. F. Degenhardt, M. A. Pfohl, L. Lennertz, L. Priebe, J. Strohmaier, S. H. Witt, A. Hofmann, T. Becker, R. Mössner, W. Maier, I. Nenadic, S. Meier, J. Buizer-Voskamp, R. A. Ophoff, D. Rujescu, I. Giegling, A. Ingason, M. Wagner, A. Meyer-Lindenberg, H. Walter, S. Moebus, A. Corvin, H. Stefánsson, T. G. Schulze, M. Rietschel, S. Cichon, M. M. Nöthen, GROUP Consortium, Wellcome Trust Case Control Consortium 2, International Schizophrenia Consortium.

58/3:30 Variants in NRG3 associated with delusion have regulatory potential and differentially bind to nuclear proteins. M. Zeledon, M. Taub, N. Eckart, M. Beer, R. Wang, M. Szymanski, P. Chen, A. E. Pulver, J. A. McGrath, P. Wolyniec, D. Avramopoulos, A. Sawa, D. Valle.

59/3:45 Testing genetic associations with addiction phenotypes using moderate-depth whole genome sequencing. S. I. Vrieze, S. Feng, X. Zhan, M. B. Miller, G. Jun, M. K. Trost, A. Tan, J. Bragg-Gresham, M. Flickinger, L. Scott, A. Locke, H. M. Kang, S. Levy, R. M. Myers, M. Boehnke, W. G. Iacono, M. McGue, G. R. Abecasis.

60/4:00 A genome-wide association study of alcohol dependence in the Irish affected sib pair study of alcohol dependence. A. E. Adkins, L. M. Hack, T. B. Bigdeli, B. T. Webb, J. C. Bettinger, A. G. Davies, M. S. Grotewiel, C. A. Prescott, D. M. Dick, K. S. Kendler, B. P. Riley.

Wednesday, October 23

2:00 PM–4:15 PM

Concurrent Platform (abstract-driven) Session A (10-18)

SESSION 16 – Expanding Knowledge of Mendelian Disorders: Genes, Phenotypes and Treatment

Room 258, Level 2, Convention Center

Moderators: Deb Krakow, UCLA
  Donna M. Martin, Univ. of Michigan

61/2:00 NIH study, Clinical and Molecular Investigations into Ciliopathies: Findings on Alström syndrome. J. D. Marshall, J. Han, J. K. Naggert, D. Yildirimli, J. Bryant, R. Fischer, W. M. Zein, K. Daryanani, B. Turkbey, E. Turkbey, C.-Y. Liu, P. Choyke, T. Heller, D. Rosing, A. Brofferio, V. Sachdev, L. Olivieri, N. Bridges, J. Graf-Myles, S. Bernstein, K. Olivier, B. Shamburek, M. Huizing, W. A. Gahl, M. Gunay-Aygun.

62/2:15 Genotype/epigenotype/phenotype correlations define Beckwith-Wiedemann syndromes. A. Mussa, A. De Crescenzo, S. Russo, L. Calzari, N. Chiesa, C. Molinatto, G. Baldassarre, D. Melis, D. Milani, M. F. Bedeschi, L. Tarani, A. Selicorni, M. Cirillo Silengo, L. Larizza, A. Riccio, G. B. Ferrero.

63/2:30 Myhre and LAPS syndromes: Clinical and molecular review of 32 patients. C. Michot, C. Le Goff, A. Afenjar, A. S. Brooks, P. M. Campeau, A. Destree, M. Di Rocco, D. Donnai, R. Hennekam, D. Heron, S. Jacquemont, P. Kannu, A. E. Lin, S. Manouvrier-Hanu, S. Mansour, S. Marlin, R. McGowan, H. Murphy, A. Raas-Rothschild, M. Rio, M. Simon, I. Stolte-Dijkstra, J. R. Stone, Y. Sznajer, J. Tolmie, J. van den Ende, N. Van der Aa, T. van Essen, A. Verloes, V. Cormier-Daire.

64/2:45 The phenotype combining Treacher Collins syndrome features with Diamond-Blackfan anemia is a heterogeneous ribosomopathy. K. Sol-Church, D. Stabley, A. Haskins Olney, C. Curry, J. Fisher, L. Pilchman, C. Schanen, J. X. Chong, D. E. Ward, K. W. Gripp, UW Ctr. for Mendelian Genomics.

65/3:00 Weaver syndrome is caused by loss-of-function mutations in EZH2. A. S. A. Cohen, D. B. Yap, X. Han, S. M. E. Lewis, C. Chijiwa, M. A. Ramos-Arroyo, D. D. Weaver, C. J. D. Ross, S. Aparício, W. T. Gibson.

66/3:15 Novel ELN mutations and vascular phenotype in autosomal dominant cutis laxa. E. Lawrence, M. McGowan, K. Levine, C. Lorenchick, S. Alkan, H. Salvaggio, A. Zaenglein, M. Bodzioch, A. Kiss, M. Siefring, Z. Urban.

67/3:30 Mutations in Lrp5 improve bone properties in a mouse model of osteogenesis imperfecta. C. M. Jacobsen, L. A. Barber, U. M. Ayturk, H. J. Roberts, M. A. Schwartz, M. Weis, D. Eyre, D. Zurakowski, A. G. Robling, M. L. Warman.

68/3:45 Teriparatide, the first anabolic agent for treatment of osteogenesis imperfecta improves bone mineral density at the hip and spine: A randomized, blinded, placebo-controlled trial. S. C. Sreenath Nagamani, J. Shapiro, S. Veith, Y. Wang, J. Lapidus, J. L. Reeder, T. M. Keaveny, D. Lee, M. A. Mullins, B. Lee, E. S. Orwoll.

69/4:00 Integrin modulating therapies prevent fibrosis and autoimmunity in genetic mouse models of scleroderma. E. E. Gerber, E. M. Gallo, S. C. Fontana, E. C. Davis, X. Zhong, F. M. Wigley, D. L. Huso, H. C. Dietz.

Wednesday, October 23

2:00 PM–4:15 PM

Concurrent Platform (abstract-driven) Session A (10-18)

SESSION 17 – Structural/Copy Number Variation and Disease

Grand Ballroom AB, Concourse Level, Westin Boston Waterfront Hotel

Moderators: Steven McCarroll, Harvard Med. Sch.
  David Miller, Boston Children's Hosp.

70/2:00 Large-scale parent-child trio sequencing highlights factors influencing spontaneous human mutation. S. Sunyaev, P. Polak, L. Francioli, W. Kloosterman, P. I. W. de Bakker, Genome of Netherlands (GoNL) Consortium.

71/2:15 Palindromic GOLGA core duplicon promotes 15q13.3 microdeletion, inversion polymorphisms, and large-scale primate structural variation. M. Y. Dennis, F. Antonacci, J. Huddleston, P. H. Sudmant, K. Meltz Steinberg, T. A. Graves, M. Malig, L. Vives, L. Denman, C. Baker, C. T. Amemiya, A. Stuart, W. J. Tang, B. Munson, J. A. Rosenfeld, L. G. Shaffer, R. K. Wilson, E. E. Eichler.

72/2:30 Large-scale genotyping of polymorphic inversions in human populations. S. Villatoro, C. Aguado, D. Vicente, D. Izquierdo, M. Puig, M. Cáceres.

73/2:45 SCRIB and PUF60 are primary drivers of the multisystemic phenotypes of the 8q23.4 CNV. C. Golzio, A. Dauber, F. M. Jodelka, C. Guenot, J. S. Beckmann, J. N. Hirschhorn, M. L. Hastings, S. Jacquemont, N. Katsanis.

74/3:00 Functional dissection of the recurrent reciprocal 1q21.1 autism-associated CNV. N. Katsanis, I. Blumenthal, A. Ragavendran, M. E. Talkowski, C. Golzio.

75/3:15 Discovery of genes responsible for neurocognitive disease by large scale integration of sequence and copy number data. B. P. Coe, K. T. Witherspoon, C. Baker, B. O'Roak, J. Schuurs-Hoeijmakers, J. Shendure, B. deVries, J. Gecz, M. Fichera, C. Romano, L. G. Shaffer, J. A. Rosenfeld, E. E. Eichler.

76/3:30 Mind the gap — Exomes and CNVs testing in primary immunodeficiencies. A. Stray-Pedersen, H. S. Sorte, P. S. Samarakoon, L. Forbes, T. Gambin, O. K. Rødningen, I. C. Hanson, L. M. Noroski, C. Davis, F. Seeborg, S. K. Nicholas, J. W. Caldwell, C. R. Beck, T. J. Vece, W. Wiszniewski, SJ Penney, S. N. Jhangiani, L. Mæhle, A. Patel, H. C. Erichsen, TE Abrahamsen, G. E. Tjonnfjord, B. E. Kristiansen, M. Kulset, L. T. Osnes, W. T. Shearer, B. Fevang, K. R. Heimdal, D. E. Undlien, R. A. Gibbs, R. Lyle, J. S. Orange, J. R. Lupski, Centers for Mendelian Genomics.

77/3:45 Absence of heterozygosity accompanying complex human genomic rearrangements: Further evidence for replicative mechanisms. C. M. B. C. Fonseca, R. Pfundt, L. W. Zuccherato, P. Liu, P. Stankiewicz, C. W. Brown, C. A. Shaw, G. Ira, P. J. Hastings, H. G. Brunner, J. R. Lupski.

78/4:00 Individual gene disruptions from balanced chromosomal rearrangements define novel neurodevelopmental loci and genomic disorders. H. Brand, V. Pillalamarri, I. Blumenthal, M. Stone, S. Pereira, C. Morton, J. Gusella, M. Talkowski.

Wednesday, October 23

2:00 PM–4:15 PM

Concurrent Platform (abstract-driven) Session A (10-18)

SESSION 18 – Inborn Errors of Metabolism: From Identification to Treatment

Grand Ballroom CDE, Concourse Level, Westin Boston Waterfront Hotel

Moderators: Irini Manoli, NHGRI/NIH
  Manuel Schiff, Univ. of Pittsburgh

79/2:00 A novel treatable disorder of protein glycosylation: Phosphoglucomutase 1 deficiency. E. Morava, T. Marquardt, J. Cegielska, K. Raymond, C. Stanley, D. Lefeber.

80/2:15 Mutations in HCFC1 a transcriptional coregulator causes a novel X-linked cobalamin disorder (cblX) with a severe neurological phenotype. T. H. Shaikh, H. C. Yu, J. L. Sloan, G. Scharer, A. Brebner, A. Quintana, N. P. Achilly, I. Manoli, C. R. Coughlin, E. A. Geiger, U. Schneck, D. Watkins, J. L. VanHove, B. Fowler, M. R. Baumgartner, D. S. Rosenblatt, C. P. Venditti.

81/2:30 Prediction of phenotypes and tetrahydrobiopterin-responsiveness in phenylketonuria using data from the genotypes and locus-specific databases. N. Blau, S. Wettstein, W. W. Yue, J. Underhaug, B. D. Marsden, A. Martinez, A. Honegger, B. Perez.

82/2:45 Three apparent pseudo-deficiency alleles in the IDUA gene identified by newborn screening. L. M. Pollard, S. R. Braddock, K. M. Christensen, D. J. Boylan, L. D. Smith, B. A. Heese, A. M. Atherton, C. E. Lawson, M. E. Strenk, M. Willing, L. Manwaring, T. C. Wood.

83/3:00 Atherosclerosis and glycosaminoglycan metabolism defects: Frequent association of endothelial dysfunction in patients with mucopolysaccharidosis. S. Yano, K. Moleley, L. Wong, C. Castelnovi, C. Azen, Z. Pavlova.

84/3:15 First results of a 6 month, open label, phase I/II clinical trial of intrathecal enzyme replacement therapy and its extension in mucopolysaccharidosis IIIA (Sanfilippo syndrome) patients. C. Breen, P. Haslett, F. A. Wijburg, J. de Ruijter, J. P. Marchal, F. Heap, S. Rust, K. Baez, N. Nair, S. A. Jones.

85/3:30 Development of AAV8-mediated gene therapy clinical trial for Crigler-Najjar syndrome type I: Optimization of liver-specific expression cassette. N. Pastore, E. Nusco, A. Auricchio, N. Brunetti-Pierri.

86/3:45 Identification of chemical and pharmacological chaperones to treat Zellweger spectrum patients with the common allele, PEX1-Gly483Asp. N. E. Braverman, S. J. Steinberg, S. Heibler, G. E. Maclean.

87/4:00 Efficacy of hematopoietic cell therapy in X-linked adrenoleukodystrophy: A multinstitutional study (ALD-101). G. Raymond, P. Orchard, P. Aubourg, M. Escolar, J. Kurtzberg, S. Paadre, J. Balser.

Thursday, October 24

8:00 AM–10:15 AM

Concurrent Platform (abstract-driven) Session B (19-27)

SESSION 19 – Hereditary Cancer Syndromes

Hall B2, Level 0 (Lower Level), Convention Center

Moderators: Katherine Nathanson, Univ. of Pennsylvania
  Melissa Southey, Univ. of Melbourne

88/8:00 Rare mutations in RINT1 predispose carriers to early-onset breast cancer. D. J. Park, K. Tao, F. Le Calvez-Kelm, T. Nguyen-Dumont, N. Robinot, F. Hammet, F. Odefrey, H. Tsimiklis, Z. L. Teo, L. B. Thingholm, C. Voegele, A. Lonie, B. J. Pope, E. M. John, I. L. Andrulis, M. B. Terry, M. Daly, S. Buys, G. G. Giles, J. L. Hopper, D. E. Goldgar, F. Lesueur, S. V. Tavtigian, M. C. Southey, Breast Cancer Family Registry, kConFab.

89/8:15 The BER glycosylase NEIL1 is a risk gene for familial breast cancer. M. R. Dufault, E. Hahnen, H. Hellebrand, J. Hauke, G. Neidhardt, S. Engert, S. Preissler-Adams, N. Arnold, T. M. Strom, K. Rhiem, B. Wappenschmidt, N. Ditsch, R. K. Schmutzler, A. Meindl.

90/8:30 More than 25% of breast cancer families with wild-type results from commercial genetic testing of BRCA1 and BRCA2 are resolved by BROCA sequencing of all known breast cancer genes. T. Walsh, S. Casadei, M. K. Lee, A. M. Thornton, G. Bernier, C. Spurrell, J. Mandell, T. Lajus, E. Swisher, M.-C. King.

91/8:45 Nine genes for inherited predisposition to breast cancer among African American women. O. I. Olopade, T. Walsh, Y. Zheng, S. Casadei, A. M. Thornton, M. K. Lee, M. Churpek, D. Huo, C. Zvosec, F. Liu, Q. Niu, J. Zhang, J. Fackenthal, M.-C. King, J. E. Churpek.

92/9:00 Germline loss-of-function mutations in 15 different DNA repair genes are present in 22% of 1412 patients with ovarian, peritoneal or fallopian tube cancers not selected for age at diagnosis or family history. M. I. Harrell, B. Norquist, T. Walsh, M. K. Lee, S. Casadei, K. P. Pennington, K. J. Agnew, A. Thornton, M. C. King, M. J. Birrer, E. M. Swisher.

93/9:15 The Mainstreaming Cancer Genetics Programme — Integrating genetic testing into routine clinical practice in the United Kingdom. N. Rahman, S. Mahamdallie, E. Ruark, H. Hanson, I. Slade, A. George, K. Snape, R. Sultan, A. Rimmer, M. Munz, G. Lunter, S. Banerjee, C. Turnbull, Mainstreaming Cancer Genetics Consortium.

94/9:30 Identification of a second major locus predisposing to an autosomal dominant inherited disorder of multiple schwannomas. L. Messiaen, J. Xie, A. P. Poplawski, Y. F. Liu, A. R. Gomes, P. Madanecki, C. Fu, M. R. Crowley, D. K. Crossman, L. Armstrong, D. Babovic-Vuksanovic, A. Bergner, J. O. Blakeley, A. Blumenthal, M. S. Daniels, H. Feit, K. Gardner, S. Hurst, C. Kobelka, C. Lee, R. Nagy, K. A. Rauen, J. M. Slopis, P. Suwannarat, J. A. Westman, A. Zanko, B. R. Korf, A. Piotrowski.

95/9:45 Identification of putative driver mutations in neurofibromatosis type 1-associated plexiform neurofibromas. A. Pemov, H. Li, N. F. Hansen, J. C. Mullikin, M. Wallace, D. R. Stewart.

96/10:00 Somatic structural and rare germline variation in childhood cancers. D. I. Ritter, B. Powell, H. Cheung, R. Gibbs, D. A. Wheeler, S. Plon.

Thursday, October 24

8:00 AM–10:15 AM

Concurrent Platform (abstract-driven) Session B (19-27)

SESSION 20 – Variants, Variants Everywhere

Grand Ballroom East, Level 3, Convention Center

Moderators: Gholson Lyon, Cold Spring Harbor Lab.
  Tuuli Lappalainen, Stanford Univ.

97/8:00 Frequency uniqueness score: Predicting the disease risk of coding variants. A. C. Alexander, B. E. Engelhardt.

98/8:15 Exome-based linkage mapping and variant prioritization for inherited retinal disorders. D. C. Koboldt, D. E. Larson, L. S. Sullivan, S. J. Bowne, R. S. Fulton, E. Sodergren, S. H. Blanton, K. Meltz Steinberg, S. P. Daiger, R. K. Wilson, G. W. Weinstock.

99/8:30 Integrative annotation of variants from 1,092 humans: Application to cancer genomics. E. Khurana, M. Gerstein, Functional Interpretation Group of 1000 Genomes Consortium.

100/8:45 Efficiency of whole exome/genome sequencing for achieving a diagnosis in rare presentations. M. C. Towne, A. H. Beggs, P. B. Agrawal.

101/9:00 Computational prediction and in vivo validation of suppressors of human disease mutations. D. M. Jordan, E. E. Davis, N. Katsanis, S. R. Sunyaev.

102/9:15 The empowered whole genome cohort: Shareable joint genome interpretation for research and personal insight. N. M. Pearson, J. Deschenes, C. Palm, D. Richards, D. Bassett.

103/9:30 Understanding molecular mechanisms of human disease mutations and coding variants through 3D protein networks. H. Yu, J. Das, Y. Guo, X. Wei, X. Wang, B. Thijssen, A. Grimson, S. M. Lipkin, A. G. Clark.

104/9:45 Evaluation of power of the Illumina HumanOmni5M-4v1 BeadChip to detect risk variants for human complex diseases. C. Xing, J. Huang, Y.-H. Hsu, A. L. DeStefano, N. L. Heard-Costa, P. A. Wolf, S. Seshadri, D. P. Kiel, L. A. Cupples, J. Dupuis.

105/10:00 Integrated analysis of protein-coding variation in over 50,000 individuals. M. Lek, D. G. MacArthur, A. Levy Moonshine, M. Rivas, S. Purcell, P. Sullivan, S. Kathiresan, M. I. McCarthy, M. Boehnke, S. Gabriel, D. M. Altshuler, G. Getz, M. J. Daly, M. A. DePristo, Exome Aggregation Consortium.

Thursday, October 24

8:00 AM–10:15 AM

Concurrent Platform (abstract-driven) Session B (19-27)

SESSION 21 – Genetic Epidemiology: Applications and Methods

Grand Ballroom West, Level 3, Convention Center

Moderators: Jo Knight, Ctr. for Addiction and Ment. Hlth., Ontario
  Braxton D. Mitchell, Univ. of Maryland Sch. of Med., Baltimore

106/8:00 The effect of CAD/MI SNPs on other vascular domains and the relation with recurrent vascular events. V. Tragante, P. A. F. M. Doevendans, H. M. Nathoe, Y. van der Graaf, W. Spiering, A. Algra, G. J. de Borst, P. I. W. de Bakker, F. W. Asselbergs.

107/8:15 Multi-trait meta-analysis of genome-wide association studies of lipid levels and BMI reveals pleiotropy. V. Lagou, R. Mägi, I. Surakka, A.-P. Sarin, M. Horikoshi, L. Marullo, T. Ferreira, G. Thorleifsson, S. Hägg, M. Beekman, C. Ladenvall, A. Mahajan, J.-J. Hottenga, J. S. Ried, T. W. Winkler, C. Willenborg, M. I. McCarthy, A. P. Morris, S. Ripatti, I. Prokopenko, ENGAGE (European Network for Genetic and Genomic Epidemiology) Consortium.

108/8:30 Genome-wide association with fasting glucose and insulin in 20,200 African Americans suggests new quantitative trait loci and allelic heterogeneity at known loci: The African American Glucose and Insulin Genetic Epidemiology (AAGILE) Consortium. J. Meigs, M.-F. Hivert, A. Morris, M. Li, M. Ng, J. Liu, R. Jensen, X. Guo, L. Yanek, M. Nalls, L. Bielak, M. Irvin, W.-M. Chen, P. An, E. Kabagambe, B. Cade, J. Wilson, MAGIC Investigators, J. Hong, D. Rybin, C.-T. Liu, AAGILE Investigators.

109/8:45 Harnessing Web 2.0 social networks for genetic epidemiology studies with millions of people. Y. Erlich, J. Kaplanis, M. Gershovits, P. Nagaraj, D. MacArthur, A. Price.

110/9:00 Integrated model of multiple types of rare variants and prior information improves the power of detecting risk genes for autism. X. He, S. J. Sanders, L. Liu, S. D. De Rubeis, E. T. Lim, J. S. Sutcliffe, G. D. Schellenberg, R. A. Gibbs, M. J. Daly, J. B. Buxbaum, M. W. State, B. Devlin, K. Roeder.

111/9:15 Tests of aggregate rare variant association applied to a multiethnic sequencing study. A. D. Ablorh, S. Lindstrom, C. A. Haiman, B. E. Henderson, L. Le Marchand, S. Lee, D. O. Stram, P. Kraft.

112/9:30 Whole-genome sequence based association studies of complex traits: The UK10K project. N. Timpson, UK10K Consortium: Cohorts.

113/9:45 Genetic variation associated with the susceptibility to herpes zoster in the eMERGE Network. D. Crosslin, D. Carrell, E. Baldwin, M. de Andrade, I. Kullo, G. Tromp, H. Kuivaniemi, K. Doheny, E. Pugh, A. Kho, M. Hayes, M. Ritchie, S. Verma, G. Armstrong, A. Saip, J. Denny, D. Crawford, P. Crane, S. Mukherjee, E. Bottinger, T. Manolio, R. Li, A. Burt, D. Kim, B. Keating, D. Mirel, E. Larson, C. Carlson, G. Jarvik, electronic Medical Records and Genomics (eMERGE) Network.

114/10:00 Whole-genome detection of disease-associated deletions or excess homozygosity in a case-control study of rheumatoid arthritis. C. C. Wu, S. Shete, E. J. Jo, Y. Xu, E. Y. Lu, W. V. Chen, C. I. Amos.

Thursday, October 24

8:00 AM–10:15 AM

Concurrent Platform (abstract-driven) Session B (19-27)

SESSION 22 – Cardiovascular Genetics: Gene Discovery through GWAS and Sequencing

Room 210, Level 2, Convention Center

Moderators: Paul W. Livermore Auer, Univ. of Wisconsin-Milwaukee
  Leslie Lange, Univ. of North Carolina at Chapel Hill

115/8:00 Linkage analysis of hypertriglyceridemia in a single large family identifies 3 novel potentially pathogenic variants. E. A. Rosenthal, J. Ranchalis, J. D. Brunzell, A. G. Motulsky, D. A. Nickerson, E. M. Wijsman, G. P. Jarvik.

116/8:15 Rare APOC3 loss-of-function variants lower plasma triglycerides and protect against clinical coronary heart disease. J. Crosby, G. M. Peloso, P. Auer, D. R. Crosslin, G. Jarvik, L. A. Cupples, A. Reiner, E. Boerwinkle, S. Kathiresan, on behalf of Exome Sequencing Project HDL/TG Working Group.

117/8:30 Novel rare and low frequency coding variants associated with LDL cholesterol levels. C. Willer, L. A. Lange, Y. Hu, H. Zhang, C. Xue, E. M. Schmidt, M. Boehnke, L. Groop, M. McCarthy, T. Meitinger, M. Fornage, C. Ballantyne, E. Boerwinkle, D. Altshuler, D.-y. Lin, G. Jarvik, L. A. Cupples, C. Kooperberg, J. G. Wilson, D. A. Nickerson, G. R. Abecasis, S. S. Rich, R. P. Tracy, NHLBI Exome Sequencing Project.

118/8:45 Association analysis of C-reactive protein levels in European Americans and African Americans sequenced through the NHLBI Exome-Sequencing Project. U. M. Schick, P. L. Auer, D. S. Kim, E. J. Benjamin, J. C. Bis, E. Boerwinkle, C. S. Carlson, J. Dupuis, M. Fornage, L. Hsu, R. D. Jackson, C. Kooperberg, L. Lange, H. Lin, S. M. Leal, A. C. Morrison, N. Pankratz, U. Peters, B. Psaty, S. S. Rich, R. Tracy, J. G. Wilson, M. D. Gross, A. P. Reiner, on behalf of NHLBI GO Exome Sequencing Project.

119/9:00 Genetic association studies illuminate the role of low frequency and rare variation in explaining the variation of blood pressure traits. A. Manning, X. Sim, H. M. Highland, M. A. Rivas, H. K. Im, A. Mahajan, A. E. Locke, N. Grarup, P. Fontanillas, A. P. Morris, T. M. Teslovich, J. Flannick, C. Fuchsberger, K. Gaulton, H. M. Kang, J. B. Meigs, C. M. Lindgren, for T2D-GENES and GoT2D.

120/9:15 Contribution of coding variation to type 2 diabetes-related quantitative traits in 13,000 exomes from multiple ancestries. X. Sim, H. M. Highland, M. A. Rivas, H. K. Im, A. K. Manning, A. Mahajan, A. E. Locke, N. Grarup, P. Fontanillas, A. P. Morris, T. M. Teslovich, J. Flannick, C. Fuchsberger, K. Gaulton, H. M. Kang, J. B. Meigs, C. M. Lindgren, T2D-GENES and GoT2D Consortia.

121/9:30 A meta-analysis of genome-wide association studies identifies a novel locus associated with thrombin generation potential. A. Rocañín-Arjó, L. Carcaillon, W. Cohen, N. Saut, M. Germain, L. Letenneur, M. Alhenc-Gelas, A. M. Dupuy, M. Bertrand, P. Amouyel, P. Y. Scarabin, D. A. Trégouët, P. E. Morange.

122/9:45 Genome-wide association analysis of blood pressure traits in nearly 30,000 African ancestry individuals reveals a common set of associated genes in African and non-African populations. N. Franceschini, E. Fox, Z. Zhang, T. Edwards, M. Nalls, Y. Sung, B. Tayo, Y. Sun, O. Gottesman, A. Adeyemo, A. Johnson, J. Young, K. Rice, H. Tang, J. Smith, G. Ehret, A. Morrison, E. Boerwinkle, B. Psaty, D. Arnett, S. Redline, R. Cooper, N. Risch, D. Rao, J. Rotter, A. Chakravarti, A. Reiner, D. Levy, B. Keating, X. Zhu, AGEN Consortium.

123/10:00 Gene pathway burden test application to cardiovascular disease using whole genome sequencing data. M. A. A. Almeida, J. P. Peralta, J. W. Kent, T. M. Teslovich, G. Jun, C. Fuchsberger, A. R. Wood, A. Manning, T. M. Frayling, P. Cingolani, D. M. Lehman, T. D. Dyer, G. Abecasis, L. Almasy, R. Duggirala, J. Blangero.

Thursday, October 24

8:00 AM–10:15 AM

Concurrent Platform (abstract-driven) Session B (19-27)

SESSION 23 – From eQTLs to Epigenetics and Beyond

Room 205, Level 2, Convention Center

Moderators: John M. Greally, Albert Einstein Col. of Med.
  Alexis Battle, Stanford Univ.

124/8:00 Interpreting eQTLs by linking enhancers to target genes. J. Wang, A. Kundaje, L. D. Ward, M. Kellis, GTEx Consortium and Roadmap Epigenomics Program.

125/8:15 Genetic architecture of regulatory variation influencing response to human rhinovirus infection. M. Caliskan, Y. Gilad, C. Ober.

126/8:30 Genome-wide association of expression response of primary immune cells identifies novel cis and trans loci specific to distinct pathogen responses. C. Ye, M. Lee, A. C. Villani, T. Raj, W. Li, T. M. Eisenhaure, S. H. Imboywa, P. I. Chipendo, K. Rothamel, K. Raddassi, M. H. Lee, I. Wood, C. McCabe, B. E. Stranger, C. O. Benoist, P. L. De Jager, A. Regev, N. Hacohen, Immunological Variation Consortium.

127/8:45 Expression QTL analysis from primary immune cells of a multi-ethnic cohort identifies novel disease-causing regulatory effects. B. E. Stranger, T. Raj, C. Ye, S. Mostafavi, K. L. Rothamel, M. Lee, J. M. Replogle, T. Feng, S. H. Imboywa, M. Lee, C. McCabe, D. Koller, A. Regev, N. Hacohen, C. O. Benoist, P. L. De Jager, Immunological Variation Consortium.

128/9:00 Allele specific expression analysis using transcriptome sequencing in three tissues of a twin cohort reveals large effect of gene-by-gene and gene-by-environment interactions. A. Buil, A. A. Brown, A. Viñuela, M. N. Davies, H. F. Zheng, J. B. Richards, K. S. Small, R. Durbin, T. D. Spector, E. T. Dermitzakis.

129/9:15 Epigenomic variation between species, tissues, populations and individuals. A. Kundaje, W. Meuleman, J. Wang, N. Kumar, S. Kyriazopoulou-Panagiotopoulou, M. Kasowski, M. Snyder, M. Kellis.

130/9:30 Predicting genome-wide DNA methylation using methylation marks, genomic position and DNA regulatory elements. W. Zhang, T. D. Spector, P. Deloukas, J. T. Bell, B. E. Engelhardt.

131/9:45 An ENU mutagenesis screen identifies the first mouse mutants of a novel epigenetic modifier, rearranged L-Myc fusion (Rlf). S. K. Harten, L. Bourke, V. Bharti, H. Oey, N. Whitelaw, L. Daxinger, E. Whitelaw.

132/10:00 Zebrafish Mutation Project: Functional genomics of disease. E. M. Busch-Nentwich, J. E. Collins, I. Sealy, N. Wali, R. J. White, C. M. Dooley, C. Scahill, S. Carruthers, Z. Pusztai, C. Herd, A. Hall, R. N. W. Kettleborough, J. Morris, J. Barrett, D. L. Stemple.

Thursday, October 24

8:00 AM–10:15 AM

Concurrent Platform (abstract-driven) Session B (19-27)

SESSION 24 – Neurogenetics: Illuminating Mechanisms

Room 253, Level 2, Convention Center

Moderators: Gary Beecham, Univ. of Miami
  Lindsay Farrer, Boston Univ.

133/8:00 Unraveling the genetic architecture of multiple sclerosis and the underlying implicated pathways. N. A. Patsopoulos, for International Multiple Sclerosis Genetics Consortium (IMSGC).

134/8:15 Autosomal dominant congenital spinal muscular atrophy is caused by mutations in BICD2, a golgin and important motor adaptor. B. Wirth, L. A. Martinez-Carrera, I. Hölker, A. Heister, A. Verrips, S. M. Hosseini-Barkooie, C. Gilissen, S. Vermeer, M. Pennings, R. Meijer, M. te Riele, C. J. M. Frijns, O. Suchowersky, L. MacLaren, S. Rudnik-Schöneborn, R. J. Sinke, K. Zerres, R. B. Lowry, H. H. Lemmink, L. Garbes, M. Synofzik, J. A. Veltman, H. J. Schelhaas, H. Scheffer, K. Neveling.

135/8:30 Rare variants in restless legs syndrome. E. C. Schulte, M. Kousi, B. Schormair, F. Knauf, P. Lichtner, C. Trenkwalder, B. Högl, B. Frauscher, K. Berger, I. Fietze, N. Gross, M. Hornyak, K. Stiasny-Kolster, W. Oertel, C. G. Bachmann, W. Paulus, A. Zimprich, A. Peters, C. Gieger, T. Meitinger, B. Müller-Myhsok, N. Katsanis, J. Winkelmann.

136/8:45 Mutations in PNPLA6 cause a range of neurodegenerative phenotypes. M. A. Gonzalez, M. Synofzik, M. Coutelier, C. Marques Lourenço, T. Haack, H. Prokisch, R. Schule, W. Marques Junior, L. Schols, G. Stevanin, S. Zuchner.

137/9:00 Targeted resequencing of 101 known and candidate epilepsy genes in 600 patients with severe epilepsies identifies recurrently mutated genes. G. L. Carvill, S. B. Heavin, J. M. McMahon, B. J. O'Roak, S. F. Berkovic, J. Shendure, I. E. Scheffer, H. C. Mefford.

138/9:15 A mouse model of Kabuki syndrome demonstrates defective hippocampal neurogenesis rescued with treatment with AR-42, a histone deacetylase inhibitor. H. T. Bjornsson, J. S. Benjamin, L. Zhang, E. E. Gerber, Y. Chen, M. C. Potter, H. C. Dietz.

139/9:30 Human iPSC-based models of neuronal ceroid lipofuscinosis capture progressive pre-storage pathology in multiple cellular compartments. J. F. Staropoli, X. Lojewski, S. Biswas, L. Haliw, A. Simas, M. K. Selig, K. A. Goss, A. Petcherski, S. H. Coppel, U. Chandrachud, S. Sheridan, K. B. Sims, J. F. Gusella, D. Lucente, D. Sondhi, R. G. Crystal, S. J. Haggarty, A. Hermann, A. Storch, S. L. Cotman.

140/9:45 Mutation in EZR inhibits the Ras/MAP pathway and causes autosomal recessive intellectual disability. R. Abou Jamra, L. B. Riecken, H. Tawamie, K. Geissler, A. Schulz, R. Buchert, S. Uebe, M. M. Nöthen, J. Schumacher, A. Ismael, A. Ekici, H. Sticht, A. Reis, H. Morrison.

141/10:00 De novo mutations in the genome organizer CTCF cause intellectual disability. C. Zweier, A. Gregor, M. Oti, E. N. Kouwenhoven, J. Hoyer, H. Sticht, A. B. Ekici, S. Kjaergaard, A. Rauch, H. G. Stunnenberg, S. Uebe, G. Vasileiou, A. Reis, H. Zhou.

Thursday, October 24

8:00 AM–10:15 AM

Concurrent Platform (abstract-driven) Session B (19-27)

SESSION 25 – Genetic Interactions in Complex Traits

Room 258, Level 2, Convention Center

Moderators: Qibin Qi, Albert Einstein Col. of Med.
  Peter Kraft, Harvard Sch. of Publ. Hlth.

142/8:00 Daylight exposure may modify the effect of variants at MTNR1B and CRY2 on glucose tolerance: The GLACIER Study. F. Renström, R. Koivula, T. V. Varga, G. Hallmans, F. B. Hu, J. C. Florez, H. Mulder, P. W. Franks.

143/8:15 NAT1 in an important genetic effect modifier of tobacco smoke exposure in multiple sclerosis susceptibility in 5,453 individuals. F. B. S. Briggs, B. Acuna, L. Shen, H. Quach, A. Bernstein, I. Kockum, A. K. Hedström, M. W. Gustavsen, P. Berg-Hansen, S. D. Bos, E. Gulowsen Celius, H. F. Harbo, L. Alfredsson, T. Olsson, C. Schaefer, L. F. Barcellos.

144/8:30 Genome-wide joint meta-analysis for interaction between genetic variants and smoking on waist circumference. A. E. Justice, T. W. Winkler, J. Ngwa, K. L. Young, D. Hadley, M. Graff, J. M. Vink, L. Xue, T. S. Ahluwalia, T. Lehtimäki, R. J. Strawbridge, M. C. Zillikens, M. F. Feitosa, N. L. Heard-Costa, J. H. Zhao, J. Luan, N. Direk, H. Tiemeier, H. J. Grabe, T. B. Harris, R. P. S. Middelberg, J. V. van Vliet-Ostaptchouk, I. M. Nolte, J. Kaprio, T. O. Kilpeläinen, I. B. Borecki, R. J. F. Loos, K. E. North, L. A. Cupples, on behalf of GIANT Consortium.

145/8:45 Interaction between genome-wide variants and physical activity on body mass index: A meta-analysis of 109,924 individuals. T. O. Kilpeläinen, R. A. Scott, A. Mahajan, L. Xue, F. Renström, M. Graff, D. Hadley, T. Workalemahu, M. den Hoed, T. W. Winkler, A. Y. Chu, N. L. Heard-Costa, T. Haller, T. S. Ahluwalia, J. V. van Vliet-Ostaptchouk, P. J. van der Most, M. L. Grove, L. Quaye, S. Snitker, E. J. C. de Geus, T. Lehtimäki, L. Qi, P. W. Franks, I. B. Borecki, K. Monda, D. I. Chasman, K. E. North, L. A. Cupples, R. J. F. Loos, GIANT Consortium.

146/9:00 Genome-wide analyses highlights gene interaction with processed meat and vegetable intake for colorectal cancer risk. J. Figueiredo, L. Hsu, E. White, A. Chan, B. Zanke, J. Potter, G. Casey, C. Hutter, H. Brenner, B. Caan, J. Chang-Claude, S. Gallinger, R. Hayes, T. Hudson, L. Le Marchand, P. Newcomb, R. Schoen, M. Slattery, U. Peters.

147/9:15 Genome wide gene-environment interaction study identifies a CYP24A1-related variant as a modifier of colorectal cancer risk associated with menopausal estrogen plus progesterone therapy. X. Garcia-Albeniz, A. Rudolph, C. M. Hutter, Y. Lin, E. White, H. Brenner, G. Casey, S. Gallinger, L. Hsu, T. J. Hudson, L. Le Marchand, J. Potter, M. Slattery, B. Zanke, P. A. Newcomb, A. T. Chan, U. Peters, J. Chang-Claude.

148/9:30 Replication of gene-gene interaction models associated with cataracts in the eMERGE Network. M. A. Hall, S. S. Verma, E. R. Holzinger, R. Berg, J. Connolly, D. C. Crawford, D. R. Crosslin, M. de Andrade, K. F. Doheny, J. L. Haines, J. B. Harley, G. P. Jarvik, T. Kitchner, H. Kuivaniemi, E. B. Larson, G. Tromp, S. A. Pendergrass, C. A. McCarty, M. D. Ritchie.

149/9:45 Evidence from multiple genome-wide association studies of a hub of gene-gene interactions affecting human HDL cholesterol levels. L. Ma, C. Ballantyne, A. Brautbar, A. Keinan.

150/10:00 Epistasis analysis for quantitative trait with next-generation sequencing data. F. Zhang, E. Boerwinkle, M. Xiong.

Thursday, October 24

8:00 AM–10:15 AM

Concurrent Platform (abstract-driven) Session B (19-27)

SESSION 26 – Advances in the Genetics of Skeletal and Morphologic Disorders

Grand Ballroom AB, Concourse Level, Westin Boston Waterfront Hotel

Moderators: Charles Venditti, NHGRI/NIH
  Jamie Fitzgerald, Oregon Hlth. & Sci. Univ.

151/8:00 Targeted capture and sequencing identifies causative alleles in simplex and multiplex consanguineous Palestinian families with orofacial clefts. H. Shahin, U. Sharaha, M. K. Lee, A. Watts, M.-C. King, J. van Aalst, T. Walsh.

152/8:15 Dominant mutations in GRHL3 cause Van der Woude syndrome and disrupt oral periderm development. M. Peyrard, E. J. Leslie, Y. A. Kousa, T. L. Smith, M. Dunnwald, M. Magnusson, B. A. Lentz, P. Unneberg, I. Fransson, H. K. Koillinen, J. Rautio, M. Pegelow, A. Karsten, L. Basel-Vanagaite, W. Gordon, B. Andersen, T. Svensson, J. C. Murray, R. A. Cornell, J. Kere, BC. Schutte.

153/8:30 A homeotic maxillary to mandibular transformation in humans resulting from loss of selective ligand affinity of the endothelin receptor type A. C. Gordon, M. Oufadem, Y. Kurihara, A. Picard, S. Breton, S. Pierrot, M.-A. Delrue, M. Biosse-Duplan, M. Guion-Almeida, P. Moura, D. Garib, D. Weaver, A. Munnich, P. Corvol, H. Kurihara, R. Zechi-Ceide, S. Lyonnet, J. Amiel.

154/8:45 Putative gain of function mutations in FAM111A result in Kenny-Caffey syndrome and osteocraniostenosis: Identification of an upstream regulator of the PTH axis. S. Unger, M. W. Gorna, A. Le Bechec, S. Do Vale-Pereira, F. Bedeschi, S. Geiberger, G. Grigelioniene, E. Horemuzova, F. Lalatta, E. Lausch, C. Magnani, S. Nampoothiri, G. Nishimura, D. Petrella, F. Rojas-Ringeling, A. Utsunomiya, B. Zabel, S. Pradervand, K. Harshman, B. Campos-Xavier, L. Bonafé, G. Superti-Furga, B. Stevenson, A. Superti-Furga.

155/9:00 Mutations in PIEZO2 cause Gordon syndrome, Marden-Walker syndrome and distal arthrogryposis type 5. M. J. McMillin, A. E. Beck, J. X. Chong, K. M. Shively, K. J. Buckingham, H. I. Gildersleeve, M. Splitt, A. S. Aylsworth, I. P. C. Krapels, C. J. Curry, M. I. Aracena, J. T. Hecht, J. A. Hurst, R. H. Scott, K. Devriendt, J. M. Graham, Jr., J. D. Smith, H. K. Tabor, J. Shendure, D. A. Nickerson, M. J. Bamshad, University of Washington Center for Mendelian Genomics.

156/9:15 Mutation in the SH2 domain of PIK3R1 cause SHORT syndrome with partial lipodystrophy. S. Johansson, K. K. Chudasama, J. Winnay, T. Claudi, R. König, I. Haldorsen, B. Johansson, J. R. Woo, D. Aarskog, J. V. Sagen, C. R. Kahn, A. Molven, P. R. Njolstad.

157/9:30 MAP4 defect underlines centrosomal organization as a central mechanism in growth regulation. C. T. Thiel, D. Zahnleiter, N. Hauer, K. Kessler, Y. Sugano, S. Neuhaus, A. B. Ekici, H. Blessing, H. Sticht, H.-G. Doerr, A. Reis.

158/9:45 Best understanding of structural and functional impact of FGFR3 mutations at the same position (K650N, K650M, K650E) leading to both mild and lethal dwarfism. D. Komla Ebri, C. Benoist-Lasselin, N. Kaci, P. Busca, G. Prestat, A. Munnich, F. Barbault, L. Legeai-Mallet.

159/10:00 X-linked osteoporosis and fractures: An unexpected genetic cause. F. S. van Dijk, M. C. Zillikens, D. Micha, M. Riessland, C. L. M. Marcelis, C. E. de Die-Smulders, J. Milbradt, A. A. M. Franken, G. J. Harsevoort, K. D. Lichtenbelt, J. E. Pruijs, M. E. Rubio-Gozalbo, R. Zwertbroek, M. Hammerschmidt, R. Bijman, C. M. Semeins, A. D. Bakker, V. Everts, J. Klein-Nulend, N. Campos-Obando, A. Hofman, A. J. M. H. Verkerk, A. G. Uitterlinden, A. Maugeri, E. A. Sistermans, Q. Waisfisz, H. Meijers-Heijboer, B. Wirth, M. E. H. Simon, G. Pals.

Thursday, October 24

8:00 AM–10:15 AM

Concurrent Platform (abstract-driven) Session B (19-27)

SESSION 27 – Causes and Consequences of Chromosomal Variations

Grand Ballroom CDE, Concourse Level, Westin Boston Waterfront Hotel

Moderators: Beverly Emanuel, Univ. of Pennsylvania
  Seema Lalani, Baylor Col. of Med.

160/8:00 Identification of rare genetic variants in high-risk ASD families and their role in a large ASD case/control population. C. Hensel, N. Matsunami, D. Hadley, G. B. Christensen, C. Kim, E. Frackelton, K. Thomas, R. Pellegrino da Silva, J. Stevens, L. Baird, B. Otterud, K. Ho, T. Varvil, T. Leppert, C. Lambert, M. Leppert, H. Hakonarson.

161/8:15 Discovery of cryptic chromosomal abnormalities in clinically-referred youth with neuropsychiatric disorders. V. Pillalamarri, A. Doyle, H. Brand, M. R. Stone, I. Blumenthal, C. O'dushlaine, E. Braaten, J. Rosenfeld, S. McCarroll, J. Smoller, M. E. Talkowski.

162/8:30 Mechanism, prevalence, and more severe neuropathy phenotype of the Charcot-Marie-Tooth, type 1A triplication. V. Gelowani, P. Liu, F. Zhang, V. Drory, S. B. Shachar, E. Roney, W. B. Burnette, J. Li, A. Orr-Urtreger, J. R. Lupski.

163/8:45 Whole genome sequencing of two individuals with excessive numbers of de novo CNVs. P. Liu, K. Walter, A. Wuster, T. Gambin, V. Gelowani, K. Writzl, S. Lindsay, C. Carvalho, M. Withers, C. Gonzaga, J. Wiszniewska, A. Patel, B. Rautenstrauss, R. Gibbs, M. Hurles, J. Lupski.

164/9:00 Utilization of next-generation sequencing to detect and assign pathogenicity to balanced rearrangements identified by conventional cytogenetics. U. Aypar, K. Pearce, E. Thorland, J. Evans, V. Sarangi, C. Wang, Y. Asmann, N. Hoppman.

165/9:15 Sequencing of unbalanced translocation junctions reveals mutational mechanisms and gene fusions. B. Weckselblatt, M. K. Rudd.

166/9:30 Identification of a deletion in the LRP1b gene associated with megalencephaly in the sudden infant death syndrome. D. S. Paterson, H. C. Kinney, K. Schmitz Abe, F. Rahimov, F. L. Trachtenberg, E. A. Haas, H. F. Krous, K. Markianos.

167/9:45 A comprehensive microarray prenatal study: Efficacy for both copy number and copy neutral changes. S. Schwartz, R. Pasion, H. Cabral, R. Burnside, I. Gadi, E. Keitges, L. Kline, V. Jaswaney, K. Phillips, H. Risheg, B. Rush, J. Shafer, H. Taylor, J. Tepperberg, P. Papenhasuen.

168/10:00 Non-random, locus-specific differences in DNA accessibility are present in homologous metaphase chromosomes. W. A. Khan, P. K. Rogan, J. H. M. Knoll.

Thursday, October 24

2:00 PM–4:15 PM

Concurrent Platform (abstract-driven) Session C (28-36)

SESSION 28 – Low Frequency Variants for Complex Traits

Hall B2, Level 0 (Lower Level), Convention Center

Moderators: Benjamin Voight, Univ. of Pennsylvania
  Ines Barroso, Wellcome Trust Sanger Inst.

169/2:00 Rare variants contributing to age-related macular degeneration — Results from the International AMD Genomics Consortium. W. M. Igl, for International AMD Genomics Consortium.

170/2:15 Identification of new rare coding variants associated with hemoglobin levels and platelet counts. P. Livermore Auer, N. Chami, U. Schick, S. de Denus, C. Carlson, M. Dube, R. D. Jackson, J. D. Rioux, C. L. Kooperberg, U. Peters, J. C. Tardif, L. Hsu, A. P. Reiner, G. Lettre.

171/2:30 Large-scale whole genome sequencing study for bone mineral density: The UK10K Consortium. H. Zheng, V. Forgetta, S. Wilson, C. Greenwood, N. Timpson, N. Soranzo, T. Spector, B. Richards.

172/2:45 Identification of 6 novel loci associated with amino acid levels using single-variant and gene-based tests. T. M. Teslovich, J. R. Perry, J. R. Huyghe, A. U. Jackson, A. Stančáková, H. M. Stringham, P. S. Chines, J. M. Romm, H. Ling, I. McMullen, R. Ingersoll, E. W. Pugh, K. F. Doheny, J. Kuusisto, F. S. Collins, K. L. Mohlke, M. Laakso, M. Boehnke.

173/3:00 Exome analysis in 65,653 European samples identifies novel low-frequency and common variants for type 2 diabetes. C. Fuchsberger, A. Mahajan, J. Flannick, D. Pasko, N. Grarup, N. Robertson, X. Sim, N. Burtt, A. Morris, on behalf of GoT2D Consortium.

174/3:15 Loss of function mutations in SLC30A8 protect against type 2 diabetes. J. Flannick, G. Thorleifsson, N. L. Beer, S. B. R. Jacobs, N. Grarup, NNF-CBMR Genetics, Go-T2D/T2D-GENES Consortia, deCODE Genetics, Pfizer-Broad-MGH-Lund T2D Project.

175/3:30 Whole genome sequencing of 2,850 Central-Northern European type 2 diabetes cases and controls reveals insights into functional mechanisms underlying disease pathogenesis. K. Gaulton, J. Flannick, C. Fuchsberger, H. M. Kang, N. Burtt, J. Ferrer, M. Stitzel, M. Kellis, M. McCarthy, D. Altshuler, M. Boehnke, GoT2D Consortium.

176/3:45 Exome chip scan of 74,000 subjects of European descent and 18,000 subjects of African descent identify novel genes with functional mutations influencing adiposity traits. I. B. Borecki, CHARGE Adiposity Working Group.

177/4:00 Large duplications are associated with increased risk of obesity. J. S. El-Sayed Moustafa, M. Falchi, R. G. Walters, I. Prokopenko, A. I. F. Blakemore, L. J. M. Coin, P. Froguel.

Thursday, October 24

2:00 PM–4:15 PM

Concurrent Platform (abstract-driven) Session C (28-36)

SESSION 29 – Selection, Demography and Functional Polymorphism

Grand Ballroom East, Level 3, Convention Center

Moderators: Xiaoming Liu, Univ. of Texas Hlth. Sci. Ctr. at Houston
  Adam Siepel, Cornell Univ.

178/2:00 A role for host-bacteria interactions in shaping patterns of genetic variation across human populations. R. Blekhman, J. K. Goodrich, K. Huang, Q. Sun, R. Bukowski, J. T. Bell, T. D. Spector, A. Keinan, R. E. Ley, D. Gevers, A. G. Clark.

179/2:15 Using ancient genomes to detect positive selection on the human lineage. K. Prüfer, M. Lachmann, C. Theunert, M. Ongyerth, G. Renaud, M. Dannemann, T. Neandertal Genome Consortium, S. Pääbo.

180/2:30 Reference sample guided pooled sequencing identifies loss-of-function patterns across human populations. A. Eran, M. Carneiro, G. del Angel, E. Banks, R. Poplin, M. Lek, G. van der Auwera, S. Fisher, S. Gabriel, D. Altshuler, D. MacArthur, M. Depristo, 1000 Genomes Project Consortium.

181/2:45 Patterns of IBD sharing inferred from whole genome sequences of 962 European Americans. C. V. Van Hout, F. Yu, X. Liu, E. Boerwinkle, A. G. Clark.

182/3:00 Reconstructing the genetic demography of the United States. R. Sebro, N. Laird, N. Risch.

183/3:15 Assessing functional potential along the human genome by integrating comparative, population, and functional genomic data. I. Gronau, B. Gulko, L. Arbiza, M. J. Hubisz, A. Siepel.

184/3:30 Genome-wide analysis of cold adaption in indigenous Siberian populations. A. Cardona, T. Antao, L. Pagani, D. J. Lawson, C. A. Eichstaedt, B. Yngvadottir, C. Tyler-Smith, M. T. T. Shwe, J. Wee, I. G. Romero, S. Raj, R. Villems, M. Metspalu, R. Nielsen, E. Willerslev, B. A. Malyarchuk, M. V. Derenko, T. Kivisild.

185/3:45 Genetic variation is a major source of transcriptional variation in human-induced pluripotent stem cells. N. Kumasaka, F. Rouhani, A. Bradley, L. Vallier, D. Gaffney.

186/4:00 Using enhancer activity regulatory motifs to explore evolutionary trajectories and disease mechanisms. L. D. Ward, W. Meuleman, P. Kheradpour, A. Kundaje, M. Kellis, Roadmap Epigenomics Mapping Consortium.

Thursday, October 24

2:00 PM–4:15 PM

Concurrent Platform (abstract-driven) Session C (28-36)

SESSION 30 – Statistical Methods for Family Data

Grand Ballroom West, Level 3, Convention Center

Moderators: Shamil Sunyaev, Brigham and Women's Hosp.
  Nathan L. Tintle, Dordt Col., IA

187/2:00 Adjusting family relatedness in data-driven burden test of rare variants. Q. Zhang, L. Wang, I. B. Borecki, M. A. Province.

188/2:15 Fast and accurate pedigree-based imputation from sequenced data in a founder population. O. E. Livne, L. Han, G. Alkorta-Aranburu, W. Wentworth-Sheilds, L. L. Pesce, C. Ober, M. Abney, D. Nicolae.

189/2:30 Multiple genetic variant association testing by collapsing and kernel methods with pedigree or population structured data. D. J. Schaid, S. K. McDonnell, J. P. Sinnwell, S. N. Thibodeau.

190/2:45 Evidence for causality of rare variants based on exact sharing probabilities in affected relatives. I. Ruczinski, A. Bureau, M. M. Parker, M. A. Taub, M. L. Marazita, J. C. Murray, J. E. Bailey-Wilson, C. D. Cropp, E. Mangold, M. Noethen, J. B. Hetmanski, P. Balakrishnan, H. Wang, H. Ling, A. F. Scott, T. H. Beaty.

191/3:00 A generalized sparse regression model with adjustment of pedigree structure for variant detection from next-generation sequencing data. S. Cao, H. Qin, H. Deng, Y. Wang.

192/3:15 Haplotype phasing across the full spectrum of relatedness. J. O'Connell, O. Delaneau, N. Pirastu, S. Ulivi, M. Cocca, M. Traglia, J. Huang, J. E. Huffman, I. Rudan, R. McQuillan, R. M. Fraser, H. Campbell, O. Polasek, C. Hayward, A. F. Wright, V. Vitart, P. Navarro, J. F. Zagury, J. F. Wilson, D. Toniolo, P. Gasparani, N. Soranzo, J. Marchini.

193/3:30 The theory of genetic interactions and its application to the problem of missing heritability. A. Young, R. Durbin.

194/3:45 Tracing individual ancestry in a principal components space. C. Wang, L. Liang, G. Abecasis, X. Lin.

195/4:00 Multiple HLA loci and energy metabolism genes are targeted by recent positive selection in an Ethiopian population. F. Tekola-Ayele, A. Adeyemo, E. Hailu, A. Aseffa, G. Davey, M. J. Newport, C. N. Rotimi.

Thursday, October 24

2:00 PM–4:15 PM

Concurrent Platform (abstract-driven) Session C (28-36)

SESSION 31 – Advances and References in Genomic Technology

Room 210, Level 2, Convention Center

Moderators: Daniel G. MacArthur, Massachusetts Gen. Hosp./Broad Inst.
  Fuli Yu, Baylor Col. of Med.

196/2:00 Statistical model for the joint estimation of mRNA isoforms and individual-specific expression from RNA-seq data. F. Mordelet, B. E. Engelhardt.

197/2:15 Choosing an RNA-seq aligner for QTL and ASE analysis in the Genotype-Tissue Expression Project. D. S. DeLuca, T. Lappalainen, P. Kheradpour, M. Sammeth, J. Monlong, P. Ribeca, E. Palumbo, A. Battle, E. Gelfand, R. Guigo, K. Ardlie, G. Getz, GTEx Consortium.

198/2:30 mRNA and small RNA sequencing of 465 HapMap cell lines: The feasibility of multicenter RNA-seq studies. P. A. C. Hoen, M. R. Friedlander, J. Almlof, M. Sammeth, I. Pulyakhina, S. Y. Anvar, J. F. J. Laros, O. Karlberg, J. T. den Dunnen, G. J. B. van Ommen, I. G. Gut, R. Guigo, X. Estivill, A. C. Syvanen, E. T. Dermitzakis, T. Lappalainen, GEUVADIS Consortium.

199/2:45 Complete resequencing of extended genomic regions using fosmid targeting and PacBio’s single molecule real-time (SMRT®) long-read sequencing technology. D. E. Geraghty, C. W. Pyo, K. Wang, R. Wang, Y. S. Pyon, K. Eng, B. Bowman, S. Ranade.

200/3:00 Platinum genomes: A systematic assessment of variant accuracy using a large family pedigree. M. A. Eberle, M. Kallberg, H.-Y. Chuang, P. Tedder, S. Humphray, D. Bentley, E. H. Margulies.

201/3:15 Sensitive and quantitative measurement of nuclease-mediated genome editing at human endogenous loci using SMRT sequencing. A. Hendel, E. Kildebeck, E. Fine, J. Clark, G. Bao, M. Porteus.

202/3:30 Mining genomic feature sets and identifying significant biological relationships with BedTools2. A. Quinlan, N. Kindlon.

203/3:45 Creating a single haplotype human genome assembly. T. Graves, W. Warren, B. Fulton, K. Meltz Steinberg, R. Agarwala, V. Schneider, D. Church, E. Eichler, R. Wilson.

204/4:00 A generalized human reference as a graph of genomic variation. E. Garrison, D. Kural, A. Ward, W. P. Lee, G. Marth.

Thursday, October 24

2:00 PM–4:15 PM

Concurrent Platform (abstract-driven) Session C (28-36)

SESSION 32 – Genetic Testing for Neurodevelopmental Disease: Genotype: Phenotype Challenges

Room 205, Level 2, Convention Center

Moderators: Miriam H. Meisler, Univ. of Michigan
  David R. Adams, NHGRI/NIH

205/2:00 Clinical experience implementing chromosomal microarray analysis in a clinical psychiatric practice for adults with autism spectrum disorders and related neurodevelopmental disorders. K. B. Teed, A. Vahabzadeh, J. C. Cubells.

206/2:15 New insights into the spectrum of pathogenic variation in epilepsy gained from molecular diagnostic testing of 1600 individuals. S. Aradhya, E. Butler, D. McKnight, A. Shanmugham, C. Downtain, A. Entezam, G. Richard.

207/2:30 Pathogenic rare copy number variants in community-based schizophrenia suggest a potential role for clinical microarrays. A. S. Bassett, G. A. Costain, A. Lionel, D. Merico, P. J. Forsythe, K. Russell, C. Lowther, T. Yuen, J. Husted, D. J. Stavropoulos, M. Speevak, E. W. C. Chow, C. R. Marshall, S. W. Scherer.

208/2:45 Genetic assessment of congenital brain malformations. U. Hehr, T. Rödl, S. M. Herbst, S. Schirmer, T. Geis, B. Kasper, G. Schuierer, J. Winkler, G. Uyanik.

209/3:00 Investigation of CASK gene aberrations in 38 patients with severe intellectual disability, microcephaly and disproportionate pontine and cerebellar hypoplasia. S. Hayashi, O. Nobuhiko, J. Takanashi, J. Inazawa.

210/3:15 A homozygous PDE6D mutation in Joubert syndrome impairs targeting of farnesylated INPP5E protein to the primary cilium. S. Thomas, K. J. Wright, S. Le Corre, A. Micalizzi, M. Romani, A. Abhyankar, J. Saada, I. Perrault, J. Amiel, J. Litzler, E. Filhol, N. Elkhartoufi, M. Kwong, J. L. Casanova, N. Boddaert, W. Baehr, S. Lyonnet, A. Munnich, L. Burglen, N. Chassaing, F. Encha-Ravazi, M. Vekemans, J. G. Gleeson, E. M. Valente, P. K. Jackson, I. A. Drummond, S. Saunier, T. Attié-Bitach.

211/3:30 Assessment of incidental findings in whole exome sequences from the Baylor-Hopkins Center for Mendelian Genomics. J. Jurgens, N. Sobreira, H. Ling, E. Pugh, E. Cirulli, F. Schiettecatte, K. Doheny, A. Hamosh, D. Valle.

212/3:45 Deep sequencing in extended pedigrees reveals a major rare non-synonymous variant influencing the de novo ceramide synthesis pathway. J. E. Curran, P. J. Meikle, J. M. Weir, J. B. Jowett, T. M. Teslovich, G. Jun, S. Kumar, M. Almeida, J. M. Peralta, C. Fuchsberger, A. R. Wood, A. Manning, T. M. Frayling, P. Gingolani, R. Sladek, D. M. Lehman, G. Abecasis, M. C. Mahaney, T. D. Dyer, L. Almasy, R. Duggirala, J. Blangero, T2D-GENES Consortium.

213/4:00 From embryonic lethal to no phenotype: What autozygome can teach us about loss of function in the human genome. F. S. Alkuraya.

Thursday, October 24

2:00 PM–4:15 PM

Concurrent Platform (abstract-driven) Session C (28-36)

SESSION 33 – Gene Regulation — At a Multitude of Levels

Room 253, Level 2, Convention Center

Moderators: Michael Zwick, Emory Univ.
  Sara Wheelan, Johns Hopkins Univ.

214/2:00 The evolutionary dynamics of regulatory DNA in the mouse and human genomes. J. Vierstra, E. Rynes, R. Sandstrom, R. E. Thurman, J. A. Stamatoyannopoulos.

215/2:15 Widespread exonic transcription factor binding directs codon usage and protein evolution. A. B. Stergachis, E. Haugen, A. Shafer, W. Fu, B. Vernot, J. M. Akey, J. A. Stamatoyannopoulos.

216/2:30 Short tandem repeat polymorphisms create an abundant source of expression variability. M. Gymrek, S. Georgiev, B. Markus, J. Chen, P. Villarreal, J. Pritchard, Y. Erlich.

217/2:45 RNA-DNA sequence differences occur within seconds following RNA exit PolII active sites and are responsive to cellular stress. V. G. Cheung, I. X. Wang, L. Core, H. Kwak, L. Brady, A. Bruzel, A. L. Richards, M. Wu, J. T. Lis.

218/3:00 RNA-seq transcriptome profiling uncovers how structural variants influence alternative splicing. E. Ait Yahya Graison, A. Necsulea, A. Reymond.

219/3:15 Exploring regulatory and loss-of-function variation in personalized multi-tissue transcriptomes using allele-specific expression. T. Lappalainen, M. A. Rivas, M. Lek, M. Pirinen, J. Maller, K. Kukurba, E. Tsang, D. DeLuca, M. Sammeth, Geuvadis Consortium, M. I. McCarthy, C. D. Bustamante, S. B. Montgomery, K. Ardlie, D. G. MacArthur, E. T. Dermitzakis, GTEx Consortium.

220/3:30 Analysis of the genetic variation and age interplay on gene expression using RNA-seq data from multiple tissues. A. Viñuela, M. N. Davies, A. Buil, A. A. Brown, H. F. Zheng, J. B. Richards, K. S. Small, R. Durbin, E. T. Dermitzakis, T. D. Spector.

221/3:45 Transcriptomes of individual cells. C. Borel, P. G. Ferreira, E. Falconnet, P. Ribaux, S. E. Antonarakis, E. T. Dermitzakis.

222/4:00 A low-frequency variant in a lincRNA doubles the risk of pneumococcal bacteraemia in Kenyan children. A. Rautanen, M. Pirinen, T. C. Mills, S. J. Chapman, V. Naranbhai, J. A. Scott, T. N. Williams, P. Donnelly, A. V. S. Hill, C. A. Spencer, Wellcome Trust Case Control Consortium 2.

Thursday, October 24

2:00 PM–4:15 PM

Concurrent Platform (abstract-driven) Session C (28-36)

SESSION 34 – Cardiovascular Genetics: Exome Sequencing and Animal Models

Room 258, Level 2, Convention Center

Moderators: Xiaofeng Zhu, Case Western Reserve Univ.
  Bart L. Loeys, Univ. of Antwerp

223/2:00 Identifying multiple causative genes at a single GWAS locus. M. Flister, S. Tsaih, B. Endres, A. Geurts, J. Lazar, M. Dwinell, C. Moreno, H. Jacob.

224/2:15 Gene silencing and haploinsufficiency of Csk in GWAS locus 15q24 increase blood pressure. B. Oh, H. Lee, S. Ji, S. Park, M. Kim, B. Jigden, J. Lim, Y. Lee.

225/2:30 A novel genetic basis for systemic vasculitis: Systemic and cutaneous polyarteritis nodosa are caused by recessive mutations in an immune-related gene. R. Segel, S. B. Pierce, P. Elkan-Navon, T. Walsh, S. Padeh, J. Barash, A. Zlotogorski, Y. Y. Berkun, J. J. Press, M. Mukamel, P. J. Hashkes, E. Ling, L. L. Harel, M. Tekin, F. Yalcinkaya, O. Kasapcopur, E. F. Emirogullari, M. K. Lee, R. E. Klevit, P. F. Renbaum, A. Weinberg-Shukron, S. Zeligson, D. Marek-Yagel, M. Shohat, A. Singer, E. Pras, A. A. Rubinow, Y. Anikster, M. C. King, E. Levy-Lahad.

226/2:45 BMP9 mutations cause a vascular anomaly syndrome with phenotypic overlap with hereditary hemorrhagic telangiectasia. J. McDonald, W. Wooderchak-Donahue, B. O'Fallon, P. Upton, W. Li, B. Roman, S. Young, P. Plant, G. Fülöp, C. Langa, N. Morrell, L. Botella, C. Bernabeu, D. Stevenson, J. Runo, P. Bayrak-Toydemir.

227/3:00 Identification of a novel cause of X-linked heterotaxy. M. Tariq, A. E. Cast, J. W. Belmont, S. M. Ware.

228/3:15 Novel and recurrent gain-of-function mutation in PRKG1 causes thoracic aortic aneurysms and acute aortic dissections. D. Guo, E. Regalado, D. E. Casteel, R. L. Santos-Cortez, L. Gong, J. J. Kim, S. Dyack, S. G. Horne, G. Chang, G. Jondeau, C. Boileau, J. S. Collelli, Z. Li, S. M. Leal, J. Shendure, M. J. Rieder, M. J. Bamshad, D. A. Nickerson, C. Kim, D. M. Milewicz, GenTAC Registry Consortium; NHLBI-Go Exome Sequencing Project.

229/3:30 Mutations in the DCHS1 gene cause mitral valve prolapse in humans. R. Durst, D. S. Peal, A. deVlaming, M. Leyne, M. Talkowski, M. Perrocheau, C. Jett, C. Simpson, M. R. Stone, F. Charles, C. Chiang, J. A. Rosenfeld, X. Jeunemaitre, A. Hagege, N. Bouatia-Naji, F. N. Delling, LA. Freed, C. Dina, J. J. Schott, K. D. Irvine, Y. Mao, K. Sauls, A. Wessels, T. Motiwala, K. Williams, R. R. Markwald, R. A. Levine, D. J. Milan, R. A. Norris, S. A. Slaugenhaupt.

230/3:45 Robust epistasis between the genes encoding a TGFβ effector and its regulatory microRNA governs modification of cardiovascular phenotypes in TGFβ vasculopathies. J. Calderon, H. Dietz.

231/4:00 ERK activation unifies deleterious gene-by-gene and gene-by-environment interactions in Marfan syndrome. J. J. Doyle, A. J. Doyle, N. Wilson, D. Bedja, J. Pardo-Habashi, L. Myers, K. Braunstein, N. Huso, S. Bachir, O. Squires, B. Rusholme, A. George, M. Lindsay, D. Huso, C. Thomas, D. Judge, H. C. Dietz.

Thursday, October 24

2:00 PM–4:15 PM

Concurrent Platform (abstract-driven) Session C (28-36)

SESSION 35 – Genomic Medicine: Counseling, Education and Health Services

Grand Ballroom AB, Concourse Level, Westin Boston Waterfront Hotel

Moderators: Wendy Uhlmann, Univ. of Michigan
  Katherine Kim, Lurie Children's Hosp. of Chicago

232/2:00 Reasons why patients decline whole genome sequencing in the MedSeq Project. D. M. Lautenbach, J. L. Vassy, K. D. Christensen, A. L. McGuire, H. L. Rehm, M. F. Murray, C. Y. Ho, C. A. MacRae, C. E. Seidman, R. M. Miller, C. Liu, R. C. Green.

233/2:15 How do research participants perceive "uncertainty" in genomic sequencing? B. Biesecker, L. Biesecker, P. Han.

234/2:30 Factors influencing healthcare utilization in response to personal genetic testing. S. S. Kalia, K. D. Christensen, C. A. Chen, J. L. Mountain, T. A. Moreno, J. S. Roberts, R. C. Green, for PGen Study Group.

235/2:45 Does personal genome testing drive service utilization in an adult preventive medicine clinic? N. Hoang, R. Hayeems, J. Davies, L. Velsher, J. Aw, S. Pu, S. Wodak, S. Chenier, J. Stavropoulos, R. Babul-Hirji, R. Weksberg, C. Shuman.

236/3:00 Opportunity and cost of clinical whole genome sequencing. F. Dewey, M. Grove, C. Pan, B. Goldstein, J. Bernstein, H. Chaib, R. Goldfeder, K. Ormond, C. Caleshu, K. Kingham, T. Klein, M. Whirl-Carrillo, K. Sakamoto, M. Wheeler, A. Butte, J. Ford, L. Boxer, J. Ioannidis, A. Yeung, R. Altman, T. Assimes, M. Snyder, E. Ashley, T. Quertermous.

237/3:15 Cost-effectiveness analysis of next-generation sequencing in etiologic evaluations for prelingual hearing loss. M. E. Nunes, N. T. Manzano, J. L. Natoli, K. A. Wendt.

238/3:30 Documentation of medical decision-making for genetic testing in the health record. M. T. Scheuner, J. Peredo, T. J. Sale, B. T. Tran, A. T. Jones, A. B. Hamilton, L. Hilborne, I. M. Lubin.

239/3:45 Medical genetics and genomics: Parallel revolutions in science and undergraduate medical education. S. Dasgupta, K. Hyland, K. Garber, J.-A. Gold, H. Toriello, K. Weissbecker, D. Waggoner.

240/4:00 Genomic medicine in primary care: Views of Ontario family physicians. S. Morrison, J. Allanson, F. A. Miller, J. A. Permaul, B. J. Wilson, J. C. Carroll.

Thursday, October 24

2:00 PM–4:15 PM

Concurrent Platform (abstract-driven) Session C (28-36)

SESSION 36 – Biochemical and Clinical Consequences of Mitochondrial Dysfunction

Grand Ballroom CDE, Concourse Level, Westin Boston Waterfront Hotel

Moderators: Nancy E. Braverman, McGill Univ.
  Devin Oglesbee, Mayo Clin.

241/2:00 Phenotype and genotype in 17 patients with succinate-CoA ligase deficiency caused by mutations in SUCLA2 and SUCLG1. E. Oestergaard, M. Rasmussen, H. Amartino, I. F. de Coo, D. C. Buhas, S. Mesli, K. Naess, M. Tulinius, N. Darin, M. Duno, P. Jouvencel, I. Redonnet-Vernhet, F. Wibrand, E. Holme.

242/2:15 Restoration of the mitochondrial citrate transporter by overexpression of SLC25A1 in primary deficient fibroblasts of patients with combined D-2- and L-2-hydroxyglutaric aciduria. G. S. Salomons, E. A. Struys, A. Pop, E. E. Jansen, M. R. Fernandez Ojeda, W. A. Kanhai, M. Kranendijk, S. J. M. van Dooren, M. R. Bevova, E. A. Sistermans, A. W. M. Nieuwint, M. Barth, T. Ben-Omran, G. F. Hoffmann, P. de Lonlay, M. T. McDonald, A. Meberg, A. C. Mühlhausen, C. Muntau, J.-M. Nuoffer, R. Parini, M.-H. Read, A. Renneberg, R. Santer, T. Strahleck, E. van Schaftingen, M. S. van der Knaap, C. Jakobs, B. Nota.

243/2:30 Unprocessed RNA intermediates interfere with mitochondrial translation and cause respiratory chain deficiency. R. Kopajtich, T. B. Haack, P. Freisinger, T. Wieland, J. Rorbach, T. J. Nicholls, E. Baruffini, A. Walther, K. Danhauser, F. A. Zimmermann, R. A. Husain, H. Mundy, I. Ferrero, T. M. Strom, T. Meitinger, R. W. Taylor, M. Minczuk, J. A. Mayr, H. Prokisch.

244/2:45 Mutations in the cytochrome c1 subunit of respiratory chain complex III cause insulin-responsive hyperglycemia and recurrent ketoacidosis. J. Christodoulou, P. Gaignard, M. Menezes, M. Schiff, A. Bayot, M. Rak, H. Ogier de Baulny, C.-H. Su, M. Gilleron, A. Lombes, H. Abida, A. Tzagoloff, L. Riley, S. T. Cooper, K. Mina, M. R. Davis, R. J. N. Allcock, N. Kresoje, N. G. Laing, D. R. Thorburn, A. Slama, P. Rustin.

245/3:00 Mutations in FBXL4 cause mitochondrial encephalopathy and a disorder of mitochondrial DNA maintenance. R. W. Taylor, J. W. Yarham, A. Besse, P. Wu, E. A. Faqeih, A. M. Al-Asmari, M. A. M. Saleh, W. Eyaid, A. Hadeel, L. He, F. Smith, S. Yau, E. M. Simcox, S. Miwa, T. Donti, K. K. Ab-Amero, L.-J. Wong, W. J. Craigen, B. H. Graham, K. L. Scott, R. McFarland, P. E. Bonnen.

246/3:15 A lipomatosis endophenotype in methylmalonic acidemia: Evidence from patients and mice. I. Manoli, J. R. Sysol, M. K. Crocker, G. Niu, J. Storrar, S. Mendelson, J. L. Sloan, C. Wang, Y. Ktena, P. M. Zerfas, V. Hoffman, H. J. Vernon, A. Hamosh, J. C. Reynolds, X. Chen, O. Gavrilova, J. A. Yanovski, C. P. Venditti.

247/3:30 Moonlighting in mitochondria: ACAD9 plays a dual role in energy metabolism. M. Schiff, B. M. Haberberger, E. S. Goetzman, A. W. Mohsen, H. Prokisch, J. Vockley.

248/3:45 Primary ovarian insufficiency is caused by recessive partial loss-of-function mutations in genes for mitochondrial protein homeostasis. S. B. Pierce, T. Walsh, S. Gulsuner, M. K. Lee, M.-C. King.

249/4:00 mtDNA mutations variously impact mtDNA maintenance throughout the human embryo/fetal development. S. Rondeau, S. Monnot, P. Vachin, E. Herzog, B. Bessiere, N. Gigarel, D. Samuels, L. Hesters, N. Frydman, G. Chalouhi, S. Gobin Limballe, M. Rio, A. Rotig, A.-S. Lebre, A. Benachi, L. Salomon, A. Munnich, J.-P. Bonnefont, J. Steffann.

Thursday, October 24

4:30 PM–6:30 PM

Concurrent Invited Session II (37-43)

SESSION 37 – Community Efforts to Decipher the Phenotypic Impact of Genomic Variation

Grand Ballroom West, Level 3, Convention Center

Moderators: David H. Ledbetter, Geisinger Hlth. Syst., Danville, PA
  Joyce A. Mitchell, Univ. of Utah

Significant decreases in the cost of sequencing have led to the generation of large amounts of genomic data from patients, both in the research and clinical settings. However, as more and more variants are identified in individuals with and without disease, interpreting these variants has become a bottleneck, particularly given that a massive percentage of genetic variation is rare or weak in its effect. It has become clear that the only path forward is to enable a broad community effort in data sharing. This session will address the critical components of data sharing needed to support a community effort in deciphering the phenotypic impact of genomic variation. Speakers will cover the development of standards for documenting phenotypes and classifying variants with respect to pathogenicity. Speakers will also provide an update on NCBI's public resources, including the ClinVar database, as a mechanism for data sharing. Progress on populating the database with useful data and optimizing it for use in advancing genomic medicine will be discussed.


4:30 PM   Developing approaches to support the community in the evaluation, deposition and curation of genomic variants. C. L. Martin. Geisinger Hlth. Syst., Danville, PA.

5:00 PM   Assessing the evidence for causality of sequence variants: Establishing community standards. D. MacArthur. Massachusetts Gen. Hosp.

5:30 PM   Developing standards to represent human phenotypes. A. Hamosh. Johns Hopkins Univ. Sch. of Med.

6:00 PM   Using ClinVar as a resource to evaluate genomic variation: A clinical laboratory's perspective. S. J. Bale. GeneDx Inc., Gaithersburg, MD.

Thursday, October 24

4:30 PM–6:30 PM

Concurrent Invited Session II (37-43)

SESSION 38 – Genetics of Non-communicable Diseases in sub-Saharan Africa

Room 258, Level 2, Convention Center

Moderators: Eleftheria Zeggini, Wellcome Trust Sanger Inst., Hinxton, U.K.
  Adebowale Adeyemo, NHGRI/NIH

Genome-wide association studies (GWAS) have revolutionized the field of complex trait genetics but the vast majority of GWAS conducted to date have been carried out in populations of European descent. There is a widely-recognized paucity of well-powered genetic association studies in African populations, mainly driven by global inequalities in resources. Sustainable research infrastructure and enhanced collaborative networks for genomic studies supported by research funding bodies (e.g. through the H3Africa Initiative) are transforming the landscape. Pronounced genetic diversity across ethnic groups in sub-Saharan Africa (SSA), in conjunction with low levels of linkage disequilibrium (LD) and differences in haplotype structure, give rise to challenges when conducting large-scale genomic epidemiology studies in SSA populations. Emerging SSA GWAS can lead to novel discoveries and additionally inform strategies for designing powerful trans-ethnic meta-analysis and fine-mapping studies.


4:30 PM   The African Genome Variation Project. F. Tekola-Ayele. NHGRI/NIH.

5:00 PM   Developing genomic research in Africa: The case for sickle cell disease. J. Makani. Muhimbili Univ. of Hlth. and Allied Sci., Tanzania.

5:30 PM   Discovering podoconiosis susceptibility genes: From molecules to disease control for a neglected tropical disease. M. Newport. Brighton and Sussex Med. Sch.

6:00 PM   Genomic studies of cardiometabolic traits in sub-Saharan Africa. M. Sandhu. Wellcome Trust Sanger Inst., Hinxton, U.K.

Thursday, October 24

4:30 PM–6:30 PM

Concurrent Invited Session II (37-43)

SESSION 39 – Guilty by Annotation: The Role of Non-coding Variation in Phenotypic Variation and Disease

Grand Ballroom East, Level 3, Convention Center

Moderators: Stephen B. Montgomery, Stanford Univ.
  Emmanouil T. Dermitzakis, Univ. of Geneva

Functional genomic sequencing has highlighted extensive non-coding genome function. New transcribed sequences and protein-DNA binding regions have being increasingly identified en masse. To understand the impact of diverse genetic variation and somatic mutation, even those unique to single individuals, current and future studies will leverage information from these increasingly high-throughput functional genomics assays. Such information, when integrated together into models that predict trait predisposition will likely improve our ability to understand diverse etiologies of rare and complex disease. This session will discuss how genetic variation influences noncoding genome function through (1) expression genetic studies and (2) epigenetic studies and highlight how such information can be used to identify noncoding variants influencing or underlying (3) cancer, (4) loss of function variation and complex disease.


4:30 PM   Finding causal regulatory variants with genome and transcriptome sequencing. E. T. Dermitzakis. Univ. of Geneva.

5:00 PM   Regulatory genomics and epigenomics of complex disease genetics for fine-mapping and genome-wide integration. M. Kellis. MIT.

5:30 PM   Functional analysis of polymorphisms identified using genome-wide association studies. J. Taipale. Univ. of Helsinki.

6:00 PM   Interpreting loss-of-function variation and complex disease association using RNA-seq and ChIP-seq data. S. B. Montgomery. Stanford Univ.

Thursday, October 24

4:30 PM–6:30 PM

Concurrent Invited Session II (37-43)

SESSION 40 – Human Genetics of Common Infectious Diseases

Room 210, Level 2, Convention Center

Moderators: Laurent Abel, INSERM/Univ. Paris Descartes
  Erwin Schurr, McGill Univ.

Epidemiological and experimental evidence is accumulating to indicate that human genetics plays a major role in the development of infectious diseases after exposure to most microbes. Many studies have shown that rare life-threatening infectious diseases in children can result from Mendelian predispositions leading to selective susceptibility to a given microbe. However, the genetic determinism of most common infectious diseases, especially in adults, remains unclear and involves more complex genetic predisposition. Limited success has been achieved so far in the genetic dissection of common infectious diseases using genome-wide approaches such as GWAS or positional cloning strategies.) Alternative strategies are needed and will be discussed and illustrated in four major infectious diseases (HIV infection, malaria, tuberculosis and leprosy) such as: 1) decreasing genetic heterogeneity by focusing on subgroups of patients defined on the basis of individual/clinical factors (e.g. age and specific phenotypes in leprosy) or extrinsic factors (e.g. pathogen variability in tuberculosis); 2) searching for rare variants through high-throughput sequencing (in HIV infection); 3) using new approaches to define candidate regulatory regions (in tuberculosis and malaria); and 4) using HLA expression data as a quantitative trait to provide functional validation of initial association findings (HIV infection). The human genetic dissection of infectious diseases is of major importance to develop new approaches for prevention and treatment based on pathophysiology (e.g. boosting or restoring a specific immune response) at a time when the emergence and spread of new and drug-resistant infectious agents pose vital threats to humankind.


4:30 PM   Immunogenetic variation characterizing exceptional control of HIV. M. Carrington. Frederick Natl. Lab., Frederick, MD.

5:00 PM   Human genetics and the risk of infectious diseases. D. B. Goldstein. Duke Univ. Sch. of Med.

5:30 PM   Human genetics of leprosy: novel insights. E. Schurr. McGill Univ.

6:00 PM   Human genetic studies on tuberculosis and malaria. R. Horstmann. Bernhard Nocht Inst. for Trop. Med., Hamburg.

Thursday, October 24

4:30 PM–6:30 PM

Concurrent Invited Session II (37-43)

SESSION 41 – Informed Consent for Whole Genome Sequencing: Experience and Implications for Practice

Hall B2, Level 0 (Lower Level), Convention Center

Moderators: Stephanie M. Fullerton, Univ. of Washington Sch. of Med.
  Holly K. Tabor, Seattle Children's Hosp.

Whole genome sequencing (WGS), and related next-gen approaches to genetic investigation, have emerged as predominant research strategies with tremendous analytical and clinical promise. While the number of individuals whose genomes have been sequenced is expanding rapidly, best practice with respect to informed consent for such sequencing is not yet settled. Not only are the benefits and risks of involvement imperfectly understood, the near-certain prospect of generating clinically relevant findings must be communicated, and where possible, participant preferences with respect to the offer of particular types of findings solicited. Clearly conveying such complexities in a time-limited invitation to participate in research, and/or testing in a clinical setting, is challenging and important questions remain with regard to the types of information conveyed, the modes of communication employed, the expertise required of the individuals doing the consenting, the range of choices presented, and the ability to revisit consent preferences as the study unfolds. These and related challenges will be discussed, and empirical data on the efficacy and acceptability of specific approaches in a range of studies from the NHGRI and NCI supported Return of Result and Clinical Sequencing Exploratory Research Programs, will be presented.


4:30 PM   Research goals and informed consent in clinical genomics research. J. C. Sapp. NHGRI/NIH.

5:00 PM   Informed consent and its role in eliciting result return preferences. W. K. Chung. Columbia Univ.

5:30 PM   Consent, assent, and WGS studies of children. I. A. Holm. Boston Children's Hosp.

6:00 PM   Informed consent for large-scale clinical mutation testing: Anticipating the future. R. R. Sharp. Cleveland Clin.

Thursday, October 24

4:30 PM–6:30 PM

Concurrent Invited Session II (37-43)

SESSION 42 – Multimodal Treatment of Lysosomal Storage Diseases as a Portal to Emergent Genetic Therapies

Room 205, Level 2, Convention Center

Moderator: Ari Zimran, Shaare Zedek Med. Ctr., Jerusalem

The Orphan Drug Act, enacted 30 years ago, enabled sufferers of rare disorders to benefit from commitment of pharmaceutical companies to prioritize development of orphan drugs for circumscribed patient populations. Among the first options was intravenous Enzyme Replacement Therapy (ERT) for visceral signs and symptoms of Gaucher disease which has proven to be safe and effective (placental Ceredase® and recombinant Cerezyme®, Genzyme Corporation; Cambridge MA) as have the company's impressive international compassionate programs. Biosimilar ERT with VPRIV® (Shire HGT, Cambridge MA) and Elelyso® (Protalix Therapeutics, Carmiel Israel) were introduced prior to (FDA) regulatory approval (February 2010 and May 2012, respectively) because of a global shortage in Cerezyme supply. Nonetheless, despite their putative increased safety (e.g., lower antibody rates and non-mammalian system, respectively) and possible improved efficacy, these are also expensive and intravenous. Other modalities, particularly substrate reduction therapy (SRT) and pharmacological chaperones (PC) administered orally, may provide added safety, convenience, quality of life, and may prove to be considerably less costly. We will provide updated profiles on these different treatment modalities in the context of therapeutic models for other single gene disorders. Nevertheless, the availability of a specific therapy, especially for the patients who present at an early age, has altered the composite patient profiles of patients, for instance since the devastating and life-threatening sequelae are less likely to occur as early as they once did. Thus, the current concerns in the post-specific therapy era are radically different than heretofore and will be presented in the context of various LSDs.


4:30 PM   Enzyme replacement therapy. G. A. Grabowski. Cincinnati Children's Hosp.

5:00 PM   Substrate reduction therapy. G. Pastores. NYU Sch. of Med.

5:30 PM   Pharmacologic chaperones. O. Goker-Alpan. Ctr. for Clin. Trials, O&O Alpan, Fairfax, VA.

6:00 PM   Future perspectives. D. Elstein. Shaare Zedek Med. Ctr., Jerusalem.

Thursday, October 24

4:30 PM–6:30 PM

Concurrent Invited Session II (37-43)

SESSION 43 – Nonhuman Primate Genomics: Evolutionary Insights and Relevance to Human Phenotypes

Room 253, Level 2, Convention Center

Moderators: Jeffrey M. Kidd, Univ. of Michigan
  Tomas Marques-Bonet, CSIC-Univ. Pompeu Fabra, Barcelona

In the last 20 years, there have been tremendous advances in our understanding of the genetic diversity of the human species. However, a systematic effort to obtain comparable datasets for other primates species (great apes, Old World monkeys and New World monkeys) has been somewhat forgotten. Human variation can only be interpreted if we have a complete understanding of the biological processes that shape it. In the last years, greatly aided by advances in sequencing capacities, research in primate genomics has expanded such that the field of primate population genomics has emerged. The benefits of such efforts are multifaceted and include a variety of disciplines in biology including human evolution and the use of primates as model organisms to study human diseases. This symposium brings together expert talks from the broad categories of genome evolution, population genetics, and complex trait genetics to describe recent advances in primate population genomics and to relate the continued relevance of non-human primates for understanding human genetic diversity.


4:30 PM   Great ape versus human genetic diversity: The Great Ape Genome Project. T. Marques-Bonet. CSIC-Univ. Pompeu Fabra, Barcelona.

5:00 PM   Where ancestry runs deep: Ancient balancing selection in humans. M. Przeworski. Univ. of Chicago.

5:30 PM   Genomic insights into chromosomal evolution in Gibbons. L. Carbone. Oregon Hlth. & Sci. Univ.

6:00 PM   Mapping complex traits in non-human primates. N. Freimer. UCLA.

Thursday, October 24

6:45 PM–7:45 PM

SESSION 44 – ASHG Next: The Future of Genetics and the Future of Your Society

Room 253, Level 2, Convention Center

Moderators: Jeff Murray, Univ. of Iowa
  Cynthia C. Morton, Brigham and Women's Hosp

ASHG is currently engaged in strategic planning that will guide the Society for the next three to five years. Join fellow ASHG members, the elected leadership, and the staff to help chart the future of your professional society. Come prepared to discuss the role of ASHG in the future of human genetics and genetic medicine and to provide your thoughts on the annual meeting, the American Journal of Human Genetics, and new services for members.

This session will be an interactive session. Be sure to bring your fully-charged mobile device, with the audience response app downloaded. In advance of the session, go to the iTunes store, Android Market or Blackberry Market to download the ResponseWare app. You can also go to to participate or you can scan the QR code below. Enter ASHG as the session ID. Keypads are available to those without a mobile device.

Light refreshments will be available.


Friday, October 25

8:00 AM–10:15 AM

Concurrent Platform (abstract-driven) Session D (45-53)

SESSION 45 – Mo' Data, Mo' Problems?

Hall B2, Level 0 (Lower Level), Convention Center

Moderators: Luke Jostins, Oxford Univ.
  Christopher Brown, Univ. of Pennsylvania

250/8:00 Selecting likely causal genes, pathways and relevant tissues from genome-wide association studies of complex traits by data-driven expression-prioritized integration. T. H. Pers, J. Karjalainen, J. N. Hirschhorn, L. Franke, Genetic Investigation of ANthropometric Traits (GIANT) Consortium.

251/8:15 Non-targeted metabolite profiling in large human population-based studies: A new data analysis workflow and metabolome-wide association study of C-reactive protein. A. Ganna, T. Fall, W. Lee, C. D. Broeckling, J. Kumar, S. Hägg, P. K. E. Magnusson, J. E. Prenni, L. Lind, Y. Pawitan, E. Ingelsson.

252/8:30 Transcription factor and chromatin features predict genes associated with eQTLs. D. Y. Wang, A. Rendon, L. Wernisch.

253/8:45 Combining regulatory domain and genetic variation information to identify cell types, regulatory elements, and causal genetic variants that influence human disease. E. Schmidt, J. Chen, C. Willer, Metabochip GIANT-BMI and ICBP.

254/9:00 Genome-wide expression quantitative trait loci: Results from the NHLBI’s SABRe CVD Initiative. R. Joehanes, T. Huan, C. Yao, X. Zhang, S. Ying, M. Feolo, N. Sharopova, T. Przytycka, A. Sturcke, A. A. Schaffer, N. Heard-Costa, H. Chen, P. Liu, R. Wang, K. A. Woodhouse, N. Raghavachari, J. Dupuis, A. D. Johnson, C. J. O'Donnell, P. J. Munson, D. Levy.

255/9:15 A hierarchical multiscale model to infer transcription factor occupancy from chromatin accessibility data. A. Raj, H. Shim, Y. Gilad, M. Stephens, J. Pritchard.

256/9:30 Development of a methods-based proficiency test for next-generation sequencing. N. Aziz, J. Durtschi, Q. Zhao, L. Bry, D. Driscoll, J. Gibson, W. Grody, M. Hedge, G. Hoeltge, D. Leonard, J. Merker, L. Palicki, R. S. Robetorye, I. Schrijver, K. Weck, T. Hambuch, T. Harkins, D. Ballinger, K. Voelkerding.

257/9:45 An integrated nexus of >12,000 genome sequences and analysis tools facilitates novel gene discovery. J. Reid, A. Carroll, N. Veeraraghavan, C. Gonzaga-Jauregui, A. Morrison, T. Gambin, A. Sundquist, M. Bainbridge, M. Dahdouli, Z. Huang, A. Li, F. Yu, R. Daly, J. Lupski, G. Duyk, R. Gibbs, E. Boerwinkle.

258/10:00 Pulling out the 1%: Whole-genome in-solution capture for the targeted enrichment of ancient DNA sequencing libraries. C. D. Bustamante, M. L. Carpenter, J. D. Buenrostro, C. Valdiosera, H. Schroeder, M. E. Allentoft, M. Sikora, M. Rasmussen, S. Guillén, G. Nekhrizov, K. Leshkatov, D. Dimitrova, N. Theodossiev, D. Pettener, D. Luiselli, A. E. Moreno, S. Gravel, Y. Li, J. Wang, M. T. P. Gilbert, E. Willerslev, W. J. Greenleaf.

Friday, October 25

8:00 AM–10:15 AM

Concurrent Platform (abstract-driven) Session D (45-53)

SESSION 46 – Cancer Genomics

Grand Ballroom East, Level 3, Convention Center

Moderators: Michael Rossi, Emory Univ.
  Jun Z. Li, Univ. of Michigan

259/8:00 Network analysis of mutations across cancer types. M. D. M. Leiserson, F. Vandin, H.-T. Wu, J. Dobson, A. Gonzalez-Perez, D. Tamborero, N. Lopez-Bigas, B. Raphael.

260/8:15 The landscape of tumor suppressors in primary tumors. P. Van Loo, J. Cheng, H. K. M. Vollan.

261/8:30 Recurrent somatic mutation altering DNA-binding motif of transcription factor YY1 explains pathogenesis of insulin-producing adenomas. M. K. Cromer, M. Choi, C. Nelson-Williams, A. L. Fonseca, J. W. Kunstman, R. M. Korah, J. O. Overton, S. Mane, B. Kenney, C. D. Malchoff, P. Stalberg, G. Akerström, G. Westin, P. Hellman, T. Carling, P. Björklund, R. P. Lifton.

262/8:45 Somatic L1 retrotransposition occurs early during colorectal tumorigenesis. S. Solyom, A. D. Ewing, N. Baker, A. Gacita, L. D. Wood, S. J. Meltzer, B. Vogelstein, K. W. Kinzler, H. H. Kazazian.

263/9:00 Transcriptome sequence analysis of human colorectal cancer samples reveals cancer functional attributes. H. Ongen, T. F. Orntoft, J. B. Bramsen, B. Oster, L. Romano, A. Planchon, C. L. Andersen, E. T. Dermitzakis.

264/9:15 Comparative whole genome sequencing to identify candidate somatic driver mutations of Li-Fraumeni syndrome sarcomagenesis in humans and mice. J. Wong, L. C. Strong, G. Lozano, L. L. Bachinski, R. Krahe.

265/9:30 Comprehensive transcriptome and epigenome sequencing of hypoxic breast cancer reveals non-coding RNAs associated with clinicopathological features. H. Choudhry, J. Schodel, S. Oikonomopoulos, C. Camps, P. Ratcliffe, A. Harris, D. Mole, I. Ragoussis.

266/9:45 Addressing the complexity of cancer: Integrative genomic and transcriptomic analysis of 775 human cancer cell line reveals novel drivers and regulatory programs. A. C. Villani, C. Ye, A. Regev, N. Hacohen.

267/10:00 Diagnostic yield of clinical tumor exome sequencing for newly diagnosed pediatric solid tumor patients. D. W. Parsons, A. Roy, F. A. Monzon, D. H. López-Terrada, M. M. Chintagumpala, S. L. Berg, S. G. Hilsenbeck, T. Wang, R. A. Kerstein, S. Scollon, K. Bergstrom, U. Ramamurthy, D. A. Wheeler, C. M. Eng, Y. Yang, J. G. Reid, D. A. Muzny, R. A. Gibbs, S. E. Plon.

Friday, October 25

8:00 AM–10:15 AM

Concurrent Platform (abstract-driven) Session D (45-53)

SESSION 47 – Demography In and Out of Africa

Grand Ballroom West, Level 3, Convention Center

Moderators: Jeffrey M. Kidd, Univ. of Michigan
  Philip Awadalla, Univ. of Montreal

268/8:00 Simultaneous estimation of population size changes and splits times from population level resequencing studies. M. Forest, J. Marchini, S. Myers.

269/8:15 Inferring complex demographies from PSMC coalescent rate estimates: African substructure and the Out-of-Africa event. S. Gopalakrishnan, P. Grabowski, M. C. Turchin, B. Henn, J. Kidd, G. Perry, A. Gebremedhin, C. Beall, C. D. Bustamante, A. Di Rienzo, Y. Gilad, A. A. Palmer, J. K. Pritchard.

270/8:30 Out of Africa, which way? L. Pagani, T. Kivisild, S. Shiffels, A. Scally, Y. Chen, Y. Xue, P. Danecek, J. Maslen, M. Haber, R. Ekong, T. Oljira, E. Mekonnen, D. Luiselli, E. Bekele, P. Zalloua, C. Tyler-Smith.

271/8:45 Insights into the genetic architecture of African genomes: The African Genome Variation Project. I. Tachmazidou, for AGVP Investigators.

272/9:00 Genetic evidence for multiple episodes of population mixture in southern and eastern African history. J. Pickrell, N. Patterson, P. Loh, M. Lipson, B. Berger, M. Stoneking, B. Pakendorf, D. Reich.

273/9:15 Inferring the evolutionary history and the genetic basis of small stature in African Pygmies from whole-genome sequencing data. M. Sikora, E. Patin, H. Costa, K. Siddle, B. M. Henn, J. M. Kidd, R. Kita, M. C. Yee, P. Verdu, L. Barreiro, J. M. Hombert, E. Heyer, C. D. Bustamante, L. Quintana-Murci.

274/9:30 Reconstructing the population genetic history of the Caribbean. A. Moreno Estrada, S. Gravel, F. Zakharia, J. L. McCauley, J. K. Byrnes, C. R. Gignoux, P. Ortiz Tello, K. Sandoval, P. J. Norman, P. Parham, J. C. Martinez Cruzado, E. Gonzalez Burchard, M. L. Cuccaro, E. R. Martin, C. D. Bustamante.

275/9:45 Selective interference driven by variable recombination impacts mutation load in humans. J. Hussin, Y. Idaghdour, A. Hodgkinson, J.-C. Grenier, J.-P. Goulet, E. Gbeha, E. Hip-Ki, Y. Payette, C. Boileau, P. Awadalla.

276/10:00 Human population assembly and error-correction of sequence reads. Z. Iqbal, S. McCarthy, H. Zheng Bradley, C. Xiao, A. Marcketta, G. McVean.

Friday, October 25

8:00 AM–10:15 AM

Concurrent Platform (abstract-driven) Session D (45-53)

SESSION 48 – Fine-Mapping and Function of Candidate Loci

Room 210, Level 2, Convention Center

Moderators: Paivi Pajukanta, UCLA
  Soumya Raychaudhuri, Brigham and Women's Hosp.

277/8:00 Fine mapping of the MHC in >60,000 samples by the International IBD Genetics Consortium: Identification of multiple predisposing and protective variants that are mostly distinct between Crohn's disease and ulcerative colitis. P. Goyette, on behalf of International Inflammatory Bowel Disease Genetics Consortium (IIBDGC).

278/8:15 Mapping the shared and distinct HLA alleles for seropositive and seronegative rheumatoid arthritis. B. Han, S. Eyre, D. Diogo, J. Bowes, Y. Okada, L. Padyukov, R. Plenge, L. Klareskog, J. Worthington, P. K. Gregersen, P. I. W. de Bakker, S. Raychaudhuri.

279/8:30 Common genetic variants of autoimmunity confer susceptibility to candididemia. V. Magadi Gopalaiah, S. Cheng, M. D. Johnson, S. S. Smeekens, L. A. B. Joosten, J. R. Perfect, B. Kullberg, C. Wijmenga, M. G. Netea.

280/8:45 PXK and Lupus: Defining novel immunobiology for an SLE risk gene. S. E. Vaughn, I. T. W. Harley, C. Foley, L. C. Kottyan, K. M. Kaufman, J. B. Harley, SLEGEN.

281/9:00 Allelic heterogeneity of and interactions between polymorphic RET enhancers affecting Hirschsprung disease risk. S. Chatterjee, A. Kapoor, A. Chakravarti.

282/9:15 Identification of human craniofacial, thyroid and heart enhancers at the FOXE1 locus. A. C. Lidral, S. A. Bullard, R. A. Cornell, G. Bonde, A. Visel, L. M. Moreno, J. Machida, B. Amendt, M. L. Marazita.

283/9:30 Irf6 homeostasis is required for neurulation through a direct interaction with Tfap2a. Y. A. Kousa, H. Zhu, A. Kinoshita, W. D. Fakhouri, M. Dunnwald, R. R. Roushangar, T. J. Williams, B. A. Amendt, Y. Chai, R. H. Finnell, B. C. Schutte.

284/9:45 Deletion of a distant-acting enhancer on Chr16p13.3 causes recessive intractable diarrhea of infancy syndrome (IDIS). D. Oz-Levi, I. Bar-Joseph, T. Olender, E. K. Ruzzo, D. Yagel, H. Reznik-Wolf, A. Alkelai, R. Milgrom, C. Hartman, R. Shamir, R. Kleta, L. Pennacchio, D. B. Goldstein, E. Pras, Y. Anikster, D. Lancet.

285/10:00 The role of SIX6 in primary open-angle glaucoma. M. Ulmer, Y. Liu, E. Oh, Y. Liu, L. Pasquale, J. Wiggs, A. Ashley-Koch, R. Allingham, M. Hauser, NEIGHBORHOOD Consortium.

Friday, October 25

8:00 AM–10:15 AM

Concurrent Platform (abstract-driven) Session D (45-53)

SESSION 49 – New Genes and Disorders

Room 205, Level 2, Convention Center

Moderators: Howard P. Levy, Johns Hopkins Univ.
  David Sweetser, Massachusetts Gen. Hosp.

286/8:00 A dominant-negative GFI1B mutation causes autosomal dominant gray platelet syndrome. L. Van Laer, D. Monteferrario, N. A. Bolar, K. Hebeda, S. Bergevoet, H. Veenstra, B. Laros, M. MacKenzie, E. Fransen, G. Van Camp, F. Preijers, S. Salemink, W. van Heerde, G. Huls, J. H. Jansen, M. Kempers, B. A. van der Reijden, B. L. Loeys.

287/8:15 Identification of disease causing mutations in a new congenital neutrophil defect syndrome. T. Vilboux, A. Lev, M. C. Malicdan, S. Amos, R. Sood, Y. Anikster, C. Klein, W. A. Gahl, R. Somech.

288/8:30 A functional variant in the CFI gene confers a high risk of age-related macular degeneration. A. den Hollander, J. P. H. van de Ven, S. C. Nilsson, P. L. Tan, G. H. S. Buitendijk, T. Ristau, F. C. Mohlin, S. B. Nabuurs, F. E. Schoenmaker-Koller, D. Smailhodzic, P. A. Campochiaro, D. J. Zack, M. R. Duvvari, B. Bakker, C. C. Paun, C. J. F. Boon, A. G. Uitterlinden, S. Liakopoulos, B. J. Klevering, S. Fauser, M. R. Daha, N. Katsanis, C. C. W. Klaver, A. M. Blom, C. B. Hoyng.

289/8:45 Recurrent genomic mutation 507delT in three lipoid proteinosis (Urbach-Wiethe) pedigrees from central Iran. L. Youssefian, H. Vahidnezhad, M. Daneshpazhooh, S. Abdollahzadeh, H. Talari, C. Chams-Davatchi, S. Akhondzadeh, R. Mobasher, M. Tabrizi.

290/9:00 The neuronal endopeptidase ECEL1 is a frequent cause of autosomal recessive distal arthrogryposis associated with limited knee flexion, ptosis, and limb muscle and tongue atrophy. K. Dieterich, S. Quijano-Roy, N. Monnier, J. Zhou, J. Faure, D. Avila-Smirnow, R. Y. Carlier, C. Laroche, P. Marcorelles, S. Mercier, A. Megabarne, S. Odent, N. Romero, D. Sternberg, I. Marty, B. Estournet, P.-S. Jouk, J. Melki, J. Lunardi.

291/9:15 Expanding molecular basis for rasopathies: A new player? M. Ludwig, C. Y. Hung, J. L. McCauley, J. Dallman, E. J. Back, I. Mihalek, G. X. Shi, D. A. Andres, O. Bodamer.

292/9:30 MC3R modifies CF lung disease by increasing the level of CFTR. J. Park, J. Pilewski, D. Belchis, S. Blackman, G. R. Cutting.

293/9:45 Combined exome and whole-genome sequencing identifies mutations in ARMC4 as a cause of primary ciliary dyskinesia. A. Onoufriadis, A. Shoemark, M. Munye, C. James, E. M. Rosser, C. Bacchelli, S. L. Hart, M. Schmidts, J. E. Danke-Roelse, G. Pals, C. Hogg, E. M. K. Chung, UK10K, H. M. Mitchison.

294/10:00 Identification of novel molecular defects in chronic intestinal pseudo-obstruction. G. Romeo, E. Bonora, F. Bianco, L. Cordeddu, M. D'Amato, G. Lindberg, M. Bamshad, D. Nickerson, Z. Mungan, K. Cefle, S. Palanduz, S. Ozturk, T. Ozcelik, A. Gedikbasi, V. Stanghellini, R. Cogliandro, E. Boschetti, C. Graziano, M. Seri, R. De Giorgio, University of Washington Center for Mendelian Genomics (UW CMG).

Friday, October 25

8:00 AM–10:15 AM

Concurrent Platform (abstract-driven) Session D (45-53)

SESSION 50 – Neurodegenerative Disease and the Aging Brain

Room 253, Level 2, Convention Center

Moderators: Jake McCauley, Univ of Miami
  Christine Van Broeckhoven, Univ. of Antwerp

295/8:00 Rare highly penetrant variants of late onset Alzheimers disease. J. Rehker, R. Levy, R. Nesbitt, Q. Yi, B. Martin, D. Nickerson, W. Raskind, J. Shendure, Z. Brkanac.

296/8:15 The identification of high-penetrance variants in late-onset Alzheimer disease by whole exome sequencing in extended families. M. A. Kohli, B. W. Kunkle, A. C. Naj, L.-S. Wang, K. L. Hamilton, R. M. Carney, W. R. Perry, P. L. Whitehead, J. R. Gilbert, E. R. Martin, G. W. Beecham, R. P. Mayeux, J. L. Haines, L. A. Farrer, G. D. Schellenberg, S. Zuchner, M. A. Pericak-Vance, Alzheimer’s Disease Genetics Consortium (ADGC).

297/8:30 Functional rare genetic variation in Alzheimer’s disease: An exome-wide association study in the CHARGE consortium. J. Jakobsdottir, S. J. van der Lee, J. C. Bis, V. Chouraki, A. V. Smith, A. L. DeStefano, J. Brody, N. Amin, L. J. Launer, C. A. Ibrahim-Verbaas, S. Choi, A. Beiser, R. Au, P. A. Wolf, O. L. Lopez, M. A. Ikram, A. Hofman, A. G. Uitterlinden, D. Levy, C. J. O'Donnell, M. L. Grove, E. Boerwinkle, A. L. Fitzpatrick, B. Psaty, S. Seshadri, V. Gudnason, C. M. van Duijn.

298/8:45 Whole exome sequencing in early-onset Alzheimer disease families identifies rare variants in multiple Alzheimer-related genes and processes. B. W. Kunkle, M. A. Kohli, B. N. Vardarajan, C. Reitz, A. C. Naj, P. L. Whitehead, W. R. Perry, E. R. Martin, G. W. Beecham, J. R. Gilbert, L. A. Farrer, J. L. Haines, G. D. Schellenberg, R. P. Mayeux, M. A. Pericak-Vance, Alzheimer's Disease Genetics Consortium.

299/9:00 Integrated whole transcriptome and DNA methylation analysis identifies new gene network in Alzheimer disease. C. E. Humphries, M. A. Kohli, P. W. Whitehead, G. Beecham, D. C. Mash, M. A. Pericak-Vance, J. Gilbert.

300/9:15 Novel mutations uncovered from exome sequencing of Norwegian families with Parkinson's disease. M. Lin, J. Aasly, D. Evans, C. Vilarino-Guell, B. Shah, C. Szu Tu, H. Han, H. Sherman, C. Thompson, M. Toft, K. Wirdefeldt, A. C. Belin, M. S. Petersen, J. Trinh, V. Silva, F. Pishotta, M. Farrer, GEO-PD Consortium.

301/9:30 Gene-environment interaction reveals hidden heritability: Plasma vitamin D concentration and its interaction with vitamin D receptor gene polymorphisms in Parkinson disease. L. Wang, M. L. Evatt, L. Maldonado, W. R. Perry, J. C. Ritchie, G. W. Beecham, E. R. Martin, J. L. Haines, M. A. Pericak-Vance, J. M. Vance, W. K. Scott.

302/9:45 Genetic variants in longevity gene KLOTHO are associated with increased brain volumes in aging. J. S. Yokoyama, V. E. Sturm, L. W. Bonham, E. Klein, K. Arfanakis, L. Yu, G. Coppola, J. H. Kramer, D. A. Bennett, L. Mucke, B. L. Miller, D. B. Dubal.

303/10:00 ENIGMA2: Genome-wide scans of subcortical brain volumes in 16,125 subjects from 28 cohorts. S. Medland, Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium.

Friday, October 25

8:00 AM–10:15 AM

Concurrent Platform (abstract-driven) Session D (45-53)

SESSION 51 – Epigenetics: From Genomes to Genes

Room 258, Level 2, Convention Center

Moderators: Erica Davis, Duke Univ.
  Hans Bjornsson, Johns Hopkins Univ. Sch. of Med.

304/8:00 Epigenome-wide association studies in the era of meta-epigenomics. J. M. Greally, N. A. Wijetunga, F. Delahaye, Y. M. Zhao, A. Golden, J. C. Mar, F. H. Einstein.

305/8:15 Genome-wide DNA methylation analysis of uniparental disomy cases reveals many novel imprinted loci in the human genome. R. S. Joshi, P. Garg, C. Borel, F. Cheung, A. Guilmatre, A. J. Sharp.

306/8:30 Correlation between CpG DNA methylation levels in peripheral CD4+ T cells and brain in aging individuals. C. M. McCabe, L. L. Rosenkrantz, G. Srivastava, A. Kaliszewska, S. Imboywa, J. Schneider, D. A. Bennett, P. L. De Jager.

307/8:45 Genome-wide analysis of Mecp2 dependent DNA methylation and hydroxymethylation at base-resolution in neurons. K. E. Szulwach, M. Yu, X. Li, C. R. Street, C. He, P. Jin.

308/9:00 Random replication of the inactive X chromosome. A. Koren, S. A. McCarroll.

309/9:15 The epigenetic profile of the SOX9 regulatory region appears Y chromosome dependent. G. Houge, H. Lybæk.

310/9:30 Global reduction of 5-hydroxymethylcytosine in a FMR1 premutation mice model. B. Yao, L. Lin, C. Street, Z. Zalewski, J. Galloway, D. Nelson, P. Jin.

311/9:45 Coordination of engineered factors with TET1/2 promotes early stage epigenetic modification during somatic cell reprogramming. Y. Li, G. Zhu, F. Zhu, T. Wang, W. Jin, W. Mu, W. Lin, W. Tan, W. Li, Y. Feng, S. Warren, Q. Sun, D. Chen, P. Jin, State Key Lab. of Reproductive Biology and State Key Lab. of Biomembrane and Membrane Biotechnology.

312/10:00 SMCHD1 mutations in facioscapulohumeral muscular dystrophy type 2. R. J. L. F. Lemmers, M. P. Nieuwenhuizen, P. J. van der Vliet, M. Vos-Versteeg, J. Balog, J. J. Goeman, D. G. Miller, S. J. Tapscott, S. Saconni, R. Tawil, B. Bakker, S. M. van der Maarel.

Friday, October 25

8:00 AM–10:15 AM

Concurrent Platform (abstract-driven) Session D (45-53)

SESSION 52 – New Frontiers in Pharmacogenetics

Grand Ballroom AB, Concourse Level, Westin Boston Waterfront Hotel

Moderators: Joshua Lewis, Univ. of Maryland, Baltimore
  Eileen Dolan, Univ. of Chicago

313/8:00 A genome-wide meta-analysis of the response to inhaled bronchodilators among subjects with chronic obstructive pulmonary disease. M. Hardin, M. H. Cho, M. McDonald, E. Wan, D. A. Lomas, H. O. Coxson, L. D. Edwards, W. MacNee, J. Vestbo, J. C. Yates, A. Agusti, P. Calverley, B. Celli, C. Crim, S. Rennard, E. Wouters, P. Bakke, E. A. Regan, B. Make, A. Litonjua, J. E. Hokanson, J. D. Crapo, T. H. Beaty, E. K. Silberman, C. P. Hersh, ECLIPSE and COPDGene Investigators.

314/8:15 Genome-wide association study of opioid-induced vomiting in the 23andMe cohort. J. L. Mountain, N. Eriksson, J. Y. Tung, A. S. Shmygelska, H. L. McLoed, U. Francke, A. K. Kiefer, D. A. Hinds.

315/8:30 Transcriptome profiling of human airway smooth muscle cells stimulated with dexamethasone identifies CRISPLD2 as a regulator of steroid and immune response. B. E. Himes, X. Jiang, P. Wagner, R. Hu, B. Klanderman, Q. Duan, J. Lasky-Su, C. Nikolos, W. Jester, M. Johnson, R. A. Panettieri, Jr., K. G. Tantisira, S. T. Weiss, Q. Lu.

316/8:45 Potential of integrating human genetics and electronic medical records for drug discovery: The example of TYK2 and rheumatoid arthritis. D. Diogo, K. P. Liao, R. S. Fulton, R. R. Graham, J. Cui, J. C. Denny, T. Behrens, M. F. Seldin, P. K. Gregersen, E. Mardis, R. M. Plenge, The RACI, i2b2-Rheumatoid Arthritis, CORRONA.

317/9:00 Rare variants contribute to bronchodilator drug response in Latino children with asthma. D. G. Torgerson, K. A. Drake, C. R. Gignoux, J. M. Galanter, L. A. Roth, S. Huntsman, D. Hu, C. Eng, S. W. Yee, L. Lin, C. D. Campbell, E. E. Eichler, R. D. Hernandez, K. M. Giacomini, E. G. Burchard, GALA II Investigators.

318/9:15 Characterization of statin dose-response within electronic medical records. W. Q. Wei, Q. P. Feng, L. Jiang, M. S. Waitara, O. F. Iwuchukwu, D. M. Roden, M. Jiang, H. Xu, R. M. Krauss, J. I. Rotter, D. A. Nickerson, R. L. Davis, R. L. Berg, P. L. Peissig, C. A. McCarty, R. A. Wilke, J. C. Denny.

319/9:30 Genome-wide analysis of creatine kinase levels in statin-users. M. P. Dubé, R. Zetler, Y. Feroz Zada, V. Normand, I. Mongrain, N. Laplante, A. Barhdadi, G. Asselin, S. Provost, J. D. Rioux, S. deDenus, E. Kritikou, J. Turgeon, M. S. Phillips, J. C. Tardif.

320/9:45 The return of pharmacogenomic variants in the MedSeq Project: Reporting approach and physician response. J. B. Krier, H. M. McLaughlin, W. J. Lane, D. Metterville, I. Leshchiner, J. L. Vassy, C. MacRae, M. S. Lebo, D. Lautenbach, R. C. Green, H. L. Rehm.

321/10:00 Genetic evidence improves chances of drug discovery success. M. R. Nelson, H. Tipney, J. L. Painter, J. Shen, P. Nicoletti, Y. Shen, A. Floratos, P. C. Sham, M. J. Li, J. Wang, P. Agarwal, J. C. Whittaker, P. Sanseau.

Friday, October 25

8:00 AM–10:15 AM

Concurrent Platform (abstract-driven) Session D (45-53)

SESSION 53 – Genomic Approaches for Study of Rare Neurogenetic Disorders

Grand Ballroom CDE, Concourse Level, Westin Boston Waterfront Hotel

Moderators: Brunhilde Wirth, Univ. Hosp. Cologne
  Margit Burmeister, Univ. of Michigan

322/8:00 A novel mitochondrial SLC25A gene causes CMT and optic atrophy. A. J. Abrams, M. A. Gonzalez, A. P. Rebelo, I. J. Campeanu, F. G. Speziani, A. Nemeth, J. Dallman, S. Züchner.

323/8:15 Molecular defects in the motor adaptor BICD2 cause proximal spinal muscular atrophy with autosomal-dominant inheritance. K. Peeters, I. Litvinenko, B. Asselbergh, L. Almeida-Souza, T. Chamova, T. Geuens, E. Ydens, M. Zimoń, J. Irobi, E. De Vriendt, V. De Winter, T. Ooms, V. Timmerman, I. Tournev, A. Jordanova.

324/8:30 AMPD2 regulates de novo GTP synthesis and is mutated in a new form of pontocerebellar hypoplasia. V. Cantagrel, N. Akizu, J. Schroth, J. Van Vleet, N. Cai, K. Vaux, A. Crawford, J. S. Silhavy, F. M. Sonmez, F. Celep, A. Oraby, M. Zaki, R. Al-Baradie, E. Faqeih, E. Nickerson, S. Gabriel, T. Morisaki, E. W. Holmes, J. G. Gleeson.

325/8:45 Truncating mutations of MAGEL2 cause autism and Prader-Willi syndrome-like phenotypes. C. P. Schaaf, M. L. Gonzalez-Garay, F. Xia, L. Potocki, K. W. Gripp, B. Zhang, B. A. Peters, M. A. McElwain, R. Drmanac, A. L. Beaudet, C. T. Caskey, Y. Yang.

326/9:00 Defective ubiquitination underlies oligogenic cerebellar degeneration and reproductive endocrine axis defects. M. Kousi, D. Margolin, Y. M. Chan, V. Muto, S. Servidei, E. T. Lim, J. D. Schmahmann, M. Hadjivassiliou, J. E. Hall, I. Adam, A. Dwyer, L. Plummer, S. V. Aldrin, J. O'Rourke, A. Kirby, K. Lage, A. Milunsky, J. M. Milunsky, J. Chan, E. T. Hedley-Whyte, M. J. Daly, M. Tartaglia, S. B. Seminara, N. Katsanis.

327/9:15 Periventricular heterotopia in 6q terminal deletion syndrome: Role of the C6orf70 gene. V. Conti, A. Carabalona, E. Pallesi-Pocachard, E. Parrini, R. Leventer, E. Buhler, G. McGillivray, F. Michel, P. Striano, D. Mei, F. Watrin, S. Lise, A. Pagnamenta, J. Taylor, U. Kini, J. Clayton-Smith, F. Novara, O. Zuffardi, W. Dobyns, I. Scheffer, S. Robertson, S. Berkovic, A. Represa, D. Keays, C. Cardoso, R. Guerrini.

328/9:30 A gene implicated in the neurobehavioural abnormalities of Williams-Beuren syndrome, GTF2IRD1, encodes a novel epigenetic regulator. P. Carmona-Mora, J. Widagdo, F. Tomasetig, K. M. Taylor, Y. Cha, R.T-W Pang, N. A. Twine, M. R. Wilkins, P. W. Gunning, E. C. Hardeman, S. J. Palmer.

329/9:45 Targeted high-throughput sequencing of 220 genes identifies a high proportion of causative mutations in over 80 patients with undiagnosed intellectual disability. C. Redin, S. Le Gras, J. Lauer, A. Creppy, Y. Herenger, V. Geoffroy, Y. Alembik, M. Doco-Fenzy, B. Doray, P. Edery, S. El Chehadeh, L. Faivre, E. Flori, B. Isidor, G. Lesca, A. Masurel, B. Jost, J. Muller, B. Gérard, J. L. Mandel, A. Piton.

330/10:00 Genetic analysis and new gene discovery in nemaline myopathy. V. A. Gupta, G. Ravenscroft, R. Shaheen, E. J. Todd, L. C. Swanson, M. Shiina, K. Ogata, C. Hsu, N. F. Clarke, B. T. Darras, M. Farrar, A. Hashem, N. Manton, F. Muntoni, K. N. North, S. Sandaradura, I. Nishino, Y. K. Hayashi, C. A. Sewry, E. Thompson, T. W. Yu, C. A. Brownstein, R. Allcock, M. R. Davis, C. Wallgren-Petterson, N. Matsumoto, F. S. Alkuraya, N. G. Laing, A. H. Beggs.

Friday, October 25

2:00 PM–4:15 PM

Concurrent Platform (abstract-driven) Session E (54-62)

SESSION 54 – Hundreds of New GWAS Loci

Hall B2, Level 0 (Lower Level), Convention Center

Moderators: Ching-Ti Liu, Boston Univ.
  Orli Bahcall, Nature Genetics

331/2:00 Large scale meta analysis of 250,000 individuals reveals novel biological pathways involved in adult human height. T. Esko, A. R. Wood, S. Vedantam, J. Yang, T. H. Pers, S. I. Berndt, M. N. Weedon, G. Lettre, J. O'Connell, D. I. Chasman, G. Abecasis, M. E. Goddard, R. J. F. Loos, E. Ingelsson, P. M. Visscher, J. H. Hirschhorn, T. M. Frayling, on behalf of GIANT Consortium.

332/2:15 Opening the X files: Chromosome X-wide association study reveals new loci for fasting insulin and height and evidence for incomplete dosage compensation. T. Tukiainen, M. Pirinen, A.-P. Sarin, C. Ladenvall, J. Kettunen, T. Lehtimäki, M.-L. Lokki, M. Perola, J. Sinisalo, E. Vlachopoulou, J. G. Eriksson, L. Groop, A. Jula, M.-R. Järvelin, O. T. Raitakari, V. Salomaa, S. Ripatti.

333/2:30 Expanded and novel loci for A1c levels identified through a trans-ethnic meta-analysis approach in European and African American ancestry samples. E. Wheeler, M.-F. Hivert, C.-T. Liu, on behalf of MAGIC and AAGILE.

334/2:45 Genome-wide association study for serum metabolome reveals 57 associated loci for biomarkers of complex metabolic diseases. J. Kettunen, T. Haller, A. Demirkan, R. Rawal, T. Tukiainen, T. Esko, L. C. Karssen, C. Gieger, H. K. Dharuri, J. B. van Klinken, K. W. van Dijk, M. Waldenberger, M. Ala-Korpela, P. Soininen, A. J. Kangas, T. Lehtimäki, M. Perola, C. van Duijn, J. G. Eriksson, T. Illig, A. Metspalu, A. Jula, M.-R. Järvelin, J. Kaprio, O. Raitakari, V. Salomaa, A. Palotie, S. Ripatti.

335/3:00 Using correlated phenotypes to functionally classify GWAS loci. N. Eriksson, J. Y. Tung, D. A. Hinds.

336/3:15 Meta-analysis of SNP associations with body mass index in >339,000 individuals gives new genetic and biological insights into the underpinnings of obesity. E. K. Speliotes, A. E. Locke, S. Berndt, B. Kahali, A. Justice, T. Pers, J. Yang, F. Day, S. Gustafsson, C. Powell, S. Vedantam, D. C. Croteau-Chonka, T. Winkler, A. Scherag, I. Barroso, J. S. Beckmann, C. M. Lindgren, C. J. Willer, P. Visscher, K. L. Mohlke, K. E. North, E. Ingelsson, J. N. Hirschhorn, R. J. F. Loos, for GIANT Consortium.

337/3:30 Large-scale association analysis identifies novel loci associated with waist-to-hip ratio and suggests underlying biological mechanisms. D. Shungin, D. C. Croteau-Chonka, A. E. Locke, T. W. Winkler, T. Ferreira, R. Magi, T. H. Pers, A. E. Justice, R. J. Strawbridge, C. Fox, K. E. North, E. Speliotes, I. Heid, I. Barroso, R. J. Loos, L. A. Cupples, P. W. Franks, E. Ingelsson, A. Morris, K. L. Mohlke, C. M. Lindgren, on behalf of Genetic Investigation of ANthropometric Traits (GIANT) Consortium.

338/3:45 Chipping away at the common variant genetics of age related macular degeneration. L. G. Fritsche, on behalf of International AMD Genomics Consortium.

339/4:00 Genetics and biology of rheumatoid arthritis contribute to drug discovery. Y. Okada, D. Wu, C. Terao, K. Ikari, Y. Kochi, K. Ohmura, A. Suzuki, H. Yamanaka, J. Denny, J. Greenberg, R. Graham, M. Brown, S. Bae, J. Worthington, L. Padyukov, L. Klareskog, P. Gregersen, P. Visscher, K. Siminovitch, R. Plenge, RACI Consortium, GARNET Consortium.

Friday, October 25

2:00 PM–4:15 PM

Concurrent Platform (abstract-driven) Session E (54-62)

SESSION 55 – Impact of Bottlenecks and Population Growth on Rare Variation

Grand Ballroom East, Level 3, Convention Center

Moderators: Itsik Pe'er, Columbia Univ.
  Shamil Sunyaev, Brigham and Women's Hosp.

340/2:00 The Ashkenazi Jewish genome. S. Carmi, E. Kochav, K. Hui, X. Liu, J. Xue, F. Grady, S. Guha, K. Upadhyay, S. Mukherjee, B. M. Bowen, V. Joseph, A. Darvasi, K. Offit, L. Ozelius, I. Peter, J. Cho, H. Ostrer, G. Atzmon, L. Clark, T. Lencz, I. Pe'er.

341/2:15 Rare variant sharing reveals population histories. I. Mathieson, G. McVean.

342/2:30 High risk population isolate reveals low frequency variants predisposing to intracranial aneurysms. M. I. Kurki, E. I. Gaál, J. Kettunen, T. Lappalainen, V. Anttila, F. N. G. van 't Hof, M. von und zu Fraunberg, H. Lehto, A. Laakso, R. Kivisaari, T. Koivisto, A. Ronkainen, J. Rinne, L. A. L. Kiemeney, S. H. Vermeulen, M. Kaunisto, J. G. Eriksson, T. Lehtimäki, O. T. Raitakari, V. Salomaa, M. Gunel, E. T. Dermitzakis, Y. M. Ruigrok, G. J. E. Rinkel, M. Niemelä, J. Hernesniemi, S. Ripatti, P. I. W. de Bakker, A. Palotie, J. E. Jääskeläinen.

343/2:45 Rare variant association studies: What population genetics models teach us about power and study design. B. M. Neale, O. Zuk, E. Hechter, K. Samocha, M. J. Daly, S. Sunyaev, S. Schaffner, E. Lander.

344/3:00 Finnish founding bottleneck leads to excess of damaging loss-of-function variants with medically relevant associations. E. T. Lim, P. Würtz, A. S. Havulinna, P. Palta, T. Tukiainen, Sequencing Initiative Suomi Project.

345/3:15 A rare functional variant in APOC3 is associated with lipid traits and has risen in frequency in distinct population isolates. E. Zeggini, G. Dedoussis, L. Southam, A.-E. Farmaki, G. R. S. Ritchie, D.-K. Xifara, A. Matchan, K. Hatzikotoulas, N. W. Rayner, Y. Chen, C. Kiagiadaki, K. Panoutsopoulou, J. Schwartzentruber, L. Moutsianas, E. Tsafantakis, C. Tyler-smith, G. McVean, Y. Xue, I. Tachmazidou, UK10K Consortium.

346/3:30 The impact of recent human demography on deleterious mutation load and the genetic architecture of disease susceptibility. G. Sella, Y. Simons, M. C. Turchin, J. K. Pritchard.

347/3:45 Inferring ancient demography using whole-genome sequences from multiple individuals. M. Steinruecken, J. Kamm, Y. Song.

348/4:00 Inferring human population history and gene flow from multiple genome sequences. S. Schiffels, R. Durbin.

Friday, October 25

2:00 PM–4:15 PM

Concurrent Platform (abstract-driven) Session E (54-62)

SESSION 56 – Haplotypes, Imputation and Interactions

Grand Ballroom West, Level 3, Convention Center

Moderators: Josee Dupuis, Boston Univ. Sch. of Publ. Hlth
  Michael Nothnagel, Univ. of Cologne

349/2:00 A haplotype map derived from whole genome low-coverage sequencing of over 25,000 individuals. J. Marchini, on behalf of Haplotype Consortium.

350/2:15 Statistical estimation of haplotype sharing from unphased genotype data. D. Xifara, I. Mathieson, I. Tachmazidou, G. Dedoussis, L. Southam, K. Panoutsopoulou, K. Hatzikotoulas, E. Zeggini, G. McVean.

351/2:30 HapFABIA: Identification of very short segments of identity by descent via biclustering. S. Hochreiter, G. Povysil.

352/2:45 A new method for genotype calling and phasing for the 1000 Genomes Project leads to improved downstream imputation accuracy. O. Delaneau, A. Menelaou, J. Marchini, 1000 Genomes Project Consortium.

353/3:00 Identification of genetic epistasis in regulation of gene expression via variance expression quantitative trait loci. A. Brown, A. Buil, M. N. Davies, A. Viñuela, T. Lappalainen, H. F. Zheng, J. B. Richards, K. S. Small, T. D. Spector, E. T. Dermitzakis, R. Durbin.

354/3:15 Association and replication of SNP-SNP interactions for hundreds of gene expression phenotypes. A. Fish, W. Bush.

355/3:30 Gene-gene interaction analysis for next-generation sequencing. J. Zhao, Y. Zhu, M. Xiong.

356/3:45 Capturing the geographic and genetic components controlling individual genetic regulation of cardio-metabolic quantitative traits. Y. Idaghdour, J. P. Goulet, J. C. Grenier, E. Gbeha, A. Hodgkinson, V. Bruat, T. de Malliard, J. Hussin, E. Hip-Ki, P. Awadalla.

357/4:00 Identification of a set of highly constrained genes from exome sequencing data. K. E. Samocha, E. B. Robinson, B. M. Neale, M. J. Daly.

Friday, October 25

2:00 PM–4:15 PM

Concurrent Platform (abstract-driven) Session E (54-62)

SESSION 57 – Autism and Neurodevelopmental Disorders

Room 210, Level 2, Convention Center

Moderators: Santhosh Girirajan, Pennsylvania State Univ.
  Dimitrios Avramopoulos, Johns Hopkins Univ.

358/2:00 Utility of a strategic next-generation sequencing approach to genomic diagnosis of patients with neurodevelopmental disorders. S. Soden, C. Saunders, E. Farrow, N. Miller, L. Smith, D. Dinwiddie, A. Atherton, J. LePichon, B. Heese, A. Abdelmoity, N. Safina, A. Modrcin, L. Willig, S. Kingsmore.

359/2:15 De novo mutations in autism spectrum disorders revealed by whole genome sequencing. Y. H. Jiang, R. Yuen, X. Jin, M. Wang, N. Chen, X. Wu, J. Ju, J. Mei, Y. Shi, L. Zwaigenbaum, M. T. Carter, C. Chrysler, L. Drmic, L. Lau, D. Mercio, A. Thompson, M. Uddin, B. Thiruvahindrapuram, E. Anagnostou, S. Walker, R. Ring, J. Wang, C. Lajonchere, J. Wang, A. Shihi, P. Szatmari, H. Yang, G. Dawson, Y. Li, S. W. Scherer.

360/2:30 Recurrently mutated genes contribute to the risk for developing sporadic autism spectrum disorder. B. J. O'Roak, E. A. Boyle, K. T. Witherspoon, B. Martin, C. Lee, L. Vives, E. Karakoc, J. Hiatt, D. A. Nickerson, R. Bernier, J. Shendure, E. E. Eichler.

361/2:45 Identification of biological pathways associated with phenotypically-defined subgroups of autism spectrum disorders. O. J. Veatch, B. L. Yaspan, M. A. Pericak-Vance, J. L. Haines.

362/3:00 De novo mutation in the dopamine transporter gene associates dopamine dysfunction with autism spectrum disorder. N. G. Campbell, P. J. Hamilton, S. Sharma, K. Erreger, F. H. Herborg, C. Saunders, A. N. Belovich, E. H. Cook, U. Gether, H. S. Mchaourab, H. J. Matthies, A. Galli, J. S. Sutcliffe.

363/3:15 Analysis of synaptic function during neurogenesis and maturation in homogeneous populations of autism-affected GABAergic and glutamatergic neurons. B. A. DeRosa, K. C. Belle, J. M. Van Baaren, J. M. Lee, M. L. Cuccaro, J. M. Vance, M. A. Pericak-Vance, D. M. Dykxhoorn.

364/3:30 Disruption of the ASTN2 / TRIM32 locus at chr9q33.1 in gender modulated risk for autism, ADHD and other neurodevelopmental phenotypes. K. Tammimies, A. C. Lionel, A. K. Vaags, J. A. Rosenfeld, J. W. Ahn, A. Noor, C. K. Runke, V. Pillalamarri, M. T. Carter, C. Fagerberg, B. R. Lowry, M. J. Gazzellone, R. K. C. Yuen, S. Walker, B. A. Fernandez, D. Tolson, D. S. Cobb, P. A. Arnold, P. Szatmari, R. Schachar, C. R. Marshall, C. Brasch-Andersen, M. Speevak, M. Fichera, C. M. Ogilvie, D. J. Stavropoulos, Y. Shen, J. C. Hodge, M. E. Talkowski, S. W. Scherer.

365/3:45 TBC1D24, responsible for early-onset epilepsies associated with intellectual disabilities, plays a role in the formation and maturation of cerebral cortex. A. Falace, E. Buhler, M. Fadda, F. Watrin, P. Lippiello, E. Pallesi-Pocachard, P. Baldelli, F. Benfenati, F. Zara, A. Represa, A. Fassio, C. Cardoso.

366/4:00 Transcriptional consequences of 16p11.2 microdeletion/microduplication syndrome in human lymphoblasts and mouse cortex. I. Blumenthal, A. Ragavendran, S. Erdin, L. Klei, J. Guide, M. Stone, C. Ernst, J. Levin, V. Wheeler, K. Roeder, B. Devlin, J. F. Gusella, M. E. Talkowski.

Friday, October 25

2:00 PM–4:15 PM

Concurrent Platform (abstract-driven) Session E (54-62)

SESSION 58 – Cardiovascular Genetics: Functional Characterization and Clinical Applications

Room 205, Level 2, Convention Center

Moderators: Dan E. Arking, Johns Hopkins Univ. Sch. of Med.
  Myriam Fornage, Univ. of Texas Hlth Sci. Ctr. at Houston

367/2:00 A homozygous mutation in Smoothened, a member of the Sonic hedgehog (SHH)-GLI pathway is involved in human syndromic atrioventricular septal defect. W. S. Kerstjens-Frederikse, Y. Sribudiani, M. E. Baardman, L. M. A. Van Unen, R. Brouwer, M. van den Hout, C. Kockx, W. Van IJcken, A. J. Van Essen, P. A. Van Der Zwaag, G. J. Du Marchie Sarvaas, R. M. F. Berger, F. W. Verheijen, R. M. W. Hofstra.

368/2:15 Identification of PRDM16 as a disease gene for left ventricular non-compaction and the efficient generation of a personalized disease model in zebrafish. A.-K. Arndt, S. Schaefer, R. Siebert, S. A. Cook, H.-H. Kramer, S. Klaassen, C. A. MacRae.

369/2:30 Mutation and copy number variation of FOXC1 causes cerebral small vessel disease. C. R. French, S. Seshadri, A. L. Destefano, M. Fornage, D. J. Emery, M. Hofker, J. Fu, A. J. Waskiewicz, O. J. Lehmann.

370/2:45 Genetic association of common variants with a rare cardiac disease, the Brugada syndrome, in a multi-centric study. C. Dina, J. Barc, Y. Mizusawa, C. A. Remme, J. B. Gourraud, F. Simonet, P. J. Schwartz, L. Crotti, P. Guicheney, A. Leenhardt, C. Antzelevitch, E. Schulze-Bahr, E. R. Behr, J. Tfelt-Hansen, S. Kaab, H. Watanabe, M. Horie, N. Makita, W. Shimizu, P. Froguel, B. Balkau, M. Gessler, D. Roden, V. M. Christoffels, H. Le Marec, A. A. Wilde, V. Probst, J. J. Schott, R. Redon, C. R. Bezzina.

371/3:00 Loss-of-function mutations in CECR1, encoding adenosine deaminase 2, cause systemic vasculopathy with fever and early onset strokes. Q. Zhou, A. Zavialov, M. Boehm, J. Chae, M. Hershfield, R. Sood, S. Burgess, A. Zavialov, D. Chin, C. Toro, R. Lee, M. Quezado, A. Ombrello, D. Stone, I. Aksentijevich, D. Kastner.

372/3:15 Genetic influence on LpPLA2 activity at baseline as evaluated in the exome chip-enriched GWAS study among ~13600 patients with chronic coronary artery disease in the STABILITY (STabilisation of Atherosclerotic plaque By Initiation of darapLadIb TherapY) trial. L. Warren, L. Li, D. Fraser, J. Aponte, A. Yeo, R. Davies, C. Macphee, L. Hegg, L. Tarka, C. Held, R. Stewart, L. Wallentin, H. White, M. Nelson, D. Waterworth.

373/3:30 Genome-wide association study identifies common and rare genetic variants in caspase-1-related genes that influence IL-18 regulation in patients with acute coronary syndrome. A. Johansson, N. Eriksson, E. Hagström, C. Varenhorst, A. Åkerblom, M. Bertilsson, T. Axelsson, B. J. Barratt, R. C. Becker, A. Himmelmann, S. James, H. A. Katus, G. Steg, R. F. Storey, A. Syvänen, L. Wallentin, A. Siegbahn.

374/3:45 Prevalence and predictors of pneumothorax in patients with connective tissue disorders enrolled in the GenTAC (National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions) Registry. J. P. Habashi, G. L. Oswald, K. W. Holmes, E. M. Reynolds, S. LeMaire, W. Ravekes, N. B. McDonnell, C. Maslen, R. V. Shohet, R. E. Pyeritz, R. Devereux, D. M. Milewicz, H. C. Dietz, GenTAC Registry Consortium.

375/4:00 Surprising clinical lessons from targeted next-generation sequencing of thoracic aortic aneurysmal genes. B. Loeys, D. Proost, G. Vandeweyer, S. Salemink, M. Kempers, G. Oswald, H. Dietz, G. Mortier, L. Van Laer.

Friday, October 25

2:00 PM–4:15 PM

Concurrent Platform (abstract-driven) Session E (54-62)

SESSION 59 – Prenatal and Reproductive Genetics

Room 253, Level 2, Convention Center

Moderators: David Chitayat, Mount Sinai Hosp., Toronto
  Mary E. Norton, Stanford Univ.

376/2:00 Noninvasive fetal trisomy test: A large-scale clinical practice in 78,289 cases. F. Chen, X. Pan, X. Li, H. Ge, S. Chen, H. Jiang.

377/2:15 Comparison of three single-cell whole genome amplification methods for detection of genomic aberrations by array CGH: A step towards noninvasive prenatal diagnosis using intact fetal cells. A. Breman, W. Bi, C. A. Shaw, I. Van den Veyver, C. J. Shaw, A. Stubbs, M. Withers, G. Fruhman, A. Patel, J. R. Lupski, A. Beaudet.

378/2:30 Next-generation sequencing based preimplantation genetic testing of 24-chromosome aneuploidy and monogenic disorders. N. R. Treff, X. Tao, A. Fedick, D. Taylor, K. H. Hong, E. J. Forman, R. T. Scott, Jr.

379/2:45 Genetic normalization of differentiating aneuploid cleavage stage embryos. P. R. Brezina, R. Ross, A. T. Benner, R. P. Dicky, R. Kaufmann, R. Anchan, Y. Zhao, A. Barker, K. J. Tobler, G. R. Cutting, W. G. Kearns.

380/3:00 Maternal age dependent loss of SMC1β transcripts in human oocytes. V. Jobanputra, S. K. Nurudeen, M. Shirazi, R. W. Prosser, A. Naini, J. K. Kline, M. V. Sauer, D. Warburton.

381/3:15 A clinical algorithm for efficient, high-resolution cytogenomic analysis of uncultured perinatal tissue samples: Study of more than 700 cases. G. Maire, A. Xuan Tong Yu, E. Kolomietz.

382/3:30 Whole genome oligonucleotide-SNP arrays in prenatal diagnosis: advancement in identification of clinically significant chromosomal abnormalities. T. Sahoo, L. P. Ross, K. A. Kopita, L. W. Mahon, J.-C. J. Wang, M. Hemmat, B. T. Wang, F. Z. Boyar, M. Haddadin, M. M. Elnaggar, R. Owen, A. Anguiano.

383/3:45 The fetal FMR1 premutation phenotype: Clues from the amniotic fluid transcriptome. L. M. Zwemer, S. L. Nolin, P. Okamoto, M. Eisenberg, D. W. Bianchi.

384/4:00 The wide spectrum of alpha and beta-tubulinopathies in foetus : From microlissencephaly to asymmetrical multifocal polymicrogyria. N. Bahi-Buisson, K. Poirier, C. Fallet-Bianco, Y. Saillour, S. Valence, N. Lebrun, M. Ossando, F. Razavi, T. Attie Bittach, F. Guimot, S. Blesson, B. Doray, B. Lhermitte, E. Andrini, P. S. Jouk, C. Rouleau, M. C. Addor, F. Jossic, P. Marcorelles, L. Loeuillet, A. Gelot, A. Laquerriere, L. Pinson, P. Loget, F. Chapon, P. Dias, N. Revencu, F. J. Fourniol, C. Beldjord, J. Chelly.

Friday, October 25

2:00 PM–4:15 PM

Concurrent Platform (abstract-driven) Session E (54-62)

SESSION 60 – Ethical, Legal, Social and Policy Issues

Room 258, Level 2, Convention Center

Moderators: Dawn Allain, The Ohio State Univ.
  Barbara Biesecker, NHGRI/NIH

385/2:00 Practical assessment of incidental finding recommendations for use in clinical exome testing. M. C. Dulik, E. T. DeChene, L. K. Conlin, S. Mulchandani, A. Santani, J. L. Abrudan, M. J. Italia, M. Sarmady, J. C. Perin, B. Bernhardt, C. A. Stolle, R. E. Pyeritz, A. Wilkens, S. E. Noon, P. S. White, I. D. Krantz, N. B. Spinner.

386/2:15 Individual expectations for return of secondary results from exome sequencing. H. K. Tabor, J. Crouch, A. A. Lemke, K. M. Dent, A. G. Shankar, S. M. Jamal, J. H. Yu, M. J. Bamshad.

387/2:30 The benefits and risks of wanting it all: How parents plan to manage their children’s exome sequencing results. J. Yu, J. Crouch, A. A. Lemke, A. G. Shankar, K. M. Dent, M. J. McMillin, S. M. Jamal, M. J. Bamshad, H. K. Tabor.

388/2:45 Evaluation of clinical utility of whole genome sequencing: The WGS500 programme. J. Taylor, G. McVean, A. Wilkie, J. Bell, P. Ratcliffe, D. Bentley, P. Donnelly, WGS500 Consortium.

389/3:00 International views on sharing incidental findings from whole genome research. A. Middleton, M. Parker, E. Bragin, C. F. Wright, H. V. Firth, M. Hurles, DDD Study.

390/3:15 No evidence for increase in screening among women given report of moderately higher than average risk for breast cancer from personal genomics services: The PGen Study. S. W. Gray, H. Q. Rana, S. Gollust, C. A. Chen, S. Kalia, J. Mountain, T. Moreno, J. S. Roberts, R. C. Green, for PGen Study Group.

391/3:30 Context is complex: Attitudes to incorporating genomic risk profiling into population screening programs. S. G. Nicholls, H. Etchegary, J. C. Carroll, D. Castle, L. Lemyre, B. K. Potter, J. Little, B. J. Wilson, on behalf of CIHR Emerging Team in Genomics and Screening.

392/3:45 How do citizens balance the benefits and burdens of newborn screening? A choice experiment. F. A. Miller, R. Z. Hayeems, Y. Bombard, C. Cressman, C. J. Barg, J. C. Carroll, B. Wilson, J. Little, D. Avard, J. Allanson, P. Chakraborty, Y. Giguere, D. A. Regier.

393/4:00 Identifying genetic relatives without compromising privacy. E. Eskin, D. He, N. Furlotte, R. Ostrovsky, A. Sahai.

Friday, October 25

2:00 PM–4:15 PM

Concurrent Platform (abstract-driven) Session E (54-62)

SESSION 61 – Genomics of Developmental Disorders

Grand Ballroom AB, Concourse Level, Westin Boston Waterfront Hotel

Moderators: Karen Avraham, Tel Aviv Univ.
  Margarit Urbanek, Northwestern Univ., Chicago

394/2:00 Targeted sequencing of GPI anchor synthesis pathway genes identifies a new causal gene of hyperphosphatasia with mental retardation. P. Krawitz, Y. Murakami, A. Riess, M. Hietala, U. Krueger, N. Zhu, T. Kinoshita, S. Mundlos, J. Hecht, P. Robinson, D. Horn.

395/2:15 1000 trio exomes: Insights into severe developmental disorders. M. Van Kogelenberg, T. Fitzgerald, W. Jones, J. C. Barret, M. Hurles, on behalf of DDD Project.

396/2:30 Atypical Rett Syndrome: Is it really more common in females? K. Cusmano-Ozog, P. Tanpaiboon, L. Harris, J. Turner, L. Kehoe, T. Biagi, B. Lanpher.

397/2:45 Common molecular networks in Rett, Angelman, Smith-Magenis, Potocki-Lupski, Pitt-Hopkins, and chromosome 2q23.1 deletion syndromes contribute to intellectual disability, seizures, sleep, language, behavior and autism spectrum disorder. S. V. Mullegama, B. Burns, Z. Shah, R. Tahir, W.-H. Tan, S. H. Elsea.

398/3:00 MBD5 deletion disrupts circadian gene expression and is associated with sleep disturbance in the 2q23.1 deletion syndrome. S. H. Elsea, S. V. Mullegama, Z. Shah, R. Tahir, L. Pugliesi.

399/3:15 Lysyl-tRNA synthetase (KARS) mutations cause autosomal recessive nonsyndromic hearing impairment DFNB89. R. Santos-Cortez, K. Lee, Z. Azeem, P. J. Antonellis, L. M. Pollock, S. Khan, Irfanullah, P. B. Andrade-Elizondo, I. Chiu, M. D. Adams, S. Basit, J. D. Smith, D. A. Nickerson, B. M. McDermott, Jr., W. Ahmad, S. M. Leal, Univ. of Washington Ctr. for Mendelian Genomics.

400/3:30 Multiple de novo variants resulting in combined axial hypotonia with dyskinesia and facial myokymia. A. Torkamani, J. Friedman, C. S. Bloss, S. Topol, E. J. Topol, Q. Chen, N. J. Schork, W. H. Raskind, A. Torkamani.

401/3:45 Dominant β-catenin mutations cause intellectual disability with recognizable syndromic features. T. Kleefstra, V. Tucci, M. H. Willemsen, A. Hardy, I. Heise, S. Maggi, W. Wissink-Lindhout, A. Vulto-van Silfhout, B. B. A. deVries, Z. Iqbal, H. G. Brunner, W. N. Nillesen, H. G. Yntema, H. Hilton, M. Simon, S. Tsaftaris, H. van Bokhoven, A. Constestabile, T. Nieus, A. Raimondi, B. Greco, D. Cantatore, L. Gasparini, L. Berdondini, A. Bifone, J. Veltman, L. Peart-Vissers, A. Gozzi, S. Wells, P. M. Nolan.

402/4:00 Defective initiation of glycosaminoglycan synthesis due to B3GALT6 mutations causes a pleiotropic Ehlers-Danlos syndrome-like connective tissue disorder. F. Malfait, A. Kariminejad, T. Van Damme, C. Gauche, D. Syx, F. Merhi-Soussi, S. Gulberti, S. Symoens, S. Vanhauwaert, A. Willaert, B. Bozorgmehr, M. Kariminejad, I. Hausser, S. Fournel-Gigleux, A. De Paepe.

Friday, October 25

2:00 PM–4:15 PM

Concurrent Platform (abstract-driven) Session E (54-62)

SESSION 62 – Prostate and GI Cancer Susceptibility

Grand Ballroom CDE, Concourse Level, Westin Boston Waterfront Hotel

Moderators: Gail Jarvik, Univ. of Washington
  Liesel M. FitzGerald, Cancer Epidemiol. Ctr.

403/2:00 Whole exome sequencing of 2126 African American prostate cancer cases and controls from the Multiethnic Cohort. K. A. Rand, N. Rohland, A. Tandon, R. Do, X. Sheng, D. V. Conti, B. E. Henderson, C. A. Haiman, D. Reich.

404/2:15 Identification of Y chromosomes associated with risk for prostate cancer. L. A. Cannon-Albright, J. M. Farnham, C. C. Teerlink, R. A. Stephenson.

405/2:30 Genome-wide scan identifies a novel locus associated with aggressive prostate cancer. S. I. Berndt, Z. Wang, M. Yeager, W. R. Diver, S. Gapstur, V. L. Stevens, D. Albanes, S. Weinstein, J. Virtamo, J. Cornu, O. Cussenot, G. Cancel-Tauset, S. Lindström, P. Kraft, D. Hunter, L. Amundadottir, A. Black, J. Sampson, K. Jacobs, M. Tucker, S. J. Chanock.

406/2:45 Frequent germline mutations in DNA repair genes in familial prostate cancer cases. D. Leongamornlert, E. Saunders, T. Dadaev, M. Tymrakiewicz, C. Goh, S. Jugurnauth-Little, I. Kozarewa, K. Fenwick, I. Assiotis, D. Barrowdale, K. Govindasami, M. Guy, E. Sawyer, R. Wilkinson, A. Antoniou, R. Eeles, Z. Kote-Jarai.

407/3:00 Pleiotropic effect of rare mutation in HOXB13 on multiple cancers detected in a cohort of >100K individuals via imputation. J. Witte, T. Hoffmann, L. Sakoda, L. Shen, E. Jorgenson, M. Asgari, D. Corley, L. Habel, L. Kushi, M. Kwan, C. Schaffer, S. Van Den Eeden, N. Risch.

408/3:15 Detection of large rearrangements in PMS2. D. Mancini-DiNardo, J. W. Landon, S. Rajamani, K. Moyes, C. Arnell, I. Dorweiler, K. Bowles, B. Leclair, B. Roa.

409/3:30 Functional analysis of the chr13q22.1 pancreatic cancer risk locus suggests allele-specific effects on DIS3 expression. J. Hoskins, A. Ibrahim, H. Parikh, J. Kim, J. Jia, I. Collins, G. Petersen, L. Amundadottir.

410/3:45 Genome-wide association study of colorectal adenoma in the Nurses’ Health Study and the Health Professionals Follow-Up Study. A. D. Joshi, A. Hazra, C. Chen, R. B. Hayes, P. Kraft, U. Peters, A. T. Chan.

411/4:00 Large numbers of individuals required to classify and define risk for a rare VUS in known cancer risk genes. B. H. Shirts, A. G. Jacobsen, G. P. Jarvik, B. L. Browning.

Friday, October 25

4:30 PM–4:50 PM

SESSION 63 – ASHG Award for Excellence in Human Genetics Education Presentation

Hall B2, Level 0 (Lower Level), Convention 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.

Erin Carter
Hosp. for Spec. Surg., Weill Cornell Med. Col.


Jessica G. Davis, MD
Assoc. Prof.,Clin. Pediat., Weill Cornell Med. Col.
Assoc. Attending Pediatrician, New York-Presbyterian Hosp. and Hosp. for Spec. Surg.

Dr. Davis is being recognized for her passion and achievements in genetics education, which have had a profound influence on her patients and colleagues in clinical practice and training, including physicians, trainees, and genetic counselors. Her role in helping develop medical genetics is evident in her many accomplishments, which include the development of the Sarah Lawrence genetic counseling training program. Dr. Davis's support for counseling was essential to the establishment of genetic counseling as a discipline in the practice of human genetics. In addition, Dr. Davis has worked closely with several disease-specific advocacy groups, especially those involved with Marfan syndrome, directed outreach programs in New York State/Long Island for community-based clinicians, and taught genetics to high school teachers at the DNA Learning Center at the Cold Spring Harbor Laboratory.

"Long before ASHG officially acknowledged the high value of education, Dr. Davis's name was synonymous with education in medical and human genetics," said Roberta A. Pagon, MD, Professor of Pediatrics at the University of Washington, who helped to nominate Dr. Davis for the award. "Dr. Davis's contributions to education in human genetics reflect the hands-on, just-get-started approach of the days when formal programs and funding for education in genetics were almost non-existent. It was enterprising, dedicated, and caring educators such as Dr. Davis who laid the foundation for the educational efforts that we take for granted today."

Weill Cornell Medical College recognized Dr. Davis with its annual Award for Teaching Excellence in 2000.

Past Recipients: Alan E.H. Emery (2012); 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).


Friday, October 25

4:50 PM–5:30 PM

SESSION 64 – ASHG William Allan Award Presentation

Hall B2, Level 0 (Lower Level), Convention 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.

Evan E. Eichler, Univ. of Washington, Seattle

Aravinda Chakravarti, PhD
Prof., Depts. Med., Pediat., and Molec. Biol. and Genet., McKusick-Nathans Inst. of Genet. Med., Johns Hopkins Univ.

Dr. Chakravarti was chosen for this prestigious award for his many contributions to human genetics, ranging from population genetics to the molecular genetics of complex disease. In addition to developing several critical genomics methods that have been adopted by scientists worldwide, Dr. Chakravarti played a crucial role in the identification of the gene mutation associated with cystic fibrosis, the segmental aneuploidy for Charcot-Marie-Tooth type 1A and discovered common variants associated with susceptibility to autism. He pioneered linkage disequilibrium mapping to identify a recombination hotspot in the beta-globin locus and used these insights for identifying the key genes and non-coding enhancer mutations responsible for Hirschsprung disease, thereby elucidating its multifactorial basis. He helped to design and participate in the HapMap and 1000 Genomes Projects that sampled and analyzed human genetic variation across populations worldwide.

A member of the Institute of Medicine, Dr. Chakravarti chaired the sub-committee for the third-five-year plan for the Human Genome Project, from 1997 to 2000, as a member of the National Human Genome Research Institute's advisory council. He is co-Editor-in-Chief of Genome Research and the Annual Review of Genomics and Human Genetics, and a member of the editorial boards of numerous international journals such as the European Journal of Human Genetics and Journal of Genetics..

The Allan Award also recognizes Dr. Chakravarti's long-standing service to ASHG as a board member, president, and mentor to many members of the Society.

Past Recipients: Uta Francke (2012); 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, October 25

5:30 PM–6:30 PM

SESSION 65 – ASHG Membership and Business Meeting

Hall B2, Level 0 (Lower Level), Convention 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 2013. Discussion from the floor is encouraged.


Saturday, October 26

8:00 AM–8:20 AM

SESSION 66 – ASHG Victor A. McKusick Leadership Award Presentation

Hall B2, Level 0 (Lower Level), Convention Center

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

Joel N. Hirschhorn, Boston Children's Hosp., Harvard Med. Sch. and Broad Inst.


Kurt Hirschhorn, MD
Professorial Lecturer of Pediat., Human Genet., Med., and Genet. and Genomics Sci., Mount Sinai Sch. of Med.


Rochelle Hirschhorn, MD
Res. Prof. and Prof. Emerita of Med., Cell Biol. and Pediat., Dept. of Med., New York Univ., Langone Med. Ctr.

The McKusick Award honors the combined contributions of Drs. Kurt and Rochelle Hirschhorn, who have been members of ASHG for over 40 years and have provided dedicated leadership to the genetics community and the Society, including, service as president and member of the board of directors of ASHG (Kurt), the Program Committee (both), and AJHG's editorial board (both). Both also have been elected to the National Academy of Sciences' Institute of Medicine.

In 2010, Rochelle Hirschhorn was honored with the NYU Langone Medical Center's Master Scientist Award. Dr. Hirschhorn, who was the center's Chief of the Division of Medical Genetics for 24 years, has been a leader and role model in the advancement of women in medicine and genetics. In 1986, she was the first woman elected to the Interurban Clinical Club, founded in 1905, and soon thereafter was elected president of the group. Her major discoveries include clarifying the sequence of acid alpha glucosidase and most of its defects in Pompe Disease and delineating the genetic structure and pathophysiology of adenosine deaminase (ADA) deficiency, an autosomal recessive metabolic disorder that causes immunodeficiency. She also described the phenomenon of reverse mutations as a cause of "self-cure" in ADA deficient patients and predicted the utility of gene therapy for ADA deficiency. Rochelle was the Distinguished Alumna at Barnard College, which is awarded to only one alumna per year.

Kurt Hirschhorn has received multiple awards in genetics and pediatrics, including ASHG's Allan Award and Excellence in Education Award, the March of Dimes' Colonel Sanders Lifetime Achievement Award, and the Howland Award in Pediatrics. At Mount Sinai School of Medicine, he was the Chief of one of the first Divisions of Genetics for eight years and Chair of Pediatrics for 18 years. In addition to serving as a mentor to numerous trainees and faculty, he helped establish the first Master's level genetic counseling program at Sarah Lawrence College. His major scientific achievements include discovery, characterization, and application of the mixed-lymphocyte reaction and the early and sustained use of cytogenetics to discover and describe multiple human chromosomal disorders, including the Wolf-Hirschhorn syndrome, also called 4p- syndrome.

Drs. Hirschhorn, who have been married for over 60 years, have co-authored more than 20 papers or chapters published during the period 1959 to 2011, in addition to their many papers published independently.

Past Recipients: Francis S. Collins (2012); Leon E. Rosenberg (2011); Charles J. Epstein (2010); Arno G. Motulsky (2009); Victor A. McKusick (2008); Walter Nance (2007); David Rimoin (2006).


Saturday, October 26

8:20 AM–8:30 AM

SESSION 67 – C.W. Cotterman Awards Announcement

Hall B2, Level 0 (Lower Level), Convention 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.


Natalie Powers, Yale Univ.

Pier Francisco Palamara, Columbia Univ.


Saturday, October 26

8:30 AM–8:40 AM

SESSION 68 – ASHG Charles J. Epstein Trainee Awards for Excellence in Human Genetics Research: Announcement of Winners

Hall B2, Level 0 (Lower Level), Convention Center

Presenter: C. E. Pearson, Awards Committee ChairHosp. 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 to honor the late Dr. Charles Epstein.

63 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.


Saturday, October 26

8:40 AM–9:10 AM

SESSION 69 – ASHG Curt Stern Award Presentation

Hall B2, Level 0 (Lower Level), Convention 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.

Haig Kazazian, Johns Hopkins Univ.


John V. Moran, PhD
Prof. of Human Genet. and Int. Med., Dept. of Int. Med., Univ. of Michigan

Dr. Moran, a Howard Hughes Medical Institute Investigator, has been a leader in research on genome instability and the biology of DNA sequences that can "jump" to new genomic locations, known as Long INterspersed Element-1 (LINE-1 or L1) retrotransposons. Using an assay to monitor L1 mobility (i.e., retrotransposition) in cultured cells, Dr. Moran's laboratory has gained insights into the mechanism of human L1 retrotransposition, identified host factors that regulate L1 retrotransposition, and expanded our understanding of the impact of L1 retrotransposition on the human genome. Dr. Moran's research also has demonstrated the importance of L1 retrotransposition in shaping the human genome through evolutionary time, and has led to a greater appreciation of how ongoing L1 retrotransposition contributes to human genetic diversity.

The Curt Stern Award also recognizes Dr. Moran's mentorship of graduate students and postdoctoral researchers as well as his stalwart support of, and service to ASHG.

Past Recipients: Jay Shendure (2012); 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


Saturday, October 26

9:30 AM–11:30 AM

Concurrent Invited Session III (70-76)

SESSION 70 – Design, Content and EMR Integration of Clinical Sequencing Reports

Grand Ballroom West, Level 3, Convention Center

Moderators: Robert C. Green, Brigham and Women's Hosp./Harvard Med. Sch.
  Heidi L. Rehm, Partners Ctr. for Personalized Genet. Med., Cambridge, MA

This session will present data and describe recent developments in the design, content and implementation of clinical reports for exome and genome sequencing. Presenters will initially discuss how such a report may be designed, how much information it should present on primary and secondary findings and how accessible it should be to clinicians who are not genetic specialists. Data will be presented on how well clinicians understand and can effectively use such reports in clinical practice. As clinical sequencing becomes more common, the integration of such reports to the electronic medical record (EMR) will be critical. Data will be presented on how ongoing clinical genomics research programs are attempting to integrate findings with the EMR and on the usability of specific solutions to scaling such integration and providing decision support.


9:30 AM   Design and implementation of the General Genome Report. R. C. Green. Brigham and Women's Hosp./Harvard Med. Sch.

10:00 AM   Reporting results not directly related to the indication for testing. C. Eng. Baylor Col. of Med.

10:30 AM   Approaches to integrating next-generation sequencing into the electronic health record. P. Tarczy-Hornoch. Univ. of Washington.

11:00 AM   Scaling genomic reporting and clinical decision support. H. L. Rehm. Partners Ctr. for Personalized Genet. Med., Cambridge, MA.

Saturday, October 26

9:30 AM–11:30 AM

Concurrent Invited Session III (70-76)

SESSION 71 – More or Less: Copy Number Variation and Human Adaptation

Room 258, Level 2, Convention Center

Moderators: Chack-Yung Yu, The Ohio State Univ.
  Ed J. Hollox, Univ. of Leicester

Inter-individual copy number variation (CNV) of genomic DNA sequences is an important mechanism that drives the diversity of phenotypes and contributes to differential disease susceptibilities. The role of gene loss and gene gain in evolution has been discussed for many years. However, only recently have studies shown that continuous gain or loss of DNA sequences have played an important role in the speciation of humans and other primates, and of adaptation within a species to different environments. Phenotypes involved include human-specific brain morphology, the lack of a penile spline in men, and variation in resistance to infectious disease between populations. Genetic mechanisms include duplication and divergence of coding DNA sequences, and deletion of regulatory DNA sequences. Scientific approaches range from detailed structural and functional characterization of single loci to genomewide overviews across multiple species. In this session, we will present an overview of the latest research, demonstrating the long strides that have been made in linking the evolution of phenotype to molecular changes in the genome.


9:30 AM   Evolution of segmental duplications and novel neural genes. E. E. Eichler. Howard Hughes Med. Inst. and Univ. of Washington.

10:00 AM   Human-specific loss of regulatory DNA and the evolution of human-specific traits. D. M. Kingsley. Howard Hughes Inst. and Stanford Univ. Sch. of Med.

10:30 AM   Primate structural genomic variation evolving under positive selection. C. Lee. Brigham and Women's Hosp.

11:00 AM   Structural variation of beta-defensins: Welcome to the dynamic genome. E. J. Hollox. Univ. of Leicester, U.K.

Saturday, October 26

9:30 AM–11:30 AM

Concurrent Invited Session III (70-76)

SESSION 72 – Somatic Mutations in Human Disease — Piecing Together the Mosaic

Room 210, Level 2, Convention Center

Moderators: Leslie Biesecker, NHGRI/NIH
  William Dobyns, Univ. of Washington

Our field is dominated by three genetic disease concepts' ‘simple’ Mendelian disorders, complex disorders, and the complex somatic genetics of cancer. Recently, a new model is coming to the fore, that of the simple mosaic disorder – disorders caused by mosaicism for a mutation in a single gene. This model is on the rise because recent genomic techniques have improved detection of genomic alterations in mosaic tissues. These developments are accelerating the discovery of a wide array of human disease that is attributable to mosaic mutations. While it has long been known that gonadal mosaicism can explain recurrence of dominant disorders and that cancer is a complex mosaic genomic disease, only now are we beginning to appreciate the breadth and frequency of mosaic disorders. While the mosaic disorders of dermatologic disorders and overgrowth are most readily recognizable, mosaicism can affect any tissue and may explain a substantial fraction of human disease. The session will begin with the phenotypes of mosaic disorders, emphasizing dermatologic disorders to set the clinical context for the session. Second will be a review of the molecular genetics of mosaic cytogenetic and copy number variation, as elucidated initially by microscopic and now SNP array analysis. Third will be an overview of the disorders caused by mosaic point mutations in genes and we will close with a presentation on how lessons from cancer relate to simple mosaicism. These presentations will provide the participants with a broad overview and understanding of the role of somatic variation in human disease.


9:30 AM   The clinical manifestations of mosaicism. R. Happle. Freiburg Univ. Med. Ctr., Germany.

10:00 AM   Cytogenetics and the historical context of mosaicism. N. Spinner. Univ. of Pennsylvania.

10:30 AM   Single gene mutations and mosaic genetic disease. L. Biesecker. NHGRI/NIH.

11:00 AM   The mosaic landscape of cancer. E. Mardis. Washington Univ. Sch. of Med.

Saturday, October 26

9:30 AM–11:30 AM

Concurrent Invited Session III (70-76)

SESSION 73 – Tandem Repeat-Associated Epigenetic Mechanisms in Neuromuscular Disorders

Room 205, Level 2, Convention Center

Moderators: Paul J. Hagerman, Univ. of California, Davis, Sch. of Med.
  Laura Ranum, Col. of Med., Univ. of Florida

This session will consider four classes of repeat-expansion disorders, each with a distinct epigenetic mechanism, all of which are linked through repeat-length regulation of pathogenesis. The remarkable range of mechanisms include decreased epigenetic repression through macrosatellite contraction; toxic RNA gain-of-function and epigenetic silencing as outcomes of CGG-repeat expansion, with the switch in mechanisms depending only on the length of the CGG repeat; shifts to non-canonical translation initiation and the production of potentially toxic peptide products (CAG-repeat disorders); and epigenetic gene silencing associated with long-intronic GAA-repeat expansions. The session will highlight the newly acquired knowledge from basic research in the area of repeat-associated disorders, will describe new research tools and methodologies that have made the research advances possible, and will relate how such knowledge can be used to guide the diagnosis and treatment of these and other repeat-associated disorders.


9:30 AM   Facioscapulohumeral dystrophy: An epigenetic disease with genetic modifiers. S. Tapscott. Fred Hutchinson Cancer Res. Ctr., Seattle.

10:00 AM   Mechanisms of pathogenesis in fragile X-associated disorders. P. J. Hagerman. Univ. of California, Davis, Sch. of Med.

10:30 AM   Repeat associated non-ATG translation in microsatellite expansion disorders: Lessons from SCA8 and myotonic dystrophy. L. Ranum. Col. of Med., Univ. of Florida.

11:00 AM   Development of histone deacetylase inhibitors as therapeutics for Friedreich's ataxia. J. Gottesfeld. The Scripps Res. Inst.

Saturday, October 26

9:30 AM–11:30 AM

Concurrent Invited Session III (70-76)

SESSION 74 – Twin Studies: Helping Us Understand and Exploit the Genome (In Honor of Walter Nance's Contributions to Human Genetics on his 80th Birthday)

Hall B2, Level 0 (Lower Level), Convention Center

Moderators: Rita M. Cantor Chiu, David Geffen Sch. of Med. at UCLA
  Cynthia C. Morton, Brigham and Women's Hosp.

This session will focus on current realized and proposed successes in genetic epidemiology and genomics using twins. The history of twin studies will be summarized, and current applications to genetic epidemiology which illuminate the question of ‘missing heritability’ and refocus investigations will be presented. The use of twin registries and large population samples will be contrasted. Methods that reveal pathways for complex disorders will be discussed. Applications that have successfully developed baseline information regarding DNA, genes, structural variants, epigenetics and gene expression will be presented. The overarching rationale will be to celebrate Walter Nance's creative contributions to twin studies and to encourage ASHG researchers and clinicians to see their value and apply them. Information regarding availability of twin resources and how to interpret the results of twin research will be included.


9:30 AM   Twin studies in the non-molecular era. W. Nance. Virginia Commonwealth Univ.

10:00 AM   Twin studies as a tool in genetic epidemiology. N. Risch. UCSF.

10:30 AM   Twin studies as a powerful approach to identifying and understanding molecular pathways that underlie complex traits. N. Martin. Queensland Inst. of Med. Res., Brisbane.

11:00 AM   Twin studies as a valuable approach to omics research. T. Spector. Kings Col. London.

Saturday, October 26

9:30 AM–11:30 AM

Concurrent Invited Session III (70-76)

SESSION 75 – Where Do Risk Variants Act? Interrogating Genomic Studies of Multiple Human Tissues

Room 253, Level 2, Convention Center

Moderators: Chris Cotsapas, Yale Sch. of Med.
  Kristin Ardlie, Broad Inst. of MIT and Harvard

We now know thousands of genetic variants that influence a range of human traits and disease outcomes. As most of these variants are non-coding, the challenge is to understand what gene regulatory processes they perturb – and in which cell types. To do so requires comprehensive regulatory profiles across human tissues. Several large-scale projects are currently addressing this need, using genomic technologies such as RNA sequencing and epigenetic profiling to describe detailed regulatory profiles across large cohorts of donors. The task now is to uncover which genetic variants affect gene regulation in each tissue, and how this results in organism-level phenotypic changes. This session will bring together leaders of projects including GTEx, the ENCODE, the Roadmap Epigenome Project and ImmVar, who will describe their ongoing efforts to create meaningful regulatory profiles across tissues, how these may be used to mechanistically interpret GWAS and medical resequencing results and identify relevant cell-types for disease.


9:30 AM   Leveraging gene expression data to understand cell autonomous effects of inflammatory disease variants. P. L. De Jager. Brigham and Women's Hosp.

10:00 AM   Cross-tissue meta-analytic approaches result in large gains in regulatory variant identification. B. Raby. Brigham and Women's Hosp.

10:30 AM   Unique opportunities for scientific discovery in transcriptome studies across multiple tissues. N. Cox. Univ. of Chicago.

11:00 AM   Regulatory effect mapping of trait-associated variation identifies causal cell types. J. Stamatoyannopoulos. Univ. of Washington.

Saturday, October 26

9:30 AM–11:30 AM

Concurrent Invited Session III (70-76)

SESSION 76 – Whole Genome Sequencing for Every Baby? Where Diagnostic and Screening Applications Collide

Grand Ballroom East, Level 3, Convention Center

Moderators: James O'Leary, Genet. Alliance, Washington, DC
  Natasha Bonhomme, Genet. Alliance, Washington, DC

With the transition from research to clinical applications of whole genome/exome sequencing (WG/ES) well under way, it is critical that we focus on the future public health applications of these technologies. What decisions (knowingly or unknowingly) are being made now regarding the development of these technologies that will affect their viability for use in public health screening? What would it mean for these technologies to enter mainstream use and become integrated into state newborn screening (NBS) programs? This session will not only explore the potential of WGS in the newborn period, but also its appropriateness. What research has been completed or needs to be completed to properly address the ethical, legal and social issues surrounding this application? And finally, what are the practical hopes and concerns that researchers, clinicians, public health practitioners, consumers, and policy-makers have about a potential future where every baby receives WGS at birth?


9:30 AM   Genomic technology and newborn screening — pros and cons. O. A. Bodamer. Univ. of Miami Miller Sch. of Med.

10:00 AM   WGS in newborn screening: What are we screening for? J. R. Botkin. Univ. of Utah.

10:30 AM   Parental interest in whole genome sequencing of newborns. A. Goldenberg. Case Western Reserve Univ.

11:00 AM   Does the public want to have every baby sequenced at birth? Public participation and expectations of WGS. Y. Bombard. Univ. of Toronto, Li Ka Shing Knowledge Inst., Toronto.

Saturday, October 26

11:45 AM–1:15 PM

SESSION 77 – ASHG Distinguished Speakers Invited Symposium: Medical Systems Genomics

Hall B2, Level 0 (Lower Level), Convention Center

Moderators: Jeff Murray, Univ. of Iowa
  Andrew G. Clark, Cornell Univ.

This symposium will provide the ASHG community with an update from a trio of trailblazing experts on the state of the art of Systems Biology and its applications to medical genetics. Aviv Regev, Marc Vidal, and Garry Nolan will provide varying perspectives on the use of omics data to build predictive models of physiological states of the cell and the organism, including diseased states. These integrative approaches can provide a particularly informative picture of changes in cellular function mediated by cancer, pathogen response, and other stresses. They will challenge us with what the prospects are for methods like these to deliver improved insights regarding disease risk and therapeutic interventions. The speakers will conclude by gazing into the future, providing a vision of where systems medicine will be going in the next decade.

Marc Vidal

Dana-Farber Inst.

Harvard Univ.

Aviv Regev

Massachusetts Institute of Technology/HHMI

Garry Nolan
Stanford University


   Interactome networks and human disease. M. Vidal. Dana-Farber Cancer Inst., Harvard Univ.

   Reconstructing cellular circuits: From individual to single cell variation in immune cells. A. Regev. Broad/MIT/HHMI.

   A Definable "Structure" for the Immune System and Cancers at the Single Cell Level. G. Nolan. Stanford School of Medicine.


Contact Meeting Management


The American Society of Human Genetics, Incorporated | 9650 Rockville Pike, Bethesda, Maryland 20814 • 1-866-HUM-GENE • (301) 634-7300
Privacy Policy