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American Society of Human Genetics - San Diego - October 18-22, 2014 Contact Search

Saturday, October 18

5:00 PM–5:30 PM

1. ASHG Presidential Address: The Time of Our Lives

Hall B1, Ground Level, Convention Center

Cynthia Casson Morton, Brigham and Women's Hospital/Harvard Medical School

While every instant ever known to me as a human geneticist has been exciting, we now live in a moment in history when our science is poised as never before to improve personal and public health. The rapidity of technological advances in sequencing has been nothing short of amazing, and the biomedical applications of genomics surround us and are steadily increasing. Presently, we face formidable challenges in variant interpretation and in the optimal way to deliver information from genetic tests. We find ourselves engaged in frequent discourse about how to validate the function of variants and what results should be communicated to individuals. Yet, we have a history of delivering genetic information that is of uncertain clinical significance and that is incidental in nature. I believe this experience has prepared us for our next steps in this journey, and that we will go forward in earnest on a daily basis to provide state-of-the-art knowledge to all those who seek our assistance. It is our privilege. But it also is our responsibility to improve that knowledge at the greatest possible speed. How will we go about this task? This will be a legacy of our times, and is the time of our lives as human geneticists.



Saturday, October 18

5:30 PM–6:50 PM

2. Plenary Abstracts Featured Presentation I

Hall B1, Ground Level, Convention Center

Moderator: Andrew S. McCallion, Johns Hopkins Univ, Baltimore

These sessions include a diverse set of presentations selected from the top-rated abstracts. Each author will give a 15-minute presentation, with an additional five minutes for discussion.


1/5:30 The UK10K project: Rare variants in health and disease. N. Soranzo, UK10K Consortium.

2/5:50 Human-specific gene evolution and structural diversity of the chromosome 16p11.2 autism CNV. X. Nuttle, G. Giannuzzi, M. H. Duyzend, P. H. Sudmant, O. Penn, G. Chiatante, M. Malig, J. Huddleston, L. Denman, L. Harshman, C. Baker, A. Raja, K. Penewit, F. Antonacci, R. Bernier, A. Reymond, E. E. Eichler.

3/6:10 Discovery and functional characterization of recurrent gene fusions from 7,470 primary tumor transcriptomes across 28 human cancers. C. Bandlamudi, P. Lin, J. Tian, R. Grossman, K. White.

4/6:30 Phase III trial of afamelanotide 16 mg subcutaneous bioresorbable implants for the treatment of erythropoietic protoporphyria. R. J. Desnick, K. E. Anderson, D. M. Bissell, J. R. Bloomer, H. L. Bonkovsky, M. Lebwohl, H. Lim, C. Parker, J. Phillips, H. Naik, M. Balwani.

Sunday, October 19

8:00 AM–9:30 AM

3. Distinguished Speakers Symposium: Separating Signal from Noise

Hall B1, Ground Level, Convention Center

Moderators: Cynthia Casson Morton, Brigham and Women's Hosp/Harvard Med Sch
  Andrew S. McCallion, Johns Hopkins Univ, Baltimore

This symposium will address the challenges inherent in the pursuit of genome sequencing/genomic data as a universal diagnostic/prognostic/therapeutic guide in human disease research and clinical application. This discussion, which will include experts from outside the ASHG community, will highlight the challenges and opportunities presented by big data in the genomics era.


8:00 AM   Genomic Analytics with IBM Watson. A. Royyuru. IBM Watson Research Center.

8:30 AM   Lessons from a Mixed Marriage: Big Sequencing Meets Big Data. D. Glazer. Google.

9:00 AM   Medicine and Public Health. M. Khoury. CDC.

Sunday, October 19

10:00 AM–12:00 PM

Concurrent Invited Session I

4. Beyond Canonical CNVs: Interpreting Other Forms of Genomic Structural Variation

Room 6CF, Upper Level, Convention Center

Moderators: Ryan E. Mills, Univ Michigan, Ann Arbor
  Jan Korbel, European Molec Biol Lab (EMBL), Heidelberg, Germany

Although the past decade has greatly expanded our knowledge of copy number variation (CNVs) and their role in human health and disease, technological limitations have hampered the discovery and characterization of several remaining forms of structural variation, including multi-allelic CNVs, sequence insertions, as well as balanced inversions. The emergence of longer sequencing reads coupled with advances in computational approaches for structural variant inference has now allowed for the accurate detection of balanced rearrangements as well as insertions of repetitive, retroduplicated, and non-template genomic material, and can be used as a starting point to dissect the structure of genomic loci that have undergone repeated duplications. In this session, we will describe the progress that has been made in examining these important forms of structural variation with the latest technologies and assessing their impact on population diversity and evolution. We will also discuss the analysis and interpretation of multi-allelic genomic regions. Topics will include an exploration into functional effects at the transcriptome level as well as genetic and epigenetic preferences for variant formation mechanisms. A retrospective look at what was missed in previous large-scale studies will also be discussed.


10:00 AM   Analysis of SVs in human populations. M. Gerstein. Yale Univ, New Haven.

10:30 AM   Complex and multi-allelic forms of copy number variation. S. McCarroll. Harvard Med Sch, Boston.

11:00 AM   Genomic landscape of polymorphic nuclear mitochondrial insertions in humans and other primates. R. E. Mills. Univ Michigan, Ann Arbor.

11:30 AM   Discovery and impact of balanced inversion polymorphisms. J. Korbel. European Molec Biol Lab (EMBL), Heidelberg, Germany.

Sunday, October 19

10:00 AM–12:00 PM

Concurrent Invited Session I

5. Beyond Mendel: Complexities of Simple Mendelian Disorders

Room 20A, Upper Level, Convention Center

Moderators: Jeenah Park, Johns Hopkins Sch Med, Baltimore
  Shira G. Ziegler, Johns Hopkins Sch Med, Baltimore

Single-gene disorders are called Mendelian disorders because they display patterns of inheritance largely consistent with Mendel’s laws. Single-gene disorders with classic Mendelian inheritance can be autosomal or sex-linked, and dominant or recessive. The more we learn about the molecular etiology of classic Mendelian disorders, the more we realize that our view of disease transmission frequently represents an oversimplification of reality. For instance, patients with the same disorder, which is inherited in a monogenic fashion following the Mendelian model, often exhibit a wide range of phenotypic presentation/severity. Identification of the specific disease genes has played a significant role in improving our understanding of gene functions and biological pathways associated with the corresponding diseases. Nonetheless, we should look for ways in which we can close the gap in our understanding of the factors that modify disease severity. What makes these so-called “simple” Mendelian disorders complex? To answer this question, we will explore four classic Mendelian disorders – Cystic Fibrosis, Retinitis Pigmentosa, Spinocerebellar Ataxia, and Muscular Dystrophy – many of which are characterized by vast phenotypic heterogeneity. Allelic heterogeneity and non-penetrance can obscure the patterns of inheritance and make it difficult to predict the consequence of each mutation. Moreover, genetic modifiers modulate so-called Mendelian phenotypes more than we have appreciated. Through a deeper understanding of the allelic contribution and interactions with other factors, we can broaden our view and integrate new insights uncovered by recent research on disease etiology, progression, and differential therapeutic strategies.


10:00 AM   Elucidating the contribution of CFTR allelic variation and modifier genes to phenotypic variation in cystic fibrosis. J. Park. Johns Hopkins Sch Med, Baltimore.

10:30 AM   Opening Pandora’s box: The molecular basis of non-penetrance in PRPF31-associated retinitis pigmentosa. A. M. Rose. UCL Inst Ophthalmol, London, United Kingdom.

11:00 AM   RNA-sequencing reveals a complex role of Ataxin-1 in SCA1. M. A. Ingram. Univ Minnesota, Minneapolis.

11:30 AM   The muscular dystrophies: Revealing the genetic and phenotypic variability. N. M. Vieira. Boston Children’s Hosp, Harvard Med Sch.

Sunday, October 19

10:00 AM–12:00 PM

Concurrent Invited Session I

6. Crowdsourced Genetics

Room 6AB, Upper Level, Convention Center

Moderators: Itsik Pe'er, Columbia Univ, New York
  Yaniv Erlich, Whitehead Inst Biomed Res, Cambridge, MA

Crowd science aims to leverage the power of the masses to tackle scientific tasks that are challenging to address with traditional methodologies. The history of crowd science goes back to Galton, who was the first to report that estimations by a large number of amateurs can collectively yield similar values to precise measurements by conventional means. In the last few years, we have witnessed renewed interest in crowd science approaches. The advent of social media has created vast opportunities to partner with large crowds and engage individuals to participate in various parts of the scientific process. This session will present crowd science models that have been successfully applied to fundamental challenges in human genetics. First, we will show how crowd data mining by citizen genealogists enabled the building of an ultra-large family tree of millions of people, which provided sufficient statistical power to dissect the genetic architecture of complex traits. Second, we will show how crowd computation leverages the brainpower of hundreds of thousands of gamers to fold proteins, a challenging problem for traditional bioinformatics algorithms. Third, we will show crowd experiments that integrate genetic signals and clinical data to gain insight into drug repositioning for type 2 diabetes and inflammatory bowel disease. Finally, we will present the successful crowdfunding for research on a very rare genetic disorder, fatal familial insomnia, using Together, this session will highlight technical frameworks and methodologies for crowd science in human genetics and common themes and lessons learned from reaching out to the crowd.


10:00 AM   Crowd mining: Dissecting the genetic architecture of complex traits with millions of people. Y. Erlich. Whitehead Inst Biomed Res, Cambridge, MA.

10:30 AM   Crowd computing: Scientific discoveries by protein folding game. F. Khatib. Univ Massachusetts Dartmouth.

11:00 AM   Crowd experiments: Translating a trillion points of data into new disease insights. A. Butte. Stanford Univ.

11:30 AM   Crowd funding: A personal quest to cure prion disease. S. Vallabh, E. Minikel. PrionAlliance, Boston.

Sunday, October 19

10:00 AM–12:00 PM

Concurrent Invited Session I

7. Curiouser and Curiouser! Navigating Career Transitions and Challenges in Genetics

Room 20BC, Upper Level, Convention Center

Moderators: Amy L. Stark, Univ Chicago
  Krista A. Geister, Seattle Children's

The training of a young geneticist prepares him or her to make decisions regarding the planning and execution of genetic research. However, there are some components of a successful career that are not incorporated in formalized training programs. The majority of this type of learning is achieved through mentoring and life experience. For example, the act of self-promotion may seem straightforward, but there are different and more effective ways to promote oneself at various stages of one’s career. What are the secrets to success at various stages? What are these unforeseen challenges facing young scientists, and how can they be met? How does one bring together clinical and basic science interests together to form a productive and stimulating career? What are the challenges that face women and how can they be over overcome? The goal of this session is to answer these questions and many more with presentations from individuals with experience in tackling the numerous challenges trainees experience as they progress in their careers.


10:00 AM   When, where, why, what, and how: Finding/recruiting for the right postdoctoral position. B. E. Stranger. Univ Chicago.

10:30 AM   Clinical connection: Careers in genetic diagnostics. K. Deak. Duke Univ, Durham.

11:00 AM   Launching your academic career: Take off the training wheels and enjoy the ride. S. Camper. Univ Michigan, Ann Arbor.

11:30 AM   Hitting your Stride with Work and Life: Balancing a Career in Genetics with Family Life. M. Urbanek. Northwestern Univ, Chicago.

Sunday, October 19

10:00 AM–12:00 PM

Concurrent Invited Session I

8. Targeted Drug Therapies for Progressive Genetic Disorders

Room 6DE, Upper Level, Convention Center

Moderators: Joseph G. Hacia, Univ Southern California, Los Angeles
  Nancy E. Braverman, McGill Univ, Montreal

Expanded newborn screening and genome sequencing provide powerful means to identify individuals with progressive genetic disorders at an early or presymptomatic stage of disease. This presents an unprecedented opportunity for therapeutic interventions that delay disease onset and/or halt progression before irreversible damage occurs. Here, we will review recent progress towards developing drug therapies targeted to the molecular mechanisms underlying diverse progressive genetic disorders including cystic fibrosis, Duchenne muscular dystrophy, lysosomal storage disorders, and tuberous sclerosis. We will discuss large-scale NIH drug screening initiatives and highlight an FDA-approved mutation-specific drug therapy for cystic fibrosis as a model in which disease identification at birth can precede clinical symptoms. Furthermore, we will describe results from clinical trials that evaluate the efficacy of rationally designed drug therapies that target dysfunctional cell regulation at the level of signaling and growth factor pathways.


10:00 AM   Drug screening for genetic disorders: Recent progress and future developments. J. Inglese. NCATS/NIH, Rockville.

10:30 AM   Genotype-specific targeted small molecule therapies for cystic fibrosis. B. Ramsey. Univ Washington Sch Med, Seattle.

11:00 AM   Exon skipping and nonsense suppressor therapies to treat Duchenne muscular dystrophy. S. F. Nelson. UCLA.

11:30 AM   Targeting molecular signaling pathways to treat Mendelian disorders with progressive neurologic involvement. M. J. Gambello. Emory Univ Sch Med, Atlanta.

Sunday, October 19

10:00 AM–12:00 PM

Concurrent Invited Session I

9. The X-Factor of Complex Disease: From Evolution to Association Studies of the X Chromosome

Room 30, Upper Level, Convention Center

Moderators: Alon Keinan, Cornell Univ, Ithaca
  Melissa A. Wilson Sayres, Arizona State Univ, Tempe

Despite sexual dimorphism of most complex human diseases studied in genome-wide association studies, the sex chromosomes have been mostly omitted. Not only can they explain a portion of “missing heritability” of currently available genotyping data across thousands of studies, but without appropriate methods they will remain unexplored in the era of sequence-based studies. Many problems need to be resolved for the X chromosome to be studied thoroughly. In this session speakers will describe progress and novel results in the understanding X-inactivation, interpretation of the unique patterns of population genetic variation on the X and, importantly, how these lead to exciting new methods for analyzing the X chromosome in association and functional studies of complex human diseases and quantitative traits. Novel X-linked complex disease risk loci underlying several diseases will be presented, as well as how X-inactivation can be studied to better understand the function of long noncoding RNA. The session will show how ignoring the sex chromosomes may affect interpretations of population and medical genetic data and will demonstrate that understanding its role in medical genetics and its unique response to evolutionary history, is an important step towards uncovering sexual dimorphism in disease etiology.


10:00 AM   Population genomics of sex chromosome evolution. M. A. Wilson Sayres. Arizona State Univ,Tempe.

10:30 AM   Contrasting the Impact of Natural Selection on the X chromosome and Autosomes amongst Apes. K. R. Veeramah. Department of Ecology and Evolution, Stony Brook University.

11:00 AM   Methods for association studies of the X chromosome and their application to unraveling its role in autoimmune diseases. A. Keinan. Cornell Univ, Ithaca.

11:30 AM   Dosage regulation of the X chromosome: Role of Sex Differences in Health and Disease. C. Disteche. Univ of Washington, Seattle.

Sunday, October 19

10:00 AM–12:00 PM

Concurrent Invited Session I

10. Using Zebrafish to Model Human Genetic Disease Variation

Room 29, Upper Level, Convention Center

Moderators: Barry H. Paw, Brigham and Women's Hosp, Boston
  Nicholas Katsanis, Duke Univ, Durham

As genomic sequences become more available, the bottleneck in human genetics is shifting from identifying genetic variants to understanding their function. Model organisms that are genetically tractable are a powerful tool for rapidly screening variants. As a vertebrate with relatively fast development, Danio rerio (zebrafish) is often an ideal organism for assessing the phenotypic impact of sequence changes. This session will provide insight into the technologies used to manipulate zebrafish, as well as several examples of major ongoing projects that are using zebrafish as a crucial component of a human genetics clinical research program. The speakers will describe projects that have implicated numerous genes in kidney disease, developmental disorders, and cardiac diseases, and directions for future research and clinical application.


10:00 AM   Coupling exome sequencing and functional modeling in neonates. N. Katsanis. Duke Univ, Durham.

10:30 AM   From association to mechanism: Using zebrafish to evaluate GWAS loci. D. J. Milan. Massachusetts Gen Hosp, Charlestown.

11:00 AM   Zebrafish genome editing tools using random and targeted engineering for individualized medicine applications. S. C. Ekker. Mayo Clin Col Med, Rochester.

11:30 AM   Using zebrafish genetics to discover the developmental basis of human disease. C. B. Moens. Fred Hutchinson Cancer Res Ctr, Seattle.

Sunday, October 19

10:00 AM–12:00 PM

Concurrent Invited Session I

11. Whole Genome/Exome Sequencing: Patient Expectations, Literacy, and Preferences for Genomic Information

Room 20D, Upper Level, Convention Center

Moderators: Amy L. McGuire, Baylor Col Med, Houston
  Gail Henderson, Univ North Carolina Sch Med, Chapel Hill

A primary challenge in the integration of whole genome and whole exome sequencing into clinical care is to develop best practices for offering testing and communicating test results to patients in a way that is highly responsive to patients’ expectations, genetic knowledge and literacy, and preferences for genomic information. In 2010 the NIH initiated a Clinical Sequencing Exploratory Research (CSER) program intended to develop methods needed for clinical integration of whole genome and whole exome sequencing and to conduct ethical, legal, and psychosocial research to help inform the responsible application of genomic sequencing to clinical practice. During this session we will report baseline findings from four NHGRI-funded CSER studies, summarize lessons learned, and discuss implications of our data for offering and conducting clinical sequencing in diverse patient populations.


10:00 AM   The MedSeq Pilot Project: Patient perspectives from a randomized trial of whole genome sequencing. A. L. McGuire. Baylor Col Med, Houston.

10:30 AM   The CanSeq Project: Opportunities and challenges of integrating whole exome sequencing into the care of advanced care patients. S. Gray. Dana Farber Cancer Inst, Brookline, MA.

11:00 AM   NCGENES: Factors related to expectations for WES testing and decisions to receive incidental findings among a diverse patient population. C. Rini. Univ North Carolina at Chapel Hill.

11:30 AM   PEDISEQ: Parent perspectives and the inclusion of children in decisions about whole exome sequencing. B. A. Bernhardt. Perelman Sch Med, Univ Pennsylvania, Philadelphia.

Sunday, October 19

1:30 PM–3:30 PM

Concurrent Platform Session A

12. Patterns and Determinants of Genetic Variation: Recombination, Mutation, and Selection

Hall B1, Ground Level, Convention Center

Moderators: Emilia Huerta-Sanchez, UC Berkeley
  Joseph Pickrell, New York Genome Center

5/1:30 Re-engineering meiotic recombination in the mouse. E. Hatton, B. Davies, J. Hussin, F. Pratto, D. Biggs, N. Altemose, N. Hortin, C. Preece, D. Moralli, A. Gupta-Hinch, K. Brick, C. Green, D. Camerini-Otero, S. Myers, P. Donnelly.

6/1:45 Examining variation in recombination levels in the human female: A test of the production line hypothesis. R. Rowsey, J. Gruhn, K. Broman, P. Hunt, T. Hassold.

7/2:00 The fine-scale landscape of meiotic gene conversion. A. L. Williams, J. Blangero, M. Przeworski.

8/2:15 Recombination maps for Latino populations based on ancestry inference. S. Shringarpure, D. Wegmann, C. Gignoux, B. Maples, A. Ferrer-Admetlla, A. Moreno-Estrada, K. Sandoval, C. Eng, S. Huntsman, A. Ko, T. Tusie-Luna, C. Aguilar-Salinas, P. Pajukanta, D. Torgerson, E. Burchard, J. Below, B. Pasaniuc, S. Gravel, J. Novembre, C. Bustamante.

9/2:30 The human X chromosome is the target of megabase wide selective sweeps associated with multi-copy genes expressed in male meiosis and involved in reproductive isolation. M. H. Schierup, K. Munch, K. Nam, T. Mailund, J. Y. Dutheil.

10/2:45 New insights on human de novo mutation rate and parental age. W. S. W. Wong, B. Solomon, D. Bodian, D. Thach, R. Iyer, J. Vockley, J. Niederhuber.

11/3:00 Cholera resistance in Bangladesh: Combining signals of ancient, pathogen-driven selection with genome-wide association to understand immune response. E. K. Karlsson, I. Shylakhter, F. Qadri, J. B. Harris, S. B. Calderwood, E. T. Ryan, R. C. LaRocque, P. C. Sabeti.

12/3:15 Direct detection of genetic dominance from natural variation in human populations. D. Balick, R. Do, D. Reich, S. Sunyaev.

Sunday, October 19

1:30 PM–3:30 PM

Concurrent Platform Session A

13. Genomic Studies of Autism

Room 6AB, Upper Level, Convention Center

Moderators: James S. Sutcliffe, Vanderbilt Sch Med, Nashville
  Alex Bassuk, Univ Iowa, Iowa City

13/1:30 Exome analyses reveal new autism genes in synaptic, transcriptional, and chromatin networks. S. De Rubeis, K. Roeder, B. Devlin, M. J. Daly, J. D. Buxbaum, The Autism Sequencing Consortium.

14/1:45 Defining the contribution of different classes of de novo mutation to autism. I. Iossifov, B. J. O'Roak, S. J. Sanders, N. Krumm, M. Ronemus, D. Levy, J. Shendure, E. E. Eichler, M. W. State, M. Wigler.

15/2:00 Brain-expressed exons under purifying selection are enriched for de novo mutations in autism spectrum disorder. M. Uddin, K. Tammimies, G. Pellecchia, B. Alipanahi, P. Hu, Z. Wang, D. Pinto, L. Lau, T. Nalpathamkalam, C. Marshall, B. Blencowe, B. Frey, D. Merico, R. Yuen, S. Scherer.

16/2:15 The landscape and clinical impact of cryptic structural variation in autism and related neuropsychiatric disorders. H. Brand, V. Pillalamarri, R. Collins, S. Eggert, M. Stone, I. Blumenthal, C. O'Doushlaine, E. Braaten, J. Rosenfeld, S. Mccarroll, J. Smoller, A. Doyle, M. Talkowski.

17/2:30 Diagnostic utility of whole exome sequencing and chromosomal microarray in a clinically well-defined autism spectrum disorder cohort. K. Tammimies, B. A. Fernandez, S. Walker, B. Thiruvahindrapuram, G. Kaur, A. C. Lionel, W. Roberts, R. Weksberg, J. L. Howe, M. Uddin, R. K. C. Yuen, Z. Wang, L. Lau, P. Szatmari, K. Whitten, C. Vardy, V. Crosbie, B. Tsang, R. Liu, L. D'Abate, S. Luscombe, T. Doyle, S. Stuckless, D. Merico, D. J. Stavropoulos, C. R. M. Marshall, S. W. Scherer.

18/2:45 Integrative functional genomics following suppression of CHD8 identifies transcriptional signatures that are enriched for autism genes and macrocephaly. M. Biagioli, A. Sugathan, C. Golzio, I. Blumenthal, S. Erdin, P. Manavalan, A. Ragavendran, D. Lucente, J. Miles, S. D. Sheridan, A. Stortchevoi, S. J. Haggarty, J. F. Gusella, N. Katsanis, M. E. Talkowski.

19/3:00 Transcriptional consequences of 16p11.2 microdeletion/microduplication syndrome in mouse cortex converges on genes and pathways associated with autism and known intellectual disability syndromes. I. Blumenthal, A. Ragavendran, S. Erdin, C. Golzio, A. Sugathan, J. Guide, V. Wheeler, A. Reymond, N. Katsanis, J. F. Gusella, M. E. Talkowski.

20/3:15 Most genetic risk for autism resides with common variation. J. D. Buxbaum, B. Devlin, K. Roeder, Population-based Autism Genetics and Environment Study (PAGES) Consortium.

Sunday, October 19

1:30 PM–3:30 PM

Concurrent Platform Session A

14. Statistical Methods for Pedigree-Based Studies

Room 6CF, Upper Level, Convention Center

Moderators: Ingrid Borecki, Washington Univ in St. Louis
  France Gagnon, Univ Toronto, Canada

21/1:30 Utilizing rare variants for phasing and imputation in pedigrees. A. Blackburn, J. Blangero, H. Göring.

22/1:45 The “Jackpot” Effect: When do family samples provide more power to detect trait-associated rare variants? S. Feng, G. Pistis, A. Mulas, M. Zoledziewska, F. Busonero, S. Sanna, D. Liu, F. Cucca, G. R. Abecasis.

23/2:00 Sequence kernel association test for multivariate quantitative phenotype in family samples. Q. Yan, B. Li, W. Chen, N. Liu.

24/2:15 Genetic network inference in studies of multiple phenotypes from related individuals. J. Marchini, A. Dahl, V. Hore.

25/2:30 G-STRATEGY: Optimal selection of individuals to genotype in genetic association studies with related individuals. M. Wang, J. Jakobsdottir, A. V. Smith, M. S. McPeek.

26/2:45 Using a population-based linkage analysis approach to identify transcript QTL in skeletal muscle tissues in a founder population. W.-C. Hsueh, S. Kobes, R. L. Hanson.

27/3:00 Testing for disease association with rare compound heterozygous and recessive mutations in case-parent sequencing studies. A. Allen, Y. Jiang, J. McCarthy.

28/3:15 Statistical approaches for rare-variant association testing in affected sibships. M. P. Epstein, E. Ware, M. A. Jhun, L. F. Bielak, W. Zhao, J. Smith, P. A. Peyser, S. L. R. Kardia, G. A. Satten.

Sunday, October 19

1:30 PM–3:30 PM

Concurrent Platform Session A

15. Prostate Cancer: Expression Informing Risk

Room 6DE, Upper Level, Convention Center

Moderators: Paul Scheet, Univ Texas, MD Anderson Cancer Ctr, Houston
  Amanda E. Toland, The Ohio State Univ, Columbus

29/1:30 Functional partitioning of prostate cancer heritability in European Americans and African Americans from AAPC and BPC3 consortia reveals tissue specific regulation. B. Pasaniuc, A. Gusev, F. R. Schumacher, S. Lindstrom, M. Pomerantz, F. Li, H. Long, P. Kraft, A. L. Price, M. Freedman, C. A. Haiman, BPC3 Consortium, AAPC Consortium.

30/1:45 Prostate cancer risk locus at 8q24 as a regulatory hub by physical interactions with multiple genomic loci across the genome. M. Du, T. Yuan, K. Schilter, R. Dittmar, A. Mackinnon, X. Huang, M. Tschannen, E. Worthey, H. Jacob, S. Xia, J. Gao, L. Tillmans, Y. Lu, P. Liu, S. Thibodeau, L. Wang.

31/2:00 Genome-wide association study of 35K men with 300K prostate specific antigen measures identifies numerous novel loci: potential for personalized screening for prostate cancer. J. S. Witte, T. J. Hoffmann, L. Sakoda, E. Jorgenson, D. S. Aaronson, J. Shan, L. A. Habel, J. C. Presti, C. Schaefer, N. Risch, S. K. Van Den Eeden.

32/2:15 Germline sequencing for genetic markers of aggressive prostate carcinoma susceptibility. D. Koboldt, K. Kanchi, D. Larson, R. Fulton, E. Mardis, A. Kibel.

33/2:30 Identification of candidate target genes for prostate cancer risk-SNPs utilizing a normal prostate tissue eQTL dataset. S. N. Thibodeau, A. J. French, S. K. McDonnell, J. C. Cheville, S. Middha, S. M. Riska, S. Baheti, Z. C. Fogarty, L. S. Tillmans, M. C. Larson, N. B. Larson, A. A. Nair, D. R. O'Brien, J. I. Davila, Y. Zhang, L. Wang, J. M. Cunninghman, D. J. Schaid.

34/2:45 Association of prostate cancer risk variants with gene expression in normal prostate and tumor tissue. K. L. Penney, J. A. Sinnott, S. Tyekucheva, T. Gerke, I. Shui, P. Kraft, H. D. Sesso, M. L. Freedman, M. Loda, L. A. Mucci, M. J. Stampfer.

35/3:00 Discovery and functional characterization of an oncogenic PTEN mutation: Implications for personalized cancer genome therapy. H. A. Costa, M. G. Leitner, M. L. Sos, A. Mavrantoni, A. Rychkova, M. C. Yee, F. M. De La Vega, J. M. Ford, K. M. Shokat, D. Oliver, C. R. Halaszovich, C. D. Bustamante.

36/3:15 Convergent Genomics Validates C2orf43 Role in Prostate Cancer. B. B. Currall, K. E. Wong, N. G. Robertson, A. Lunardi, M. Reschke, P. P. Pandolfi, C. C. Morton.

Sunday, October 19

1:30 PM–3:30 PM

Concurrent Platform Session A

16. Variant Calling: What Makes the Difference?

Room 20A, Upper Level, Convention Center

Moderators: Deanna M. Church, Personalis, Menlo Park, CA
  Aaron Quinlan, Univ Virginia, Charlottesville

37/1:30 Alignment to an ancestry specific reference genome discovers additional variants among 1000 Genomes ASW Cohort. R. A. Neff, J. Vargas, G. H. Gibbons, A. R. Davis.

38/1:45 Detecting novel sequence insertions in 3000 individuals from short read sequencing data. B. Kehr, P. Melsted, A. Jónasdóttir, A. Jónasdóttir, A. Sigurðsson, A. Gylfason, D. Guðbjartsson, B. V. Halldórsson, K. Stefánsson.

39/2:00 SNAP: Fast, accurate sequence alignment enabling biological applications. R. Pandya, W. Bolosky, M. Zaharia, T. Sittler, K. Curtis, C. Hartl, A. Fox, S. Schenker, I. Stoica, D. Patterson.

40/2:15 Precise identification of copy number variants in whole-genome data using median coverage profiles. G. Glusman, T. Farrah, D. E. Mauldin, A. B. Stittrich, S. Ament, L. Rowen, J. C. Roach, M. Brunkow, M. Robinson, A. F. A. Smit, R. Hubley, D. Bodian, J. Vockley, I. Shmulevich, J. Niederhuber, L. Hood.

41/2:30 Accurate read mapping using a graph-based human pan-genome. W. Lee, E. Garrison, D. Kural, G. Marth.

42/2:45 The impact of GRCh38 on clinical sequencing. D. M. Church, J. Harris, G. Bartha, M. Pratt, A. Patwardhan, S. Chervitz, S. Kirk, M. Clark, S. Garcia, J. West, R. Chen.

43/3:00 Optimized exome sequencing for discovery research: Improved metrics and methods to enhance variant discovery across the biomedical footprint of the genome. M. Pratt, S. Luo, G. Bartha, J. Harris, N. Leng, C. Haudenschild, R. Chen, J. West.

44/3:15 SpeedSeq: A 24-hour alignment, variant calling, and genome interpretation pipeline. C. Chiang, R. M. Layer, G. G. Faust, M. R. Lindberg, A. R. Quinlan, I. M. Hall.

Sunday, October 19

1:30 PM–3:30 PM

Concurrent Platform Session A

17. New Genes, Incidental Findings and Unexpected Observations Revealed by Exome Sequencing

Room 20BC, Upper Level, Convention Center

Moderators: Joris A. Veltman, Radbound Univ Med Ctr, Nijmegen, Netherlands
  Thomas Meitinger, Technical Univ Munich, Munich, Germany

45/1:30 Genomic sequencing approach identifies novel rare variants in patients with Mendelian neurologic diseases. E. Karaca, D. Pehlivan, T. Harel, S. Weitzer, H. Shiraishi, T. Gambin, Y. Bayram, W. Wiszniewski, S. N. Jhangiani, G. Yesil, S. Isikay, O. Ozalp Yuregir, S. Bozdogan, H. Aslan, T. Tos, D. Gul, B. Yilmaz, O. Cogulu, K. Karaer, H. Ulucan, D. Muzny, M. Seven, A. Yuksel, T. Clausen, T. Tuschl, A. Hess, R. A. Gibbs, J. Martinez, J. M. Penninger, J. R. Lupski.

46/1:45 Individualized iterative phenotyping for genome-wide analysis of loss of function mutations. J. J. Johnston, K. Lewis, D. Ng, L. N. Singh, J. Wynter, C. Brewer, B. P. Brooks, I. Brownell, F. Candotti, S. G. Gonsalves, P. S. Hart, H. H. Kong, K. I. Rother, R. Sokolic, B. D. Solomon, W. M. Zein, D. N. Cooper, P. D. Stenson, J. C. Mullikin, L. G. Biesecker.

47/2:00 Genomic approach identifies novel proteins necessary for inner ear function and development across multiple species. O. Diaz-Horta, M. Grati, C. Abad, A. DeSmidt, G. Bademci, A. Subasioglu-Uzak, J. Foster II, S. Tokgoz-Yilmaz, D. Duman, F. B. Cengiz, S. H. Blanton, X. Z. Liu, A. Farooq, Z. Lu, K. Walz, M. Tekin.

48/2:15 A Drosophila genetic resource to study human disease genes and its use for gene discovery in human exome data. M. F. Wangler, S. Yamamoto, M. Jaiswal, W. L. Charng, T. Gambin, E. Karaca, G. Mirzaa, W. Wiszniewski, H. Sandoval, N. Haelterman, V. Bayat, D. Pehlivan, S. Penney, L. Vissers, S. Jhangiani, S. Tsang, Y. Xie, Y. Parman, E. Battaloglu, D. Muzny, Z. Liu, R. Clark, C. Curry, E. Boerwinkle, W. Dobyns, R. Allikmets, R. Gibbs, R. Chen, J. R. Lupski, H. Bellen.

49/2:30 Genome sequencing identifies major causes of severe intellectual disability. C. Gilissen, J. Y. Hehir-Kwa, D. Thung, M. van de Vorst, B. W. M. van Bon, M. H. Willemsen, M. Kwint, I. M. Janssen, A. Hoischen, A. Schenck, R. Leach, R. Klein, R. Tearle, T. Bo, R. Pfundt, H. G. Yntema, B. B. A. de Vries, T. Kleefstra, H. G. Brunner, L. E. L. M. Vissers, J. A. Veltman.

50/2:45 Assessment of the success rate of two years of large-scale exome sequencing efforts to identify genes for Mendelian conditions at the University of Washington Center for Mendelian Genomics. J. X. Chong, J. Shendure, D. A. Nickerson, M. J. Bamshad, University of Washington Center for Mendelian Genomics.

51/3:00 A comparative analysis of allele frequencies for incidental findings among five populations based on the analyses of 11K whole exome sequences. T. Gambin, S. Jhangiani, J. E. Below, J. Staples, A. Morrison, A. Li, I. Campbell, W. Wiszniewski, D. M. Muzny, M. N. Bainbridge, R. A. Gibbs, J. R. Lupski, E. Boerwinkle.

52/3:15 Why next-generation sequencing studies may fail: Challenges and solutions for gene identification in the presence of familial locus heterogeneity. R. L. P. Santos-Cortez, A. U. Rehman, M. C. Drummond, M. Shahzad, K. Lee, R. J. Morell, M. Ansar, A. Jan, X. Wang, A. Aziz, S. Riazuddin, J. D. Smith, G. T. Wang, Z. M. Ahmed, K. Gul, A. E. Shearer, R. J. H. Smith, J. Shendure, M. J. Bamshad, D. A. Nickerson, J. Hinnant, S. N. Khan, R. A. Fisher, W. Ahmad, K. H. Friderici, S. Riazuddin, T. B. Friedman, E. S. Wilch, S. M. Leal, University of Washington Center for Mendelian Genomics.

Sunday, October 19

1:30 PM–3:30 PM

Concurrent Platform Session A

18. Type 2 Diabetes Genetics

Room 20D, Upper Level, Convention Center

Moderators: Maggie Ng, Wake Forest Sch Med, Winston-Salem
  Craig Hanis, Univ Texas Hlth Sci Ctr, Houston

53/1:30 Genome-wide association study imputed to 1000 Genomes reveals 18 novel associations with type 2 diabetes. R. A. Scott, R. Magi, A. P. Morris, L. Marullo, K. Gaulton, M. Boehnke, J. Dupuis, M. I. McCarthy, L. J. Scott, I. Prokopenko, DIAGRAM+ Consortium.

54/1:45 Genome-wide association and exome sequence data analysis for more than 100 traits in Mexican Americans. J. E. Below, B. E. Cade, D. Aguilar, E. Brown, H. M. Highland, S. Redline, G. I. Bell, N. J. Cox, C. L. Hanis.

55/2:00 Three common recessive variations explain more than 20% of all cases of type 2 diabetes in Greenland. A. Albrechtsen, I. Moltke, M. E. Jørgensen, P. Bjerregaard, E. V. R. Appel, R. Nielsen, O. Pedersen, N. Grarup, T. Hansen.

56/2:15 A low frequency AKT2 coding variant enriched in the Finnish population is associated with fasting insulin levels. A. K. Manning, H. H. Highland, X. Sim, N. Grarup, T. Tukiainen, J. Gasser, A. Mahajan, M. A. Rivas, A. E. Locke, J. Tuomilehto, M. Laakso, S. Ripatti, J. B. Meigs, D. Altshuler, M. Boehnke, M. I. McCarthy, A. L. Gloyn, C. M. Lindgren, T2D Genes, GoT2D.

57/2:30 Association of genetic variants with metabolic traits and multiple disease outcomes to inform therapeutic target validation: Strengths and limitations of a GLP1R variant. D. F. Freitag, R. A. Scott, L. Li, J. L. Aponte, S. M. Willems, J. Wessel, A. Y. Chu, S. Wang, P. Munroe, M. den Hoed, I. B. Borecki, C. Liu, G. M. Peloso, J. M. M. Howson, A. S. Butterworth, J. Danesh, J. Dupuis, J. I. Rotter, J. B. Meigs, M. O. Goodarzi, S. O'Rahilly, M. G. Ehm, N. J. Wareham, D. Waterworth, CVD50 Consortium, CHARGE Consortium, CHD Exome+ Consortium, CARDIOGRAM Exome.

58/2:45 Dense fine-mapping reveals FOXA2-bound sites as a genomic marker of type 2 diabetes risk. K. J. Gaulton, T. M. Teslovich, T. Ferreira, M. Reschen, A. Mahajan, Y. Lee, M. van de Bunt, N. W. Rayner, A. Raimondo, C. O'Callaghan, A. L. Gloyn, A. P. Morris, M. I. McCarthy, DIAGRAM Consortium.

59/3:00 Integrated analysis of pancreatic islet eQTLs and regulatory state maps identifies putative causal mechanisms at T2D-associated loci. M. van de Bunt, J. E. Manning Fox, K. J. Gaulton, A. Barrett, X. Q. Dai, M. Ferdaoussi, P. E. MacDonald, M. I. McCarthy, A. L. Gloyn.

60/3:15 T2D-associated ARAP1 regulates GTPase activity, insulin processing and secretion in the pancreatic beta cell. J. R. Kulzer, R. C. McMullan, M. P. Fogarty, K. L. Mohlke.

Sunday, October 19

1:30 PM–3:30 PM

Concurrent Platform Session A

19. Genomic Methods in Clinical Practice

Room 28, Upper Level, Convention Center

Moderators: Yaping Yang, Baylor Col Med, Houston
  Swaroop Aradhya, Invitae Inc, Palo Alto

61/1:30 Discordant non-invasive prenatal testing and cytogenetic results: Is there a cause for concern? J. Wang, T. Sahoo, S. Schonberg, K. Kopita, L. Ross, K. Patek, C. Strom.

62/1:45 Implementation of microarray analysis for oncology samples: Effectiveness for detection of both copy number changes and copy-neutral loss of heterozygosity. S. Schwartz, R. Burnside, I. Gadi, V. Jaswaney, E. Keitges, A. Penton, K. Phillips, H. Risheg, J. Schleede, J. Tepperberg, P. Papenhausen.

63/2:00 A cost-effective screen for identifying novel transposable element insertions in human genomes. E. M. Kvikstad, G. Lunter.

64/2:15 NUC-seq: Single-cell exome sequencing using G2/M nuclei. M. L. Leung, Y. Wang, J. Waters, N. E. Navin.

65/2:30 Simple and robust NGS RNA-based assay to assess impact of VUS on splicing. E. Girard, J. Tarabeux, E. Bernard, A. Collet, A. Legrand, V. Moncoutier, C. Dehainault, J. P. Vert, D. Stoppa-Lyonnet, N. Servant, C. Houdayer.

66/2:45 Making sense of sequence variation in PPARG: A comprehensive experimental approach. A. Majithia, J. Flannick, T. Mikkelsen, D. Altshuler.

67/3:00 Molecular combing for fascioscapulohumeral dystrophy type 1: Benefits of direct visualization of DNA fibers. C. M. Strom, J. C. Wang, X. J. Yang, B. H. Nguyen, V. Sulcova, P. Chan, Y. Liu, A. Anguiano, F. Z. Boyar.

68/3:15 An augmented exome providing accurate structural variant detection. A. Patwardhan, S. Chervitz, M. Li, J. Harris, G. Bartha, D. Newburger, M. Pratt, S. Garcia, J. Tirch, N. Leng, C. Haudenschild, S. Luo, D. Church, J. West, R. Chen.

Sunday, October 19

1:30 PM–3:30 PM

Concurrent Platform Session A

20. Genetics and Mechanisms in Neurological Disorders

Room 29, Upper Level, Convention Center

Moderators: Nara Sobreira, Johns Hopkins Univ, Baltimore
  Peng Jin, Emory Univ Sch Med, Atlanta

69/1:30 Mutations in TENM4, a regulator of axon guidance and central myelination, cause essential tremor. H. Hor, L. Francescatto, L. Bartesaghi, S. Ortega-Cubero, M. Kousi, O. Lorenzo- Betancor, F. J. Jiménez-Jiménez, A. Gironell, J. Clarimón, O. Drechsel, J. A. G. Agúndez, D. Kenzelmann Broz, R. Chiquet-Ehrismann, A. Lleó, F. Coria, E. García-Martin, H. Alonso-Navarro, M. J. Martí, J. Kulisevsky, C. N. Hor, S. Ossowski, R. Chrast, N. Katsanis, P. Pastor, X. Estivill.

70/1:45 Mitochondrial serine protease HTRA2 p.G399S in a 6-generation kindred with Essential Tremor and Parkinson’s Disease. H. Unal Gulsuner, S. Gulsuner, N. Durmaz Mercan, O. E. Onat, T. Walsh, H. Shahin, O. Dogu, T. Kansu, H. Topaloglu, B. Elibol, C. Akbostanci, M.-C. King, T. Ozcelik, A. B. Tekinay.

71/2:00 De novo mutations in SIK1 dysregulate HDAC5-MEF2C activity and cause Ohtahara syndrome and infantile spasms. J. N. Hansen, C. Snow, E. Tuttle, D. Ghoneim, C. Smyser, C. A. Gurnett, M. Shinawi, W. B. Dobyns, J. Wheless, M. W. Halterman, L. A. Jansen, B. M. Paschal, A. R. Paciorkowski.

72/2:15 Haploinsufficiency of Pumilio1 leads to SCA1-like neurodegeneration by increasing wild-type Ataxin1 levels in a miRNA-independent manner. V. A. Gennarino, R. Singh, J. J. White, K. Han, A. De Maio, P. Jafar-Nejad, A. di Ronza, H. Kang, H. T. Orr, R. V. Sillitoe, H. Y. Zoghbi.

73/2:30 Exome sequencing unveils novel disease-causing variation in Charcot-Marie-Tooth disease and suggests genetic burden contributes to phenotypic variability and complex neuropathy. C. Gonzaga-Jauregui, T. Harel, T. Gambin, M. Kousi, L. B. Griffin, M. N. Bainbridge, K. S. Lawson, D. Pehlivan, Y. Okamoto, M. Withers, P. Mancias, A. Slavotinek, P. J. Reitnauer, M. Shy, T. O. Crawford, M. Koenig, M. T. Goksungur, S. Jhangiani, J. Willer, B. N. Flores, W. Wiszniewski, A. Antonellis, N. Katsanis, D. M. Muzny, E. Boerwinkle, R. A. Gibbs, J. R. Lupski, Baylor-Hopkins Center for Mendelian Genomics.

74/2:45 Genome-wide association study identifies common variants associated with general and MMR vaccine-related febrile seizures. B. Feenstra, B. Pasternak, F. Geller, L. Carstensen, T. Wang, F. Huang, J. L. Eitson, M. V. Hollegaard, H. Svanström, M. Vestergaard, D. M. Hougaard, J. W. Schoggins, L. Y. Jan, M. Melbye, A. Hviid.

75/3:00 A genome-wide meta-analysis of migraine in more than 59,000 cases and 313,000 controls reveals 29 new loci, increasing the total number of risk loci to 42. P. Gormley, V. Anttila, M. Muona, A. Palotie, on behalf of the International Headache Genetics Consortium (IHGC).

76/3:15 Brain somatic mutations cause focal cortical dysplasia type II in human and mouse. J. S. Lim, W. I. Kim, H. C. Kang, S. H. Kim, A. H. Park, S. Kim, D. Kim, D. S. Kim, J. H. Lee.

Sunday, October 19

1:30 PM–3:30 PM

Concurrent Platform Session A

21. Developmental Genetics: Immunodeficiencies and Autoimmune Disorders

Room 30, Upper Level, Convention Center

Moderators: Wendy K. Chung, Columbia Univ, New York
  Simon Mallal, Vanderbilt Sch Med, Nashville

77/1:30 Parallel studies in humans and dogs implicate ADAMTS20 in cleft lip and palate formation. Z. Wolf, B. Arzi, E. Leslie, J. Shaffer, H. Brand, C. Willet, N. Karmi, T. McHenry, E. Feingold, X. Wang, J. Murray, M. Marazita, C. Wade, D. Bannasch.

78/1:45 Identification of a novel susceptibility locus for nonsyndromic cleft lip and palate at chromosome 15q13. K. U. Ludwig, A. C. Boehmer, H. Peters, D. Graf, P. Gültepe, P. A. Mossey, R. P. Steegers-Theunissen, M. Rubini, M. M. Nöthen, M. Knapp, E. Mangold.

79/2:00 Variants in developmental genes confer risk of hypospadias. F. Geller, B. Feenstra, L. Carstensen, T. H. Pers, I. A. L. M. van Rooij, I. B. Körberg, S. Choudhry, J. Karjalainen, T. H. Schnack, M. V. Hollegaard, W. F. J. Feitz, N. Roeleveld, D. M. Hougaard, J. N. Hirschhorn, L. S. Baskin, A. Nordenskjöld, L. F. M. van der Zanden, M. Melbye.

80/2:15 Increased frequency of de novo predicted deleterious variants in non-isolated congenital diaphragmatic hernia. L. Yu, A. Sawle, J. Wynn, G. Aspelund, C. Stolar, M. Arkovitz, D. Potoka, K. Azarow, G. Mychaliska, Y. Shen, W. Chung.

81/2:30 A mutation in transferrin receptor 1 that disrupts iron internalization causes a novel immunodeficiency. S. E. Boyden, H. H. Jabara, J. Chou, N. Ramesh, M. J. Massaad, L. Notarangelo, M. D. Fleming, W. Al-Herz, L. M. Kunkel, R. S. Geha.

82/2:45 TRNT1 missense mutations define an autoinflammatory disease characterized by recurrent fever, severe anemia, and B-cell immunodeficiency. M. Stoffels, Q. Zhou, A. Giannelou, D. Stone, A. Sediva, S. Rosenzweig, J. Edwan, M. Pelletier, K. Bishop, B. Carrington, R. Sood, E. F. Remmers, K. Barron, I. Aksentijevich, D. L. Kastner.

83/3:00 COPA mutations disrupt intracellular transport and cause a novel autoimmune syndrome characterized by chronic pulmonary disease with pulmonary hemorrhages. W. Wiszniewski, L. B. Watkin, B. Jessen, T. Vece, L. Forbes, C. Gonzaga-Jauregui, S. N. Jhangiani, D. M. Muzny, E. Boerwinkle, R. A. Gibbs, A. Shum, J. Orange, J. R. Lupski.

84/3:15 Mendelian genetic studies of immune disorders to identify novel targets for therapeutic intervention. J. McElwee, X. Chen, J. Lyons, G. Sun, X. Yu, J. Milner, Y. Liuv, Z. Deng, A. Almeida de Jesus, R. Goldbach-Mansky, Y. Zhang, H. Matthews, H. Su, M. Lenardo.

Monday, October 20

8:00 AM–8:25 AM

22. Plenary Abstracts Featured Presentation II

Hall B1, Ground Level, Convention Center

Moderator: Kay E. Davies, Univ. Oxford, UK

85/8:00 The Human Knockout Project: systematic discovery of loss-of-function variants in humans. K. J. Karczewski, V. Narasimhan, M. Lek, M. Rivas, S. Balasubramanian, M. Gerstein, B. Keating, T. Lappalainen, A. Palotie, M. Daly, D. van Heel, R. Trembath, R. Durbin, D. G. MacArthur.

Monday, October 20

8:30 AM–8:45 AM

23. ASHG Award for Excellence in Human Genetics Education Presentation

Hall B1, Ground 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.

Shawn E. McCandless
Case Western Reserve University


Suzanne B. Cassidy, MD
Clinical Professor of Pediatrics in Division of Medical Genetics
University of California, San Francisco

Well-known for her clinical and research leadership in Prader-Willi syndrome, Dr. Cassidy has played key roles in the genetics education of medical students, residents, and trainees as well as of patients and their families. She has developed a variety of educational materials, including three editions of the textbook Management of Genetic Syndromes, and clinical genetics training programs across the country.

Throughout her career, Dr. Cassidy has received numerous honors for her research and teaching, including election to several advisory boards, founding editorship for clinical genetics in the journal Genetics in Medicine, and visiting professorships at institutions in the United States and abroad. She was also a member of the founding Residency Review Committee for Medical Genetics when the field was first recognized as a medical specialty, and has served on the American Board of Medical Genetics and Genomics. She currently serves as president of the International Prader-Willi Syndrome Organisation.

A longtime member of ASHG, Dr. Cassidy belonged to the Society’s Information and Education Committee from 1987-1990, participated in its Rapid Action Task Force on Genetic Testing in 1995, and was a member of its Nominating Committee in 2007. She also served on the ASHG Board of Directors from 1993-1995.

Past Recipients: Jessica G. Davis (2013); Alan Emery (2012); Giovanni Romeo (2011); Thomas D. Gelehrter (2010); Bruce R. Korf (2009); John Carey, Lynn Jorde, and Louisa Stark (2008); Robert Elston (2007); Roberta "Bonnie" Pagon (2006); Joseph McInerney (2005).


Monday, October 20

8:45 AM–9:00 AM

24. ASHG Victor A. McKusick Leadership Award Presentation

Hall B1, Ground 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.

Rod R. McInnes
Lady Davis Research Institute
Jewish General Hospital


David Valle, MD
Henry J. Knott Professor and Director, McKusick-Nathans Institute of Genetic Medicine
Professor, Departments of Biology and Ophthalmology, Johns Hopkins University School of Medicine

Dr. Valle’s research has focused on the genetic factors underlying human health and disease, including specific genetic diseases as well as the broader gene-protein interactions that contribute to various health conditions. Notable achievements include characterizing the molecular basis of many single-gene disorders, developing mouse models to study human disorders, and analyzing genetic variants associated with psychiatric diseases such as schizophrenia. In addition, he has led efforts to improve genetics education by developing medical genetics curricula; editing the widely-used biochemical genetics textbook The Metabolic and Molecular Bases of Inherited Disease; and directly training more than 500 students, fellows, and clinical residents.

Dr. Valle was inducted into the Institute of Medicine of the National Academy of Sciences in 2002 and named a Fellow of the American Association for the Advancement of Science in 2007. He has received numerous awards for his research and teaching, including the March of Dimes Foundation’s Colonel Harland Sanders Award for Lifetime Achievement in Genetics Research and Education in 2003 and several honorary lectureships.

An ASHG member since 1982, Dr. Valle belonged to ASHG’s Nominating Committee from 1995-1996 and its Awards Committee from 2001-2003, and was Chair of the Awards Committee from 2006-2008. He served on the Editorial Board of The American Journal of Human Genetics from 1989-1991, and since 1992, has co-directed the annual Short Course in Medical and Experimental Mammalian Genetics. In addition, Dr. Valle was part of ASHG’s Board of Directors from 1990-1992 and 2002-2005, including a year as its President in 2003.

Past Recipients: Kurt and Rochelle Hirschhorn (2013); Francis Collins (2012); Leon E. Rosenberg (2011); Charles J. Epstein (2010); Arno G. Motulsky (2009); Victor A. McKusick (2008); Walter Nance (2007); David Rimoin (2006).


Monday, October 20

9:00 AM–9:30 AM

25. ASHG Curt Stern Award Presentation

Hall B1, Ground Level, Convention Center

The Curt Stern Award honors the memory of Curt Stern (1902-1981) as an outstanding pioneering human geneticist. This award is presented yearly for outstanding scientific achievements in human genetics that occurred in the first 10 years of a research career, while the recipient is still in an early career stage. The work may be a single major discovery or a series of contributions on a similar or related topic.

Michael Boehnke
University of Michigan


Gonçalo R. Abecasis, DPhil
Felix Moore Collegiate Professor of Biostatistics, University of Michigan School of Public Health

Aarno Palotie
Massachusetts General Hospital


Mark J. Daly, PhD
Associate Professor of Medicine and Chief of the Analytic and Translational Genetics Unit, Massachusetts General Hospital/Harvard Medical School
Senior Associate Member, Broad Institute

This year’s Curt Stern Award honors the early-career contributions of two human geneticists, Gonçalo R. Abecasis and Mark J. Daly.

Dr. Abecasis has developed statistical and mathematical methods for the analysis of genetic data that have evolved into standard tools in human genetics. In an era of exponential growth in genetic data, his software helps geneticists analyze studies of families and unrelated individuals, characterize variation among genomes, study connections between genetic variation and human disease, and integrate information across gene-mapping studies. He has also led scientific consortia studying a variety of human traits ranging from obesity and heart disease to age-related vision loss, and is currently using next-generation sequencing technology to study large collections of human genomes.

Dr. Daly has made key advances in the genetic mapping of common diseases, including the development of the first human genome maps of single-nucleotide polymorphisms. He also helped establish a framework for the association of portions of the genome to complex disease risk and the regulation of gene expression. In addition, he has led scientific consortia focusing on genome mapping, inflammatory bowel disease, autism, and schizophrenia, and has contributed to statistical methods and software tools that are routinely used by human geneticists worldwide.

Publisher Thomson-Reuters has listed both Dr. Abecasis and Dr. Daly multiple times among the world’s most cited scientific authors, and they have worked together on the International HapMap Project and the 1000 Genomes Project. Both awardees have also made substantial contributions to ASHG, as longtime members of the Society and frequent presenters at its Annual Meeting.

Past Recipients: John F. Moran (2013); 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).


Monday, October 20

9:30 AM–10:00 AM

26. ASHG William Allan Award Presentation

Hall B1, Ground Level, Convention Center

The William Allan Award is the top prize given by the American Society of Human Genetics. It was established in 1961 in memory of William Allan (1881-1943), who was one of the first American physicians to conduct extensive research in human genetics. The Allan Award is presented annually to recognize substantial and far-reaching scientific contributions to human genetics, carried out over a sustained period of scientific inquiry and productivity.

Haig Kazazian
Johns Hopkins University


Stuart H. Orkin, MD
David G. Nathan Professor of Pediatrics, Harvard Medical School
Chairman, Department of Pediatric Oncology, Dana-Farber Cancer Institute
Associate Chief of Hematology/Oncology, Boston Children’s Hospital
Investigator, Howard Hughes Medical Institute

Dr. Orkin has pioneered research into the genetics of blood diseases, including identifying the primary mutations that cause them, defining factors that regulate how these mutations are expressed in blood cells, and applying these findings to medicine. In the 1970s and early 1980s, his laboratory comprehensively defined mutations that lead to the β-thalassemias, and in the mid-1980s, they became the first group to successfully clone a gene causing a disease without already knowing the encoded protein. More recently, Dr. Orkin’s laboratory characterized the switch from fetal to adult hemoglobin, including its regulation and the basis for genetic variation. They are currently exploring ways to translate these insights into new treatments for thalassemias and sickle cell anemia.

Dr. Orkin was elected to the National Academy of Sciences (NAS) in 1991 and the Institute of Medicine in 1992. In 2005, he received the Association of American Medical Colleges Distinguished Research Award and in 2013, he received the NAS Jessie Stevenson Kovalenko Medal. In addition to his contributions to human genetics, Dr. Orkin is a longtime member of ASHG and has served on the editorial board of The American Journal of Human Genetics.

Past Recipients: Aravinda Chakravarti (2013); Uta Francke (2012); John M. Opitz (2011); Jurg Ott (2010); Huntington F. Willard (2009); Haig Kazazian (2008); Arthur Beaudet (2007); Dorothy Warburton (2006); Francis Collins (2005).


Monday, October 20

10:30 AM–12:30 PM

Concurrent Platform Session B

27. Cloudy with a Chance of Big Data

Hall B1, Ground Level, Convention Center

Moderators: Paul Flicek, European Bioinformatics Inst, Cambridge, UK
  Terry Gaasterland, UC San Diego

86/10:30 Using compressed data structures to capture variation in thousands of human genomes. S. A. McCarthy, Z. Lui, J. T. Simpson, Z. Iqbal, T. M. Keane, R. Durbin.

87/10:45 Exploring genetic variation and genotypes among millions of genomes. R. M. Layer, A. R. Quinlann.

88/11:00 Databases, genome repositories, and clinical applications to interpret personal genome for precision and preventative therapies. R. Chen.

89/11:15 DbGaP genotype fingerprint collection. Y. Jin, S. Stefanov, S. Dracheva, Z. Wang, N. Sharopova, A. Sturcke, S. Sherry, M. Feolo.

90/11:30 Integrated analysis of microRNA expression, UTR binding sites, and human variation in ocular tissues. T. Gaasterland, A. N. Dubinsky, L. E. Edsall, T. S. Mondala, P. Ordoukhanian, S. R. Head.

91/11:45 Second-generation PLINK: Rising to the challenge of larger and richer datasets. C. C. Chang, C. C. Chow, L. C. A. M. Tellier, S. Vattikuti, S. M. Purcell, J. J. Lee.

92/12:00 Microtask crowdsourcing for annotating diseases in PubMed abstracts. A. I. Su, B. M. Good, M. Nanis.

93/12:15 Automating literature reviews: Predicting variant pathogenicity using the bibliomic index. C. A. Cassa, D. M. Jordan, S. R. Sunyaev.

Monday, October 20

10:30 AM–12:30 PM

Concurrent Platform Session B

28. Architecture and Impact of Human Knockout Alleles

Room 6AB, Upper Level, Convention Center

Moderators: Tuuli Lappalainen, Columbia Univ, New York
  Eric Boerwinkle, Baylor Col Med, Houston

94/10:30 Integrated analysis of protein-coding variation in over 90,000 individuals from exome sequencing data. D. G. MacArthur, M. Lek, E. Banks, R. Poplin, T. Fennell, K. Samocha, B. Thomas, K. Karczewski, S. Purcell, P. Sullivan, S. Kathiresan, M. I. McCarthy, M. Boehnke, S. Gabriel, D. M. Altshuler, G. Getz, M. J. Daly, Exome Aggregation Consortium.

95/10:45 Identification of a large set of rare complete human knockouts. P. Sulem, H. Helgason, A. Oddson, H. Stefansson, SA. Gudjonsson, F. Zink, E. Hjartasson, G. Sigurdsson, A. Jonasdottir, A. Sigurdsson, O. Magnusson, A. Kong, A. Helgason, U. Thorsteinsdottir, G. Masson, D. Gudbjartsson, K. Stefansson.

96/11:00 Making sense of nonsense: Consequence of premature stop mutations. S. Balasubramanian, Y. Fu, M. Pawashe, M. Jin, J. Liu, D. MacArthur, M. Gerstein.

97/11:15 Analysis of stop-gain and frameshift variants in human innate immunity genes. A. Rausell, P. Mohammadi, PJ. McLaren, I. Bartha, I. Xenarios, J. Fellay, A. Telenti.

98/11:30 Insights into protein truncating variation from high-quality indel calling in 1000 UK population exomes - implications for disease gene discovery and clinical utility. E. Ruark, A. Renwick, E. Ramsay, S. Seal, K. Snape, S. Hanks, A. Rimmer, M. Munz, A. Elliott, G. Lunter, N. Rahman.

99/11:45 Exome sequencing of fit adults with high parental relatedness identifies over 600 rare human gene knockouts. V. Narasimhan, K.J. Karczewski, K.A. Hunt, Y. Xue, P. Danecek, S. Mccarthy, C. Tyler-Smith, C. Griffiths, J. Wright, E.R. Maher, . Macarthur, R.C. Trembath, D.A. van Heel, R.M. Durbin.

100/12:00 Analysis of loss-of-function variants in 8,612 deeply-phenotyped individuals identifies novel loci for common chronic disease. A. H. Li, A. C. Morrison, G. Metcalf, L. A. Cupples, J. A. Brody, L. M. Polfus, B. Yu, N. Veeraraghavan, X. Liu, T. Lumley, D. Muzny, T. H. Mosley, R. A. Gibbs, E. Boerwinkle.

101/12:15 Loss-of-function variants influence the human metabolome. B. Yu, A.H. Li, G. Metcalf, D.M. Muzny, A.C. Morrison, T.H. Mosley, R.A. Gibbs, E. Boerwinkle.

Monday, October 20

10:30 AM–12:30 PM

Concurrent Platform Session B

29. Population Structure, Admixture, and Human History

Room 6CF, Upper Level, Convention Center

Moderators: Eimear Kenny, Icahn Sch Med Mount Sinai, New York
  Jeff Kidd, Univ Michigan, Ann Arbor

102/10:30 Capture of 390,000 SNPs in dozens of ancient central Europeans reveals a population turnover in Europe thousands of years after the advent of farming. I. Lazaridis, W. Haak, N. Patterson, N. Rohland, S. Mallick, B. Llamas, S. Nordenfelt, E. Harney, A. Cooper, K. W. Alt, D. Reich.

103/10:45 Insights into British and European population history from ancient DNA sequencing of Iron Age and Anglo-Saxon samples from Hinxton, England. S. Schiffels, W. Haak, B. Llamas, E. Popescu, L. Loe, R. Clarke, A. Lyons, P. Paajanen, D. Sayer, R. Mortimer, C. Tyler-Smith, A. Cooper, R. Durbin.

104/11:00 Fine-scale population structure in Europe. S. Leslie, G. Hellenthal, S. Myers, P. Donnelly, International Multiple Sclerosis Genetics Consortium.

105/11:15 The population structure and demographic history of Sardinia in relationship to neighboring populations. J. Novembre, C. Chiang, J. Marcus, C. Sidore, M. Zoledziewska, M. Steri, H. Al-asadi, G. Abecasis, D. Schlessinger, F. Cucca.

106/11:30 Population structure in African-Americans. S. Gravel, M. Barakatt, B. Maples, M. Aldrich, E. E. Kenny, C. D. Bustamante, S. Baharian.

107/11:45 Genetic testing of 400,000 individuals reveals the geography of ancestry in the United States. Y. Wang, J. M. Granka, J. K. Byrnes, M. J. Barber, K. Noto, R. E. Curtis, N. M. Natalie, C. A. Ball, K. G. Chahine.

108/12:00 Statistical inference of archaic introgression and natural selection in Central African Pygmies. P. Hsieh, J. D. Wall, J. Lachance, S. A. Tishkoff, R. N. Gutenkunst, M. F. Hammer.

109/12:15 Inferences about human history and natural selection from 280 complete genome sequences from 135 diverse populations. S. Mallick, D. Reich, Simons Genome Diversity Project Consortium.

Monday, October 20

10:30 AM–12:30 PM

Concurrent Platform Session B

30. Neurogenetics: From Gene to Mechanism (I)

Room 6DE, Upper Level, Convention Center

Moderators: Stephanie Bielas, Univ Michigan, Ann Arbor
  Stephan Züchner, Univ Miami, Miami

110/10:30 Galanin mutations in temporal lobe epilepsy. M. Guipponi, A. Chentouf, K. E. B. Webling, K. Freimann, A. Crespel, C. Nobile, T. Dorn, J. Hansen, J. Lemke, G. Lesca, F. Becker, U. Stephani, H. Muhle, I. Helbig, P. Ryvlin, E. Hirsch, G. Rudolf, C. Gehrig, F. Santoni, M. Pizzato, U. Langel, S. E. Antonarakis.

111/10:45 Homozygous mutations in SLC6A17 are causative for autosomal recessive intellectual disability. H. van Bokhoven, Z. Iqbal, M. H. Willemsen, MA. Papon, H. Venselaar, W. M. Wissink-Lindhout, M. Benevento, A. T. Vulto-van Silfhout, L. E. L. M. Vissers, A. P.M. de Brouwer, N. Nadif Kasri, T. F. Wienker, H. Hilger Ropers, L. Musante, K. Kahrizi, H. Najmabadi, F. Laumonnier, T. Kleefstra.

112/11:00 De novo KCNB1 mutations in epileptic encephalopathy. A. Torkamani, K. Bersell, B. S. Jorge, R. L. Bjork, J. R. Friedman, C. S. Bloss, S. E. Topol, G. Zhang, J. Lee, J. Cohen, S. Gupta, S. Naidu, C. G. Vanoye, A. L. George, J. A. Kearney.

113/11:15 A Drosophila genetic resource facilitates the identification of variants in ANKLE2 in a unique family with severe microcephaly. W.-L. Charng, M. Jaiswal, N. Link, S. Yamamoto, T. Gambin, E. Karaca, G. Mirzaa, W. Wiszniewski, B. Xiong, V. Bayat, T. Harel, D. Pehlivan, S. Penney, L. E. Vissers, J. de Ligt, S. Jhangiani, D. Muzny, R. D. Clark, C. J. Curry, E. Boerwinkle, W. B. Dobyns, R. A. Gibbs, R. Chen, M. F. Wangler, H. J. Bellen, J. R. Lupski.

114/11:30 Additive toxicity of SOX10 mutation underlies a complex neurological phenotype of PCWH. K. Inoue, Y. Ito, N. Inoue, Y. U. Inoue, S. Nakamura, Y. Matsuda, M. Inagaki, T. Ohkubo, J. Asami, Y. W. Terakawa, S. Kohsaka, Y. Goto, C. Akazawa, T. Inoue.

115/11:45 Paving the road to elaborate the genetics of intellectual disabilities. H. Najmabadi, H. Hu, Z. Fattahi, S. Abedini, M. Hosseini, F. Larti, R. Jazayeri, M. Oladnabi, M. Mohseni, T. Wienker, L. Musante, K. Kahrizi, H. H. Ropers.

116/12:00 KIRREL3, associated with intellectual disability and autism, functions as a presynaptic organizer and interacts with proteins with roles in neurodevelopment. A. K. Srivastava, Y. F. Liu, Y. Luo, A. Chaubey, H.-G. Kim, S. M. Sowell.

117/12:15 The importance of neurosteroid hormones in the pathogenesis of protocadherin 19 female limited epilepsy and intellectual disability (PCDH19-FE). J. Gecz, C. Tan, E. Ranieri, D. Pham, C. Shard, K. Hynes, E. Douglas, L. S. Nguyen, M. Corbett, D. Leach, G. Buchanan, E. Haan, L. G. Sadleir, C. Depienne, R. S. Moller, R. Guerrini, C. Marini, S. F. Berkovic, I. E. Scheffer.

Monday, October 20

10:30 AM–12:30 PM

Concurrent Platform Session B

31. Cardiovascular Genetics I: Single Gene Stories

Room 20A, Upper Level, Convention Center

Moderators: Pinar Bayrak-Toydemir, Univ. Utah, Salt Lake City
  Eric Villard, INSERM/UPMC, Paris, France

118/10:30 Mutations in SGOL1 cause a novel cohesinopathy affecting heart and gut rhythm. N. Gosset, P. Chetaille, J.-M. Côté, C. Houde, C. Preuss, S. Burkharda, J. Castilloux, J. Piché, S. Leclerc, F. Wünnemann, M. Thilbault, C. Gagnon, A. Galli, E. Tuck, G.-R. X. Hickson, N. El Amine, F. LeDeist, E. Lemyre, P. De Santa Barbara, S. Faure, A. Jonzon, M. Cameron, H. Dietz, E. Gallo-McFarlane, W. Benson, Y. Shen, M. Jomphe, S.-J. M. Jones, J. Bakkers, G. Andelfinger.

119/10:45 Functional characterization of long-QT syndrome- and sudden infant death-associated OLFML2B mutations. T. A. Plötz, C. J. Gloeckner, A. Kiper, M. Vennemann, M. Kartmann, M. Schell, H. Prucha, C. Congiu, Z. Schäfer, S. Hauck, I. Sinicina, E. Kremmer, B. M. Beckmann, F. Domingues, T. Meitinger, A. Peters, M. Cohen, S. Kääb, J. J. Schott, E. R. Behr, T. Bajanowski, S. Just, H. W. Mewes, M. Ueffing, N. Decher, M. Näbauer, A. Pfeufer.

120/11:00 EIF2AK4 (GCN2) mutations cause pulmonary veno-occlusive disease, a severe form of pulmonary hypertension. F. Soubrier, M. Eyries, D. Montani, B. Girerd, C. Perret, A. Leroy, C. Lonjou, N. Chelghoum, F. Coulet, D. Bonnet, P. Dorfmuller, E. Fadel, O. Sitbon, G. Simonneau, D.-A. Tregouet, M. Humbert.

121/11:15 Delineation and therapeutic implications of a modifier locus of aortic aneurysm in Marfan syndrome. A. Doyle, J. Doyle, K. Kent, L. Myers, N. Wilson, N. Huso, D. Bedja, M. Lindsay, J. Pardo-Habashi, B. Loeys, J. De Backer, A. De Paepe, H. Dietz.

122/11:30 Mutations in FOXE3/Foxe3 cause familial thoracic aortic aneurysms and dissections. S. Q. Kuang, O. Medina-Martinez2, D. C. Guo, L. Gong, E. S. Regalado, C. Boileau, G. Jondeau, S. K. Prakash, A. M. Peters, H. Pannu, M. J. Bamshad, J. Shendure, D. A. Nickerson, C. L. Reynolds, M. Jamrich, D. M. Milewicz.

123/11:45 Titin truncations: dissection of genotype and cardiac phenotype. A. Roberts, J. Ware, D. Herman, S. Schafer, J. Baksi, R. Buchan, R. Walsh, S. John, S. Wilkinson, L. Felkin, A. Bick, F. Mazzarotto, M. Radke, M. Gotthardt, P. Barton, N. Hubner, J. Seidman, C. Seidman, S. Cook.

124/12:00 FLNC is a novel gene for dilated cardiomyopathy in two families. R. L. Begay, A. Martin, S. L. Graw, D. B. Slavov, C. A. Tharp, M. Sweet, F. Brun, K. L. Jones, K. Gowan, D. Miani, G. Sinagra, L. Mestroni, D. M. Garrity, M. R. G. Taylor.

125/12:15 Genome-wide association study on secundum atrial septal defects. L. Rodriguez-Murillo, M. Parfenov, I. Peter, W. K. Chung, L. Mitchell, A. J. Agopian, C. Seidman, J. Seidman, B. D. Gelb, Pediatric Cardiac Genomics Consortium.

Monday, October 20

10:30 AM–12:30 PM

Concurrent Platform Session B

32. Molecular Insights into Mendelian Disorders

Room 20BC, Upper Level, Convention Center

Moderators: Daryl Scott, Baylor Col Med, Houston
  Ethylin W. Jabs, Mount Sinai Sch Med, New York

126/10:30 Clinical comparison of Kabuki syndrome with KMT2D and KDM6A mutations. N. Miyake, E. Koshimizu, N. Matsumoto, N. Niikawa.

127/10:45 Mutations in KMT2D, ZBTB24, and KMT2A in patients with clinical diagnosis of Kabuki syndrome lead to shared epigenetic abnormalities of target genes. N. Sobreira, L. Zhang, C. Ongaco, J. Romm, M. Baker, K. Doheny, D. Bertola, K. Chong, A. B. A. Perez, M. Melaragno, V. Meloni, C. Ladd-Acosta, D. Valle, H. T. Bjornsson.

128/11:00 Noonan syndrome due to RIT1 mutations: Further clinical and molecular delineation in 32 cases. A. Verloes, A. Caye, A. Dieux Coeslier, C. Baumann, C. Vincent-Delorme, P. Bouvagnet, A. David, D. Lacombe, P. Blanchet, B. Isidor, M. Rio, D. Héron, S. Sauvion, J. L. Alessandri, V. Drouin-Garraud, B. Doray, N. Pouvreau, A. Cavé.

129/11:15 Whole exome sequencing in 78 Noonan syndrome individuals identifies two new candidate genes. G. L. Yamamoto, R. Atique, M. Aguena, L. Testai, M. Buscarilli, A. Jorge, A. C. Pereira, A. Malaquias, C. A. Kim, M. R. Passos-Bueno, D. R. Bertola.

130/11:30 NSD1+/- DNA methylation (DNAm) signature: A novel functional diagnostic tool for Sotos syndrome. S. Choufani, C. Cytrynbaum, B. H. Y. Chung, A. L. Turinsky, D. Grafodatskaya, Y. A. Chen, H. M. Luk, I. F. M. Lo, S. T. S. Lam, D. J. Stavropoulos, B. Gibson, M. Reardon, M. Brudno, R. Mendoza-Londono, D. Chitayat, R. Weksberg.

131/11:45 A new neurodevelopmental-congenital heart disease syndrome caused by variants in a novel disease gene, TELO2. J. You, N. Sobreira, D. Gable, J. Jurgens, D. Valle, M. Armanios, J. Hoover Fong.

132/12:00 A novel variant in tenascin-X may be associated with an Ehlers Danlos phenotype in patients with congenital adrenal hyperplasia. R. Morissette, W. Chen, Z. Xu, J. Dreiling, M. Quezado, N. McDonnell, D. Merke.

133/12:15 The impairment of MAGMAS function in humans is responsible for a severe skeletal dysplasia. C. Mehawej, A. Delahodde, L. Legeai-Mallet, V. Delague, N. Kaci, J.-P. Desvignes, Z. Kibar, J.-M. Capo-Chichi, E. Chouery, A. Munnich, V. Cormier-Daire, A. Mégarbané.

Monday, October 20

10:30 AM–12:30 PM

Concurrent Platform Session B

33. Genomic Alterations of Tumors

Room 20D, Upper Level, Convention Center

Moderators: John McPherson, Ontario Inst Cancer Res, Toronto
  Li Ding, Washington Univ in St. Louis

134/10:30 Analysis of mutational landscape and genetic heterogeneity in liver cancer with whole genome sequencing. A. Fujimoto, M. Furuta, Y. Shiraishi, H. H. Nguyen, D. Shigemizu, K. Gotoh, Y. Kawakami, T. Nakamura, M. Ueno, S. Ariizumi, T. Shibata, H. Ojima, K. Shimada, S. Hayami, Y. Shigekawa, H. Aikata, K. Arihiro, H. Ohdan, S. Marubashi, T. Yamada, O. Ishikawa, M. Kubo, S. Hirano, M. Yamamoto, H. Yamaue, K. Chayama, S. Miyano, T. Tsunoda, H. Nakagawa.

135/10:45 Abundant somatic L1 retrotransposition occurs early during colorectal and pancreatic tumorigenesis. S. Solyom, A. D. Ewing, A. Gacita, L. D. Wood, F. Ma, A. Makohon-Moore, D. Xing, R. Hruban, C. A. Iacobuzio-Donahue, S. J. Meltzer, B. Vogelstein, K. W. Kinzler, H. H. Kazazian.

136/11:00 Cis-regulatory drivers in colorectal cancer. H. Ongen, C. L. Andersen, J. B. Bramsen, B. Oster, M. H. Rasmussen, P. G. Ferreira, J. Sandoval, E. Vidal, N. Whiffin, I. Tomlinson, R. S. Houlson, M. Esteller, T. F. Orntoft, E. T. Dermitzakis.

137/11:15 Somatic mutations modulate ceRNA drivers of tumorigenesis. J. He, H.-S. Chiu, P. Sumazin, A. Califano.

138/11:30 Divergence between high metastatic tumor burden and low circulating tumor DNA concentration in metastasized breast cancer. M. Heidary, M. Auer, P. Ulz, E. Heitzer, E. Petru, C. Gasch, S. Riethdorf, O. Mauermann, I. Lafer, G. Pristauz, S. Lax, K. Pantel, JB. Geigl, MR. Speicher.

139/11:45 Extrachromosomal driver mutations in glioblastoma and low grade glioma. S. I. Nikolaev, F. Santoni, M. Garieri, P. Makrythanasis, E. Falconnet, M. Guipponi, A. Vannier, I. Radovanovic, F. Bena, K. Schaller, V. Dutoit, V. Clement-Schatlo, P.-Y. Dietrich, S. E. Antonarakis.

140/12:00 Automated tumor phylogeny reconstruction using multi-sample deep sequencing somatic variants. V. Popic, R. Salari, D. Kashef-Haghighi, D. Newburger, R. West, S. Batzoglou.

141/12:15 Development and validation of a ultra-high depth FFPE targeted exome sequencing platform for routine cancer patient care. K. Chen, F. Meric-Bernstam, H. Zhao, Q. Zhang, N. Ezzeddine, L. Tang, P. Song, Y. Qi, Y. Mao, T. Chen, Z. Chong, W. Zhou, X. Zheng, A. Johnson, S. Kopetz, M. Davies, J. DeGroot, S. Moulder, K. Aldape, M. Routbort, R. Luthra, K. Shaw, J. Mendelsohn, G. Mills, A. Eterovic.

Monday, October 20

10:30 AM–12:30 PM

Concurrent Platform Session B

34. Metabolic Disorders: New Diagnostics and Pathogenic Insights

Room 28, Upper Level, Convention Center

Moderators: Bruce Barshop, UC San Diego
  Tina Cowan, Stanford Univ, Palo Alto

142/10:30 Novel insights regarding the pathogenesis and treatment of pseudoxanthoma elasticum. S. G. Ziegler, C. R. Ferreira, A. B. Pinkerton, J. L. Millan, W. A. Gahl, H. C. Dietz.

143/10:45 Decipher mitochondrial disorders using exome sequencing. R. Kopajtich, T. Haack, L. Kremer, C. Biagosch, B. Haberberger, T. Wieland, T. Schwarzmayr, P. Freisinger, T. Klopstock, J. Mayr, W. Sperl, M. Minczuk, T. M. Strom, T. Meitinger, H. Prokisch.

144/11:00 Distinct clinical phenotypes in two unrelated patients with mutations in the TRNT1 gene encoding tRNA nucleotidyl transferase. F. Sasarman, I. Thiffault, W. Weraarpachai, S. Salomon, C. Maftei, J. Gauthier, N. Webb, O. Elpeleg, C. Brunel-Guitton, G. Mitchell, E. A. Shoubridge.

145/11:15 Mutation in the tRNA-modification enzyme GTPBP3 causes hypertrophic cardiomyopathy with abnormal respiratory chain assembly. M. Metodiev, Z. Assouline, M. Rio, F. Feillet, B. Mousson de Cameret, D. Chretien, A. Munnich, A. Rötig.

146/11:30 Application of cellular O-linked glycomics analysis for the diagnosis of protein glycosylation disorders. M. He, X. Li, M. Raihan, L. Tan, M. Bennett, W. Gahl, M. Davids, M. Kane, C. F. Boerkoel.

147/11:45 Metabolic diversion towards non-toxic metabolites for therapy of primary hyperoxaluria type 1. R. Castello, R. Borzone, P. Annunziata, P. Piccolo, N. Brunetti-Pierri.

148/12:00 Transcriptome and microRNA profiling reveals deregulated microRNAs and mRNAs in the brain of neuronopathic Gaucher disease mice. Y. Sun, N. Dasgupta, Y. Xu, B. Liou, R. Li, Y. Peng, M. Pandey, S. Tinch, V. Inskeep, G. A. Grabowski.

149/12:15 A mouse model of cblA class isolated methylmalonic acidemia displays reduced survival, growth failure, renal disease and secondary mitochondrial dysfunction. M. W. Epping, C. X. Wang, P. M. Zerfas, G. Elliot, L. Li, I. Manoli, C. P. Venditti.

Monday, October 20

10:30 AM–12:30 PM

Concurrent Platform Session B

35. Looking between the Streetlamps: Variant Phasing and Imputation

Room 29, Upper Level, Convention Center

Moderators: Heather Cordell, Newcastle Univ, Newcastle, UK
  Dale Nyholt, QIMR, Herston, Australia

150/10:30 A genotype likelihood based phasing and imputation method for massive sample sizes of low-coverage sequencing data. W. Kretzschmar, J. Marchini, The Haplotype Reference Consortium.

151/10:45 Imputation server: Next-generation genotype imputation service. C. Fuchsberger, L. Forer, S. Schönherr, F. Kronenberg, G. Abecasis.

152/11:00 Improved haplotype phasing using identity by descent. B. L. Browning, S. R. Browning.

153/11:15 Reducing pervasive false positive identical-by-descent segments detected by large-scale pedigree analysis. E. Y. Durand, N. Eriksson, C. Y. McLean.

154/11:30 Parente2: A fast and accurate method for detecting identity by descent. S. Bercovici, J. M. Rodriguez, L. Huang, S. Batzoglou.

155/11:45 Underdog: A fully-supervised phasing algorithm that learns from hundreds of thousands of samples and phases in minutes. K. Noto, Y. Wang, M. Barber, J. Granka, J. Byrnes, R. Curtis, N. Myres, C. Ball, K. Chahine.

156/12:00 Fast PCA of very large samples in linear time. K. J. Galinsky, P. Loh, G. Bhatia, S. Georgiev, S. Mukherjee, N. J. Patterson, A. L. Price.

157/12:15 Fast detection of IBD segments associated with quantitative traits in genome-wide association studies. Z. Wang, E. Kang, B. Han, S. Snir, E. Eskin.

Monday, October 20

10:30 AM–12:30 PM

Concurrent Platform Session B

36. Chromatin, Gene Regulation and Expression

Room 30, Upper Level, Convention Center

Moderators: Reid Alisch, Univ Wisconsin, Madison
  Tony Capra, Vanderbilt Univ, Nashville

158/10:30 Large-scale profiling of sequence variation affecting transcription factor occupancy in vivo. M. T. Maurano, E. Haugen, R. Sandstrom, J. Vierstra, J. A. Stamatoyannopoulos.

159/10:45 Consider the geneset: Why the transcripts used for variant annotation matter. A. Frankish, J.M. Mudge, R. Petryszak, G.R.S. Ritchie, A. Brazma, J.L. Harrow, GENCODE Consortium.

160/11:00 Multi-sample isoform quantification from RNA-seq. A. E. Byrnes, J. B. Maller, A. R. Sanders, J. Nemesh, T. Sullivan, H. H. Göring, J. Duan, W. Moy, E. I. Drigalenko, P. V. Gejman, B. M. Neale.

161/11:15 Characterizing the genetic architecture of gene expression variation in wild baboons via RNA sequencing. X. Zhou, J. Tung, S. Alberts, J. Altmann, M. Stephens, Y. Gilad.

162/11:30 Genetic control of chromatin in a human population. O. Delaneau, S. Waszak, A. Gschwind, H. Kilpinen, S. Raghav, R. Witwicki, A. Orioli, M. Wiederkehr, M. Gutierrez-Arcelus, N. Panousis, A. Yurovsky, T. Lappalainen, L. Romano-Palumbo, A. Planchon, D. Bielser, I. Padioleau, G. Udin, S. Thurnheer, D. Hacker, N. Hernandez, A. Reymond, B. Deplancke, E. Dermitzakis.

163/11:45 Chromatin accessibility profiling of developing cerebellar granule neurons reveals novel neuronal enhancers and regulatory scheme for ZIC transcription factors. C. L. Frank, F. Liu, R. Wijayatunge, L. Song, C. M. Vockley, A. Safi, G. E. Crawford, A. E. West.

164/12:00 Identification and characterization of enhancer and target gene pairs in mammalian genomes. Y.-C. Hwang, C.-F. Lin, O. Valladares, J. Malamon, Q. Zheng, B. Gregory, L.-S. Wang.

165/12:15 Domains of genome-wide gene expression dysregulation in Down syndrome. S. E. Antonarakis, A. Letourneau, F. A. Santoni, X. Bonilla, M. R. Sailani, D. Robyr, D. Gonzalez, J. Kind, C. Chevalier, R. Thurman, R. S. Sandstrom, Y. Hibaoui, M. Garieri, K. Popadin, E. Falconnet, M. Gagnebin, M. Gehrig, A. Vannier, M. Guipponi, E. Migliavacca, S. Deutsch, A. Feki, J. Stamatoyannopoulos, Y. Herault, B. van Steensel, R. Guigo, C. Borel.

Monday, October 20

4:30 PM–6:30 PM

Concurrent Platform Session C

37. From Bytes To Phenotypes

Hall B1, Ground Level, Convention Center

Moderators: Ada Hamosh, Johns Hopkins Univ, Baltimore
  Steven E. Brenner, UC Berkeley

166/4:30 Investigation of synthetic association in GWAS using pheWAS and exome sequencing. L. Bastarache, J. Bochenek, T. Edwards, Y. Xu, J. Pulley, E. Bowton, H. Mo, W. Wei, L. Wiley, D. Roden, J. Denny.

167/4:45 Beware of circularity: A critical assessment of the state of the art in deleteriousness prediction of missense variants. C. A. Azencott, D. Grimm, J. W. Smoller, L. Duncan, K. Borgwardt.

168/5:00 Application of clinical text data for phenome-wide association studies. S. J. Hebbring, M. Rastegar-Mojarad, Z. Ye, J. Mayer, C. Jacobson, S. Lin.

169/5:15 The warped linear mixed model: Finding optimal phenotype transformations yields a substantial increase in signal in genetic analyses. N. Fusi, C. Lippert, N. Lawrence, O. Stegle.

170/5:30 PhenomeCentral: An integrated portal for sharing patient phenotype and genotype data for rare genetic disorders. M. Brudno, M. Girdea, O. J. Buske, S. Dumitriu, H. Trang, T. Hartley, D. Smedley, S. Kohler, P. N. Robinson, T. E. Dudding, H. Lochmuller, C. F. Boerkoel, W. A. Gahl, K. Boycott, Canadian CARE for RARE, NIH Undiagnosed Diseases Program, RD-Connect, CARE for RARE Australia.

171/5:45 Facilitating the interpretation of rare pathogenic variation in a clinical setting with DECIPHER. G. J. Swaminathan, E. Bragin, E. A. Chatzimichali, S. Brent, A. P. Bevan, H. V. Firth, M. E. Hurles.

172/6:00 GeneMatcher: A matching tool for identification of individuals with mutations in the same gene. A. Hamosh, N. Sobreira, F. Schiettecatte, D. Valle.

173/6:15 Findings from the Critical Assessment of Genome Interpretation, a community experiment to evaluate phenotype prediction. S. E. Brenner, J. Moult, CAGI Participants.

Monday, October 20

4:30 PM–6:30 PM

Concurrent Platform Session C

38. Rare Mutations, Well Done

Room 6AB, Upper Level, Convention Center

Moderators: Doug Kiel, Harvard Univ, Boston
  Gina Peloso, Mass Gen Hosp, Boston

174/4:30 The UG2G initiative: A study of disease susceptibility in 7000 individuals from Uganda using whole genome sequencing and genotyping approaches. D. Gurdasani, T. Carstensen, S. Fatumo, C. S. Franklin, E. Wheeler, I. Tachmazidou, J. Huang, A. Karabarinde, G. Asiki.

175/4:45 Long-range haplotype mapping in Hispanic/Latinos reveals loci for short stature. G. Belbin, D. Ruderfer, K. Slivinski, M.C. Yee, J. Jeff, O. Gottesman, E.A. Stahl, R.J.F. Loos, E.P. Bottinger, E.E. Kenny.

176/5:00 A haplotype reference panel of over 31,000 individuals and next-generation imputation methods. S. Das, on behalf of Haplotype Reference Consortium.

177/5:15 A rare variant local haplotype sharing method with application to admixed populations. S. Hooker, G. T. Wang, B. Li, Y. Guan, S. M. Leal.

178/5:30 Rare mutations associating with serum creatinine and chronic kidney disease. G. Sveinbjornsson, E. Mikaelsdottir, R. Palsson, O. S. Indridason, H. Holm, A. Jonasdottir, A. Helgason, S. Sigurdsson, A. Jonasdottir, A. Sigurdsson, G. I. Eyjolfsson, O. Sigurdardottir, O. T. Magnusson, A. Kong, G. Masson, P. Sulem, I. Olafsson, U. Thorsteinsdottir, D. F. Gudbjartsson, K. Stefansson.

179/5:45 Rare coding variants in collagen genes increase risk of adolescent idiopathic scoliosis. G. Haller, D. Alvarado, J. Buchan, K. McCall, P. Yang, C. Cruchaga, M. Harms, A. Goate, M. Willing, E. Baschal, N. Miller, C. Wise, M. Dobbs, C. Gurnett.

180/6:00 Rare coding variants are associated with osteoporotic fracture: A large-scale exome-chip analysis of 44,130 adult Caucasian men and women in CHARGE and GEFOS consortia. Y. Hsu, K. Estrada, P. Leo, A. Teumer, C. Liu, C. Medina-Gomez, H. Zheng, R. Minster, L.P. Lyytikäinen, R. Pengelly, R. Cruz Guerrero, L. Oei, M. Claussnitzer, M. Kahonen, C. Cooper, A. Hannemann, D. Karasik, A. Uitterlinden, L.A. Cupples, J.A. Riancho Moral, J. Holloway, E. Duncan, T. Lehtimäki, T. Harris, H. Wallaschofski, B. Richards, F. Rivadeneira, M. Brown, D. Chasman, D. Kiel.

181/6:15 Exploring the role of rare and low-frequency coding variants in adult height using an ExomeChip. M. Graff, K. Sin lo, K. Stirrups, C. Medina-Gomez, T. Esko, N. L. Heard-Costa, A. E. Justice, T. W. Winkler, L. Southam, C. Shurmann, J. Czajkowski, Y. Lu, K. L. Young, T. L. Edwards, A. Giri, C. Lindgren, I. B. Borecki, K. E. North, M. McCarthy, J. N. Hirschhorn, P. Deloukas, F. Rivadeneira, T. M. Frayling, R. J. F. Loos, G. Lettre, for BBMRI, GOT2D, CHARGE, and GIANT Consortia.

Monday, October 20

4:30 PM–6:30 PM

Concurrent Platform Session C

39. Cardiovascular Genetics II: Genetic Discovery and Characterization

Room 6CF, Upper Level, Convention Center

Moderators: Alex Reiner, Univ Washington, Seattle
  Hooman Allayee, Univ Southern California, Los Angeles

182/4:30 Increased frequency of de novo copy number variations in congenital heart disease by integrative analysis of SNP array and exome sequence data. J. T. Glessner, A. G. Bick, K. Ito, J. Homsy, L. Rodriguez-Murillo, M. Fromer, E. Mazaika, B. Vardarajan, M. Italia, J. Leipzig, S. R. DePalma, R. Golhar, S. J. Sanders, B. Yamrom, M. Ronemus, I. Iossifov, A. J. Willsey, M. W. State, J. R. Kaltman, P. S. White, Y. Shen, D. Warburton, M. Brueckner, C. Seidman, E. Goldmuntz, B. D. Gelb, R. Lifton, J. Seidman, W. K. Chung, H. Hakonarson.

183/4:45 Context-specific eQTLs implicate differential genomic regulatory mechanisms in obese and lean Finns. A. Ko, R. C. Cantor, E. Nikkola, M. Alvarez, B. Pasaniuc, K. L. Mohlke, M. Boehnke, F. S. Collins, J. Kuusisto, M. Laakso, P. Pajukanta.

184/5:00 Use of low read depth whole genome sequence data to examine the genomic architecture of commonly measured lipid sub-fractions: The UK10K study. J. Huang, J. Min, V. Iotchkova, M. Mangino, A. Gaye, M. Kleber, G. Malerba, M. Cocca, T. Michela, I. Tachmazidou, H. Chheda, A. Manning, A. Wood, R. Scott, T. Gaunt, W. Zhang, F. Rivadeneira, N. Soranzo, N. Timpson, UK10K Consortium Cohorts Group.

185/5:15 Population-specific imputations identify a deleterious coding variant in ABCA6 associated with cholesterol levels: The genome of the Netherlands. C. M. Van Duijn, E. M. van Leeuwen, M. A. Swertz, D. I. Boomsma, P. E. Slagboom, G. B. van Ommen, C. Wijmenga, P. I. W. de Bakker, on behalf of CHARGE Lipids WG and Genome of the Netherlands Consortium.

186/5:30 Null alleles at NPC1L1, the therapeutic target for the LDL-lowering drug ezetimibe, and protection from coronary heart disease. N. Stitziel, S. Kathiresan, Myocardial Infarction Genetics Consortium.

187/5:45 Trans-ethnic genome-wide association study identifies 15 new genetic loci influencing blood pressure traits and implicates a role for DNA methylation: the International Genetics of Blood Pressure Study. M. Loh, F. Takeuchi, N. Verweij, X. Wang, W. Zhang, International Genetics of Blood Pressure Study.

188/6:00 Pathologically different than coronary artery disease, myocardial infarction has a minimal heritable component. B. Horne, S. Knight.

189/6:15 Is type 2 diabetes a causal risk factor for coronary artery disease? Multivariate Mendelian randomization to test causal relationships among cardiometabolic traits. R. Do, M. Daly, B. Neale, S. Kathiresan.

Monday, October 20

4:30 PM–6:30 PM

Concurrent Platform Session C

40. Genetics of Complex Neuropsychiatric Disorders

Room 6DE, Upper Level, Convention Center

Moderators: Minerva Carrasquillo, Mayo Clin, Jacksonville, FL
  Tao Wang, Johns Hopkins Univ, Baltimore

190/4:30 Vertical transmission of autism spectrum disorder. N. Risch, L. Shen, Y. Qian, M. Massolo, L. Croen.

191/4:45 Epidemiological and genomic studies suggest a significant effect of comorbidity of intellectual disability towards estimates of autism prevalence. S. Girirajan, J. A. Rosenfeld, A. Polyak.

192/5:00 Partial deletion of the monoamine oxidase A (MAOA) gene in a three-generation family with two severely affected intellectually disabled males and a healthy female carrier. N. de Leeuw, M. I. Schouten, R. van Beek, R. Pfundt, M. M. Verbeek, H. G. Brunner.

193/5:15 A Drosophila model for 16p11.2 deletion shows differential sensitivity to gene dosage. J. Iyer, L. Pizzo, T. Le, P. Patel, L. Thomas, K. Vadodaria, S. Girirajan.

194/5:30 The discovery of integrated gene networks for autism. O. Penn, F. Hormozdiari, E. Borenstein, E. E. Eichler, SSC Sequencing Consortium.

195/5:45 Transcriptome sequencing of human aging brain tissue uncovers widespread genetic effects on splicing alternations in Alzheimer’s disease. T. Raj, J. Xu, C. McCabe, J. A. Schneider, N. Pochet, D. A. Bennett, P. L. De Jager.

196/6:00 Exome array analysis of 30,582 individuals confirms late-onset Alzheimer’s disease (LOAD) risk from common variants and identifies novel rare LOAD susceptibility variants: The International Genomics of Alzheimer’s Project. A. C. Naj, S. J. van der Lee, M. Vronskaya, R. Sims, J. Jakobsdottir, C. van Duijn, L.-S. Wang, P. Amouyel, S. Seshadri, J. Williams, G. Schellenberg, International Genomics of Alzheimer's Project (IGAP).

197/6:15 Low-frequency variant imputation identifies rare variant candidate loci in a genome-wide association study of late-onset Alzheimer disease. K. L. Hamilton, B. W. Kunkle, A. C. Naj, W. R. Perry, A. Partch, O. Valladeres, L. S. Wang, G. Jun, J. Chung, M. A. Schmidt, G. W. Beecham, E. R. Martin, R. P. Mayeux, J. L. Haines, L. A. Farrer, G. D. Schellenberg, Alzheimer's Disease Genetics Consortium.

Monday, October 20

4:30 PM–6:30 PM

Concurrent Platform Session C

41. Statistical Methods for Population Based Studies

Room 20A, Upper Level, Convention Center

Moderators: Peter N. Robinson, Charite-Universitatsmedizin, Berlin, Germany
  John Witte, UC, San Francisco

198/4:30 Leveraging genetic variation from over 55,000 exomes to explore patterns of functional constraint on human protein-coding genes. K. Samocha, M. Lek, D. MacArthur, M. Daly, Exome Aggregation Consortium.

199/4:45 Unveiling the genetic architectures of rare coding variants in blood lipids levels via large scale meta-analysis. D. Liu, on behalf of Global Lipids Genetics Consortium.

200/5:00 Efficient Bayesian mixed model analysis increases association power in large cohorts. P. Loh, G. Tucker, B. Bulik-Sullivan, B. J. Vilhjalmsson, H. K. Finucane, K. Galinsky, D. I. Chasman, B. M. Neale, B. Berger, N. Patterson, A. L. Price.

201/5:15 Recent demography and natural selection hamper power of rare variant association tests. L. H. Uricchio, J. S. Witte, R. D. Hernandez.

202/5:30 A statistical framework to leverage broad metabolite data in elucidating the associations between genetics and disease. C. Churchhouse, Slim Initiative in Genomic Medicine for the Americas (SIGMA) Type 2 Diabetes Consortium.

203/5:45 Prioritizing functional variants in genetic association studies. S. Sengupta, X. Wen, G. Abecasis.

204/6:00 A practical guide to study design, sample size requirements and statistical analyses methods for rare variant disease association studies. S. M. Leal, G. T. Wang, D. Zhang, Z. He, H. Dai, B. Li.

205/6:15 A logistic mixed model approach to obtain a reduced model score for KBAC to adjust for population structure and relatedness between samples. G. Linse Peterson, J. Grover, B. Vilhjalmsson, G. Christensen, A. Scherer.

Monday, October 20

4:30 PM–6:30 PM

Concurrent Platform Session C

42. Genome Variation and its Impact on Autism and Brain Development

Room 20BC, Upper Level, Convention Center

Moderators: Sébastien Jacquemont, Sainte Justine Univ Hosp Centre, Univ of Montreal
  Xander Nuttle, Univ Washington, Seattle

206/4:30 A chromosome imbalance map of the human genome. M. Zarrei, J. R. MacDonald, R. Ziman, G. Pellecchia, D. J. Stavropoulos, D. Merico, S. W. Scherer.

207/4:45 Detection of known genomic regions and intragenic copy-number changes by an expanded exon-targeted array with comprehensive coverage of genes implicated in autism spectrum disorders and intellectual disability. S. W. Cheung, P. Liu, T. Gambin, S. Gu, P. Hixson, C. Shaw, W. Bi, A. Breman, J. Smith, M. Haeri, A. N. Pursley, S. Lalani, C. Bacino, A. L. Beaudet, J. R. Lupski, P. Stankiewicz, A. Patel.

208/5:00 Identification of pathogenic CNVs in a simplex autism cohort and measurement of effect size on cognitive, adaptive, and social function. A. E. Hare, D. Moreno De Luca, K. B. Boomer, S. J. Sanders, M. W. State, M. Benedetti, A. L. Beaudet, E. H. Cook, D. M. Martin, D. H. Ledbetter, C. L. Martin.

209/5:15 Autism ten thousand genomes (AUT10K) project: A roadmap for the complete genetic landscape of autism spectrum disorder. S. W. Scherer, R. K. C. Yuen, H. Cao, X. Tong, D. Cao, Y. Sun, M. Li, W. Chen, X. Jin, J. L. Howe, C. R. Marshall, P. Szatmari, D. Merico, R. H. Ring.

210/5:30 The identification of novel autism pathogenicity genes and their associated phenotypes. H. A. F. Stessman, B. J. O'Roak, E. A. Boyle, K. T. Witherspoon, B. Martin, C. Lee, L. Vives, C. Baker, J. Hiatt, D. A. Nickerson, R. Bernier, J. Shendure, E. E. Eichler.

211/5:45 The 16p11.2 locus modulates brain structures common to autism, schizophrenia and obesity. S. Jacquemont, A. M. Maillard, A. Ruef, F. Pizzagalli, E. Migliavacca, L. Hippolyte, S. Adaszewski, J. Dukart, C. Ferrari, P. Conus, K. Männik, M. Zazhytska, V. Siffredi, P. Maeder, Z. Kutalik, F. Kherif, N. Hadjikhani, J. S. Beckmann, A. Reymond, B. Draganski, 16p11.2 European Consortium.

212/6:00 Distinct properties of de novo mutations from whole genome sequencing of 50 patient-parent trios. M. Pinelli, B. Tan, M. van de Vorst, R. Leach, R. Klein, L. E. L. Vissers, H. G. Brunner, J. A. Veltman, A. Hoischen, C. Gilissen.

213/6:15 Human frontal cortex is enriched for somatic variations under physiological oxidative stress compared to the corpus callosum from same individuals. A. Mukhopadhyay, A. Sharma, R. Kumari, B. Mehani, A. H. Ansari, B. Varma, R. Rehman, B. K. Desiraju, U. Mabalirajan, A. Agrawal.

Monday, October 20

4:30 PM–6:30 PM

Concurrent Platform Session C

43. ELSI Issues in Genetics

Room 20D, Upper Level, Convention Center

Moderators: James O'Leary, Genetic Alliance, District of Columbia
  Jennifer McCormick, Mayo Clin, Rochester, MN

214/4:30 The expansion of NIH’s genomic data sharing policy. E. Luetkemeier, K. Langlais, R. Baker, C. Fomous, T. Paine, D. Paltoo.

215/4:45 Data sharing and dbGaP: A survey of practices and opinions among human geneticists. D. Kaufman, J. Bollinger, R. Dvoskin.

216/5:00 Experience with obtaining informed consent for genomic sequencing: Developing recommendations for best practices. B. A. Bernhardt, A. N. Tomlinson, D. Lautenbach, M. I. Roche, S. R. Scollon, D. Skinner.

217/5:15 Developing a patient facing genome sequencing report: Results of key informant interviews. J. L. Williams, A. Fan, H. Stuckey, D. Zallen, J. Green, M. Bonhag, L. Feldman, M. Segal, M. S. Williams.

218/5:30 Use of My46 to return individual research results to families of children with Joubert syndrome. S. M. Jamal, A. G. Shankar, J. Dempsey, C. Isabella, J. H. Yu, J. Crouch, T. M. Harrell, M. J. Bamshad, D. Doherty, H. K. Tabor.

219/5:45 Patient preferences for the return of individual research results derived from pediatric biobank samples. S. Savage, K. Christensen, N. Huntington, E. Weitzman, S. Ziniel, P. Bacon, C. Cacioppo, R. Green, I. Holm.

220/6:00 Weapons, boxes, and credit reports: Metaphorical language in discussions of receiving exome and whole genome sequencing results. S. C. Nelson, J. Crouch, M. J. Bamshad, H. K. Tabor, J. Yu.

221/6:15 Clinical integration of next-generation sequencing: A policy analysis. A. L. McGuire, D. J. Kaufman, G. H. Javitt, P. A. Deverka, D. Messner, R. Cook-Deegan, M. A. Curnutte, J. Bollinger, R. Dvoskin, S. Chandrasekharan, B. J. Evans.

Monday, October 20

4:30 PM–6:30 PM

Concurrent Platform Session C

44. Prenatal, Perinatal, and Reproductive Genetics

Room 28, Upper Level, Convention Center

Moderators: Lee P. Shulman, Northwestern Univ, Chicago
  Nancy Rose, Intermountain Med Ctr, Salt Lake City

222/4:30 Discovery and in vivo experimental validation of a novel, non-meiotic pathway governing production of spermatozoa and oocytes in human. A. S. Lee, N. Huang, Y. Yin, R. A. Hess, L. Ma, P. N. Schlegel, A. M. Lopes, D. T. Carrell, Z. Hu, D. F. Conrad.

223/4:45 Complex dynamics of meiotic recombination initiation in laboratory mouse strains. K. Brick, F. Smagulova, R. D. Camerini-Otero, G. Petukhova.

224/5:00 Bringing homologs together: Sex- and species-specific differences in synapsis. J. Gruhn, C. Rubio, P. A. Hunt, T. Hassold.

225/5:15 Targeted resequencing identifies mutant selfish clones within the testis and unifies the concepts of somatic and germline mutation. G. J. Maher, E. Giannoulatou, S. J. McGowan, A. Goriely, A. O. M. Wilkie.

226/5:30 Prevalence of pathogenic copy number variants for specific ultrasound detected structural abnormalities using prenatal chromosomal microarray in a multi-center cohort. T. Leung, O. Chan, S.W. Cheung, Y. Kwok, K.W. Choy.

227/5:45 Comprehensive genetic analysis of pregnancy loss by chromosomal microarrays: Outcomes, benefits and challenges. T. Sahoo, M. Strecker, A. Mehta, N. Dzidic, R. W. Tyson, K. Hovanes.

228/6:00 Genomic augmentation of newborn screening. B. Solomon, D. Bodian, R. Iyer, K. Huddleston, R. Hastak, A. Chu, A. Black, G. Eley, J. Vockley, J. Niederhuber.

229/6:15 CETN1 variations cause idiopathic male infertility. D. V. S. Sudhakar, A. Khattri, R. Phanindranath, A. K. Sharma, J. Reshma Devi, M. Deenadayal, N. J. Gupta, S. Prasad, S. Yobendra, K. Thangaraj.

Monday, October 20

4:30 PM–6:30 PM

Concurrent Platform Session C

45. Advances in Defining the Molecular Mechanisms of Mendelian Disorders

Room 29, Upper Level, Convention Center

Moderators: Megan Dennis, Univ Washington, Seattle
  Ken Inoue, NCNP, Kodaira, Japan

230/4:30 Mutations in RPL17 expand the molecular basis of Diamond-Blackfan anemia and guide insights into unique biochemical signatures underscoring ribosomopathies. E. E. Davis, D. W. Reid, J. Liang, J. R. Willer, L. Fievet, Z. A. Bhuiyan, A. L. Wall, J. S. Beckmann, N. Katsanis, C. V. Nicchitta, F. Fellmann.

231/4:45 Digenic inheritance in Alport syndrome. M. Mencarelli, L. Heidet, H. Storey, M. van Geel, B. Knebelmann, C. Fallerini, L. Dosa, N. Miglietti, M. F. Antonucci, F. Cetta, A. van den Wijngaard, S. Yau, F. Mari, M. Bruttini, F. Ariani, K. Dahan, B. Smeets, C. Antignac, F. Flinter, A. Renieri.

232/5:00 PCBD1 and diabetes: A novel player with direct implications for therapy. D. Simaite, J. Kofent, M. Gong, F. Rüschendorf, S. Jia, P. Arn, K. Bentler, C. Ellaway, P. Kühnen, G. F. Hoffmann, N. Blau, F. M. Spagnoli, N. Hübner, K. Raile.

233/5:15 The Ankrd11 mutation in the Yoda mouse mirrors the human gene defect and provides new insights into KBG syndrome. K. Walz, D. Cohen, P. M. Neilsen, J. Foster II, F. Brancati, K. Demir, R. Fisher, M. Moffat, N. E. Verbeek, K. Bjorgo, A. Lo-Castro, P. Curatolo, G. Novelli, C. Abad, C. Lei, O. Diaz-Horta, J. I. Young, D. F. Callen, M. Tekin.

234/5:30 Defects in TAPT1, involved in axial skeletal patterning, cause a complex lethal recessive disorder of skeletal development. S. Symoens, A. Barnes, C. Ghistelinck, F. Malfait, K. Vleminckx, B. Guillemyn, D. Syx, W. Steyaert, E. Parthoens, M. Biervliet, G. Gillessen-Kaesbach, J. De Backer, A. Willaert, H. P. Bächinger, A. De Paepe, J. C. Marini, P. J. Coucke.

235/5:45 Mutations in KITLG, encoding KIT ligand, cause unilateral hearing loss. C. Zazo Seco, L. S. Serrao de Castro, J. W. van Nierop, M. Schraders, E. J. Verver, M. Morín, N. Maiwald, M. Wesdrop, H. Venselaar, L. Spruijt, J. Oostrik, J. Schoots, L. H. Hoefsloot, J. H. Jansen, G. Huls, M. M. Van Rossum, H. P. Kunst, M. A. Moreno-Pelayo, H. Kremer, Baylor-Hopkins Center for Mendelian Genomics.

236/6:00 Molecular pathogenesis of tuberous sclerosis complex (TSC) in patients with no mutation identified in TSC1 or TSC2. M. E. Tyburczy, Y. Chekaluk, K. Dies, M. Sahin, J. Glass, D. Franz, S. Camposano, E. Thiele, D. Kwiatkowski.

237/6:15 RAB11FIP1 interacts with the BLOC-1 complex to retrieve melanogenic proteins from the recycling pathway and a dominant negative mutation in RAB11FIP1 causes Hermanksy-Pudlak syndrome type 10. A. R. Cullinane, M. A. Merideth, M. B. Datiles, J. A. Curry, N. F. Hansen, J. K. Teer, J. G. White, J. C. Mullikin, M. Huizing, W. A. Gahl.

Monday, October 20

4:30 PM–6:30 PM

Concurrent Platform Session C

46. Epigenomics of Normal Populations and Disease States

Room 30, Upper Level, Convention Center

Moderators: Anshul Kundaje, Stanford Univ, Stanford
  Carolyn Brown, Univ of British Columbia, Vancouver

238/4:30 Genetic basis and functional consequences of chromatin state variability across individuals. F. Grubert, J. Zaugg, M. Kasowski, O. Ursu, D. Spacek, A. Martin, L. Steinmetz, A. Kundaje, M. Snyder.

239/4:45 Integration of 111 reference human epigenomes helps interpret the molecular basis of complex traits and disease. M. Kellis, Roadmap Epigenomics Consortium.

240/5:00 An imprinting map of the human placenta based on the application of a novel population genetics approach to RNAseq data. C. T. Watson, O. Rodriguez, B. Jadhav, N. Azam, D. J. Ho, K. Cheung, D. Sachs, K. Hao, R. J. Wright, E. E. Schadt, A. J. Sharp.

241/5:15 Tissue-specific patterns of imprinting revealed by analysis of monoallelic expression in human populations. T. Lappalainen, Y. Baran, E. Tsang, T. Tukiainen, M. A. Rivas, M. Pirinen, M. Gutierrez-Arcelus, The. GTEx Consortium, D. G. MacArthur, S. B. Montgomery, N. A. Zaitlen.

242/5:30 Population-scale and single-cell RNA sequencing provides insight into X chromosome inactivation. T. Tukiainen, A. Kirby, T. Lappalainen, A.-C. Villani, R. Satija, J. Maller, . GTEx Project Consortium, A. Regev, N. Hacohen, D. G. MacArthur.

243/5:45 Cis-methylation quantitative trait loci mapping of chromosome 15q25.1 in human brain reveals novel genetic associations with nicotine dependence. D. B. Hancock, J. C. Wang, N. C. Gaddis, N. L. Saccone, J. A. Stitzel, A. Goate, L. J. Bierut, E. O. Johnson.

244/6:00 Joint methylome- and genome-wide association studies in blood and brain identifies new disease mechanisms for schizophrenia. E. J. C. G. Van den Oord, A. Shabalin, G. Kumar, S. Clark, J. L. McClay, L. Y. Xie, R. Chan, Swedish Schizophrenia Consort., V. Vladimirov, C. Hultman, P. F. Sullivan, P. K. E. Magnusson, K. A. Aberg.

245/6:15 Whole genome bisulfite sequencing of acute lymphoblastic leukemia cells. P. Wahlberg, A. Lundmark, J. Nordlund, A. Raine, S. Busche, E. Forestier, T. Pastinen, G. Lönnerholm, A.-C. Syvänen.

Tuesday, October 21

8:00 AM–8:25 AM

47. Plenary Abstracts Featured Presentation III

Hall B1, Ground Level, Convention Center

Moderator: John Novembre, Univ Chicago

246/8:00 Completion of the 1000 Genomes Project: Results, lessons learned and open questions. G. Abecasis, 1000 Genomes Project.

Tuesday, October 21

8:30 AM–10:00 AM

48. ASHG/ESHG Building Bridges Session:Towards Finding Global Agreement on Topical Discussions in Genetics: Evolving Uncertainties in Genomic Medicine

Hall B1, Ground Level, Convention Center

Moderator: Barbara Biesecker, NHGRI/NIH

Introduction: Cynthia Morton, ASHG President

Uncertainty is an inherent part of genomic medicine. Uncertainty pervades the associations of genes with phenotypes, the pathogenicity of variants, the role of modifiers and environment in gene penetrance and expressivity, the natural history of genetic diseases, and the efficacy and iatrogenic effects of treatments for these diseases. Geneticists working in the laboratory, medical geneticists, and genetic counselors interpreting penetrance and data on prevention or treatment confront these uncertainties daily. The introduction of genome sequencing has increased the breadth, depth, and dimensions of these uncertainties to unprecedented levels. How these uncertainties are characterized, communicated, and managed by geneticists, health care providers, and patients is critical to the integrity of the science, the validity of clinical practice guidelines on the use of genomic information, and the adequacy of patients’ understanding of the value and limitations of genomic information.

Perceptions of uncertainty among geneticists affect how they interpret information returned to patients. Similarly, perceptions of uncertainty among practitioners affect how they obtain informed consent for sequencing, communicate results to patients, and formulate medical recommendations. Ultimately, perceptions of uncertainty affect how patients make informed decisions to undergo sequencing, learn results, and act on them. As such, there is a critical need for further research to conceptualize the varieties of uncertainties in genome sequencing, and to understand how laboratory scientists, genetics providers, and patients perceive, respond to, and manage these uncertainties.

History of uncertainty in genomic medicine. Reed Pyeritz, Univ. of Pennsylvania
Conceptualizing and communicating uncertainty. Paul Han, Maine Med. Ctr. Res. Inst.
A taxonomy of uncertainty for clinical genomics. Les Biesecker, NIH
Uncertainties in consenting to participate in sequencing studies and receive results. Barbara Biesecker, NIH
Managing the ambiguity and complexity of genome sequencing. Aad Tibben, Leiden Univ. Med. Ctr.

This "Building Bridges" session is the second in a continuing series conducted in conjunction with the European Society of Human Genetics. The first session, held in Milan in June 2014, focused on incidental findings in WGS and WES.


Tuesday, October 21

10:30 AM–12:30 PM

Concurrent Platform Session D

49. Detailing the Parts List Using Genomic Studies

Hall B1, Ground Level, Convention Center

Moderators: Meredith L. Carpenter, Stanford Univ
  Alon Keinan, Cornell Univ, Ithaca

247/10:30 Inferring the functional effects of non-synonymous variants using experimental results from deep mutational scanning. R. J. Hause, V. E. Gray, J. Shendure, D. M. Fowler.

248/10:45 Context-specific regulatory networks identify key regulators of complex traits. G. Quon, D. Marbach, S. Feizi, M. Grzadkowski, M. Kellis.

249/11:00 Allele-specific alternative splicing in diploid human genomes. N. Raghupathy, K. Choi, S. C. Munger, G. A. Churchill.

250/11:15 Developing a high-throughput CRISPR-based assay for saturation mutagenesis of human genes. M. L. Carpenter, C. Lee, N. Hammond, A. Li, A. Adams, C. D. Bustamante, M. C. Bassik.

251/11:30 Transcriptome-wide nuclease-mediated protein footprinting to identify RNA-protein interaction sites. I. Silverman, F. Li, Q. Zheng, B. Gregory.

252/11:45 Epigenome imputation leads to higher-quality datasets and helps improve GWAS interpretation. J. Ernst, A. K. Sarkar, L. D. Ward, M. Kellis.

253/12:00 Conservation of mammalian trans-regulatory circuitry under high cis-regulatory turnover. A. B. Stergachis, S. Neph, R. Sandstrom, E. Haugen, A. Reynolds, M. Zhang, R. Byron, T. Canfield, S. Stelhing-Sun, K. Lee, R. Thurman, S. Vong, D. Bates, F. Neri, M. Diegel, E. Giste, D. Dunn, S. Hansen, A. Johnson, P. Sabo, M. Wilken, T. Reh, P. Treuting, R. Kaul, M. Groudine, M. Bender, E. Borenstein, J. Stamatoyannopoulos.

254/12:15 A regulatory DNA association study between autoimmune disease risk and variation in regulatory regions that are highly unique to adaptive immune cells. A. Madar, D. Chang, A. J. Sams, F. Gao, Y. Waldman, C. Van Hout, A. G. Clark, A. Keinan.

Tuesday, October 21

10:30 AM–12:30 PM

Concurrent Platform Session D

50. Statistical Methods for Multigene, Gene Interaction and Pathway Analyses

Room 6AB, Upper Level, Convention Center

Moderators: Marcella Devoto, CHOP, Philadelphia
  David Conti, USC, Los Angeles

255/10:30 Novel kernel methods for detecting gene-environment interaction. K. A. Broadaway, R. Duncan, L. M. Almli, K. J. Ressler, B. Bradley, M. P. Epstein.

256/10:45 Gene-environment dependence creates spurious gene-environment interaction. F. Dudbridge, O. Fletcher.

257/11:00 Discovery of gene-environment and epistatic interactions affecting gene expression in the TwinsUK cohort via association mapping of variance and monozygotic twin discordance. A. Brown, A. Buil, A. Viñuela, M. Davies, K. Small, T. Spector, E. Dermitzakis, R. Durbin.

258/11:15 A statistical approach to distinguish genetic pleiotropy from clinical heterogeneity: Application to autoimmune diseases. B. Han, D. Diogo, E. A. Stahl, S. Eyre, S. Rantapää-Dahlqvist, J. Martin, T. W. Huizinga, P. K. Gregersen, J. Worthington, L. Klareskog, P. I. W. de Bakker, S. Raychaudhuri.

259/11:30 Analysis of variants obtained through whole-genome sequencing provides an alternative explanation to apparent epistasis. A. R. Wood, M. A. Tuke, M. Nalls, D. Hernandez, S. Bandinelli, A. Singleton, D. Melzer, L. Ferrucci, T. M. Frayling, M. N. Weedon.

260/11:45 A joint testing framework uncovers paradoxical SNPs, improves power, and identifies new sources of missing heritability in association studies. B. C. Brown, N. A. Patsopoulos, A. Price, L. Pachter, N. Zaitlen.

261/12:00 Valid permutation testing in the presence of polygenic variation. M. Abney.

262/12:15 Sparse Bayesian latent factor decompositions for identifying trans-eQTLs. V. Hore, J. Marchini.

Tuesday, October 21

10:30 AM–12:30 PM

Concurrent Platform Session D

51. Neurogenetics: From Gene to Mechanism (II)

Room 6CF, Upper Level, Convention Center

Moderators: Mustafa Tekin, Univ Miami
  Alessandra Renieri, Univ Siena, Italy

263/10:30 Mutations in CNTNAP1 and ADCY6 are responsible for severe arthrogryposis multiplex congenita with axoglial defects. J. Melki, J. Maluenda, A. Camus, L. Fontenas, K. Dieterich, F. Nolent, N. Monnier, P. Latour, J. Lunardi, M. Bayes, PS. Jouk, S. Sternberg, J. Warszawski, I. Gut, M. Gonzales, M. Tawk, A. Laquérriere.

264/10:45 A mutation in TMTC2 reveals a new mechanism causing sensorineural hearing loss. M. Olivier, A. Indap, Y. Zhou, J. W. Kent Jr., E. King, C. B. Erbe, R. Cole, J. Littrell, K. Merath, S. Mleziva, J. Jensen, L. S. Burg, F. Rüschendorf, J. E. Kerschner, G. Marth, N. Hübner, H. H. H. Göring, D. F. Friedland, W.-M. Kwok, C. L. Runge.

265/11:00 Understanding pathogenesis of lissencephaly with patient-derived induced pluripotent stem cells. M. Bershteyn, A. Kriegstein, A. Wynshaw-Boris.

266/11:15 Hypomorphic PCNA mutation underlies a novel human DNA repair disorder. E. L. Baple, H. Chambers, H. E. Cross, H. Fawcett, Y. Nakazawa, B. A. Chioza, G. V. Harlalka, S. Mansour, A. Sreekantan-Nair, M. A. Patton, M. Muggenthaler, P. Rich, K. Wagner, R. Coblentz, C. K. Stein, .J. I. Last, A. M. R. Taylor, A. P. Jackson, T. Ogi, A. R. Lehmann, C. M. Green, A. H. Crosby.

267/11:30 Profound neuropathy target esterase impairment results in Oliver-McFarlane syndrome. R. B. Hufnagel, G. Arno, N. D. Hein, J. Hersheson, L. A. Krueger, T. J. Jaworek, L. C. Gregory, S. Hull, V. Plagnol, C. M. Willen, T. M. Morgan, C. A. Prows, R. S. Hegde, S. Riazuddin, G. A. Grabowski, R. J. Richardson, J. P. Martinez-Barbera, T. Huang, M. T. Dattani, R. A. Sisk, H. Houlden, J. K. Fink, A. T. Moore, Z. M. Ahmed.

268/11:45 A mitochondrial origin for frontotemporal dementia and amyotrophic lateral sclerosis through CHCHD10 involvement. V. Paquis, S. Bannwarth, S. Ait-El-Mkadem, A. Chaussenot, E. C. Genin, S. Lacas-Gervais, K. Fragaki, L. Berg-Alonso, Y. Kageyama, V. Serre, D. G. Moore, A. Verschueren, C. Rouzier, I. Le Ber, G. Augé, C. Cochaud, F. Lespinasse, K. N’Guyen, A. de Septenville, A. Brice, P. Yu-Wai-Man, H. Sesaki, J. Pouget.

269/12:00 Comprehensive investigation of CASK and other relevant genes in 41 patients with intellectual disability, microcephaly and disproportionate pontine and cerebellar hypoplasia (MICPCH) using next-generation sequencing. S. Hayashi, N. Okamoto, J. Takanashi, J. Inazawa.

270/12:15 ABAT is a novel human mitochondrial DNA depletion syndrome gene linking gamma-aminobutyric acid (GABA) catabolism and mitochondrial nucleoside metabolism. P. Bonnen, A. Besse, P. Wu, F. Bruni, T. Donti, B. Graham, W. Craigen, R. McFarland, P. Moretti, S. Lalani, K. Scott, R. Taylor.

Tuesday, October 21

10:30 AM–12:30 PM

Concurrent Platform Session D

52. Contribution of Common and Rare Variation to Obesity-Related Traits

Room 6DE, Upper Level, Convention Center

Moderators: Anne Justice, Univ North Carolina, Chapel Hill
  Cecilia Lindgren, Broad Inst, Cambridge, MA

271/10:30 GWAS meta-analysis of ten studies identifies five novel loci associated with gallstone disease in European ancestry individuals. A. D. Joshi, C. Andersson, S. Buch, M. Gala, R. Noordam, A. Teumer, S. Stender, B. G. Nordestgaard, L. Weng, A. R. Folsom, P. L. Lutsey, D. Ellinghaus, W. Lieb, C. Shafmayer, B. Boehm, A. Tybjærg-Hansen, U. Völker, H. Völzke, L. Rose, P. E. Weeke, D. M. Roden, J. C. Denny, W. Tang, B. H. Stricker, J. Hampe, D. I. Chasman, A. D. Johnson, A. T. Chan.

272/10:45 Association analyses of 100,720 individuals reveal new loci associated with body fat percentage providing new insights in related cardiometabolic traits. Y. Lu, F. Day, S. Gustafsson, T. Kilpeläinen, R. Loos, on behalf of the Genetics of Body Fat Consortium.

273/11:00 Genome-wide analysis in Africans provides novel insight into the genetic basis of the metabolic syndrome. F. Tekola-Ayele, A. P. Doumatey, G. Chen, D. Shriner, A. R. Bentley, J. Zhou, A. Adeyemo, C. N. Rotimi.

274/11:15 Contribution of low-frequency variants to variation in body mass index. V. Turcot, Y. Lu, J. Czajkowski, H. M. Highland, N. G. D. Masca, A. Giri, T. L. Edwards, T. Esko, M. Graff, A. E. Justice, C. Medina-Gomez, C. Schurmann, R. A. Scott, K. Sin Lo, S. S. Sivapalaratnam, L. Southam, K. Stirrups, T. W. Winkler, H. Yaghootkar, K. L. Young, A. L. Cupples, T. M. Frayling, J. N. Hirschhorn, G. Lettre, C. M. Lindgren, K. E. North, I. B. Borecki, R. J. F. Loos, for BBMRI, GOT2D, CHARGE, and GIANT Consortia.

275/11:30 Genome-wide identification of novel genetic variants associated with erythrocyte membrane fatty acids. A. E. Locke, A. U. Jackson, A. Stancáková, Y. Wu, T. M. Teslovich, C. Fuchsberger, N. Narisu, P. Chines, R. Welch, H. M. Stringham, X. L. Sim, J. Huyghe, M. Civelek, N. K. Saleem, A. He, C. Tilford, P. Gargalovic, T. Kirchgessner, A. J. Lusis, K. Mohlke, M. Boehnke, M. Laakso.

276/11:45 Filtering for genomic nonsense to find biological significance: SLC13A1 nonsense variants enriched in a founder population are associated with reduced serum sulfate and increased aspartate aminotransferase levels. C. G. Perry, J. A. Perry, J. R. O'Connell, L. M. Yerges-Armstrong, A. R. Shuldiner.

277/12:00 Integrating metabolite, BMI and genetic data in phenotypic extremes, drawn from a population of 50,000 samples, to assess causality of metabolite levels in obesity. T. Esko, A. Metspalu, C. Clish, JN. Hirschhorn.

278/12:15 Systems genetics analyses of human adipose tissue gene expression identify cis and trans regulatory networks for cardio-metabolic traits. M. Civelek, Y. Wu, C. Pan, A. He, C. Tilford, N. K. Saleem, C. Fuchsberger, A. Locke, H. M. Stringham, A. U. Jackson, N. Narisu, P. S. Chines, Y. Zhao, P. S. Gargalovic, J. Kuusisto, P. Pajukanta, K. Hao, X. Yang, T. G. Kirchgessner, F. S. Collins, M. Boehnke, M. Laakso, K. L. Mohlke, A. J. Lusis.

Tuesday, October 21

10:30 AM–12:30 PM

Concurrent Platform Session D

53. The Dynamic Genome: Structural and Somatic Variation

Room 20A, Upper Level, Convention Center

Moderators: Alexander Hoischen, Radboud Univ, Nijmegen, Netherlands
  Santhosh Girirajan, Penn State, University Park

279/10:30 Origin, frequency and functional impact of de novo structural changes in the human genome. K. Ye, W. Kloosterman, L. C. Francioli, F. Hormozdiari, T. Marschall, J. Y. Hehir-Kwa, A. Abdellaoui, E. W. Lameijer, M. H. Moed, V. Koval, I. Renkens, M. J. van Roosmalen, P. Arp, L. Karssen, B. P. Coe, R. E. Handsaker, E. Cuppen, D. T. Thung, M. C. Wendl, A. Uitterlinden, C. M. van Duijn, M. Swertz, C. Wijmenga, G. van Ommen, P. E. Slagboom, D. I. Boomsma, A. Schonhuth, E. E. Eichler, P. I. W. de Bakker, V. Guryev.

280/10:45 Parental somatic mosaicism contributes an under-recognized source of potentially recurrent new mutations. I. M. Campbell, B. Yuan, C. Robberecht, R. Pfundt, P. Szafranski, M. M. McEntagart, S. C. S. Nagamani, A. Erez, M. Bartnik, B. Wisniowiecka-Kowalnik, K. S. Plunkett, A. N. Pursley, S. H. L. Kang, W. Bi, S. R. Lalani, C. A. Bacino, M. Vast, K. Marks, M. Patton, P. Olofsson, A. Patel, J. A. Veltman, S. W. Cheung, C. A. Shaw, L. E. L. M. Vissers, J. R. Vermeesch, J. R. Lupski, P. Stankiewicz.

281/11:00 Analysis of the genetic variation and age effects on gene expression using RNA-seq data from multiple tissues. A. Viñuela, A. A. Brown, A. Buil, M. N. Davies, P. Tsai, J. T. Bell, K. S. Small, E. T. Dermitzakis, R. Durbin, T. D. Spector.

282/11:15 Dynamics of personal omics profiles during periods of health, disease, weight gain and loss. M. Snyder, W. Zhou, B. Piening, K. Kukurba, K. Contrepois, C. Craig, R. Chen, G. Mias, J. Li-Pook-Than, S. Mitra, L. Jiang, B. Hanson, B. Leopold, S. Leopold, B. Cooper, L. Liu, V. Sikora-Wohfield, A. Butte, H. Tang, E. Sodergren, G. Weinstock, T. McLaughlin, M. Snyder.

283/11:30 Longitudinal study of whole blood transcriptomes in a twin cohort. J. Bryois, A. Buil, P. Ferreira, N. Panoussis, A. Planchon, D. Bielser, A. Viñuela, K. Small, T. Spector, E. T. Dermitzakis.

284/11:45 High-throughput determination of long interspersed element-1 integration preferences in the human genome. D. A. Flasch, A. Macia, T. Widmann, J. L. García-Pérez, T. E. Wilson, J. V. Moran.

285/12:00 Cryptic splicing adversely affects LINE-1 retrotransposition. P. A. Larson, C. R. Beck, J. V. Moran.

286/12:15 Discovery of a novel retrotransposon family in the Callithrix jacchus genome. M. K. Konkel, B. Ullmer, J. A. Walker, R. Hubley, E. L. Arceneaux, S. Sanampudi, C. C. Fontenot, A. F. A. Smit, M. A. Batzer, Common Marmoset Genome Sequencing and Analysis Consortium.

Tuesday, October 21

10:30 AM–12:30 PM

Concurrent Platform Session D

54. Expanding Clinical Phenotypes

Room 20BC, Upper Level, Convention Center

Moderators: Ozlem Goker-Alpan, Ctr Clinical Trials, Fairfax
  Mitzi L. Murray, Univ Washington, Seattle

287/10:30 Comprehensive phenotypic analysis of 19 individuals with Goltz syndrome (focal dermal hypoplasia). V. Sutton, H. Herce, T. R. Hunt, A. L. Smith, K. J. Motil, A. F. Bree, M. Fete, R. W. Goltz.

288/10:45 Multiple symmetric lipomatosis – new aspects of a forgotten syndrome. J. Schreml, A. Lindner, O. Felthaus, S. Klein, C. Pallouras, S. Schreml, I. Harsch, T. Meitinger, T. M. Strom, J. Altmüller, S. Staubach, F. G. Hanisch, H. Thiele, P. Nürnberg, L. Prantl.

289/11:00 Obstetric and gynecologic health in patients with xeroderma pigmentosum. M. Merideth, D. Tamura, J. DiGiovanna, K. Kraemer.

290/11:15 Adams-Oliver syndrome: Refining the diagnostic phenotype. S. Hassed, S. Li, J. Mulvihill, S. Palmer.

291/11:30 Alpha-fetoprotein assay on dried blood spot for hepatoblastoma screening in children with Beckwith-Wiedemann syndrome and isolated hemihyperplasia. A. Mussa, V. Pagliardini, C. Molinatto, G. Baldassarre, A. Corrias, F. Fagioli, M. Cirillo Silengo, G. B. Ferrero.

292/11:45 Clinical and radiographic study of 93 patients with a molecularly proven non-lethal type 2 collagen disorder. G. R. Mortier, R. J. A. J. Nievelstein, E. J. J. Verver, V. Topsakal, P. Van Dommelen, K. Hoornaert, M. Le Merrer, A. Zankl, M. E. H. Simon, S. F. Smithson, C. Marcelis, B. Kerr, J. Clayton-Smith, E. Kinning, S. Mansour, F. Elmslie, L. Goodwin, A. H. van der Hout, H. E. Veenstra-Knol, J. C. Herkert, A. M. Lund, R. C. M. Hennekam, A. Mégarbané, M. M. Lees, L. C. Wilson, A. Male, J. Hurst, N. V. Knoers, P. Coucke, P. A. Terhal.

293/12:00 Diagnostic criteria for Stickler syndrome based on comprehensive clinical and molecular analysis. F. Acke, P. Coucke, O. Vanakker, K. Hoornaert, I. Dhooge, A. De Paepe, E. De Leenheer, F. Malfait.

294/12:15 Updated cardiac description in Loeys Dietz syndrome. G. L. Oswald, E. M. Reynolds, H. C. Dietz, J. P. Habashi, genTAC Consortium Investigators.

Tuesday, October 21

10:30 AM–12:30 PM

Concurrent Platform Session D

55. Cancer Susceptibility Genes: Identification and Implementation

Room 20D, Upper Level, Convention Center

Moderators: Ephrat Levy-Lahad, Shaare Zedek Med Ctr, Jerusalem, Israel
  Matt Deardorff, CHOP, Philadelphia

295/10:30 Mosaic loss of chromosome Y in blood cells is associated with shorter survival and higher risk of cancer in men. L. A. Forsberg, C. Rasi, N. Malmqvist, H. Davies, S. Pasupulati, G. Pakalapati, J. Sandgren, T. Diaz de Ståhl, A. Zaghlool, V. Giedraitis, L. Lannfelt, J. Score, N. C. P. Cross, D. Absher, E. Tiensuu Janson, C. Lindgren, A. P. Morris, E. Ingelsson, L. Lind, J. P. Dumanski.

296/10:45 Genetic heritability of common non-Hodgkin lymphoma subtypes. S. I. Berndt, L. M. Morton, S. S. Wang, L. R. Teras, S. L. Slager, J. Vijai, K. Smedby, G. M. Ferri, L. Miligi, C. Magnani, D. Albanes, A. R. Brooks-Wilson, E. Roman, A. Monnereau, P. Vineis, A. Nieters, B. M. Birmann, G. G. Giles, M. P. Purdue, B. K. Link, C. M. Vajdic, A. Zeleniuch-Jacquotte, C. F. Skibola, Y. Zhang, J. R. Cerhan, Z. Wang, N. Rothman, S. J. Chanock, J. Sampson, on behalf of NHL GWAS Project.

297/11:00 A genome-wide scan identifies NFIB as important for metastasis in osteosarcoma patients. L. Mirabello, R. Koster, L. Spector, O. A. Panagiotou, P. S. Meltzer, B. Moriarty, D. Largaespada, N. Pankratz, J. M. Gastier-Foster, R. Gorlick, C. Khanna, A. M. Flanagan, R. Tirabosco, I. L. Andrulis, N. Gokgoz, J. S. Wunder, A. Patiño-Garcia, F. Lecanda, L. Sierrasesúmaga, S. R. C. de Toledo, A. S. Petrilli, M. Serra, C. Hattinger, P. Picci, S. Wacholder, L. Helman, M. Yeager, R. N. Hoover, S. J. Chanock, S. A. Savage.

298/11:15 Enrichment of colorectal cancer associations in functional regions: Insight for combining ENCODE and Roadmap Epigenomics data in the analysis of whole genome sequencing-imputed GWAS. S. Rosse, P. Auer, T. Harriason, C. Carlson, C. Qu, G. R. Abecasis, S. I. Berndt, S. Bézieau, H. Brenner, G. Casey, A. T. Chan, J. Chang-Claude, S. Chen, S. Jiao, C. M. Hutter, L. Le Marchand, S. M. Leal, P. A. Newcomb, M. L. Slattery, J. Smith, E. White, B. W. Zanke, U. Peters, D. A. Nickerson, A. Kundaje, L. Hsu.

299/11:30 Frequency and phenotypic spectrum of germline mutations in POLE and seven other polymerase genes in patients with colorectal adenomas and carcinomas. I. Spier, S. Holzapfel, J. Altmüller, B. Zhao, S. Horpaopan, S. Vogt, S. Chen, M. Morak, S. Raeder, K. Kayser, D. Stienen, R. Adam, P. Nürnberg, G. Plotz, E. Holinski-Feder, R. P. Lifton, H. Thiele, P. Hoffmann, V. Steinke, S. Aretz.

300/11:45 Impact of genetic testing on reducing colorectal cancer. D. W. Neklason, H. A. Hanson, C. Schaefer, G. Mineau, M. F. Leppert, R. W. Burt, K. R. Smith.

301/12:00 Performance of multi-gene panels for familial cancer screening in clinical cases: The ColoSeq and BROCA experience. B. H. Shirts, S. Casadei, A. Jacobson, E. Turner, J. F. Tait, M. C. King, T. Walsh, C. C. Pritchard.

302/12:15 Unanticipated germline cancer susceptibility mutations identified by clinical exome sequencing of sequentially diagnosed pediatric solid tumor patients: The BASIC3 study. S. E. Plon, S. Scollon, K. Bergstrom, T. Wang, R. A. Kerstein, U. Ramamurthy, D. M. Muzny, S. G. Hilsenbeck, Y. Yang, C. M. Eng, R. A. Gibbs, D. W. Parsons.

Tuesday, October 21

10:30 AM–12:30 PM

Concurrent Platform Session D

56. Balanced and Unbalanced Chromosomal Rearrangements

Room 28, Upper Level, Convention Center

Moderators: Terry J. Hassold, Washington State Univ, Pullman
  Christa L. Martin, Geisinger Hlth Syst, Lewisburg

303/10:30 An evidence-based dosage sensitivity map towards defining the clinical genome. E. Riggs, E. Andersen, B. Hong, H. Kearney, G. Hislop, S. Kantarci, D. Pineda-Alvarez, U. Maye, D. McMullan, M. Serrano, I. Simonic, S. South, M. Speevak, K. Smith, J. Stavropoulos, K. Wain, S. Aradhya, E. Thorland, C. Martin, on behalf of Clinical Genome Resource.

304/10:45 Next-generation sequencing of duplication CNVs reveals that most are tandem and some disrupt genes at breakpoints. K. Rudd, K. E. Hermetz, B. Weckselblatt, S. Newman.

305/11:00 Balanced chromosome rearrangements rapidly annotate the morbid human genome. T. Kammin, K. E. Wong, B. B. Currall, Z. Ordulu, H. Brand, V. Pillalamarri, C. Hanscom, I. Blumenthal, J. F. Gusella, E. C. Liao, M. E. Talkowski, C. C. Morton.

306/11:15 The perplexing prevalence of familial nested 22q11.2 deletions. D. M. McDonald-McGinn, L. DiCairano, J. T. Goulet, A. Capezzuto, A. Krajewski, C. Franconi, M. McNamara, D. E. McGinn, B. S. Emanuel, E. H. Zackai.

307/11:30 9q33.3q34.11 microdeletion: Delineation of a new contiguous gene syndrome including the STXBP1, LMX1B and ENG genes using reverse phenotyping. S. Nambot, A. Mosca Boidron, A. Masurel, M. Lefebvre, N. Marle, J. Thevenon, J. De Montléon, S. Perez Martin, M. Chouchane, E. Sapin, J. Metaizeau, V. Dulieu, F. Huet, C. Thauvin Robinet, L. Chatel, V. Abadie, G. Plessis, J. Andrieux, P. Jouk, G. Billy Lopez, C. Coutton, F. Morice Picard, M. Delrue, C. Rooryck Thambo, L. Faivre.

308/11:45 Alu-enriched genomic structure facilitates chromosome 17p13.3 region susceptibility to diverse and complex pathogenic copy number variations. S. Gu, B. Yuan, I. M. Campbell, A. Patel, C. Bacino, P. Stankiewicz, S. W. Cheung, W. Bi, J. R. Lupski.

309/12:00 Decoding NF1 intragenic copy number changes. M. Hsiao, A. Piotrowski, T. Callens, C. Fu, L. Messiaen.

310/12:15 De novo DYRK1A point mutations cause similar phenotypes to those observed in microdeletions including 21q22.13: Further evidence for DYRK1A’s critical role in brain development. J. Ji, N. Dorrani, J. Mann, J. A. Martinez-Agosto, N. Gallant, J. A. Bernstein, N. Gomez-Ospina, L. Hudgins, L. Slattery, B. Isidor, E. Obersztyn, B. Wiśniowiecka-Kowalnik, M. Fox, H. Lee, J. Deignan, E. Vilain, S. F. Nelson, W. Grody, F. Quintero-Rivera.

Tuesday, October 21

10:30 AM–12:30 PM

Concurrent Platform Session D

57. Diagnostic Yield of New Genomic Technologies

Room 29, Upper Level, Convention Center

Moderators: Heidi Rehm, Harvard Med Sch, Cambridge
  Lee Jun C. Wong, Baylor Col Med, Houston

311/10:30 Prenatal whole genome SNP array diagnosis as a first-line test: nature and prevalence of abnormal results in phenotypically normal and abnormal fetuses. F. A. T. de Vries, M. I. Srebniak, L. C. P. Govaerts, K. E. M. Diderich, R. J. H. Galjaard, A. M. S. Joosten, A. R. M. Van Opstal.

312/10:45 The clinical utility of molecular genetic testing strategies for the diagnosis of mitochondrial disorders. R. Bai, D. Arjona, J. Higgs, J. Scuffins, J. Juusola, P. Vitazka, J. Neidich, K. Retterer, K. Parsons, N. Smaoui, E. Haverfield, S. Suchy, G. Richard.

313/11:00 Pathogenic variant spectrum in newly described cancer genes on next-generation cancer panels. L. Susswein, L. Vincent, R. Klein, J. Booker, M. L. Cremona, P. Murphy, K. Hruska.

314/11:15 Exome sequencing for the diagnosis of 46,XY disorders of sex development. E. C. Delot, R. M. Baxter, V. A. Arboleda, H. Lee, H. Barseghyan, M. P. Adam, P. Y. Fechner, R. Bargman, K. Keegan, S. Travers, S. Schelley, L. Hudgins, R. P. Mathew, H. J. Stalker, R. Zori, O. K. Gordon, L. Ramos-Platt, A. Eskin, S. F. Nelson, E. Vilain.

315/11:30 Clinical exomes for hearing loss: Surprising diagnoses and better yields. L. H. Hoefsloot, I. Feenstra, I. J. de Wijs, M. H. Siers, H. P. M. Kunst, R. J. Admiraal, R. J. E. Pennings, H. Scheffer, H. Kremer, H. G. Yntema.

316/11:45 De novo mutations identified in clinical whole exome sequencing. S. Pan, F. Xia, D. Muzny, S. Plon, J. Lupski, A. Beaudet, R. Gibbs, C. Eng, Y. Yang.

317/12:00 Frequency of “ACMG-56” variants in whole genomes of healthy elderly. L. Ariniello, C. S. Bloss, G. Erickson, P. Pham, D. Boeldt, O. Libiger, N. Schork, E. Topol, A. Van Zeeland, A. Torkamani.

318/12:15 Exploring the diagnostic yield of whole exome sequencing in a broad range of genetic conditions: The first 200 cases in the NCGENES study. N. T. Strande, C. Bizon, J. K. Booker, K. R. Crooks, A. K. M. Foreman, G. T. Haskell, M. A. Hayden, K. Lee, M. Lu, L. Milko, J. M. O'Daniel, P. Owen, B. C. Powell, C. Skrzynia, C. R. Tilley, A. Treece, D. Young, K. C. Wilhelmsen, K. E. Weck, J. S. Berg, J. P. Evans.

Tuesday, October 21

10:30 AM–12:30 PM

Concurrent Platform Session D

58. Genetic/Genomic Education and Services Delivery

Room 30, Upper Level, Convention Center

Moderators: Arti Pandya, Virginia Commonwealth Univ, Richmond
  Kevin Sweet, Ohio State Univ, Columbus

319/10:30 Clinician CME tailored to individual patient's whole exome results. M. A. Giovanni, M. F. Murray.

320/10:45 Changing the landscape of genomics education through a massive open online course: Genomic medicine gets personal. B. R. Haddad, J. Russel, S. Pennestri, D. Demaree, M. Tan, B. N. Peshkin.

321/11:00 Genome: Unlocking life’s code – a museum exhibition as a model for informal genomics education. V. Bonham, C. Easter, E. Schonman, C. Daulton, R. Wise, B. Hurle, J. Witherly.

322/11:15 Human Genetics: Medical and Societal Implications. A high school course taught on a medical school campus. M. Godfrey, J. E. Bird.

323/11:30 Whole genome sequencing in a healthy population: Processes, challenges, and insights. C.S. Richards, P. Jain, M.O. Dorschner, D.A. Nickerson, G.P. Jarvik, L.M. Amendola, D.K. Simpson, A. Rope, J. Reiss, K. Kennedy, D.I. Quigley, J. Berg, C. Harding, M. Gilmore, P. Himes, B. Wilfond, K.A.B. Goddard, on behalf of NextGen Project Team.

324/11:45 Patient perceptions about the utility of family history review during whole genome sequencing: Initial findings from the MedSeq Study. K. D. Christensen, P. J. Lupo, J. O. Robinson, J. Blumenthal-Barby, J. L. Vassy, L. S. Lehmann, P. A. Ubel, J. S. Roberts, R. C. Green, A. L. McGuire, MedSeq Study Team.

325/12:00 Hereditary cancer communication with underserved patients. G. Joseph, C. Guerra.

326/12:15 Cost effectiveness of adding genes to next-generation sequencing panels for evaluation of colorectal cancer and polyposis syndromes. C. J. Gallego, B. S. Shirts, C. C. Pritchard, G. P. Jarvik, D. L. Veenstra.

Tuesday, October 21

4:30 PM–6:30 PM

Concurrent Platform Session E

59. We Have the Technology: Next-Generation Genomic Methods

Hall B1, Ground Level, Convention Center

Moderators: Melissa Gymrek, MIT, Cambridge
  Jay Shendure, Univ Washington, Seattle

327/4:30 Whole-genome single-cell haplotyping, a generic method for preimplantation genetic diagnosis. M. Zamani Esteki, E. Dimitriadou, L. Mateiu, C. Melotte, N. Van der Aa, P. Kumar, R. Das, K. Theunis, J. Cheng, E. Legius, Y. Moreau, S. Debrock, T. D’Hooghe, P. Verdyck, M. De Rycke, K. Sermon, J. R. Vermeesch, T. Voet.

328/4:45 Targeted locus amplification for hypothesis neutral next-generation sequencing and haplotyping of selected genomic loci. M. J. van Min, P. J. P. de Vree, W. de Laat, E. de Wit, M. Yilmaz, M. van de Heijning, P. Klous, P. ter Brugge, J. Jonkers, J. Foekens, J. Martens, H. K. Ploos van Amstel, P. P. Eijk, D. Sie, B. Ylstra, M. Ligtenberg, M. F. van Dooren, L. J. C. M. van Zutven, E. Splinter, S. Verbeek, K. Willems van Dijk, M. Cornelissen, A. T. Das, B. Berkhout, B. Sikkema Radatz, E. van den Berg, P. van der Vlies, Y. Wan, J. T. den Dunnen, M. Lamkanfi, Hubrecht Institute.

329/5:00 Saturation genome editing by multiplex homologous donor repair. G. M. Findlay, E. A. Boyle, R. J. Hause, J. Klein, J. Shendure.

330/5:15 Metagenomic deconvolution and species discovery in microbiomes using contact probability maps. J. N. Burton, I. Liachko, M. J. Dunham, J. Shendure.

331/5:30 Deep whole-genome sequencing based analysis of mosaic transposable mobile element insertions in adult human tissue. X. Zhu, A. Fiston-Lavier, D. Petrov, M. Snyder, D. Levinson, A. Urban.

332/5:45 Increased complexity of the human genome revealed by single-molecule sequencing. M. J. P. Chaisson, J. Huddleston, P. H. Sudmant, M. Malig, F. Hormozdiari, U. Surti, R. Wilson, M. Hunkapiller, J. Korlach, E. E. Eichler.

333/6:00 In situ genome-wide expression profiling of individual cell types. C. Kodira, A. Sood, L. Newberg, A. Miller, F. Ginty, E. McDonough, Y. Sui, A. Bordwell, Q. Li, S. Kaanumalle, K. Desai, Z. Pang, E. Brogi, S. Larson, I. Mellinghoff.

334/6:15 Whole-genome sequencing characterizes multiple mutational mechanisms resulting from off-target effects of CRISPR-Cas9 and TALEN treatments in human embryonic stem cells. R. L. Collins, A. Veres, H. Brand, A. Ragavendran, S. Erdin, Q. Ding, B. S. Gosis, K. Musunuru, M. E. Talkowski.

Tuesday, October 21

4:30 PM–6:30 PM

Concurrent Platform Session E

60. Hereditary Breast-Ovarian Cancer

Room 6AB, Upper Level, Convention Center

Moderators: Tom Walsh, Univ Washington, Seattle
  Sam Hanash, Univ Texas MD Anderson Cancer Ctr., Houston

335/4:30 Constitutional BRCA1 methylation is a major predisposition factor for high-grade serous ovarian cancer. A. Dobrovic, T. Mikeska, K. Alsop, G. V. Zapparoli, I. L. Candiloro, J. George, G. Mitchell, D. Bowtell, Australian Ovarian Cancer Study.

336/4:45 Candidate causal variants from three independent genetic signals at the 5q11.2 breast cancer risk locus regulate MAP3K1. D. M. Glubb, K. A. Pooley, K. Michailidou, M. J. Maranian, K. B. Meyer, J. A. Betts, K. M. Hillman, S. Kaufmann, G. Chenevix-Trench, D. F. Easton, A. M. Dunning, S. L. Edwards, J. D. French, Breast Cancer Association Consortium.

337/5:00 A profile of inherited predisposition to breast cancer among Nigerian women. Y. Zheng, T. Walsh, F. Yoshimatsu, M. Lee, S. Gulsuner, S. Casadei, A. Rodriguez, T. Ogundiran, C. Babalola, O. Ojengbede, D. Sighoko, R. Madduri, M.-C. King, O. Olopade.

338/5:15 Estimates for inherited mutations in breast cancer susceptibility genes among triple-negative breast cancer patients. F. Couch, S. N. Hart, P. Sharma, A. Ewart Toland, X. Wang, P. Miron, J. E. Olson, A. Godwin, V. S. Pankratz, C. Olswold, M. W. Beckmann, W. Janni, B. Rack, A. Ekici, D. J. Slamon, I. Konstantopoulou, F. Fostira, G. Fountzilas, L. Pelttari, S. Yao, J. Garber, A. Cox, H. Brauch, C. Ambrosone, H. Nevanlinna, D. Yannoukakos, S. L. Slager, C. M. Vachon, D. M. Eccles, P. A. Fasching.

339/5:30 Inherited mutations in ovarian cancer - PALB2 and BARD1 are likely ovarian cancer susceptibility genes. B. Norquist, M. I. Harrell, M. F. Brady, T. Walsh, M. K. Lee, S. Gulsuner, Q. Yi, S. Casadei, S. Bernards, S. A. Davidson, R. S. Mannel, P. A. DiSilvestro, M. C. King, M. J. Birrer, E. M. Swisher.

340/5:45 Implementing PALB2 gene testing in breast and ovarian cancer patients in UK. N. Rahman, E. Ruark, S. Seal, A. Renwick, E. Ramsay, S. Powell, M. Warren-Perry, H. Hanson, C. Lord, C. Turnbull.

341/6:00 Functional variant assays for predicting breast cancer risks of genetic variants in the DNA double-stranded break repair pathway. H. Ostrer, A. Pearlman, K. Upadhyay, Y. Shao, J. Loke.

342/6:15 Genome-wide association study of progression-free survival in ovarian cancer patients treated with carboplatin and paclitaxel identifies an enhancer that regulates three nearby genes. G. Chenevix-Trench, Y. Lu, J. Beesley, K. Hillman, S. Edwards, S. Johnatty, S. Macgregor, B. Gao, J. French, A. deFazio, on behalf of Ovarian Cancer Association Consortium.

Tuesday, October 21

4:30 PM–6:30 PM

Concurrent Platform Session E

61. Genomic Studies of Schizophrenia and Bipolar Disorder

Room 6CF, Upper Level, Convention Center

Moderators: Michael Epstein, Emory Univ, Altanta
  Laura Scott, Univ Michigan, Ann Arbor

343/4:30 Emerging patterns of schizophrenia risk conferred by de novo mutation. D. Howrigan, B. Neale, K. Samocha, J. Moran, K. Chambert, S. Rose, M. Fromer, S. Chandler, N. Laird, H. G. Hwu, W. J. Chen, S. Faraone, S. Glatt, M. Tsuang, S. McCarroll.

344/4:45 Discoveries from a genome-wide analysis of CNVs in the PGC study of schizophrenia. J. Sebat, C. R. Marshall, D. Howrigan, D. Merico, B. Thiruvahindrapuram, W. Wu, M. O'Donovan, S. Scherer, B. Neale, Schizophrenia and CNV analysis groups of Psychiatric Genomics Consortium.

345/5:00 A functional role for non-coding variation in schizophrenia genome-wide significant loci. P. Sklar, A. Mitchell, G. Voloudakis, V. Pothula, E. Stahl, A. Georgakopoulos, D. Ruderfer, J. Fullard, A. Charney, Y. Okada, K. Siminovitch, J. Worthington, L. Padyukov, L. Klareskog, P. Gregersen, R. Plenge, S. Raychaudhuri, M. Fromer, S. Purcell, K. Brennand, M. Fromer, N. Robakis, E. Schadt, S. Akbarian, P. Roussos.

346/5:15 Comprehensive, integrative and hypothesis-free pathway analysis of genome-wide association data highlights synaptic transmission, dendritic spines and the post-synaptic density in schizophrenia. T. H. Pers, S. Ripke, L. Franke, J. N. Hirschhorn, for the Psychiatric Genetics Consortium.

347/5:30 Integrating network analyses and genetics with large-scale RNA-sequencing of schizophrenia brains. M. Fromer, for CommonMind Consortium, Swedish Schizophrenia Consortium, Schizophrenia Working Group of PGC.

348/5:45 RNAseq transcriptome study implicates immune-related genes in schizophrenia. A. R. Sanders, E. I. Drigalenko, J. Duan, W. Moy, J. Freda, MGS Collaboration, H. H. H. Göring, P. V. Gejman.

349/6:00 A rare regulatory noncoding variant in GWAS-implicated MIR137/MIR2682 locus potentially confers risk to both schizophrenia and bipolar disorder. J. Duan, J. Shi, A. Fiorentino, C. Leites, J. Chen, W. Moy, B. Alexandrov, D. He, J. Freda, A. Bishop, N. L. O’Brien, MGS, GPC, X. Chen, A. Usheva, A. McQuillin, A. R. Sanders, H. M. D. Gurling, M. T. Pato, K. S. Kendler, C. N. Pato, P. V. Gejman.

350/6:15 GWAS of bipolar 1 disorder in a multi-ethnic cohort of 72,823 identifies four novel loci. C. Schaefer, L. Shen, K. Kearney, M. McCormick, S. P. Hamilton, L. A. McInnes, V. Reus, J. Wall, P.-Y. Kwok, M. Kvale, T. J. Hoffmann, E. Jorgenson, N. Risch.

Tuesday, October 21

4:30 PM–6:30 PM

Concurrent Platform Session E

62. From Association to Function in Complex Traits

Room 6DE, Upper Level, Convention Center

Moderators: Kyle Gaulton, Univ Oxford, UK
  Nadav Ahituv, UC San Francisco

351/4:30 Partitioning heritability by functional category using summary statistics. H. Finucane, B. Bulik-Sullivan, A. Gusev, G. Trynka, P. Loh, H. Xu, C. Zang, S. Ripke, S. Purcell, M. Daly, E. Stahl, S. Raychaudhuri, S. Lindstrom, N. Patterson, B. Neale, A. Price, Schizophrenia Working Group of Psychiatric Genetics Consortium.

352/4:45 Identification of multiple regulatory variants at the GALNT2 human high-density lipoprotein cholesterol locus. T. S. Roman, A. F. Marvelle, M. P. Fogarty, S. Vadlamudi, M. L. Buchkovich, J. R. Huyghe, C. Fuchsberger, A. U. Jackson, K. J. Gaulton, A. J. Gonzalez, P. Soininen, A. J. Kangas, J. Kuusisto, M. Ala-Korpela, M. Laakso, M. Boehnke, K. L. Mohlke.

353/5:00 A PAX1enhancer locus increases risk of idiopathic scoliosis in females. C. Wise, S. Sharma, D. Londono, W. Eckalbar, X. Gao, I. Kou, A. Takahashi, M. Matsumoto, J. A. Herring, D. K. Burns, S. Ikegawa, N. Ahituv, D. Gordon.

354/5:15 Characterization of the type 2 diabetes-associated KLF14 trans-regulatory network. K. Small, L. Quaye, A. Hough, M. Todorcevic, A. Mahajan, M. Horikoshi, A. Buil, A. Vinuela, C. Glastonbury, A. Brown, J. Bell, A. Gloyn, R. Cox, F. Karpe, M. McCarthy.

355/5:30 mRNA-seq of 278 diverse skeletal muscle biopsies reveals mechanistic insights about type 2 diabetes genetic risk and identifies disease state specific eQTLs. J. R. Huyghe, S. C. J. Parker, M. R. Erdos, H. Koistinen, P. S. Chines, R. Welch, X. Wen, H. Jiang, N. Narisu, L. Taylor, B. Wolford, L. J. Scott, H. Stringham, L. Kinnunen, T. Blackwell, A. U. Jackson, Y. Lee, A. J. Swift, L. Bonnycastle, M. L. Stitzel, R. M. Watanabe, K. Mohlke, T. Lakka, M. Laakso, J. Tuomilehto, F. S. Collins, M. Boehnke.

356/5:45 Genetic analyses of hepatic steatosis GWAS associated loci. E. K. Speliotes, Y. Chen, A. W. Tai.

357/6:00 FOXO3 regulates fetal hemoglobin levels in sickle cell anemia. V. Sheehan, Y. Zhang, J. Crosby, R. Ware, E. Boerwinkle.

358/6:15 Susceptibility to tuberculosis is associated with the ASAP1 gene that regulates dendritic cell migration. Y. Luo, J. Curtis, H. L. Zenner, D. Cuchet-Lourenco, C. Wu, K. Lo, M. Maes, A. Alisaac, E. Stebbings, J. Z. Liu, O. Ignatyeva, Y. Balabanova, V. Nikolayevskyy, P. Nürnberg, R. Horstmann, F. Drobniewski, V. Plagnol, J. C. Barrett, S. Nejentsev.

Tuesday, October 21

4:30 PM–6:30 PM

Concurrent Platform Session E

63. Therapy for Genetic Disorders

Room 20A, Upper Level, Convention Center

Moderators: Gerald Raymond, Univ Minnesota, Minneapolis
  Michael J. Gambello, Emory Univ Sch Med, Atlanta

359/4:30 Targeting calpains: A therapeutic strategy for the treatment of TGFβ-mediated mesenchymal transition and associated pathologies. D. Kim, R. Gould, J. Butcher, H. Dietz.

360/4:45 Metabolic regulation by the MeCP2/HDAC3 transcriptional corepressor complex points to new therapeutic targets in Rett syndrome. S. M. Kyle, C. M. Buchovecky, M. J. Justice.

361/5:00 Increasing IKAP expression by mRNA splicing modification improves phenotype in a mouse model of familial dysautonomia. E. Morini, P. Dietrich, M. Salani, F. Urbina, M. Nilbratt, I. Dragatsis, S. Slaugenhaupt.

362/5:15 Impact of early hormonal therapy on the neurobehavioral profile of boys with 47, XXY (Klinefelter syndrome) at 9 years of age. C. Samango-Sprouse, D. C. Gibbs, E. Stapelton, T. Sadeghin, A. L. Gropman.

363/5:30 A causative role for oxytocin in pregnancy-induced aortic dissection in Marfan syndrome mouse models. J. P. Habashi, E. M. Gallo, N. Huso, Y. Chen, D. Bedja, D. Huso, H. C. Dietz.

364/5:45 Most participants in the agalsidase beta phase 3 clinical trial in patients with classic Fabry disease experienced no severe clinical events during a 10-year follow-up period. D. P. Germain, J. Charrow, R. J. Desnick, J. T. Ebels, N. Guffon, J. Kempf, R. H. Lachmann, R. Lemay, G. E. Linthorst, S. Packman, C. R. Scott, S. Waldek, D. G. Warnock, N. J. Weinreb, W. R. Wilcox.

365/6:00 ENGAGE: A phase 3, randomized, double blind, placebo-controlled, multi-center study to investigate the efficacy and safety of eliglustat in adults with Gaucher disease type 1: 18-month results. M. Balwani, D. Amato, M. Dasouki, G. Pastores, S. Packman, S. Assouline, P. Mistry, A. Ortega, S. Shankar, M. Solano, J. Angell, L. Ross, J. Peterschmitt.

366/6:15 Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3. N. Khan, M. Auranen, I. Paetau, E. Pirinen, L. Euro, C. Carroll, J. Auwerx, A. Suomalainen.

Tuesday, October 21

4:30 PM–6:30 PM

Concurrent Platform Session E

64. Exome Sequencing as Standard of Care in Clinical Genetics

Room 20BC, Upper Level, Convention Center

Moderators: Livija Medne, CHOP, Philadelpia
  Carol Saunders, Children's Mercy Hosp, Kansas City

367/4:30 Transition from clinically fully validated panels to medically relevant exome. L. Wong, V. W. Zhang, E. S. Schmitt, J. Wang.

368/4:45 How well do whole exome sequencing results correlate with clinical findings? A study of 89 Mayo Clinic biobank samples. S. Middha, N. M. Lindor, S. K. McDonnell, K. J. Johnson, J. E. Olson, E. D. Wieben, G. Farrugia, J. R. Cerhan, S. N. Thibodeau.

369/5:00 Clinical whole exome sequencing reveals contribution of rare genetic events to undiagnosed disease. C. M. Eng, D. Muzny, F. Xia, Z. Niu, R. Person, Y. Ding, P. Ward, A. Braxton, M. Wang, C. Buhay, N. Veeraraghavan, A. Hawes, T. Chiang, M. Leduc, J. Beuten, J. Zhang, W. He, J. Scull, A. Willis, M. Landsverk, W. Craigen, M. Bekeirnia, P. Liu, S. Wen, W. Alcaraz, H. Cui, M. Walkiewicz, M. Bainbridge, E. Boerwinkle, A. L. Beaudet, J. R. Lupski, S. E. Plon, R. A. Gibbs, Y. Yang.

370/5:15 Clinical exome sequencing at UCLA: Diagnosis rate, variant spectrum and novel gene discoveries. H. Lee, J. L. Deignan, N. Dorrani, S. Strom, N. Ghahramani, S. Kantarci, F. Quintero-Rivera, K. Das, M. Fox, W. W. Grody, E. Vilain, S. F. Nelson.

371/5:30 Medical exome: Towards achieving complete coverage of disease related genes. A. Santani, K. McDonald, D. Mandelkar, A. Ankala, C. da Silva, Z. Yu, K. Cao, H. Sharma, R. Shakbatyan, M. Lebo, B. Funke, M. Hegde.

372/5:45 Look before you leap, and list before you look: The use of a priori curated gene lists to guide exome analysis. B. C. Powell, A. K. M. Foreman, J. M. O'Daniel, K. Lee, L. Boshe, K. R. Crooks, M. Lu, Z. Fan, J. K. Booker, K. E. Weck, J. P. Evans, J. S. Berg.

373/6:00 Validation of small-molecule metabolomic profiling for the clinical screening of inborn errors of metabolism. M. J. Miller, A. D. Kennedy, A. D. Eckhart, J. E. Wulff, M. V. Milburn, J. A. Ryals, A. L. Beaudet, Q. Sun, V. R. Sutton, S. H. Elsea.

374/6:15 Free the data: EmBase and EmVClass facilitate storage, interpretation, curation, and sharing of over 11,000 sequence variants identified through clinical testing. L. J. H. Bean, S. W. Tinker, C. da Silva, M. R. Hedge.

Tuesday, October 21

4:30 PM–6:30 PM

Concurrent Platform Session E

65. Beyond the Sequence: Genomic Regulation and Disease

Room 20D, Upper Level, Convention Center

Moderators: Stephen Meyn, Hosp for Sick Children, Toronto
  Peter Scacheri, Case Western Reserve Univ, Cleveland

375/4:30 The role of TET1-mediated demethylation in gene regulation and memory formation. A. J. Towers, XL. Li, A. L. Bey, P. Wang, YH. Jiang.

376/4:45 DNA methylation in the central nucleus of the amygdala contributes to anxious temperament in young primates. R. S. Alisch, P. Chopra, A. S. Fox, K. Chen, A. T. J. White, P. H. Roseboom, S. Keles, N. H. Kalin.

377/5:00 MicroRNA-486 overexpression delays the disease pathology of muscular dystrophy. M. S. Alexander, J. C. Casar, N. Motohashi, N. M. Vieira, I. Eisenberg, J. L. Marshall, M. J. Gasperini, A. Lek, J. A. Myers, E. A. Estrella, P. B. Kang, F. Shapiro, F. Rahimov, G. Kawahara, J. J. Widrick, L. M. Kunkel.

378/5:15 Mutations in nuclear envelope change myogenic epigenomic programs and normal cell fate. J. Perovanovic, S. Dell"orso, V. Sartorelli, K. Mamchaoui, V. Mouly, C. Vigouroux, G. Bonne, E. P. Hoffman.

379/5:30 Aberrant DNA hypermethylation of SDHC: A novel mechanism of tumor development in Carney Triad. F. Faucz, F. Haller, E. A. Moskalev, S. Batthelmeb, S. Wiemann, M. Bieg, G. Assie, J. Bertherat, I.-M. Schaefer, C. Otto, E. Rattenberry, E. R. Maher, P. Strobel, M. Werner, J. A. Carney, A. Hartmann, A. Agamy, C. A. Stratakis.

380/5:45 A screen-informed candidate gene approach identifies a large human telomere maintenance network. B. Holohan, W. Wright, J. Shay.

381/6:00 Association between telomere length SNPs and five cancer types: A Mendelian randomization study from the GAME-ON post-GWAS consortium. C. Zhang, S. Burgess, P. Kraft, S. Lindstrom, R. Hung, U. Peters, H. Ahsan, T. Sellers, A. Monteiro, G. Trench, J. Doherty, B. Pierce, on behalf of CORECT, DRIVE, ELLIPSE, OCAC, and TRICL studies and GAME-ON Network.

382/6:15 Imputation and subset based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33. Z. Wang, M. Zhang, B. Zhu, H. Parikh, J. Jia, C. C. Chung, J. N. Sampson, J. W. Hoskins, A. Hutchinson, L. Burdette, L. Mirabello, S. A. Savage, P. Kraft, S. J. Chanock, M. Yeager, M. T. Landi, J. Shi, N. Chatterjee, L. T. Amundadottir.

Tuesday, October 21

4:30 PM–6:30 PM

Concurrent Platform Session E

66. A Clear Vision for Genetic Eye Diseases

Room 28, Upper Level, Convention Center

Moderators: Lucia Sobrin, Harvard Univ, Cambridge
  Anand Swaroop, NEI/NIH, Bethesda

383/4:30 Genome-wide analysis of mitochondrial single nucleotide polymorphism (mtSNP)-nuclear SNP interaction in age-related macular degeneration. P. J. Persad, M. D. Courtenay, G. Wang, P. W. Gay, W. Cade, A. Agarwal, S. G. Schwartz, J. L. Kovach, M. A. Brantley, R. J. Sardell, J. N. Cooke Bailey, J. L. Haines, M. A. Pericak-Vance, W. K. Scott.

384/4:45 Unravelling the complex genetics of age-related macular degeneration — The International AMD Genomics Consortium. V. Cipriani, on behalf of International AMD Genomics Consortium.

385/5:00 Whole-genome sequencing study of ~6,000 samples for age-related macular degeneration. A. Kwong, X. Zhan, L. G. Fritsche, J. Bragg-Gresham, K. E. Branham, M. Othman, A. Boleda, L. Gieser, R. Ratnapriya, D. Stambolian, E. Y. Chew, A. Swaroop, G. Abecasis.

386/5:15 Examining the casual role of central corneal thickness in glaucoma: A Mendelian randomization approach. C. Y. Cheng, T. H. Tham, J. M. Liao, T. Y. Wong, T. Aung.

387/5:30 The role of rare TIMP3 mutations in age-related macular degeneration. L. G. Fritsche, International AMD Genomics Consortium.

388/5:45 High-throughput screening of 51 known causative genes in families with congenital cataract. S. Javadiyan, J. Craig, S. Sharma, K. Lower, K. Burdon.

389/6:00 Primary cilia mediate retinal development and photoreceptor homeostasis. C. Carter, A. Drack, Q. Zhang, N. Nuangchamnong, C. Searby, V. C. Sheffield.

390/6:15 Using zebrafish to assess novel therapeutics and model the eye disease of cblC disease. N. P. Achilly, J. L. Sloan, K. Bishop, M. S. Jones, R. Sood, C. P. Venditti.

Tuesday, October 21

4:30 PM–6:30 PM

Concurrent Platform Session E

67. Autoimmune Genes: Discovery and Function

Room 29, Upper Level, Convention Center

Moderators: Yukinoki Okada, Tokyo Med and Dent Univ
  Lisa Barcellos, UC Berkeley

391/4:30 A trans-ethnic genome-wide association study of 21,483 cases and 97,977 controls identifies 27 genetic susceptibility variants for atopic dermatitis. L. Paternoster, M. Standl, H. Baurecht, J. Waage, M. Hotze, J. A. Curtin, K. Bønnelykke, D. Glass, D. A. Hinds, E. Melen, P. Sleiman, B. Feenstra, M. Pino-Yanes, H. T. den Dekker, M. Bustamante, I. Marenholz, B. Jacobsson, A. D. Irvine, A. C. Alves, M. M. Groen-Blokhuis, A. Franke, M. Ferreira, M. Tamari, N. Probst-Hensch, K. Williams, D. P. Strachan, S. J. Brown, J. Heinrich, D. M. Evans, S. Weidinger, on behalf of EAGLE Eczema Consortium.

392/4:45 Trans-ancestral ImmunoChip: SLE risk loci show enrichment for NK cytotoxicity and cell adhesion pathways. D. S. Cunninghame Graham, J. A. Kelly, C. D. Langefeld, R. R. Graham, P. M. Gaffney, T. J. Vyse, SLE ImmunoChip Consortium.

393/5:00 Eight amino acid positions in five HLA class I and II genes explain the MHC association to type 1 diabetes risk. X. Hu, B. Han, S. Onengut-Gumuscu, W. Chen, A. J. Deutsche, T. L. Lenz, P. I. W. de Bakker, S. S. Rich, S. Raychaudhuri.

394/5:15 Increased risk of rheumatoid arthritis among shared epitope-negative mothers with shared epitope-positive children: Results from the mother-child immunogenetic study in autoimmunity. G. I. Cruz, L. A. Criswell, X. Shao, H. Quach, J. A. Noble, N. A. Patsopoulos, M. P. Busch, L. F. Barcellos.

395/5:30 Steroid-responsive genes play a major role in the genetic basis of sexual dimorphism in complex human disease. L. A. Weiss, K. M. Tsang, B. Adviento, K. A. Aldinger, H. Lee, K. Kim, R. J. Schmidt, S. F. Nelson, P. Levitt, D. G. Amaral, I. Hertz-Picciotto, C. Ladd-Acosta, M. D. Fallin, L. A. Croen, N. Zaitlen.

396/5:45 Functional characterization of a multiple sclerosis associated variant in IL7Ra. S. G. Gregory, G. Galarza-Muñoz, F. B. Briggs, L. Bergamaschi, S. Arvai, X. Shao, L. F. Barcellos, M. A. Garcia-Blanco.

397/6:00 UBE2L3 polymorphism amplifies NF-kB activation and promotes B cell development linking linear ubiquitination to multiple autoimmune diseases. M. J. Lewis, S. Vyse, A. M. Shields, S. Boeltz, D. Leirer, P. A. Gordon, T. D. Spector, P. J. Lehner, H. Walczak, T. J. Vyse.

398/6:15 A recombination allele of the lipase gene CEL and its pseudogene CELP encodes a hybrid protein and is a genetic risk factor for chronic pancreatitis. K. Fjeld, J. Rosendahl, J. M. Chen, D. Lasher, M. Cnop, B. B. Johansson, M. Ringdal, E. Masson, J. Mayerle, J. Mössner, C. Ruffert, S. Steine, E. Tjora, J. Torsvik, C. Ferec, F. U. Weiss, H. Witt, M. M. Lerch, P. R. Njølstad, S. Johansson, A. Molven.

Tuesday, October 21

4:30 PM–6:30 PM

Concurrent Platform Session E

68. Pharmacogenetics: From Association to Action

Room 30, Upper Level, Convention Center

Moderators: Bill Nyhan, UC San Diego
  Cornelia Van Duijn, Erasmus MC, Rotterdam, Netherlands

399/4:30 Clozapine-induced agranulocytosis/granulocytopenia is associated with rare HLA-DQB1 and HLA-B alleles. J. I. Goldstein, L. F. Jarskog, I. Cascorbi, M. Dettling, A. K. Malhotra, J. Nielsen, D. Rujescu, T. Werge, D. L. Levy, R. C. Josiassen, J. L. Kennedy, J. A. Lieberman, M. J. Daly, P. F. Sullivan, Clozapine Induced Agranulocytosis Consortium.

400/4:45 New susceptibility gene IKZF1 for cold medicine-related Stevens-Johnson syndrome/toxic epidermal necrolysis with severe mucosal involvement. M. Ueta, H. Sawai, C. Sotozono, Y. Hitomi, N. Kaniwa, M.K. Kim, K.Y. Seo, K.C. Yoon, C.K. Joo, C. Kannabiran, T.H. Wakamatsu, V. Sangwan, V. Rathi, S. Basu, T. Ozeki, T. Mushiroda, E. Sugiyama, K. Maekawa, R. Nakamura, M. Aihara, K. Matsunaga, A. Sekine, J.A.P. Gomes, J. Hamuro, Y. Saito, M. Kubo, S. Kinoshita, K. Tokunaga.

401/5:00 Prospective participant selection and ranking to maximize actionable PGx variants and discovery in the eMERGE Network. D. Crosslin, A. Gordon, P. Robertson, D. Hanna, D. Carrell, A. Scrol, I. Kullo, M. de Andrade, E. Baldwin, J. Grafton, K. Doheny, P. Crane, R. Li, S. Stallings, S. Verma, J. Wallace, M. Ritchie, M. Dorschner, E. Larson, D. Nickerson, G. Jarvik, electronic Medical Records and Genomics (eMERGE) Network.

402/5:15 Real-time pharmacogenomics: Genetic factors impacting phenylephrine response during surgery. J. M. Jeff, T. Joesph, K. Slivinski, M. Yee, A. Owusu Obeng, S. B. Ellis, E. P. Bottinger, O. Gottesman, M. A. Levin, E. E. Kenny.

403/5:30 PGRN Network-wide Project: Transcriptome analysis of pharmacogenes in human tissues. C. E. French, A. Chhibber, E. R. Gamazon, S. W. Yee, X. Qin, E. Theusch, A. Webb, S. T. Weiss, M. W. Medina, E. G. Schuetz, A. L. George, R. M. Krauss, C. Q. Simmons, S. E. Scherer, N. J. Cox, K. M. Giacomini, S. E. Brenner.

404/5:45 Transcriptome prediction in relevant tissues reveals mechanisms of drug-induced peripheral neuropathy. H. E. Wheeler, B. P. Schneider, D. L. Kroetz, K. Owzar, D. L. Hertz, H. L. McLeod, E. R. Gamazon, K. P. Shah, K. D. Miller, G. W. Sledge, N. J. Cox, M. E. Dolan, H. K. Im.

405/6:00 Evidence for extensive pleiotropy among pharmacogenes. M. T. Oetjens, W. S. Bush, J. C. Denny, K. A. Birdwell, H. H. Dilks, S. A. Pendergrass, M. D. Ritchie, D. C. Crawford.

406/6:15 Identifying risk variants for dihydropyrimidine dehydrogenase deficiency using an isogenic system of expression. S. M. Offer, S. Shrestha, C. R. Jerde, R. B. Diasio.

Wednesday, October 22

9:00 AM–11:00 AM

Concurrent Invited Session II

69. Circulating Cell-Free Nucleic Acids as Clinical Biomarkers

Room 6AB, Upper Level, Convention Center

Moderators: Glenn E. Palomaki, Women & Infants Hosp/Alpert Med Sch at Brown Univ, Providence
  YMD Lo, Chinese Univ Hong Kong

Circulating cell-free nucleic acids were reported in 1948, and by 1996 it was clear that cancer patients had tumor-specific DNA in circulation. In 1997, cell-free fetal DNA was identified in maternal circulation, and subsequent studies have found circulating RNA as well as micro RNA. With the advent of next-generation sequencing, circulating cell-free nucleic acids (ccfNA) have been explored as clinical biomarkers for a wide variety of clinical conditions such as fetal chromosomal or genetic disorders, cancer diagnosis/prognosis, transplantation medicine and coronary heart disease. In this session, four disparate methods for testing and interpreting ccfNA biomarkers will be presented, for the four clinical conditions listed.


9:00 AM   Sequencing circulating cell-free DNA in maternal plasma to identify Down syndrome. G. E. Palomaki. Women & Infants Hosp/Alpert Med Sch at Brown Univ, Providence.

9:30 AM   Circulating cell-free DNA enables the non-invasive diagnosis of rejection and infection in organ transplantation. I. De Vlaminck. Stanford Univ, Palo Alto.

10:00 AM   Circulating microRNAs as biomarkers for cardiovascular risk. A. Zampetaki. Kings Col London, London, United Kingdom.

10:30 AM   Genome-wide plasma DNA sequencing as a universal approach for cancer detection. Y.M.D. Lo. Chinese Univ Hong Kong.

Wednesday, October 22

9:00 AM–11:00 AM

Concurrent Invited Session II

70. Genomic Medicine Case Conference: Illustrative Clinical Examples

Room 20D, Upper Level, Convention Center

Moderators: Ian Krantz, Children's Hosp, Philadelphia
  Gail P. Jarvik, Univ Washington, Seattle

The advent of high-throughput and genomic medicine has abruptly changed clinical practice. We hope to provide an educational session that uses a case conference style to outline issues relevant to the clinical application of genomics. Each speaker will present 1-3 informative cases. Taken together, these cases will demonstrate facets that include the challenges of patient education and consent, variant interpretation and annotation, novel variant detection, incidental findings, incorporation of direct to consumer results, involvement of multiple medical specialists to evaluate patients and family members for manifestations of incidental findings, and other counseling issues. Each speaker’s talk will be limited to 15-20 minutes of the 30 minute block, to maximize discussion from the audience and the other speakers. The moderator will provide a very brief overview and introduce the speakers.


9:00 AM   Variant interpretation challenges in WGS cases from the MedSeq Study. H. Rehm. Harvard Univ, Cambridge.

9:30 AM   Genomic tests in pediatric patients. C. Eng. Baylor Col Med, Houston.

10:00 AM   Return of “actionable”, uncertain, and incidental findings in cancer. L. A. Garraway. Harvard Med Sch, Broad Inst, Boston.

10:30 AM   Cases demonstrating counseling issues in genomic medicine. L. Amendola. Univ Washington, Seattle.

Wednesday, October 22

9:00 AM–11:00 AM

Concurrent Invited Session II

71. Genomic Variation: Interpreting the Uninterpreted

Room 20A, Upper Level, Convention Center

Moderator: Douglas M. Fowler, Univ Washington, Seattle

The advent of high-throughput DNA sequencing has revealed an immense amount of variation in human genomes. The use of exome and genome sequencing in the clinic and the proliferation of direct-to-consumer genetic testing has intensified the pressure to understand how variation impacts health and other traits. Adding to the challenge is the fact that much of the variation in the genome is rare or complex, making it difficult to interpret using association-based methods. Consequently, new approaches for interpreting variation are being developed, and established methods are being improved. These methods are disparate, including model-based and high-throughput approaches for directly measuring the effects of variation and computational approaches that rely on inference. Each has strengths and weaknesses in terms of scale, accuracy and clinical relevance, but they are unified by a common goal: understanding the consequences of changes in the genome. This session seeks to bring together these disparate communities to explain how these methods are making inroads into variant interpretation, discuss the prospects for solving the variant interpretation problem on a genomic scale and stimulate a discussion on new ways to approach this critical problem.


9:00 AM   Population and personal transcriptomics to elucidate disease mechanisms. E. Dermitzakis. Univ Geneva Med Sch, Geneva, Switzerland.

9:30 AM   High-throughput screening for causal non-coding variants. T. Mikkelsen. Broad Inst, Cambridge.

10:00 AM   Calibration of multiple in silico tools for predicting pathogenicity of unclassified variants in DNA repair pathway genes. S. V. Tavtigian. Univ Utah Sch Med, Salt Lake City.

10:30 AM   Sequence-function mapping to determine the impact of coding variation. D. M. Fowler. Univ Washington, Seattle.

Wednesday, October 22

9:00 AM–11:00 AM

Concurrent Invited Session II

72. Genetics of Sleep and Circadian Disorders

Room 30, Upper Level, Convention Center

Moderators: Juliane Winkelmann, Stanford Univ, Palo Alto
  Emmanuel Mignot, Stanford Ctr Sleep Sci and Med, Palo Alto

This symposium will be focused on the genetics of sleep and circadian disorders, including common and rare sleep disorders. It will first cover current topics in human sleep genetics by providing examples of recent GWAS findings with consecutive resequencing of loci. We will specifically discuss how common non-coding variants contribute to gene regulation in particular cell types, and how this knowledge has changed our basic understanding of some sleep disorders. We will also discuss new findings demonstrating an important role for immunological genetics in sleep disorders, and will describe new developments in the design, content and complementation for exome sequencing that lead to these findings. Finally, we will review our current knowledge about the role of epigenetics of circadian rhythms, and the latest findings on epigenetic modification in mice.


9:00 AM   Genetic predisposition, molecular mimicry to 2009 H1N1 influenza and resulting CD4+ T-cell autoimmunity towards hypocretin/orexin in narcolepsy. E. Mignot. Stanford Ctr Sleep Sci and Med, Palo Alto.

9:30 AM   Genetics of restless legs syndrome. J. Winkelmann. Stanford Univ, Palo Alto.

10:00 AM   Genetics of circadian disorders. L. J. Ptacek. Howard Hughes Med Inst., UCSF.

10:30 AM   Transcriptional architecture and chromatin landscape of the circadian clock in mammals. J. S. Takahashi. Univ Texas Southwestern Med Ctr, Dallas.

Wednesday, October 22

9:00 AM–11:00 AM

Concurrent Invited Session II

73. Heritability and Risk Prediction for Complex Traits: Regulatory Variants and Polygenic Models

Room 20BC, Upper Level, Convention Center

Moderators: Manolis Kellis, MIT / Broad Inst, Cambridge
  Joel Hirschhorn, Harvard Med Sch, Boston

Heritability and risk prediction studies have revealed that the genetic architecture of many complex traits involves a very large number of variants of small effect. Although common variants jointly explain more than half of narrow-sense heritability, the source of their effects remains elusive. This can be remedied by exploiting genome-wide annotations of functional non-coding regions and partitioning heritability across different functional classes of regulatory elements. Moreover, regulatory networks linking regulatory variants to their likely target genes and the biological pathways that connect them can shed light on underlying disease mechanisms and inform association studies and fine-mapping. This session will discuss recent work in understanding the relative contribution of common SNPs vs. family history, exploiting epigenomics and regulatory genomics information to understand the role of regulatory information, partitioning the heritability of complex traits across genome annotation classes, and polygenic score heritability estimates and risk prediction.


9:00 AM   Insights on complex disease architecture from epigenomics and regulatory genomics studies. M. Kellis. MIT / Broad Inst, Cambridge.

9:30 AM   Heritability of functional variant classes in schizophrenia and other traits: Regulatory elements explain more heritability than coding variants. A. Price. Harvard Sch Publ Hlth, Boston.

10:00 AM   Studies of Low Frequency Variation in Polygenic Disease adn Traits. E. Zeggini. Wellcome Trust Sanger Inst, Hixton, UK.

10:30 AM   Explaining heritability and predicting risk with polygenic scores. F. Dudbridge. London Sch Hyg & Trop Med, UK.

Wednesday, October 22

9:00 AM–11:00 AM

Concurrent Invited Session II

74. Stakeholder Engagement in Genomics Policy Development: What Is It? Why Do It? How?

Room 29, Upper Level, Convention Center

Moderators: Julie N. Harris, Kaiser Permanente, Oakland
  Amy A. Lemke, Univ Washington, Seattle

There has been a proliferation of national and international policies governing genomic data and clinical technologies over the past three years. Alongside this trend, there is also increasing recognition from the Institute of Medicine and other bodies that engaging key stakeholders in developing clinical and research policies is essential to creating sound, transparent, and trusted health policy. However, in practice, the process of stakeholder engagement is sometimes loosely defined, resulting in feedback of variable quality and utility, and there is lack of clarity on how feedback is incorporated. With the complex and evolving landscape of genomics, a re-examination of current methods for identifying and incorporating stakeholder voices in policy and guideline development is critical. Key questions to examine include: 1) Why and when is it important to engage key stakeholders in genomics policy issues? 2) What roles can stakeholders play in different stages of policy development? 3) What does stakeholder engagement mean to different groups such as clinicians, payors, and patients? 4) How do we practically engage diverse stakeholders in a cost-effective manner? In this session, we will present novel engagement models, and describe unresolved questions and challenges in stakeholder engagement and their implications for genomic policy-making. Topics include: methods for identifying, recruiting and involving stakeholders in policy debate, current issues and models for prioritizing and incorporating stakeholder data, and strategies for evaluating engagement processes.


9:00 AM   Setting priorities for stakeholder engagement in genomics. W. Burke. Univ Washington, Seattle.

9:30 AM   Harnessing social networking to empower engagement. S. Terry. Genet Alliance, Washington, DC.

10:00 AM   Participatory governance and public deliberative engagement for health and science policy. M. Burgess. Univ British Columbia, Kelowna, Canada.

10:30 AM   Challenges and opportunities for stakeholder engagement: Strategies for incorporating public feedback into biobank policy-making. B. A. Koenig. UCSF Inst Hlth & Aging.

Wednesday, October 22

9:00 AM–11:00 AM

Concurrent Invited Session II

75. Variation, Mutation, and Selection through the Lens of Regulatory Genomics

Room 6CF, Upper Level, Convention Center

Moderator: Lucas D. Ward, MIT, Cambridge

Comparative studies have shown that the majority of sequence conserved across species is noncoding, and that evolutionarily constrained sequence is strongly enriched for regulatory elements defined by functional genomics. Experimental work also suggests that epigenetic state is a determinant of mutation rate variability across the genome. Both of these observations suggest that regulatory elements, including sequences that dictate chromatin state and gene expression, play a pivotal role in shaping the landscape of mutation and selection, resulting in the sequence diversity patterns we see across and within species. This noncoding selection acts on variation that is consequential to human health and disease. This session will highlight work in regulatory genomics that explores the relationship between natural sequence variation, chromatin state, expression, and selection.


9:00 AM   The impact of chromatin on mutation rate. P. Polak. Massachusetts Gen Hosp, Charlestown.

9:30 AM   Recent purifying selection on enhancer-associated motifs. L. D. Ward. MIT, Cambridge.

10:00 AM   Genetic control of chromatin state. G. McVicker. Dana-Farber Cancer Inst / Stanford Univ, Boston.

10:30 AM   Mechanism and impact of regulatory genetic variation from chromatin state to protein expression. J. Vierstra. University of Washington, Seattle.

Wednesday, October 22

9:00 AM–11:00 AM

Concurrent Invited Session II

76. Viruses, Genomic Instability, and the Pathogenesis of Human Cancers

Room 6DE, Upper Level, Convention Center

Moderator: David E. Symer, The Ohio State Univ, Columbus

For more than a century, researchers have studied how diverse viruses can cause cancers. Groundbreaking recent molecular genetics and genomics studies have dramatically shifted our understanding of the molecular mechanisms and consequences of such viruses in disrupting genetic pathways and causing genomic instability in human cancers. The presentations in this session will address the latest breakthroughs in genetics and genomics research, addressing how several types of viruses can cause human cancers, and conversely how genomic “safe harbors” may be defined in order to improve virus-mediated gene therapy. Included in the session will be discussions of state-of-the-art research approaches using long-range genome sequencing methods, analysis of limiting numbers of cells, characterization of transcriptomes, identification of novel viral sequences, and the characterization of genomic cancer-free zones. Such advances have led to the discovery of novel viruses in cancers, and are driving current investigations into the biological and clinical significance of virus-associated genomic instability and the disruption of genetic pathways which contribute to cancer formation.


9:00 AM   Human papillomavirus induces genomic instability and disrupts cancer-causing genes in human cancers. D. E. Symer. Ohio State Univ, Columbus.

9:30 AM   New methods for haplotype resolution and the reconstruction of complex virus-associated cancer genomes. J. A. Shendure. Univ Washington, Seattle.

10:00 AM   High resolution analysis of hepatitis B virus integration in the liver cancer genome. Z. Zhang. Peking Univ, Beijing, China.

10:30 AM   Virus-mediated gene therapy and the definition of cancer-free safe harbors in the human genome. F. D. Bushman. Univ Pennsylvania, Philadelphia.

Wednesday, October 22

11:15 AM–12:30 PM

77. ASHG Membership/Business Meeting and Announcement of the C.W. Cotterman Award Winners and the Charles J. Epstein Trainee Awards for Excellence in Human Genetics Research Winners

Room 20BC, Upper Level, Convention Center

11:15 am: The Charles J. Epstein Trainee Awards for Excellence in Human Genetics Research. ASHG provides merit-based research awards for trainees (predoctoral and postdoctoral, including genetic counseling trainees) on the basis of submitted, competitive abstracts presented at the 2014 Annual Meeting.  

11:25 am: Announcement of the winners of the C.W. Cotterman Awards. Each September, the editorial board of The American Journal of Human Genetics selects two articles that best represent outstanding contributions to the field of genetics. The two awards are presented for the best papers published in AJHG during the previous year on which the first author was either a pre- or postdoctoral trainee and is an ASHG member. The awards will be presented at the ASHG 2014 Annual Meeting with a monetary award of $1000 and a plaque.  

11:35 am: ASHG Membership/Business Meeting. 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 2014. Discussion from the floor is encouraged.



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