All Numbered Sessions Listing

Tuesday, October 18

4:30 PM–5:00 PM

1. ASHG Presidential Address: Let's Make Human Genetics Great (Again): The Importance of Beauty in Science

Ballroom ABC, West Building, Convention Centre

Human genetics, as a discipline, has adopted and maintained a leadership position in the development and application of techniques and principles that have profoundly informed our understanding of evolution, biology, disease and medicine. The power of our tools to generate unbiased data at a remarkable pace has contributed to an impression of extreme opportunity for revolutionary advancement, but also a sense of overwhelming complexity without a clear path forward. The extent to which development of the next amazing technology or bigger data, time-honored strategies in our field, can yield empowering precision remains to be seen. In any event, an historical nod to transformations from chaos to clarity in other scientific disciplines suggests the need for a comprehensive initiative to achieve beauty in our science - the beauty of solutions that reconcile apparent paradox, that complement all valid points of view, that are impossibly powerful in their predictive value yet simple to the point of being intuitive - even inevitable, that resonate with fundamental tenets of humanity in both theory and application. We need to accelerate efforts to be fully deliberate, as opposed to largely opportunistic, in our efforts to harness the full spectrum of human phenotypic variation; we need to first embrace - and then tackle - the intricacies (and therapeutic opportunities) inherent to human epistasis and phenotypic modification; we need to use model systems to full advantage, including recognition that understanding the context of their occasional departure from human medical relevance has the strong potential to have human medical relevance; we need to resist the impulse to interpret a morass of positive and often contradictory signals as a manifestation that everything is possible - biology has structure that, once understood, imposes constraint and ultimately order. While the magnitude and very nature of the task at hand will require unprecedented collaboration between disciplines, the conclusion based on precedent and trajectory that our discipline, our Society and our membership are both prepared and destined to lead, seems unavoidable.

 


Tuesday, October 18

5:00 PM–6:20 PM

2. Featured Plenary Abstract Session I

Ballroom ABC, West Building, Convention Centre

Moderators: Anthony Antonellis, ASHG 2016 Program Chair
  Peter Scacheri, ASHG 2016 Program Committee

 

1/5:00 Disease heritability estimates using the electronic health records of 9 million patients. N. Tatonetti, F. Polubriaginof, K. Quinnies, R. Vanguri, A. Yahi, M. Simmerling, I. Ionita-Laza, H. Salmasian, S. Bakken, K. Kiryluk, D. Goldstein, D. Vawdrey.

2/5:20 A genome-wide compendium and functional assessment of in vivo heart enhancers. D.E. Dickel, C.H. Spurrell, I. Barozzi, Y. Zhu, Y. Fukuda-Yuzawa, M. Osterwalder, B.J. Mannion, I. Plajzer-Frick, C.S. Pickle, E. Lee, T.H. Garvin, M. Kato, J.A. Akiyama, V. Afzal, A. Visel, L.A. Pennacchio.

3/5:40 Application of a conditional allelic series of the Sloan-Kettering Institute proto-oncogene (SKI) to mechanistically dissect the TGFβ vasculopathies. B.E. Kang, D. Bedja, H.C. Dietz.

4/6:00 200 loci complete the genetic puzzle of multiple sclerosis. N. Patsopoulos, on behalf of the International Multiple Sclerosis Genetics Consortium.


Tuesday, October 18

6:25 PM–6:40 PM

3. ASHG Victor A. McKusick Leadership Award Presentation

Ballroom ABC, West Building, Convention Centre

The ASHG Victor A. McKusick Leadership Award recognizes individuals whose professional achievements have fostered and enriched the development of human genetics as well as its assimilation into the broader context of science, medicine, and health.

Introduction: Arno Motulsky and Gail Jarvik, University of Washington

Recipient:
Stanley Gartler

Stanley M. Gartler, PhD
Professor Emeritus of Medicine (Medical Genetics) and Genome Sciences, University of Washington

Dr. Gartler has worked at the University of Washington for nearly 50 years. He was a founding member of the Division of Medical Genetics in the Department of Medicine in 1957, and later a founding member of the Department of Genetics in 1959. He has spent much of his career studying X chromosome inactivation and the genetics of somatic cells, but has made key discoveries and connections outside of these areas. These cross-cutting findings include demonstrating that most human tumors are clonal, discovering HeLa contamination in many long-established cell lines, and answering fundamental questions about fetal oocytes and the fate of the X chromosome in triploid cells.

 


Tuesday, October 18

6:40 PM–6:55 PM

4. ASHG Curt Stern Award Presentation

Ballroom ABC, West Building, Convention Centre

The ASHG Curt Stern Award recognizes genetics and genomics researchers who have made significant scientific contributions during the past decade.

Introduction: Arthur Beaudet, Baylor College of Medicine

Recipient:
Brendan Lee

Brendan Lee, MD, PhD
Robert and Janice McNair Endowed Chair in Molecular and Human Genetics; Professor and Chairman, Department of Molecular and Human Genetics, Baylor College of Medicine

Throughout his career, Dr. Lee has focused on human inborn errors of metabolism and structural birth defects of the skeleton. As a trainee, he identified the first genetic cause of a human chrondrodysplasia and cloned the gene associated with Marfan syndrome. Since then, he has made important genetic, mechanistic, and clinical discoveries related to skeletal dysplasias and urea cycle disorders, translated these discoveries into therapeutic advances, and tested these therapies in clinical trials.

 


Tuesday, October 18

7:00 PM–9:00 PM

5. Poster Talks (New for 2016)

Room 119, West Building, Convention Centre

The goal of this new session is to highlight a subset of the top-scoring poster abstracts and to stimulate further discussion during the Poster Sessions. The Program Committee selected ~25 abstracts (marked by a microphone in the online program) for presentation in this session. Each presenter will have a few minutes to communicate their research. Light refreshments will be provided.

 

462F   Improving power for rare variant tests by integrating external controls. S. Lee, S. Kim, C. Fuchsberger.

959T   Opportunity and challenge of applying clinical exome for critical newborn patients: 1,000 clinical exome cases from a neonatal clinic. H. Wang, L. Yang, B. Wu, Y. Lu, B. Sun, Z. Li, B. Liu, Z. Wei, Q. Zhao, H. Sun, F. Xia, W. Zhou.

980T   What have genes got to do with it? Analyzing gene content across interpreted CNVs in the Clinical Genome Resource Structural Variation Interpretation Working Group. D.I. Ritter, E. Riggs, E. Anderson*, A. Cherry, S. Kantarci, H. Kearney, C.P. Lorentz, J.M. Meck, A. Patel, S.E. Plon, G. Raca, S. South, E. Thorland*, R. Vanzo, D. Pineda-Alvarez**, S. Aradhya**, C.L. Martin, on behalf of the Clinical Genome Resource, Co-chairs of ClinGen *Dosage WG & **SV Interpretation WG.

1906W   A robust statistical approach to refine frequency thresholds for clinical variant interpretation. N. Whiffin, E. Minikel, R. Walsh, A. O'Donnell-Luria, K. Karczewski, A.Y. Ing, B. Funke, S.A. Cook, D. MacArthur, J.S. Ware.

2148F   Dissecting the functional architecture of local and distal gene expression regulation in multiple human tissues. X. Liu, H.K. Finucane, A. Gusev, G. Bhatia, S. Gazal, B. Bulik-Sullivan, F.A. Wright, P.F. Sullivan, B.M. Neale, A.L. Price.

2173W   Mutations in MBTPS2 cause X-linked osteogenesis imperfecta and demonstrate a fundamental role for regulated intramembrane proteolysis in bone development. V. Shotelersuk, U. Lindert, W.A. Cabral, S. Ausavarat, S. Tongkobpetch, K. Ludin, A.M. Barnes, P. Yeetong, M. Weis, B. Krabichler, C. Srichomthong, E. Makareeva, A.R. Janecke, S. Leikin, B. Röthlisberger, M. Rohrbach, I. Kennerknecht, D.R. Eyre, K. Suphapeetiporn, C. Giunta, J.C. Marini.

2202F   Neurons derived from individuals with autism spectrum disorder show early impairments in synaptic functionality and network activity. D.M. Dykxhoorn, C. Garcia_Serje, B.A. DeRosa, E. Artimovich, M.W. Nestor, D. Van Booven, K.C. Belle, H.N. Cukier, M.L. Cuccaro, J.M. Vance, M.A. Pericak-Vance.

2365W   Protein replacement therapy for autosomal recessive congenital ichthyosis (ARCI). H.C. Hennies, R. Plank, G. Yealland, R. Casper, K. Obst, M. Hermann, E. Miceli, M. Calderón, S. Hedtrich, K.M. Eckl.

2715F   Loss of selective constraints drives damage to mitochondrial genomes in cancer. S. Grandhi, B. Colleen, M. Wesley, N. Ying, L. Thomas.

2756T   Estimating the joint distribution of rare variants, polygenic risk and family history to support analysis of the prospective benefits of risk-based mammographic screening. M.C. Wolfson, S. Gribble, A. Antoniou, D. Easton, N. Pashayan, A. Lee, J. Simard.

2802F   Simultaneous genetic regulatory networks inference and genomic hub identification through conditional graphical models. C.J. Conley, P. Wang, J. Peng.

2815W   Recurrent somatic copy number variation analysis identifies risk genes that modulate the survival of young women with breast cancer. C. Chi, R. Ajwad, Q. Kuang, L.C. Murphy, P. Hu.

3018F   Long-term impact of Huntington’s presymptomatic genetic testing: Interviews with at-risk individuals 20-30 years after testing. R.L. Dvoskin, J.M. Bollinger, A. McCague, K.M. Stuttgen, B. Shpritz, J. Brandt, D.J.H. Mathews.

3049W   Discordance in selected designee for return and the legal recipient of genomic findings in the event of participant death. L.M. Amendola, M. Horike-Pyne, S.B. Trinidad, S.M. Fullerton, B.J. Evans, W. Burke, G.P. Jarvik.

3058W   Motivations and concerns of biobank participants in allowing family access to research samples and data after their death. J.E. Olson, E.M. Winkler, J.T. Bublitz, M.A. Hathcock, J.E. Pacyna, J.B. McCormick, C. Radecki Breitkopf, R.R. Sharp.

3088W   Development of a practice model of genomic counseling for actionable complex disease and pharmacogenomics. K. Sweet, A.C. Sturm, S. Hovick, T. Schmidlen, E.S. Gordon, K.E. Ormond, B.A. Bernhardt, J. O'Daniel, J. McElroy, L. Scheinfeldt, A.E. Toland, J.S. Roberts, M. Christman.

3175W   A novel sgRNA tagging technology identifies and addresses heritable clonal heterogeneity in CRISPR screens. A. Biton, M. Boettcher, S. Covarrubias, J. Blau, H. Wang, N. Zaitlen, M. McManus.

3221T   Improved expression profiling and cellular localization of circRNA molecules in human samples. A. Zaghlool, A. Ameur, C. Wu, J.O. Westholm, M. Manivannan, K. Bramlett, M. Nilsson, L. Feuk.

3241W   Multigene molecular testing provides significant diagnostic yield for prenatal holoprosencephaly. S. Duffer, J. Meck, L. Vincent, E. Kramer Dugan, V. Zvereff, G. Richard.

3299T   Cell based non-invasive prenatal testing using NGS-based copy number assessment of fetal cells. A. Breman, L. Vossaert, E. Normand, J. Chow, L. U'Ren, R. Salman, S. Qdaisat, I. Van den Veyver, C. Shaw, Y. Yang, E. Chang, J. Stilwell, R. Seubert, E. Kaldjian, A. Beaudet.

3368T   Conserved and tissue-specific effects of natural genetic variation on transcript and protein abundance. S. Munger, J. Chick, P. Simecek, K. Choi, E. Huttlin, D. Gatti, S. Gygi, R. Korstanje, G. Churchill.

3379W   Population survey of copy number variation in over 85,000 exomes and associations with serum lipids from electronic health records. E.K. Maxwell, C. O'Dushlaine, J.S. Packer, S.E. McCarthy, C. Gonzaga-Jaregui, J. Staples, W.A. Faucett, J.B. Leader, I.B. Borecki, F.E. Dewey, Y.I. Chen, J.I. Rotter, J.C. Cohen, W.K. Chung, A.M. Muise, E.G. Puffenberger, E.J. Reichenberger, D. Gaudet, H.L. Kirchner, M.F. Murray, M.D. Ritchie, D.J. Carey, D.H. Ledbetter, C.L. Martin, G.D. Yancopoulos, A.R. Shuldiner, A. Baras, O. Gottesman, L. Habegger, J.G. Reid.


Wednesday, October 19

9:00 AM–10:30 AM

Concurrent Platform Session A

6. Interpreting Variants of Uncertain Significance

Ballroom A, West Building, Convention Centre

Moderators: Alex Hoischen, Radboud Univ Med Ctr, Nijmegen, Netherlands
  Michael Dorschner, Univ Washington, Seattle

 

5/9:00 Levering gene family information in gene discovery, risk assessment and missense variant interpretation in more than 9,000 trios with neurodevelopmental disorders. D. Lal, P. May, E.B. Robinson, H. Yuan, K.E. Samocha, J.A. Kosmicki, R. Krause, P. Nuernberg, S. Weckhuysen, G. Guerrini, C. Marini, P. De Jonghe, S. Biskup, A. Poduri, B.A. Neubauer, B.P. Koeleman, K. Helbig, Y.G. Weber, I. Helbig, S. Traynelis, A. Palotie, M..J. Daly.

6/9:15 Genome sequencing in a “healthy” population: Challenges of variant interpretation. S. Punj, A. Creason, J. Huang, A. Potter, M.O. Dorschner, D.A. Nickerson, G.P. Jarvik, L.M. Amendola, D. Kostiner Simpson, A. Rope, J. Reiss, T. Kauffman, M. Gilmore, P. Himes, B. Wilfond, K.A.B. Goddard, C.S. Richards, on behalf of the NextGen Project Team.

7/9:30 Identifying Mendelian disease-causing mutations by leveraging splice-affecting variant predictors provides improved guidelines for the interpretation of nonsynonymous, synonymous, and intronic variants of uncertain significance. Z.T. Soens, J. Branch, Y. Li, K. Wang, M. Xu, D. Birch, F.B. Porto, J. Sallum, P. Zhao, R. Sui, R.K. Koenekoop, R. Chen.

8/9:45 Reinterpreting variant pathogenicity: Lessons from over 60,000 human exomes. A. O'Donnell-Luria, E.V. Minikel, J.S. Ware, N. Whiffin, M. Lek, K.J. Karczewski, K.E. Samocha, M.J. Daly, D.G. MacArthur, Exome Aggregation Consortium.

9/10:00 Clinical application of a critical exon mapper to aid in determining pathogenicity of copy number variants of unknown significance. K.S. Ho, M. Uddin, C.H. Hensel, M.M. Martin, P. Mowery-Rushton, S. Page, M.A. Serrano, S. Venkatasubramanian, S. Scherer, E.R. Wassman.

10/10:15 Towards precise genetic diagnosis of human diseases: Experience with POLG-related disorders. R. Bai, D. McKnight, J. Juusola, J. Yang, Y. Xie, R. Heredia, Y. Chen, H. Yang, D. Arjona, A. Balog, J. Higgs, L. Carey, E. Butler, H. Cui, W.C. Copeland, G. Richard, S.F. Suchy.


Wednesday, October 19

9:00 AM–10:30 AM

Concurrent Platform Session A

7. Insights from Large Cohorts: Part 1

Ballroom B, West Building, Convention Centre

Moderators: Augusto Rendon, Genomics England, London, UK
  Laurent C. Francioli, Massachusetts General Hosp, Boston

 

11/9:00 Distribution and clinical impact of functional variants in 50,726 whole exome sequences from the DiscovEHR study. F. Dewey, M. Murray, J. Overton, L. Habegger, J. Leader, S. Fetterolf, C. O'Dushlaine, C. Van Hout, J. Staples, R. Metpally, H.L. Kirchner, S. Pendergrass, C. Gonzaga-Jauregui, S. Balasubramanian, A. Lopez, J. Penn, S. Mukherjee, N. Gosalia, A. Li, S. Bruse, K. Praveen, I. Borecki, G. Yancopoulos, O. Gottesman, M. Ritchie, A. Shuldiner, J. Reid, D. Ledbetter, A. Baras, D. Carey, DiscovEHR Collaboration.

12/9:15 Extending variant reference databases to over 100,000 samples. D. MacArthur, Exome Aggregation Consortium.

13/9:30 Quantifying aging signals in whole genome sequencing data. A. Bernal, M. Zhu, C. Lippert, C. Maher, R. Sabatini, T. Wong, P. Garst, E. Kostem, H. Tang, L. Pierce, K. Yocum, F. Och, C. Venter.

14/9:45 Integrating eQTLs and tissue-specificity across 44 normal human tissues with genome-wide association data helps uncover causal genes and pathways for common diseases. A.V. Segre, F. Aguet, G. Getz, K. Ardlie, GTEx Consortium.

15/10:00 Mendelian disease genes provide the ultimate confirmation of PrediXcan validity and suggest novel opportunities for translation of genetic discoveries. J.E.H. Brown, E. Gamazon, J.C. Denny, L. Basterache, H. Im, N.J. Cox.

16/10:15 The public sharing of genomic data from the DiscovEHR Collaboration. M.D. Ritchie, J. B. Leader, T.N. Person, F. E. Dewey, M.F. Murray, J.D. Overton, H.L. Kirchner, A.E. Lopez, J. Penn, I.B. Borecki, G.D. Yancopoulos, F.D. Davis, W.A. Faucett, O. Gottesman, J.G. Reid, A. Baras, D.J. Carey, A.R. Shuldiner, D.H. Ledbetter, Geisinger-Regeneron DiscovEHR Collaboration.


Wednesday, October 19

9:00 AM–10:30 AM

Concurrent Platform Session A

8. Rare Germline Variants and Cancer Risk

Ballroom C, West Building, Convention Centre

Moderators: Douglas Stewart, Natl Cancer Inst, Rockville
  Wenyi Wang, MD Anderson Cancer Ctr, Houston

 

17/9:00 Cancer risks associated with predisposition gene mutations identified by hereditary cancer panel testing of 85,000 patients. F.J. Couch, D.E. Goldgar, H. Shimelis, J. Lilyquist, C. Hu, M. Akinhanmi, J. Na, E.C. Polley, S.N. Hart, R. Huether, C. Espenschied, R. McFarland, T. Pesaran, H. LaDuca, J.S. Dolinsky.

18/9:15 Rare variant cancer association studies with heterogeneous sequencing datasets. C.D. Huff, Y. Yu, F. Hu, J. Chen, S. Chen, H. Hu, A.S. Deshpande, S. Sivakumar, Y. Liu, J. Fowler, S. Shankaracharya, B. Moore, C. Holt, Y. Ye, M. Hildebrandt, H. Zhao, P. Scheet, X. Wu, M. Yandell.

19/9:30 Whole genome sequencing identifies germline coding and non-coding variants in familial glioma. M.N. Bainbridge, G. Armstrong, M.C. Wood, S. White, D.M. Muzny, S. Jhangiani, R. Gibbs, M. Bondy.

20/9:45 Genes involved in base excision and direct DNA repair contribute to hereditary breast cancer. I. Campbell, N. Li, S. Rowley, L. Devereux, A. Trainer, P. James, Lifepool.

21/10:00 Inherited deleterious germline variants in men with prostate cancer identified by whole exome sequencing. N. De Sarkar, C. C. Pritchard, P. Nelson.

22/10:15 Ascertainment bias in predicting genetic disease risks. J. Lachance, K. Patel, A. Teng, A.J. Berens.


Wednesday, October 19

9:00 AM–10:30 AM

Concurrent Platform Session A

9. Early Detection: New Approaches to Pre- and Perinatal Analyses

Room 109, West Building, Convention Centre

Moderators: Wendy Robinson, Univ British Columbia, Vancouver
  Anne Matthews, Case Western Reserve Univ, Cleveland

 

23/9:00 The utility of whole exome sequencing in prenatal diagnosis. M. Walkiewicz, A. Braxton, P. Liu, F. Xia, W. Bi, R. Xiao, M. Leduc, J. Zhang, X. Wang, L. Meng, W. He, F. Vetrini, P. Ward, S. Narayanan, S. Nassef, S. Plon, D. Muzny, J. Lupski, R. Gibbs, I. Van den Veyver, Y. Yang, C. Eng.

24/9:15 The genomic autopsy: Using whole exome and whole genome sequencing to solve complex fetal and neonatal presentations. C.P. Barnett, A. Byrne, L. Moore, Y. Khong, N. Manton, J. Lipsett, S. Yu, M. Dinger, M. Babic, P.J. Brautigan, Q. Schwartz, P.Q. Thomas, C.N. Hahn, F. Feng, A.W. Schreiber, K. Kassahn, H.S. Scott.

25/9:30 Gene identification in fetal malformation phenotypes. I. Filges, N. Meier, O. Lapaire, S. Wellmann, P. Miny, I. Hösli, E. Bruder, S. Teranli.

26/9:45 The BabySeq Project: Preliminary findings from a randomized trial of exome sequencing in newborns. R.C. Green, I.A. Holm, H.L. Rehm, A.L. McGuire, P.B. Agrawal, R.B. Parad, M.H. Helm, C.A. Genetti, A.H. Beggs, for the BabySeq Project.

27/10:00 Clinical utility of expanded carrier screening: Reproductive behaviors of at-risk couples. K.K.L. Wong, K. Ready, C. Lieber, J.D. Goldberg, I.S. Haque, G.A. Lazarin, C. Ghiossi.

28/10:15 Noninvasive prenatal screening for common aneuploidies in a Canadian province: A cost effectiveness analysis. F. Rousseau, L. Nshimyumukiza, J.A. Beaumont, J. Duplantie, S. Langlois, J. Little, F. Audibert, C. McCabe, J. Gekas, Y. Giguère, C. Gagné, D. Reinharz.


Wednesday, October 19

9:00 AM–10:30 AM

Concurrent Platform Session A

10. Advances in Characterizing the Genetic Basis of Autism

Room 119, West Building, Convention Centre

Moderators: Tychele Turner, Univ Washington, Seattle
  Michael Talkowski, Massachusetts Gen Hosp and Harvard Med Sch, Boston

 

29/9:00 Identifying genetic ASD-risk factors in over 2,000 whole-genome sequenced familial samples. E.K. Ruzzo, L. Perez-Cano, J. Jung, D. Kashef, L. Wang, S. Sharma, M. Duda, G.M. McInnes, J.K. Lowe, D.H. Geschwind, D.P. Wall.

30/9:15 Whole genome sequence-based resource for autism research. R.K.C. Yuen, D. Merico, J.L. Howe, B. Thiruvahindrapuram, J. Whitney, R. Patel, N. Hoang, J.R. MacDonald, Z. Wang, T. Nalpathamkalam, W. Sung, S. Walker, J. Wei, C.R. Marshall, G. Pellecchia, A. Chan, L. D’Abate, M. Zarrei, M. Uddin, M. Bookman, N. Deflaux, E. Anagnostou, L. Zwaigenbaum, B.A. Fernandez, P. Szatmari, B.M. Knoppers, M. Elsabbagh, D. Glazer, M. Pletcher, S.W. Scherer.

31/9:30 Uncovering somatic mosaicism in autism. R.A. Barnard, D.R. Krupp, Y. Duffourd, S.A. Evans, S.J. Webb, R. Bernier, E. Fombonne, J.B. Riviére, B.J. O'Roak.

32/9:45 Contribution of mosaic variation to autism spectrum disorders. D. Freed, J. Pevsner.

33/10:00 Autism redefined: Genomic pathway approach to autism spectrum disorder. S. Smieszek, J.L. Haines.

34/10:15 Maternal and fetal genetic control of mid-gestational and neonatal levels of markers of immune function. M. Traglia, L.S. Heuer, K.L. Jones, C.K. Yoshida, R. Hansen, R. Yolken, O. Zerbo, G.C. Windham, M. Kharrazi, G.N. DeLorenze, P. Ashwood, L.A. Croen, J. Van de Water, L.A. Weiss.


Wednesday, October 19

9:00 AM–10:30 AM

Concurrent Platform Session A

11. New Discoveries in Skeletal Disorders and Syndromic Abnormalities

Room 207, West Building, Convention Centre

Moderators: Gudrun Rappold, Univ Heidelberg, Germany
  Catherine Keegan, Univ Michigan, Ann Arbor

 

35/9:00 DDRGK1 regulates SOX9 ubiquitination and its loss causes a human skeletal dysplasia. A.T. Egunsola, Y. Bae, M. Jiang, D.S. Liu, Y. Chen-Evenson, T. Bertin, J.T. Lu, L. Nevarez, N. Magal, E.S. Swindell, D.H. Cohn, R.A. Gibbs, P.M. Campeau, M. Shohat, B.H. Lee.

36/9:15 Heterozygosity for MYH3 mutations produce spondylocarpotarsal syndrome leading to further insights into the pathophysiology and locus heterogeneity associated with progressive vertebral fusions. J. Zieba, W. Zhang, K. Forlenza, J.H. Martin, K. Heard, D.K. Grange, M.G. Butler, T. Kleefstra, R.S. Lachman, D. Nickerson, D.H. Cohn, J.X. Chong, J.H. Bamshad, D. Krakow, University of Washington Center for Mendelian Genomics.

37/9:30 Identification of new genes responsible for syndromic developmental abnormalities using whole exome sequencing. M. Lefebvre, Y. Duffour, E. Tisserant, L. Olivier-Faivre, D. Lehalle, N. Jean Marçais, N. Laurent, M-C. Antal, S. El Chehadeh, E. Schaefer, L. Lambert, B. Leheup, B. Foliguet, J-P. Masutti, F. Arbez-Gindre, C. Quelin, S. Odent, M. Fradin, P. Loget, N. Bigi, D. Genevieve, M. Willems, S. Blesson, A. Toutain, F. Lafargue, C. Francannet, A-M. Beaufrere, P. Dechelotte, J. Thevenon, C. Thauvin.

38/9:45 Retinoic acid catabolizing enzyme CYP26C1 is a genetic modifier in SHOX deficiency. A. Montalbano, J. Juergensen, R. Roeth, B. Weiss, M. Fukami, S. Fricke-Otto, G. Binder, T. Ogata, E. Decker, G. Nuernberg, D. Hassel, G.A. Rappold.

39/10:00 SFRP4 ablation in Pyle disease reveals the differential regulation of trabecular versus cortical bone and highlights the importance of cortical bone in bone stability. A. Superti-Furga, H. Saito, P.O. Simsek Kiper, F. Gori, S. Unger, E. Hesse, K. Yamana, R. Kiviranta, N. Solban, J. Liu, R. Brommage, K. Boduroglu, L. Bonafé, B. Campos-Xavier, G. Nishimura, K.M. Girisha, H. Takita, K. Harshman, B. Stevenson, C. Rivolta, R. Baron.

40/10:15 Absence of the ER cation channel TMEM38B/TRIC-B disrupts intracellular calcium homeostasis and dysregulates collagen synthesis in recessive osteogenesis imperfecta. W.A. Cabral, M. Ishikawa, M. Garten, E.N. Makareeva, B.M. Sargent, M. Weis, A.M. Barnes, E.A. Webb, N.J. Shaw, L. Ala-Kokko, F.L. Lacbawan, W. Högler, S. Leikin, P.S. Blank, J. Zimmerberg, D.R. Eyre, Y. Yamada, J.C. Marini.


Wednesday, October 19

9:00 AM–10:30 AM

Concurrent Platform Session A

12. Obesity: It's in Your Genes

Room 211, West Building, Convention Centre

Moderators: Leslie Baier, NIDDK, NIH, Phoenix
  Jorg Hager, Nestle Inst Hlth Sc, Lausanne, Switzerland

 

41/9:00 Evidence for body mass index gene x environment interaction using 120,000 individuals from the UK Biobank study. J. Tyrrell, A.R. Wood, R.M. Ames, H. Yaghootkar, R. Beaumont, S.E. Jones, M.A. Tuke, K. Ruth, R.M. Freathy, A. Murray, Z. Kutalik, M.N. Weedon, T.M. Frayling.

42/9:15 A thrifty variant in CREBRF strongly influences body mass index in Samoans. R.L. Minster, N.L. Hawley, C.-T. Su, G. Sun, E.E. Kershaw, H. Cheng, O.D. Buhule, J. Lin, M. Sefuiva Reupena, S. Viali, J. Tuitele, T. Naseri, Z. Urban, R. Deka, D.E. Weeks, S.T. McGarvey.

43/9:30 Genetic study of body mass index in 173,430 Japanese identifies 76 new loci and highlights shared heritability with broad spectrum of complex diseases. M. Akiyama, M. Kanai, Y. Okada, A. Takahashi, Y. Momozawa, M. Ikeda, N. Iwata, S. Ikegawa, M. Hirata, K. Matsuda, T. Yamaji, M. Iwasaki, K. Sobue, M. Yamamoto, M. Kubo, Y. Kamatani.

44/9:45 Exome-wide association meta-analysis for body mass index identifies protein-altering variants revealing new insights in the biology underpinning obesity. R.J.F. Loos, V. Turcot, H.M. Highland, Y. Lu, C. Schurmann, M. Graff, A.E. Justice, R.S. Fine, K.L. Young, M. Feitosa, E. Marouli, A. Wood, L.A. Cuppens, P. Deloukas, I.B. Borecki, J.A. Pospisilik, deCODE Genetics, T.M. Frayling, G. Lettre, C.M. Lindgren, K.E. North, J.N. Hirschhorn, For the BBMRI-NL, the GOT2D, the CHARGE, and the GIANT Consortia.

45/10:00 Identification and characterisation of a novel rare variant for body fat distribution and diastolic blood pressure. K.E. Schraut, I. Williamson, P.K. Joshi, R.H. Stimson, P. Gautier, V. Emilsson, W.A. Bickmore, P. Navarro, N.M. Morton, J.F. Wilson.

46/10:15 Analysis of BMI using whole exome sequence from 49,178 individuals from the Geisinger Health System DiscovEHR study. A.H. Li, C. Gonzaga-Jauregui, G.C. Wood, U.L. Mirshahi, F. Dewey, T. Mirshahi, I. Borecki.


Wednesday, October 19

9:00 AM–10:30 AM

Concurrent Platform Session A

13. Functional Assessment of Cancer Susceptibility Regions

Room 221, West Building, Convention Centre

Moderators: Chris Amos, Dartmouth Univ, Hanover
  Zsofia Kote-Jarai, Inst Cancer Res, Sutton, UK

 

47/9:00 Heritable epimutations associated with breast cancer risk. M.C. Southey, J.E. Joo, E.M. Wong, J.L. Hopper, D.R. English, D.E. Goldgar, G.G. Giles, R.L. Milne, J.G. Dowty, kConFab and The Australian Breast Ccancer Family Study.

48/9:15 Functional annotation of breast cancer risk-associated loci identified using the OncoArray. J. Beesley, S. Kar, K.I. McCue, K. Michailidou, K.B. Kuchenbaecker, L. Fachal, D.M. Glubb, A. Lemaçon, A. Droit, P. Soucy, A.M. Dunning, J.D. French, P. Kraft, M.K. Schmidt, A.C. Antoniou, R. L. Milne, J. Simard, D.F. Easton, S.L. Edwards, G. Chenevix-Trench, Consortium of Investigators of Modifiers of BRCA1/2 and Breast Cancer Association Consortium.

49/9:30 Functional characterization of prostate cancer risk associated SNPs in the TET2 locus. S.A. Brodie, J. Boland, M. Yeager, M. Dean, M. Nickerson.

50/9:45 Developmental transcription factor NFIB is a target of oncofetal miRNAs and is linked to tumour aggressiveness in lung adenocarcinoma. D. Becker-Santos, B. C. Minatel, K. Thu, J. English, V. Martinez, C. MacAulay, W. Lockwood, S. Lam, W. Robinson, I. Jurisica, W. Lam.

51/10:00 The connection between germline risk variants and somatic mutation patterns in sarcoma. D.L. Goode, E. Galligan, S.M. Rowley, M.L. Ballinger, D.M. Thomas.

52/10:15 Functional annotation of ovarian cancer risk loci identifies regulatory mechanisms disrupted by variants and tissue of origin for disease histotypes. M.R. Jones, K. Lawrenson, C. Phelan, A. Antoniou, P. Pharoah, S. Gayther, D..J. Hazelett, Ovarian Cancer Association Consortium, Consortium of Investigators of Modifiers of BRCA1 and BRCA2.


Wednesday, October 19

9:00 AM–10:30 AM

Concurrent Platform Session A

14. Gene Regulation Dynamics Across Tissues, Contexts, and Time

Room 302, West Building, Convention Centre

Moderators: Corey T. Watson, University Louisville Sch Med
  Nicholas Banovich, Univ Chicago

 

53/9:00 Identification of thousands of context-dependent eQTLs unravelling cell type-specific signalling networks. P.A.C. Hoen, D.V. Zhernakova, P. Deelen, M. Vermaat, M. van Iterson, M. van Galen, W. Arindrarto, P. van 't Hof, H. Mei, F. van Dijk, H.J. Westra, M.J. Bonder, J. van Rooij, M. Verkerk, P.M. Jhamai, M. Moed, S.M. Kielbasa, J. Bot, M.A. Swertz, A. Isaacs, J.B.J. van Meurs, R. Jansen, B.T. Heijmans, L. Franke, Biobank-based Integrative -Omics Consortium (BIOS).

54/9:15 Local regulatory networks across two tissues and applications to analyze rare non-coding variants. O. Delaneau, K. Popadin, M. Zazhytska, S. Kumar, G. Ambrosini, A. Gschwind, C. Borel, D. Marbach, D. Lamparter, S. Bergmann, P. Bucher, S. Antonarakis, A. Reymond, E. Dermitzakis.

55/9:30 Condition specific transcription factor binding with ATAC-seq for GxE interactions. R. Pique-Regi, D. Watza, M. Estill, S. Chaudhry, F. Luca.

56/9:45 First depleted, then enriched: The evolution of transposable element co-option into gene regulatory function. J. Capra, C. Simonti, M. Pavlicev.

57/10:00 Towards a mammalian atlas of in vivo epigenetic state at single cell resolution. D.A. Cusanovich, R. Daza, J.B. Berletch, G.N. Filippova, L. Christiansen, F.J. Steemers, C.M. Disteche, C. Trapnell, J. Shendure.

58/10:15 Molecular signatures associated with Zika virus exposure in human cortical neural progenitors. F. Zhang, Y. Cheng, C. Hammack, E.M. Lee, S.C. Ogden, Z. Wen, Y. Li, B. Yao, T. Xu, L. Chen, H. Feng, Z. Wang, C. Shan, L. Huang, Z. Qin, K.M. Christian, P. Shi, M. Xia, W. Zheng, H. Wu, H. Song, H. Tang, G. Ming, P. Jin.


Wednesday, October 19

11:00 AM–1:00 PM

Concurrent Invited Session I

15. Augmenting and Interpreting Genomic Data Using Tissue- and Cell-type-specific Networks

Room 221, West Building, Convention Centre

Moderators: Kasper Lage, Massachusetts Gen Hosp / Broad Inst / Harvard Univ, Boston
  Olga Troyanskaya, Princeton Univ

 

With the unprecedented ability to interrogate genomes for variation, scalable functional interpretation of these data is now one of the major bottlenecks in science and healthcare. This is a key constraint on our efforts toward biological understanding and therapeutic intervention in human diseases. High throughput technologies in genomics, genetics, epigenetics, transcriptomics, and proteomics have led to the generation of wildly complex biological networks with tissue and cell-type resolution where genes are connected if they are functionally correlated in any of the aforementioned data types. Interpreting genetic variation using tissue and cell-type-specific networks has emerged as a powerful computational approach to augment genetic signal and point to unexpected biology with therapeutic and diagnostic value. This session will focus on statistical frameworks, web platforms, and algorithms being developed and used to interpret GWAS and exome sequencing datasets across common complex traits. First, we will provide a general introduction to the methods and history of this field. Second, we will delineate the conceptual and methodological differences for analyzing tissue-specific and cell-type-specific networks. Third, we will illustrate specific new algorithms and applications of our approaches in five complementary areas: 1) The prediction of tissue-specific protein-protein interactions from gene expression data. 2) The integration of tissue-specific transcriptional networks with GWAS data to more precisely identify disease-incriminated genes. The utility of this approach is exemplified using a kidney-specific network to identify genes underlying hypertension. 3) The construction of transcriptome-wide networks from RNA sequencing data and the development of sparse probabilistic graph models for representing the interconnected regulation of tissue-specific splicing and transcription. 4) The construction of probabilistic protein interaction networks from protein-protein interaction experiments in human excitatory neurons to interpret genetic data from psychiatric diseases. 5) The analysis of tissue and cell-type-specific transcriptional networks from the human brain to interpret genetic risk factors in autism. Overall, we wish to highlight specific methods and concepts being developed in the field to empower a wide audience to apply these approaches in their day-to-day work.

 

11:00 AM   Cell-type-specific protein interaction networks perturbed by genetics in psychiatric diseases. K. Lage. Massachusetts Gen Hosp / Broad Inst / Harvard Univ, Boston.

11:30 AM   Transcriptome-wide networks for understanding diverse categories of genetic variation. A. Battle. Johns Hopkins Univ, Baltimore.

12:00 PM   Tissue-specific networks for integrative disease gene identification. O. Troyanskaya. Princeton Univ.

12:30 PM   Building multi-omics networks for type 2 diabetes and related phenotypes. M. McCarthy. Wellcome Trust Ctr for Human Genet, Oxford, UK.


Wednesday, October 19

11:00 AM–1:00 PM

Concurrent Invited Session I

16. Celebrating the Centenary of R.A. Fisher's "The Correlation Between Relatives on the Supposition of Mendelian Inheritance"

Room 211, West Building, Convention Centre

Moderators: Benjamin Neale, Massachusetts Gen Hosp, Boston
  George Davey-Smith, Univ Bristol, Clifton, UK

 

R.A. Fisher first submitted his field-defining paper "The correlation between relatives on the supposition of Mendelian inheritance" in 1916 to the Proceedings of the Royal Society of London, but a review process involving, in Fisher's words,"a statistician who knew no biology and a biologist who knew no statistics" (Karl Pearson and Reginald Punnett) lead to rejection of the paper. A protracted process lead to the paper being destined to appear in the Eugenics Review, but the intervention and financial sponsorship by Fisher's mentor, Leonard Darwin, resulted in the paper appearing in Transactions of the Royal Society of Edinburgh in 1918. This groundbreaking paper not only established the field of quantitative genetics, but also defined the single most important statistic in data analysis, variance. Further issues of dominance, epistasis and population genetics considerations such as assortative mating were provided a full treatment. This invited session will provide a centenary perspective on this landmark achievement and what the future of the biometrical model is for understanding human variation.

 

11:00 AM   Estimation of genetic variance and inference about genetic architecture from observed genome-wide marker data. J. Yang. Univ Queensland, Brisbane, Australia.

11:30 AM   Humanizing GRML: Implications of classical genetic epidemiology for the future application of GRML to complex human traits. L. Eaves. Virginia Commonwealth Univ, Richmond.

12:00 PM   Extracting biological insight from heritability analysis. H. Finucane. MIT, Cambridge.

12:30 PM   Pinning down the contribution of rare and non-additive genetic effects to complex traits. B. Neale. Massachusetts Gen Hosp, Boston.


Wednesday, October 19

11:00 AM–1:00 PM

Concurrent Invited Session I

17. CRISPR: A New Paradigm for Forward Human Genetics

Ballroom A, West Building, Convention Centre

Moderators: Chun Jimmie Ye, UCSF
  Tuuli Lappalainen, New York Genome Ctr and Columbia Univ, New York

 

In the past decade, the genome-wide association study, a forward genetics strategy that utilizes natural genotypic and phenotypic variation, has been the workhorse for human geneticists to discover genes associated with complex disease. However, due to the lack of scalable experimental model systems to study genetic variation in human cells, our ability to understand the underlying mechanisms of how genetic variants lead to complex phenotypes is still limited. With the advent of CRISPR/Cas9 based techniques, we now have the ability to edit the human genome at unprecedented fidelity, resolution, and scale. These developments have enabled the use of synthetic mutations to perform forward genetics in cellular models to study how genotypes affect cellular phenotypes. Some applications of this approach include the functional follow-up of disease-associated variants, in vitro knock-out screens in human cells, in vitro knock-in screens of regulatory variants, and novel clinical interventions in patients. In this session, we will describe the latest developments and results in CRISPR/Cas9 editing of human cell types and a vision of the future application of genome engineering to human genetics.

 

11:00 AM   Genome-scale CRISPR screening: Technology and applications. N. Sanjana. New York Genome Ctr and NYU.

11:30 AM   Genome editing in human pluripotent stem cells for understanding the mechanisms of pancreatic development and diabetes. D. Huangfu. Mem Sloan-Kettering Cancer Ctr, New York.

12:00 PM   Engineering human T cell circuitry. A. Marson. UCSF.

12:30 PM   Functional mapping of disease-relevant regulatory elements by CRISPR/Cas9 screening. S. Orkin. Dana-Farber Cancer Inst and Harvard Med Sch, Boston.


Wednesday, October 19

11:00 AM–1:00 PM

Concurrent Invited Session I

18. Diagnostic Functional Genetics, the Essential Next Step in NGS Translation to the Bedside

Ballroom C, West Building, Convention Centre

Moderators: Robert M.W. Hofstra, Erasmus Univ Med Ctr, Rotterdam, Netherlands
  Ludwine M. Messiaen, Univ Alabama, Birmingham

 

With the first results from gene panel analysis and whole exome sequencing (WES) in diagnostic laboratories, a surge of variants of uncertain clinical significance (VOUS/'class 3') and 'class 4' variants (probable pathogenic, unconfirmed) is already flooding those labs and genetic counsellors. Several diagnostic laboratories have invested in and innovated proven applications of functional testing to be independent of research grants and availability of time. Therewith laboratories can investigate the functional effects of variants in a fluent and controlled diagnostic setting, including reimbursement for attaining stability of the process. By four experienced speakers the most effective approaches will be exemplified and discussed. Functional genetic diagnostic analysis is the vehicle for easing translation of the increasing numbers of 'difficult' gene variants to the bedside.

 

11:00 AM   Introducing functional genetic analysis in a diagnostic unit, applied to cilia function, and mTOR/RAS-pathway analysis: Approaches and possibilities. F. W. Verheijen. Erasmus Univ Med Ctr, Rotterdam, Netherlands.

11:30 AM   Insight in functional metabolomic screening (i.e., urine and plasma screening using extended mass spectronomy) for screening and verification of predictions of variants found in WES analysis. L. A. Kleijtmans. Radboud Univ Med Ctr, Nijmegen, Netherlands..

12:00 PM   Using the human splicing machinery as a screen for mutation detection of large genes and as filter identifying true missense variants from mRNA splicing variants: In- or out-of-frame, including lessons learned and follow-up. L. M. Messiaen. Univ Alabama at Birmingham.

12:30 PM   Adult zebrafish as a living model in evaluation of variants in cardiogenetics in a routine setting using echography and speckle-tracking software. D. Hassel. Univ Hosp Heidelberg, Germany.


Wednesday, October 19

11:00 AM–1:00 PM

Concurrent Invited Session I

19. Education in Action: Meeting the Challenges of 21st Century Genetics

Room 207, West Building, Convention Centre

Moderator: Marnie E. Gelbart, Harvard Med Sch, Boston

 

As the current revolution in genetics stands poised to transform healthcare, educating and engaging the broadest cross-section of society is a key step towards unlocking the opportunities for improving human health. How can we raise public awareness and foster discussion such that all individuals, regardless of geography, ethnicity or socioeconomic status, are aware of the benefits and implications of genetic technologies? This session will focus on active and scalable educational programs that are on the ground directly serving students, teachers, museum visitors, and the general public. This session will highlight four such efforts that are striving to increase trust, improve genetic literacy, and support workforce development, particularly in underserved communities. Collectively, the speakers will illustrate the impacts of a breadth of strategies acting through high schools, colleges and universities, museums, libraries, faith institutions, arts and entertainment, the political sphere, and social media. They will highlight opportunities to get involved as well as the returns for the scientific community to incorporate public feedback into its work.

 

11:00 AM   Genetic awareness for all: Sparking curiosity and discussion in classrooms, churches, Hollywood, and Washington, DC. T. Wu. Harvard Med Sch, Boston.

11:30 AM   North Carolina DNA Day: Building bridges between research institutions and high school classrooms. J. Hall. UNC Chapel Hill Sch Med.

12:00 PM   Genome: Unlocking Life's Code — Inspiring community interest and engagement through a genomics exhibition. C. Easter. NHGRI, NIH, Bethesda.

12:30 PM   Hitting the ground running: Integrating molecular genetics, bioethics, and bioinformatics in high schools, colleges, and university courses. C. Wray. Jackson Lab, Bar Harbor.


Wednesday, October 19

11:00 AM–1:00 PM

Concurrent Invited Session I

20. From GWAS and Mendelian Genes to Therapeutic Drug Targets

Ballroom B, West Building, Convention Centre

Moderators: Margaret G. Ehm, GlaxoSmithKline, King of Prussia
  Nancy J. Cox, Vanderbilt Univ, Nashville

 

The study of the genetic basis of human disease has evolved significantly in the past 10 years and for many conditions, a literature search pulls up a well-powered study of the genetic basis for that disease. Several technologies have emerged that provide the means by which to study the effects of genetic variants. The speakers in this session will outline the process of target identification and validation along with emerging methods, strategies and technologies that are being used to evaluate genes as potential drug targets and use the information to develop new medicines.

 

11:00 AM   Open innovation partnerships to bridge the gap from GWAS to drug targets. J. C. Barrett. Sanger Inst, Hinxton/Cambridge, UK.

11:30 AM   Using human genetics to discover new drug targets. R. H. Scheller. 23andMe, Mountain View.

12:00 PM   Using the BioVU catalog of gene X medical phenome for drug discovery and repurposing. N. J. Cox. Vanderbilt Univ, Nashville.

12:30 PM   DiscovEHRy of new drug targets and the implementation of precision medicine. A. R. Shuldiner. Regeneron Genet Ctr, LLC and Regeneron, Tarrytown.


Wednesday, October 19

11:00 AM–1:00 PM

Concurrent Invited Session I

21. Clinical Spotlight: Models and Approaches for Population-based Screening of Cancer Susceptibility Genes

Room 302, West Building, Convention Centre

Moderators: Amanda E. Toland, Ohio State Univ, Columbus
  Heather Hampel, Ohio State Univ, Columbus

 

Historically, genetic testing of cancer susceptibility genes has been done for individuals meeting testing guidelines based on a personal and/or family history of a cancer susceptibility syndrome. The paradigm of who should be tested is changing in some settings, resulting in the identification of pathogenic germline mutations in individuals and their family members who may otherwise not have been referred or who may not have met previous testing guidelines. There is some controversy as to whether population-based screening or testing should be done for hereditary cancer syndromes and in which settings. This session will discuss the varied models for population-based testing that have been proposed and the outcomes and impact of these ongoing efforts. The session will also include the impact of global testing of cancer patients and how this has affected treatment and management strategies.

 

11:00 AM   Community cancer genetic screening initiative: Results that one would expect...or are they? R. Myers. HudsonAlpha Inst for Biotech, Huntsville.

11:30 AM   Genomic analysis of inherited breast and ovarian cancer: From gene discovery to public health. M. King. Univ Washington, Seattle.

12:00 PM   Histology-based referral strategy for hereditary cancer testing in ovarian cancer patients. J. McAlpine. Univ BC and BC Cancer Agency, Vancouver, Canada.

12:30 PM   The Ohio Colorectal Cancer Prevention Initiative: A statewide genetic screening project. H. Hampel. Ohio State Univ, Columbus.


Wednesday, October 19

11:00 AM–1:00 PM

Concurrent Invited Session I

22. The Role of DNA Repair in Genomic Variation, Instability, and Human Disease

Room 109, West Building, Convention Centre

Moderators: Florencia Pratto, NIH, Bethesda
  Christine R. Beck, Baylor Col Med, Houston

 

Homologous and non-homologous DNA repair mechanisms are both implicated in genomic rearrangements leading to human disease and individual variation. Homologous recombination is a high fidelity mechanism by which cells can repair DNA. Although homologous recombination generally occurs between allelic sequences, when damage occurs in repetitive regions of the genome, recombination between non-allelic but highly similar DNA sequences may occur. This ectopic recombination can result in deletions, duplications, inversions and translocations. Similarly, non-homologous end joining and replicative mechanisms of DNA repair can cause genomic rearrangements. Importantly, each of these types of variants can manifest as a genomic disorder. The factors that determine the occurrence of structural variants include the frequency of DNA double-strand breaks at repetitive regions and the genomic architecture of the site. This session will examine the mechanisms that underlie structural variants, the methods by which they are detected and how an understanding of these mechanisms can aid clinical diagnosis of human disease. In this context, we will describe details about specific diseases from both a clinical and a molecular perspective and will foster a broader discussion about the translational value of such knowledge. These topics will be explored by trainees from leading groups in the field of genome rearrangement.

 

11:00 AM   Characterizing the mechanisms of structure variations incidence based on breakpoints profiles. S. Li. Yale Univ, New Haven.

11:30 AM   Genome instability caused by meiotic recombination in the germ line. F. Pratto. NIH, Bethesda.

12:00 PM   Mechanisms of rearrangements in genomic disorders: From the bedside to the bench side. C. R. Beck. Baylor Col Med, Houston.

12:30 PM   Polycystic Kidney Disease: The underlying genetic architecture may explain the susceptibility of PKD1 to mutations. C. Lin. NIH, Bethesda.


Wednesday, October 19

11:00 AM–1:00 PM

Concurrent Invited Session I

23. Unusual Suspects: A Legal Line-Up Beyond GINA

Room 119, West Building, Convention Centre

Moderator: Jennifer K. Wagner, Geisinger Hlth Syst, Danville

 

The legal implications of genetic/genomic research and the practice of precision medicine are many. By now most ASHG members are familiar with the Genetic Information Nondiscrimination Act of 2008, the United States law that prohibits acquisition and use of genetic information in health insurance and employment decisions. But other legal issues remain sources of mystery and uncertainty. An ignorance of "the law" has the potential to thwart the hard work of researchers with even the best intentions and most innovative ideas. This session will showcase four ELSI scholars who will discuss serious legal issues in four key areas: legal pressures in the practice of medicine, data sharing policy considerations for precision medicine, regulatory oversight for research with human participants, and legal processes for law enforcement and third-parties to gain access to genomic databases (proprietary, confidential, or otherwise).

 

11:00 AM   Legal norms, defensive medicine and personalized medicine. T. Caulfield. Univ Alberta, Edmonton, Canada.

11:30 AM   Obstacles to building a medical information commons. R. Cook-Deegan. Duke Univ, Durham.

12:00 PM   How meaningful is 'choice' without education? Mandated choice over participation in biospecimens research in a time of misfearing and regulatory confusion. M. N. Meyer. Union Grad Col-Icahn Sch Med at Mt Sinai Bioethics Program, Schenectady.

12:30 PM   Ready or not, here they come: Law enforcement and third-party access to genomic databases. J. K. Wagner. Geisinger Hlth Syst, Danville.


Wednesday, October 19

4:30 PM–5:50 PM

24. Featured Plenary Abstract Session II

Ballroom ABC, West Building, Convention Centre

Moderators: Anthony Antonellis, ASHG 2016 Program Chair
  Pamela Sklar, ASHG 2016 Program Committee

 

59/4:30 Direct identification of non-coding variants that modulate expression using high-throughput experimental assays. R. Tewhey, D. Kotliar, D.S. Park, E.A. Brown, S.K. Reilly, T.S. Mikkelsen, S.F. Schaffner, P.C. Sabeti.

60/4:50 Asprosin, a fasting-induced glucogenic and orexigenic protein hormone. A.R. Chopra.

61/5:10 Aggregate allelic burden for cancer risk genes associates with age at diagnosis across 8,206 exomes. J.J. Pitt, M. Bolt, D.J. Fitzgerald, L.L. Pesce, P. Van Loo, K.P. White.

62/5:30 Ultraconservation of DNA sequence provides a new lens for focusing on chromosomal structural rearrangements in neurodevelopmental disorder genomes. R.B. McCole, C.Y. Fonseka, J. Erceg, H. Brand, R. Collins, V. Pillalamarri, S. Erdin, C. Redin, M.E. Talkowski, T. Wu.


Wednesday, October 19

5:55 PM–6:25 PM

25. ASHG William Allan Award Presentation

Ballroom ABC, West Building, Convention Centre

The ASHG William Allan Award recognizes a scientist for substantial and far-reaching scientific contributions to human genetics. It was established in 1961 in memory of William Allan, MD (1881-1943), one of the first American physicians to conduct extensive research on human genetics and hereditary diseases.

Introduction: David L. Nelson, Baylor College of Medicine

Recipient:
James F Gusella

James Gusella, PhD
Bullard Professor of Neurogenetics, Department of Genetics, Harvard Medical School
Research Staff, Department of Neurology, Massachusetts General Hospital
Associate Member, The Broad Institute

Dr. Gusella pioneered the “genetic research cycle” paradigm to conceptualize genetics research from basic science to genotype-driven modeling, based on associations with human disease and translation into diagnostics, treatments, and prevention strategies. He has led numerous national and international research consortia with broad impact on human disease. Since the 1980s, his lab has made major advances in studying Huntington disease, including identifying linked markers, cloning the causal gene, and extensively describing the mutation and mechanism involved. They have also mapped and identified genes associated with other neurological and neurodevelopmental disorders. In 1999, Dr. Gusella co-founded the Developmental Genome Anatomy Project, and he continues to develop novel genome-wide strategies to identify genes critical to human development.

 


Thursday, October 20

9:00 AM–10:30 AM

Concurrent Platform Session B

26. The Landscape of Genome Alterations in Cancer

Ballroom A, West Building, Convention Centre

Moderators: Debora Ritter, Baylor Col Med, Houston
  Ekta Khurana, Weill Cornell Med Col, New York

 

63/9:00 Pediatric acute myeloid leukemia survival differences revealed by comprehensive miRNA sequence analysis. E.L. Lim, D.L. Trinh, R. Ries, Y. Ma, J. Topham, M. Hughes, E. Pleasance, A. Mungall, R. Moore, Y.J. Zhao, D.S. Gerhard, E.A. Kolb, A. Gamis, M. Smith, T.A. Alonzo, R.J. Arceci, S. Meshinchi, M.A. Marra.

64/9:15 Integrated landscape of molecular alterations in uveal melanoma. H. Anbunathan, M. Field, W. Harbour, A. Bowcock.

65/9:30 Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer. A. Fujimoto, M. Furuta, Y. Totoki, T. Tsunoda, M. Kato, H. Yamaue, K. Chayama, S. Miyano, H. Aburatani, T. Shibata, H. Nakagawa.

66/9:45 Comprehensive analysis of telomere length and telomere maintenance mechanisms across 31 human cancer types. S. Zheng, F.P. Barthel, R. Verhaak.

67/10:00 Reversion to stress-induced mutation is a hallmark of cancer. K.J. Bussey, L. Cisneros, A. Orr, M. Miocevic, C.H. Lineweaver, P. Davies.

68/10:15 DNA fragile site breakage as a measure of chemical exposure and predictor of individual susceptibility to form oncogenic rearrangements. Y. Wang, C. Lehman, Y. Nikiforov.


Thursday, October 20

9:00 AM–10:30 AM

Concurrent Platform Session B

27. Studies of Ancestry, Migration, and Admixture

Ballroom B, West Building, Convention Centre

Moderators: Joseph Lachance, Georgia Tech, Atlanta
  Alicia Martin, Broad Inst, Boston

 

69/9:00 Inferring migration and population-size surfaces across time periods. H. Al-Asadi, D. Petkova, J. Novembre, M. Stephens.

70/9:15 Genetic variation reveals migrations into the Indian subcontinent and its influence on the Indian society. A. Bose, D.E. Platt, L. Parida, P. Paschou, P. Drineas.

71/9:30 Ancestry-specific estimation of recent effective population size in the Americas. S.R. Browning, B.L. Browning.

72/9:45 Large-scale characterization of admixed populations and extensions of admixture mapping within the Population Architecture using Genomics and Epidemiology (PAGE)-II study. G.L. Wojcik, K. Nishimura, A. Reiner, C. Hodonsky, S. Shringarpure, G. Belbin, M.P. Conomos, J. Haessler, T.A. Thornton, C. Laurie, L. Hindorff, R. James, C. Haiman, L. LeMarchand, T. Matise, S. Buyske, B. Thyagarajan, C. Carlson, R. Loos, K.E. North, C. Avery, C. Kooperberg, C.D. Bustamante, C.R. Gignoux, E.E. Kenny, PAGE-II Study.

73/10:00 A complex history of archaic admixture in modern humans. R. Bohlender, Y. Yu, C. Huff, A. Rogers.

74/10:15 Ultra-fine structural inference and population assignment using IBD network clustering and classifiers accurately assign sub-continental origins represented in a large admixed U.S. cohort. E. Han, R. Curtis, P. Carbonetto, K. Noto, J. Byrnes, Y. Wang, J. Granka, A. Kermany, K. Rand, E. Elyashiv, H. Guturu, N. Myres, E. Hong, C. Ball, K. Chahine.


Thursday, October 20

9:00 AM–10:30 AM

Concurrent Platform Session B

28. Mechanisms of Gene Regulation

Ballroom C, West Building, Convention Centre

Moderators: Anshul Kundaje, Stanford Univ
  Alicia Smith, Emory Univ, Atlanta

 

75/9:00 Systematic functional dissection of common genetic variation affecting transcriptional regulation and human disease. J.C. Ulirsch, S.K. Nandakumar, L. Wang, F.C. Giani, X. Zhang, P. Rogov, A. Melnikov, P. McDonel, R. Do, T.S. Mikkelsen, V.G. Sankaran.

76/9:15 Massively parallel ChIP-reporter assays reveal synergystic clusters of transcription factor binding across the human genome. T.E. Reddy, C.M. Vockley, A.M. D'Ippolito, I.C. McDowell, W.H. Majoros, A. Safi, L. Song, G.E. Crawford.

77/9:30 Inferring the genetic architecture of cis-gene regulation and evolutionary constraint on human gene expression. E. Glassberg, Z. Gao, J. Pritchard.

78/9:45 Integrating genomic, endophenotypic, and exposure data to identifiy biomarkers of multi-drug treatment response. M-J. Fave, H.A. Edgington, J-C. Grenier, V. Bruat, P. Awadalla.

79/10:00 Comprehensive population-based genome sequencing provides insight into hematopoietic regulatory mechanisms. M. Guo, S. Nandakumar, J. Ulirsch, S. Zekavat, P. Natarajan, R. Salem, A. Metspalu, S. Kathiresan, J. Hirschhorn, T. Esko, V. Sankaran.

80/10:15 The dynamics of genome topology in response to glucocorticoid treatment. A. D'Ippolito, I. McDowell, C. Vockley, A. Barrera, L. Hong, S. Leichter, L. Bartelt, T. Reddy.


Thursday, October 20

9:00 AM–10:30 AM

Concurrent Platform Session B

29. Cancer Bioinformatics

Room 109, West Building, Convention Centre

Moderators: Angela R. Brooks-Wilson, British Columbia Genome Sci Ctr, Vancouver, Canada
  Elizabeth M. Gillanders, NCI, Rockville

 

81/9:00 Enabling petabyte-scale genomics in the cloud: Lessons from the NCI Cancer Genomics Cloud Pilots. G. Kaushik, Z. Onder, D. Locke, B. Davis-Dusenbery, D. Kural.

82/9:15 Modeling the subclonal evolution of cancer cell populations. M. Wilson Sayres, D. Chowell, J. Napier, R. Gupta, L. Faiss, C. Maley.

83/9:30 Cancer gene discovery via network analysis of somatic mutation data. I. Lee, A. Cho, J. Shim, E. Kim, F. Supek, B. Lehner.

84/9:45 Genetic determinants of translation in humans. C. Cenik, J.A. Reuter, E. Sarinay Cenik, D. Spacek, C.L. Araya, M.P. Snyder.

85/10:00 Prioritization of target drug combinations with immunotherapy using genomic data. L. Machado Colli, M. Machiela, T. Myers, L. Jessop, K. Yu, S. Chanock.

86/10:15 High performance discovery of complex genome-wide rearrangements with single molecule-based barcoded sequence reads. L.C. Xia, C. Wood, B. Lau, N.R. Zhang, H.P. Ji.


Thursday, October 20

9:00 AM–10:30 AM

Concurrent Platform Session B

30. Methods for Studying Rare Variants

Room 119, West Building, Convention Centre

Moderators: Gemma L. Carvill, Univ Washington, Seattle
  Dale Nyholt, Queensland Univ Technol, Brisbane, Australia

 

87/9:00 Using whole genome sequence data to identify causal variants affecting gene expression and disease. A. Brown, O. Delaneau, T. Spector, K. Small, E. Dermitzakis.

88/9:15 A new method for genetic region association testing with massively different sequencing depths of coverage. A.E. Hendricks, S. Billups, E. Zeggini, I. Barroso, S.A. Santorico, J. Dupuis.

89/9:30 A novel rare-variant nonparametric linkage method for analysis of complex familial diseases using whole genome and exome sequence data. L.H. Zhao, Z. He, B. Li, G.T. Wang, S.M. Leal.

90/9:45 SeqSpark: A complete analysis tool for large-scale rare variant association studies using whole genome and exome sequence data. D. Zhang, B. Li, Z. He, G.T. Wang, S.M. Leal.

91/10:00 FastSKAT: Sequence kernel association tests for large sets of markers and applications for analyzing LDL cholesterol in whole-genome sequencing data. K.M. Rice, J.A. Brody, G.M. Peloso, L.A. Cupples, T. Lumley, CHARGE Lipids Working Group.

92/10:15 Human evolutionary history has increased the role of rare variants in complex phenotypes. R. Hernandez, K. Hartman, L. Uricchio, C. Ye, N. Zaitlen.


Thursday, October 20

9:00 AM–10:30 AM

Concurrent Platform Session B

31. Mutations, Mechanisms, and Model Systems

Room 207, West Building, Convention Centre

Moderators: Derek M. Dykxhoorn, Univ Miami
  Harikiran Nistala, Regeneron Pharmaceuticals, Tarrytown

 

93/9:00 Type 2 diabetes-associated variants disrupt function of SLC16A11, a proton-coupled monocarboxylate transporter. S. Jacobs, V. Rusu, E. Hoch, on behalf of the SIGMA T2D Consortium.

94/9:15 Increased alpha tryptase copy number at TPSAB1 is associated with common elevations in basal serum tryptase level and variably expressive syndromic comorbidity. J.D. Milner, X. Yu, J.D. Hughes, Q.T. Le, G.H. Caughey, Y. Bai, T. Heller, M. Zhao, Y. Liu, M.P. O'Connell, N. Trivedi, C. Nelson, T. DiMaggio, H. Matthews, K.L. Lewis, A.J. Oler, R.J. Carlson, P.D. Arkwright, C. Hong, D.D. Metcalfe, T.M. Wilson, L.B. Schwartz, Y. Zhang, J.J. McElwee, M. Pao, S.C. Glover, M.E. Rothenberg, R.J. Hohman, L.G. Biesecker, J.J. Lyons.

95/9:30 Genetic inactivation of ANGPTL4 is associated with improved glycemic control and reduced risk of Type 2 Diabetes. C. O'Dushlaine, V. Gusarova, P. Benotti, T. Mirshahi, O. Gottesman, C. Van Hout, M. Murray, A. Mahajan, J. Nielsen, C. Emdin, R. Scott, S. Bruse, O. Holmen, D. Ledbetter, J. Reid, J. Overton, G. Yancopoulos, N. Wareham, S. Kathiresan, O. Melander, G. Abecasis, J. Florez, M. Boehnke, M. McCarthy, D. Carey, A. Shuldiner, I. Borecki, A. Baras, J. Gromada, F. Dewey, DiscovEHR Collaboration.

96/9:45 Novel long non-coding RNAs, CUPID1 and CUPID2, mediate breast cancer risk at 11q13 by modulating response to DNA damage. J. D. French, M. Moradi Marjaneh, Y.C. Lim, M. Clark, N. Bartonicek, W. Shi, T. Mercer, K. Khanna, M. Dinger, F. Al-Ejeh, J.A. Betts, S.L. Edwards.

97/10:00 Unprogrammed presentation number

98/10:15 Characterization of a new class of disease-causing variants unresponsive to current CFTR targeted therapies. S.T. Han, M.J. Pellicore, T.A. Evans, E. Davis, K.S. Raraigh, G.R. Cutting.


Thursday, October 20

9:00 AM–10:30 AM

Concurrent Platform Session B

32. Utilizing Constraint and Conservation for Functional Predictions

Room 211, West Building, Convention Centre

Moderators: Slave Petrovski, Univ Melbourne, Australia
  Mark Daly, Broad Inst, Boston

 

99/9:00 Quantifying constraint on regulatory variation across 48 human tissues improves interpretation of functional variation. T. Lappalainen, P. Mohammadi, S.E. Castel, H.E. Wheeler, H.K. Im, GTEx Consortium.

100/9:15 Systematic prediction of conserved non-exonic bases from large-scale functional genomics data. J. Ernst, O. Grujic, Y. Lee, A. Sperlea.

101/9:30 Identifying highly constrained protein-coding regions using population-scale genetic variation. J. Havrilla, B. Pedersen, R. Layer, A. Quinlan.

102/9:45 Regional analysis of variation tolerance improves variant deleteriousness prediction. K.E. Samocha, J.A. Kosmicki, K.J. Karczewski, A.H. O'Donnell-Luria, E.V. Minikel, M. Lek, D.G. MacArthur, B.M. Neale, M.J. Daly, Exome Aggregation Consortium.

103/10:00 Annotation of the human genome through conservation states aids interpretation of disease associated genetic variation. A. Sperlea, J. Ernst.

104/10:15 Assessment of genetic burden and constraint in hypertrophic cardiomyopathy genes leveraging protein structural data and large sequencing cohorts. J.R. Homburger, E.M. Green, C. Caleshu, M.S. Sunitha, R.E. Taylor, K.M. Ruppel, R. Metpally, S.D. Colan, M. Michels, S.M. Day, I. Olivotto, C.D. Bustamante, F. Dewey, C.Y. Ho, J.A. Spudich, E.A. Ashley.


Thursday, October 20

9:00 AM–10:30 AM

Concurrent Platform Session B

33. Insights into the Genetic Basis of Eye Syndromes

Room 221, West Building, Convention Centre

Moderators: Anne Slavotinek, UCSF
  Anatalia Labilloy, Cincinnati Children's Med Ctr

 

105/9:00 Recessive and dominant de novo ITPR1 mutations cause Gillespie Syndrome. L. Fares Taie, S. Gerber, K. Alzayady, L. Burglen, D. Bremond-Gignac, V. Marchesin, O. Roche, M. Rio, B. Funalot, R. Calmon, A. Durr, V. Gil-da-Silva-Lopes, M. Ribeiro Bittar, C. Orssaud, B. Heron, E. Ayoub, P. Berquin, N. Bahi-Buisson, C. Bole, C. Masson, A. Munnich, M. Simons, M. Delous, H. Dollfus, N. Boddaert, S. Lyonnet, J. Kaplan, P. Calvas, D. Yule, J.M. Rozet.

106/9:15 Photoreceptors restore retinal function and regenerate healthy outer segments after reconstitution of the BBSome in a mouse model of Bardet-Biedl Syndrome. Y. Hsu, J. Garrison, G. Kim, D. Nishimura, C. Searby, A. Schmitz, P. Datta, S. Seo, V. Sheffield.

107/9:30 Mutations in spliceosome-associated protein homolog CWC27 cause autosomal recessive syndromic retinitis pigmentosa. M. Xu, Y.A. Xie, H. Abouzeid, D. Babino, Z. Sun, A. Eblimit, I.S. Othman, A. Lehman, R. Pfundt, A. Fiorentino, R. Riveiro, J. von Lintig, V. Kheir, G. Pinton, N. Allaman-Pillet, R. Dharmat, S.A. Agrawal, Y. Li, A. Hardcastle, M.A. Lopez, H. Li, M. Cheetham, C. Ayuso, R. Chen, R. Sui, R. Allikmets, D.F. Schorderet.

108/9:45 Patients with Blepharo-Cheilo-Dontic syndrome show mutations in genes of the cadherin-catenin complex. A. Kievit, F. Tessadori, J. Douben, I. Jordens, M. Maurice, A. Hoogeboom, R. Hennekam, S. Nampoothiri, H. Kayserili, M. Castori, M. Whiteford, C. Motter, C. Melver, M. Cunningham, A. Hing, N. Mizue Kokitsu-Nakta, S. Vendramini-Pittoli, A. Richieri-Costa, A. Baas, M. Massink, K. van Gassen, J. Bakkers, F. Santos, P. Lapunzina, V. Gil-da Silva Lopes, A. Slavotinek, V. Martinez-Glez, J. de Klein, G. van Haaften, M-J. van den Boogaard.

109/10:00 803 individuals with retinal dystrophies investigated with targeted NGS of 124 genes. K. Gronskov, M. Fang, M. Bertelsen, C. Jespersgaard, X. Dang, H. Jensen, Y. Shen, N. Bech, I. Dai, T. Rosenberg, J. Zhang, L. Moller, Z. Tümer, K. Brondum-Nielsen.

110/10:15 Genome-wide association analyses using the Haplotype Reference Consortium for imputations reveals 4 novel loci involved in glaucoma endophenotypes. A. Iglesias Gonzalez, P. Bonnemaijer, H. Springelkamp, S. van der Lee, N. Amin, C.C.W. Klaver, C.M. van Duijn.


Thursday, October 20

9:00 AM–10:30 AM

Concurrent Platform Session B

34. Methods for Genome- and Transcriptome-Wide Association Studies

Room 302, West Building, Convention Centre

Moderators: Noah A. Zaitlen, UCSF
  John Eicher, NHLBI, NIH, Framingham

 

111/9:00 Transcriptome-wide association study of thirty complex traits reveals novel risk genes. G. Kichaev, N. Mancuso, H. Shi, P. Goddard, A. Gusev, B. Pasaniuc.

112/9:15 Phasing, imputation and analysis of 500,000 UK individuals genotyped for UK Biobank. J. Marchini, C. Bycroft, D. Petkova, S. Murphy, C. Freeman, P. Donnelly.

113/9:30 Improved score statistics for meta-analysis in single variant and gene-level association studies. J. Yang, S. Chen, G. Abecasis, International Age-related Macular Degeneration Genomics Consortium.

114/9:45 Searching for novel cross-phenotype associations using Bayesian meta-analysis. H. Trochet, L. Jostins, G. McVean, M. Pirinen, C. Spencer.

115/10:00 Novel schizophrenia risk genes identified through genic associations in CommonMind Consoritum and GTEx transcriptome imputation. L.M. Huckins, A. Dobbyn, D.M. Ruderfer, M. Fromer, N. Cox, H.K. Im, S. Sieberts, B. Devlin, P. Roussos, S. Purcell, P. Sklar, E.A. Stahl, CommonMind Consortium.

116/10:15 Transcriptome-wide association study of schizophrenia and chromatin activity yields mechanistic disease insights. A. Gusev, N. Mancuso, L. Song, E. Oh, S. McCarroll, B. Neale, R. Ophoff, M. O'Donovan, G. Crawford, N. Katsanis, P.F. Sullivan, B. Pasaniuc, A.L. Price, Schizophrenia Working Group of the Psychiatric Genomics Consortium.


Thursday, October 20

11:00 AM–1:00 PM

Concurrent Platform Session C

35. Statistical Pleiotropy and Multiple Phenotypes: The More, the Merrier

Ballroom A, West Building, Convention Centre

Moderators: Nancy L. Saccone, Washington Univ in St. Louis Sch Med
  Xiaofeng Zhu, Case Western Reserve Univ, Cleveland

 

117/11:00 Joint Bayesian inference of risk variants using summary statistics and epigenomic annotations across multiple traits. Y. Li.

118/11:15 Tissue-specific trans-ancestral analysis of genetically regulated expression identifies 99 known and 41 novel genes across 14 metabolic and cardiovascular traits. J.E. Below, L.E. Petty, H.M. Highland, H. Hu, P.S. de Vries, D. Aguilar, G.I. Bell, C.D. Huff, N..J. Cox, C.L. Hanis, J. Ma, E.J. Parra, M. Cruz, A. Valladares-Salgado, H.K. Im, A.C. Morrison, E. Boerwinkle.

119/11:30 Pleiotropic effects on BMI, WHR, fasting glucose, and fasting insulin levels. H.M. Highland, C.M. Sitlani, A.A. Seyerle, R. Gondalia, M. Graff, C.L. Avery, K.E. North.

120/11:45 LD Hub and MR-Base: Online platforms for performing LD score regression and Mendelian randomization analysis using GWAS summary data. D. Evans, J. Zheng, G. Hemani, B. Elsworth, H. Shihab, C. Laurin, M. Erzurumluoglu, L. Howe, K. Wade, N. Warrington, H. Finucane, A. Price, V. Anttila, L. Paternoster, R. Martin, C. Relton, G. Davey Smith, B. Neale, T. Gaunt, P. Haycock.

121/12:00 Genome-wide association study of bone mineral density in the UK Biobank Study identifies over 376 loci associated with osteoporosis. J.P. Kemp, J.A. Morris, M. Medina-Gómez, C.L. Gregson, V. Forgetta, K. Trajanoska, N.M. Warrington, J. Zheng, S. Kaptoge, F. Rivadeneira, J.H. Tobias, C.L. Ackert-Bicknell, J.B. Richards, D.M. Evans.

122/12:15 Joint re-analysis of GWAS summary statistics identifies new variants associated with human traits and diseases. B.J. Vilhjalmsson, H. Finucane, A. Gusev, A.L. Price, P. Kraft, H. Aschard.

123/12:30 Multivariate genetic risk scores can increase risk prediction accuracy for a wide range of traits. R. Maier, M. Robinson, P. Visscher, N. Wray.

124/12:45 Building the human wiring diagram from genome-phenome associations across 525 studies, 300 phenotypes and 2.5 million individuals. P. Donnelly, G. McVean, W. Ali, R. Davies, T. Down, L. Curren, J. Faria, J. Floyd, C. Franklin, J. Hall, L. Jostins, Y. Li, J. Maller, M. Pirinen, H. Taylor, C. Vangjeli, H. Wilman, S. Wilder, M.E. Weale, S. Myers, G. Lunter, M. Simpson, C. Spencer.


Thursday, October 20

11:00 AM–1:00 PM

Concurrent Platform Session C

36. Insights from Large Cohorts: Part 2

Ballroom B, West Building, Convention Centre

Moderators: Mingyao Li, Univ Pennsylvania, Philadelphia
  Bingshan Li, Vanderbilt Univ, Nashville

 

125/11:00 De-novo reconstruction of more than 6,000 pedigrees discovered from 51K de-identified exomes within the DiscovEHR cohort. J. Staples, E.K. Maxwell, C. Gonzaga-Jauregui, I.B. Borecki, M.F. Murray, D. Carey, F.E. Dewey, O. Gottesman, L. Habegger, J.G. Reid, Geisinger-Regeneron DiscovEHR.

126/11:15 Insights from expanded carrier screening of >54,000 individuals by next-generation sequencing. A.H. Birch, G. Cai, G. Mendiratta-Vij, L. Shi, X. Cai, O. Birsoy, S. Sperber, J. Liao, B. Webb, L. Elkhoury, J. McCarthy, M. Dillon, S. Van Den Berg, M. Delio, G. Diaz, F. Suer, R. Kornreich, L. Edelmann.

127/11:30 Improving biobank consent comprehension: A national randomized survey to assess the effect of a simplified form and review/retest intervention. L.M. Beskow, L. Lin, C.B. Dombeck, E. Gao, K.P. Weinfurt.

128/11:45 Large-scale genomic analyses identify one fifth of the heritable component of puberty timing and widespread non-linear associations. F. Day, on behalf of the ReproGen Consortium.

129/12:00 A large genome-wide study of age-related hearing impairment using electronic health records. T.J. Hoffmann, B.J. Keats, N. Yoshikawa, C. Schaefer, N. Risch, L.R. Lustig.

130/12:15 Identifying disease-causing genes that act through complementary modes of regulatory elements and protein altering variants in DNA samples linked to electronic medical records. X. Zhong, Q. Wei, R. Chen, Q. Wang, N.J. Cox, B. Li.

131/12:30 Thousands of novel variants influencing human blood cell variation and function: Insights from UK Biobank and INTERVAL. H. Elding, W.J. Astle, T. Jiang, D. Allen, D.J. Roberts, W.H. Owehand, J. Danesh, A.S. Butterworth, N. Soranzo.

132/12:45 Decoding 51 thousand individuals to analyze the most common genetic disorder: Hereditary hemochromatosis (HH). N.S. Kip, M. Corbali, R. Metpally, H. Williams, S. Krishnamurthy, H. Harrison, D. Carey, M. Williams, A. Baras, J. Overton.


Thursday, October 20

11:00 AM–1:00 PM

Concurrent Platform Session C

37. Hereditary Cancer Diagnostics

Ballroom C, West Building, Convention Centre

Moderators: Robin L. Bennett, Univ Washington, Seattle
  Jeffrey N. Weitzel, City of Hope, Duarte

 

133/11:00 Prevalence of mutations in high/moderate risk cancer genes in 3,488 patients tested using a uniform NGS cancer panel. G.E. Tiller, M. Alvarado, J. Goff, R. Haque.

134/11:15 Parental perspectives on whole exome sequencing in pediatric cancer: A typology of perceived utility. J. Malek, M.J. Slashinski, J.O. Robinson, A.M. Gutierrez, D.W. Parsons, S.E. Plon, A.L. McGuire, L.B. McCullough.

135/11:30 Combining linked read technology with standard target-enrichment NGS can accurately resolve short reads and distinguish variants in the Lynch/CMMRD syndrome gene, PMS2, from its pseudogene, PMS2CL. C. Kao, R. Pellegrino, F. Mafra, J. Garifallou, C. Kaminski, F. Wang, L. Tian, S. Garcia, R. Mao, W. Samowitz, C. Vance, C. Vaughn, S. Wenzel, K. Wimmer, H. Hakonarson.

136/11:45 Mismatch repair activity in non-neoplastic biallelic mismatch repair deficient cells: An explanation for the predominance of PMS2 mutations and rapid diagnosis. A.Y. Shuen, S. Lanni, Y. Lisa, G.B. Panigrahi, S. Deshmukh, B. Campbell, N. Zhukova, N. Thakkar, D. Malkin, U. Tabori, C.E. Pearson.

137/12:00 PMS2CL-hybrid alleles containing PMS2 sequence and other PMS2CL-derived large rearrangements: The importance of correct interpretation of dosage alteration analysis in PMS2. N. Singh, D. Mancini-DiNardo, B. Leclair, K. Brown, E. Goossen, K. Bowles, B. Roa, M. Jones.

138/12:15 ENIGMA quantitative and qualitative classification criteria for evaluating the clinical significance of BRCA1 and BRCA2 sequence variants. A.B. Spurdle, M.A. Parsons, F. Couch, M. de la Hoya, S. Domchek, D. Eccles, E. Gomez-Garcia, C. Houdayer, A. Mensenkamp, A. Monteiro, P. Radice, M. Southey, S. Tavtigian, A. Toland, M. Vreeswijk, B. Wappenschmidt, D.E. Goldgar, and ENIGMA collaborators.

139/12:30 Return of incidental results for BRCA1/BRCA2 to a 50,726 person cohort within a single healthcare provider organization. M.F. Murray, K. Manickam, A. H. Buchanan, D.M. Lindbuchler, M.L. Barr, A.L. Lazzeri, L.M. Gorgol, C.Z. McCormick, C.N. Flansburg, M. Hallquist, A.K. Rahm, A. Fan, W.A. Faucett, M.A. Giovanni, D.N. Hartzel, J.B. Leader, H.L. Kirchner, N.S. Abul-Husn, F.E. Dewey, R.P.R. Metpally, D.J. Carey, T.N. Person, M.D. Ritchie, D.H. Ledbetter.

140/12:45 BRCA population screening in unaffected Ashkenazi Jewish women: A randomized controlled trial of different pre-test strategies. S. Lieberman, A. Tomer, A. Ben-Chetrit, O. Olsha, S. Levin, R. Beeri, A. Raz, A. Lahad, E. Levy-Lahad.


Thursday, October 20

11:00 AM–1:00 PM

Concurrent Platform Session C

38. Novel Findings from Genome-Wide Association Studies

Room 109, West Building, Convention Centre

Moderators: Alper Uzun, Women & Infants Hosp, Providence
  Catherine Stein, Case Western Reserve Univ, Cleveland

 

141/11:00 First genome-wide significant locus for pre-eclampsia susceptibility discovered on fetal chromosome 13 near FLT1. R. McGinnis, V. Steinthorsdottir, N. Williams, V. Dolby, G. Thorleifsson, S. Shooter, L. Stefansdottir, J. Sigurdsson, A. Haugan, S. Chappell, T. Jääskeläinen, G. Silva, L.C. Vestrheim Thomsen, W.K. Lee, E. Staines-Urias, J. Kemp, F. Dudbridge, J.P. Casas, T. Hegay, N. Simpson, J. Walker, N. Zakhidova, D. Lawlor, G. Syvatova, D. Najmutdinova, P. Magnus, A.C. Iversen, H. Laivuori, L. Morgan, InterPregGen Consortium.

142/11:15 Genome-wide meta-analysis of polycystic ovary syndrome in women of European ancestry identifies novel loci. T. Karaderi, C. Meun, T. Laisk-Podar, F.T.J. Lin, W. Wu, A. Mahajan, B.H. Mullin, M.R. Jones, F.R. Day, on behalf of the PCOS Consortium.

143/11:30 83 rare and low-frequency coding variants implicate specific genes affecting human height variation. E. Marouli, M. Graff, C. Medina-Gomez, K. Sin lo, A. Wood, T.R. Kjaer, R.S. Fine, C. Schurmann, C. Oxvig, Z. Kutalik, F. Rivadeneira, R.J.F. Loos, T.M. Frayling, J.N. Hirschhorn, G. Lettre, P. Deloukas, For deCODE Genetics, the BBMRI-NL, the GOT2D, the CHARGE, and the GIANT Consortia.

144/11:45 Large-scale genome wide association of human body proportion (sitting height ratio) identifies 161 associated loci. K. Tsuo, R.M. Salem, R. Fine, M. Guo, Y. Chan, S. Vedantam, J.N. Hirschhorn.

145/12:00 Genome-wide association study with replication implicates WFS1 in cisplatin-associated hearing loss and reveals an enrichment of SNPs in Mendelian genes for deafness. H.E. Wheeler, E.R. Gamazon, R.D. Frisina, C. Perez-Cervantes, O. El Charif, S.D. Fossa, D.R. Feldman, R. Hamilton, D.J. Vaughn, C.J. Beard, C. Fung, L.H. Einhorn, C. Kollmannsberger, J. Kim, T. Mushiroda, M. Kubo, S. Ardeshir-Rouhani-Fard, N.J. Cox, M.E. Dolan, L.B. Travis, The Platinum Study Group.

146/12:15 DNMT3B SNP contributes to nicotine dependence across 16 GWAS samples of European and African ancestry and influences expression of DNMT3B in cerebellum. D.B. Hancock, G.W. Reginsson, S.M. Lutz, R. Sherva, A. Loukola, C. Minica, X. Chen, C.A. Markunas, K.A. Young, F. Gu, D.W. McNeil, B. Qaiser, M.T. Landi, P. Madden, L.A. Farrer, J. Vink, N.L. Saccone, M.C. Neale, H.R. Kranzler, M.L. Marazita, D. Boomsma, T.B. Baker, J. Gelernter, J. Kaprio, N.E. Caporaso, T.E. Thorgeirsson, J.E. Hokanson, L.J. Bierut, K. Stefansson, E.O. Johnson.

147/12:30 Genetic variants associated with lung function predict chronic obstructive pulmonary disease (COPD) susceptibility. N.R.G. Shrine, L.V. Wain, M. Soler Artigas, I.P. Hall, M.D. Tobin, BiLEVE,SpiroMeta,UKHLS,COPDGene,ECLIPSE,NETT/NAS,GenKOLS,LHS,lung eQTL study,DiscovEHR,deCODE,BioMe.

148/12:45 29 novel associations for male pattern baldness provide new insights into aetiology and genetic correlations. N. Pirastu, P.K. Joshi, T. Esko, J.F. Wilson.


Thursday, October 20

11:00 AM–1:00 PM

Concurrent Platform Session C

39. Digging Deep into Structural Variation

Room 119, West Building, Convention Centre

Moderators: Carolyn Sue Richards, Oregon Hlth & Sci Univ, Portland
  Mari Tokita, Baylor Col Med, Houston

 

149/11:00 Multiplexed super-resolution imaging of chromosome structure in situ with DNA-PAINT. B.J. Beliveau, H.M. Sasaki, F. Schüder, S.K. Saka, M. Dai, P. Yin.

150/11:15 Unbalanced constitutional chromothripsis are recombinant chromosomes of cryptic parental balanced chromothripsis. N. Kurtas, A. Provenzano, V. Orlandini, L. Xumerle, S. Bargiacchi, L. Leonardelli, U. Giussani, A. Pansa, R. Artuso, A. Vetro, E. Errichiello, M. Delledonne, S. Giglio, O. Zuffardi.

151/11:30 Quantification, sub-family classification and genomic origin of transcribed Alu in age-related macular degeneration. M.E. Kleinman, J.T. Lowery, C. Liu, B.J. Fowler, D. Lou, K. Mohan, S.C. Prajapati, Y. Hirano, A.K. Berner, J. Roney, J.L. Abney, B.D. Gelfand, M. Keddache, A.G. Hernandez, J. Liu, J. Ambati.

152/11:45 Structural variation landscape across 26 human populations reveals population specific variation patterns in complex genomic regions. P. Kwok, C. Chu, A. Hastie, E. Lam, A. Leung, L. Li, C. Lin, J. McCaffrey, Y. Mostovoy, A. Naguib, S. Pastor, A. Poon, R. Rajagopalan, M. Sakin, J. Sibert, W. Wang, E. Young, H. Cao, T. Chan, K. Yip, M. Xiao.

153/12:00 Visualizing structural variation at the single cell level to explore human genome heterogeneity. A.D. Sanders, M. Hills, D. Porubsky, V. Guryev, E. Falconer, P.M. Lansdorp.

154/12:15 Data double take: Three examples of atypical pathogenic alterations detected in exome sequencing data. J.M. Hunter, C. Mroske, K. Helbig, B. Barrows, J. Cook, W. Mu, J. Capasso, A.V. Levin, M.J. Butte, R.S. Finkel, H. Lu, K.D.F. Hagman, S. Tang, W. Alcaraz.

155/12:30 CNV and homozygosity mapping from HiSeq X whole genome sequencing data: Fit for clinical use. B.A. Lundie, M. Buckley, M.J. Cowley, M.E. Dinger, D. Fatkin, M. Field, V. Gayevskiy, C. Horvat, A.E. Minoche, G. Peters, C. Puttick, T. Roscioli, A. Zankl.

156/12:45 NGS facilitates identification of retrotransposon insertional mutations in hereditary cancer genes. Y. Qian, D. Mancini-DiNardo, H.C. Cox, T. Judkins, M. Elias, N. Singh, K. Brown, B. Coffee, K. Bowles, B. Roa.


Thursday, October 20

11:00 AM–1:00 PM

Concurrent Platform Session C

40. The Molecular Basis of Genetic Syndromes

Room 207, West Building, Convention Centre

Moderators: Jan M. Friedman, Children's & Women's Hosp, Vancouver, Canada
  Natalia Gomez-Ospina, Stanford Univ

 

157/11:00 Identification of 5 new genes and characterization of 3 ciliary modules implicated in oro-facial-digital syndromes. A. Bruel, B. Franco, Y. Duffourd, J. Thevenon, L. Jego, E. Lopez, J. Deleuze, R. Giles, C. Johnson, M. Huynen, L. Burglen, M. Morleo, G. Pierquin, B. Doray, I. Panigrahi, D. Gaillard, B. Aral, S. Phadke, L. Pasquier, S. Saunier, A. Mégarbané, O. Rosnet, M. Leroux, J. Wallingford, O. Blacque, M. Nachury, T. Attie-Bittach, J. Rivière, L. Faivre, C. Thauvin-Robinet.

158/11:15 Rare genetic variations in MEPE are associated with otosclerosis and craniofacial bone disorder with facial paresis and mixed hearing loss. H. Van Bokhoven, I. Schrauwen, L. Tomas-Roca, U. Altunoglu, M. Wesdorp, H. Valgaeren, M. Sommen, M. Rahmouni, E. van Beusekom, M.J. Huentelman, E. Offeciers, I. dHooghe, R. Vincent, A. Huber, P. Van de Heyning, F. Di Berardino, E. De Leenheer, C. Gilissen, C.W. Cremers, B. Verbist, A.P.M. de Brouwer, G.W. Padberg, R. Pennings, H. Kayserili, H. Kremer, G. Van Camp.

159/11:30 KIAA1109 variants are associated with a severe syndromic brain development disorder with arthrogryposis. N. Voisin, H. Shamseddin, F. Tran Mau Them, E. Preiksaitiene, R. Fish, L. Gueneau, L. Ambrozaityte, A. Morkuniene, N. Guex, B. Roechert, S. Pradervand, I. Xenarios, M. Neerman-Arbez, C. Shaw-Smith, V. Kucinskas, J. Chelly, F.S. Alkuraya, A. Reymond, Deciphering Developmental Disorders (DDD) Study.

160/11:45 Mutations in CDC45, encoding an essential component of the pre-initiation complex, cause Meier-Gorlin Syndrome and craniosynostosis. L.S. Bicknell, A. Fenwick, M. Kliszczak, F. Cooper, J. Murray, L. Sanchez-Pulido, S.R.F. Twigg, A. Goriely, S.J. McGowan, K. Miller, I.B. Taylor, C. Logan, M. Koopmans, C.P. Ponting, A.P. Jackson, A.O.M. Wilkie, W. Niedzwiedz, Meier-Gorlin Syndrome Clinical Consortium.

161/12:00 Phenotype and genotype in 52 patients with Rubinstein-Taybi Syndrome caused by EP300 mutations. J. Van Gils, P. Fergelot, M. Van Belzen, D. Lacombe, R.C. Hennekam, EP300 Working Group.

162/12:15 A synergistic effect of laminin and P4HA2 mutant genes deregulates ECM remodeling causing a novel developmental syndrome. F. Napolitano, S. Sampaolo, A. Tirozzi, F. Gianfrancesco, G. Di Iorio, T. Esposito.

163/12:30 Identification of a RAI1-associated disease network. M.N. Loviglio, C.R. Beck, T. Harel, W. Bi, M. Leleu, N. Guex, A. Niknejad, E.S. Chen, S. Gu, J. White, I. Crespo, J. Yan, W. Charng, C.A. Shaw, Z. Coban-Akdemir, J. Rougemont, I. Xenarios, J.R. Lupski, A. Reymond.

164/12:45 Combined next generation sequencing techniques untangle the genomic structure of complex nonrecurrent deletions in subjects with Smith-Magenis syndrome and reveal a strong bias to paternally deleted chromosomes. C. Fonseca, C.R. Beck, Z.C. Akdemir, Z. Chong, E.S. Chen, P.C. Thorton, P. Liu, B. Yuan, M. Withers, S.N. Jhangiani, A.C. English, D.M. Muzni, R.A. Gibbs, C.A. Shaw, P.J. Hastings, J.R. Lupski.


Thursday, October 20

11:00 AM–1:00 PM

Concurrent Platform Session C

41. Interpreting the Transcriptome in Health and Disease

Room 211, West Building, Convention Centre

Moderators: Alexis Battle, Johns Hopkins Univ, Baltimore
  Taru Tukiainen, Inst for Molec Med Finland, Helsinki

 

165/11:00 Comprehensive analysis of RNA-sequencing to find the source of every last read across 544 individuals from 53 tissues. S. Mangul, H. Yang, N. Zaitlen, S. Shifman, E. Eskin.

166/11:15 The incorporation of whole blood and fibroblast RNAseq with whole exome sequencing implicates LZTR1 in a novel syndrome with features of rasopathy and mitochondrial dysfunction. M. Jain, L.C. Burrage, J.A. Rosenfeld, B.C. Dawson, X. Yang, C.A. Bacino, A. Balasubramanyam, P.M. Moretti, S.K. Nicholas, J.S. Orange, E. Roeder, L.T. Emrick, B.H. Graham, J.W. Belmont, N. Hanchard, W.J. Craigen, B.H. Lee, Members of the Undiagnosed Diseases Network.

167/11:30 Improving genetic diagnosis in Mendelian disease with transcriptome sequencing. B.B. Cummings, M. Lek, T. Tukiainen, J. Marshall, F. Zhao, B. Weisburd, S. Donkervoort, R. Foley, L. Waddell, S. Sandaradura, G. O'Grady, E. Oates, J. Dowling, N.F. Clarke, S.T. Cooper, C. Bonnemann, D.G. MacArthur.

168/11:45 Implementation and clinical utility of transcriptome sequencing: Experience from neuromuscular disorders. M.R. Hegde, B.R. Nallamilli, G. Gibson, D. Arafat, H.P. Subramanian, C. da Silva.

169/12:00 The impact of genome structural variation on human gene expression. A.J. Scott, C. Chiang, J.R. Davis, E.K. Tsang, X. Li, Y. Kim, F.N. Damani, S.B. Montgomery, A. Battle, D.F. Conrad, I.M. Hall, GTEx Consortium.

170/12:15 Systematic computational identification and experimental verification of variants that activate exonic and intronic cryptic splice sites. M. Lee, P. Roos, N. Sharma, T.A. Evans, M.J. Pellicore, S. Stanley, S. Khalil, A.N. Lam, B. Vecchio-Pagan, M. Armanios, G.R. Cutting.

171/12:30 Major changes in mitochondrial RNA processing in human cancers. A. Hodgkinson, Y. Idaghdour.

172/12:45 An IL-6 targeted therapeutic modulates eQTL in whole blood. E.E. Davenport, M. Gutierrez-Arcelus, K. Slowikowski, J.S. Beebe, B. Zhang, M. Vincent, S. Raychaudhuri.


Thursday, October 20

11:00 AM–1:00 PM

Concurrent Platform Session C

42. Craniofacial and Ocular Malformations

Room 221, West Building, Convention Centre

Moderators: Joseph T. Shieh, UCSF
  Katrina M. Dipple, UCLA

 

173/11:00 Heterozygous mutations in MAFB cause Duane retraction syndrome and inner ear defects. J.G. Park, M.A. Tischfield, A.A. Nugent, L. Cheng, S.A. Di Gioia, W.-M. Chan, G. Maconachie, T.M. Bosley, C.G. Summers, D.G. Hunter, C.D. Robson, I. Gottlob, E.C. Engle.

174/11:15 Mutations in SMCHD1 are the predominant cause of arhinia and a form of muscular dystrophy. H. Brand, N. Shaw, Z.A. Kupchinsky, H. Bengani, T.I. Jones, L. Plummer, S. Erdin, K.A. Williamson, J. Rainger, K.E. Samocha, R.L. Collins, D. Lucente, C. Seabra, Y. An, A. Lek, S. Pereira, T. Kammin, M. Nassan, J.K. Rainger, E.C. Liao, C.C. Morton, N. Katsanis, J.F. Gusella, J.A. Marsh, D.G. Macarthur, W. Crowley, P.L. Jones, E.E. Davis, D.R. FitzPatrick, M.E. Talkowski.

175/11:30 The phenotypic spectrum of arhinia associated with mutations in SMCHD1: From isolated arhinia to Bosma arhinia microphthalmia syndrome. N.D. Shaw, H. Brand, Z.A. Kupchinsky, J.M. Graham, J.R. Willer, A. Verloes, A. Rauch, K. Steindl, L.A. Schimmenti, B. Brasseur, C. Cesaretti, J.E. Garcia-Ortiz, T.P. Buitrago, O.P. Silva, B. Loeys, A. Kaindl, C.H. Cho, J. Law, N. Ferraro, D. Sato, C. Jacobsen, J. Tryggestad, J.D. Hoffman, V. van Heyningen, S.B. Seminara, W.J. Crowley, A. Lin, D.R. Fitzpatrick, M.E. Talkowski, E.E. Davis.

176/11:45 De novo gain-of-function mutations in the epigenetic regulator SMCHD1 cause Bosma arhinia microphthalmia syndrome. C. Gordon, S. Xue, G. Yigit, H. Filali, K. Chen, N. Rosin, K. Yoshiura, M. Oufadem, T. Beck, A. Sefiani, H. Kayserili, J. Murphy, C. Chatdokmaiprai, A. Hillmer, D. Wattanasirichaigoon, S. Lyonnet, A. Javed, M. Blewitt, J. Amiel, B. Wollnik, B. Reversade.

177/12:00 Identification of non-coding variants at 1p22 that are pathogenic for nonsyndromic orofacial clefting. R. Cornell, H. Liu, E. Leslie, M. Dunnwald, M. Marazita, A. Lidral.

178/12:15 Biallelic sequence variants in INTS1 in patients with developmental delays, cataracts and craniofacial anomalies. A. Slavotinek, D. Lessel, A.M. Innes, M. Krall, D. Schneidman, R. Lamont, D. Baillat, E. Wagner, G. Mancini.

179/12:30 Mutations in MYT1, encoding the myelin transcription factor, are a rare cause of OAVS, within the RA signaling pathway. C. Rooryck, M. Berenguer, E. Lopez, A. Tingaud-Sequeira, S. Marlin, A. Toutain, F. Denoyelle, A. Picard, S. Charron, G. Mathieu, H. de Belvalet, B. Arveiler, P..J. Babin, S. Bragagnolo, A.B. Perez, M.I. Melaragno, M. Colovati, D. Lacombe.

180/12:45 A genotype-first approach identifies gain-of-function mutations of TFE3 in a novel syndrome with intellectual disability, seizures, facial dysmorphism, short stature and obesity. D. Lehalle, M. Avila, L. Duplomb-Jego, Y. Duffourd, P. Kuentz, J. St-Onge, T. Jouan, J. Thevenon, C. Thauvin-Robinet, P. Vabres, L. Faivre, J. Betschinger, J.B. Rivière.


Thursday, October 20

11:00 AM–1:00 PM

Concurrent Platform Session C

43. Toward Therapeutic Discovery in Neurological and Neuromuscular Disorders

Room 302, West Building, Convention Centre

Moderators: Susan A. Slaugenhaupt, Mass Gen Hosp, Boston
  M. Chiara Manzini, George Washington Univ, Washington, DC

 

181/11:00 Histone methylation-demethylation defects in forms of intellectual disability and refractory epilepsy. L. Poeta, A. Padula, A. Ranieri, B. Attianese, M. Valentino, C. Shoubridge, K. Helin, J. Gecz, E. Di Schiavi, S. Filosa, C. Schwartz, L. Altucci, H. van Bokhoven, M.G. Miano.

182/11:15 Shared therapeutic approaches are justified by common morphological and transcriptome changes in Rett spectrum disorders. E. Landucci, L. Bianciardi, S. Daga, A.M. Pinto, E. Frullanti, M. Brindisi, S. Butini, V. Imperatore, F. Ariani, S. Brogi, G. Campiani, A. Renieri, I. Meloni.

183/11:30 Diet rescues lethality in a model of NGLY1 deficiency, a rare deglycosylation disorder. C.Y. Chow, K.G. Owings.

184/11:45 A platform for genotype-phenotype correlation in iPSC-derived oligodendrocytes identifies patient-specific defects in children with Pelizaeus-Merzbacher Disease. Z. Nevin, R. Karl, D. Factor, P. Douvaras, J. Laukka, V. Fossati, G. Hobson, P. Tesar.

185/12:00 Exon inclusion for the treatment of splice site mutation in merosin-deficient congenital muscular dystrophy. D.U. Kemaladewi, E. Hyatt, M. Ding, X. Zhu, E.A. Ivakine, R.D. Cohn.

186/12:15 Antisense oligonucleotide therapy for the fatal epilepsy Lafora disease. T.R. Grossman, S. Ahonen, J. Turnbull, L.A. Hettrick, H. Kordasiewicz, M. Katz, M.L. McCaleb, P. Wang, X. Zhao, B.A. Minassian.

187/12:30 Minimal cerebellar genetic modification associated with ASO reduction of ATXN2 expression and delayed SCA2 mouse motor and neurophysiological phenotypes. S.M. Pulst, M. Schneider, P. Meera, K. Figueroa, F. Rigo, F. Bennett, T. Otis, D.R. Scoles.

188/12:45 Treatment of Niemann-Pick disease, type C1 subjects with intrathecal VTS-270 (2-hydroxypropyl-β-cyclodextrin). F.D. Porter, N.Y. Farhat, E.A. Ottinger, J.C. McKew, L. Weissfeld, B. Machielse, E.M. Berry-Kravis, C.H. Vite, S.U. Walkley, D.S. Ory, TRND Team.


Thursday, October 20

4:30 PM–6:00 PM

44. Presidential Symposium: Mentoring in a Challenging Environment

Ballroom ABC, West Building, Convention Centre

Moderators: Hal Dietz, ASHG 2016 President
  Anthony Antonellis, ASHG 2016 Program Chair

 

The American Society of Human Genetics is a diverse community that includes basic scientists, physician scientists, clinicians, and genetic counselors, at many stages of career development. Meeting the mentoring needs of both senior and junior Society members is becoming increasingly complex in the face of a rapidly evolving financial and scientific environment. While challenges are evident, they can be more than offset by an expanding range of interests, talents, opportunity and influence by students and practitioners of human genetics. Such remarkable times will require extraordinary mentoring skills, flexibility and partnerships. Through the use of personal experiences and practical insight, a panel of leaders representing basic research, multidisciplinary initiatives focusing on clinical priorities and industry will address issues facing the modern mentor, with the overarching goal of preparing the next generation of human geneticists tasked with realizing the full potential of precision medicine.


Huda Y. Zoghbi

Lon Cardon

Kym M. Boycott

 

4:30 PM   Introduction. H. Dietz. ASHG 2016 President.

4:35 PM   A career in balance. H. Y. Zoghbi. Baylor Col Med, Houston.

5:00 PM   Change, continuity and choice: Careers in genetics in academia versus industry. L. R. Cardon. GlaxoSmithKline, King of Prussia.

5:25 PM   Supporting a Canadian rare disease collaborative network to enable success and maximize the opportunity of a transformative technology. K. M. Boycott. Univ Ottawa, Canada.

5:50 PM   Panel discussion/Q&A. H. Dietz. ASHG 2016 President.


Friday, October 21

7:45 AM–7:50 AM

45. C.W. Cotterman Awards Announcements

Room 109, West Building, Convention Centre

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 with a monetary award and certificate.

 


Friday, October 21

7:50 AM–7:55 AM

46. Announcement of the Finalists for the Charles J. Epstein Trainee Awards for Excellence in Human Genetics Research

Room 109, West Building, Convention Centre

ASHG provides merit-based research awards for trainees (predoctoral and postdoctoral, including genetic counseling trainees) on the basis of submitted, competitive abstracts and on-site presentations at the 2016 Annual Meeting. This year’s 18 finalists will be acknowledged during ASHG NEXT and the Business Meeting on Friday morning.

 


Friday, October 21

7:55 AM–8:45 AM

47. ASHG Business Meeting/ASHG NEXT

Room 109, West Building, Convention Centre

The ASHG Board of Directors and committee chairs will present reports highlighting current Society business, including finances. This is an opportunity for members to learn about recent ASHG activities and to provide suggestions to the Society’s leadership. There will be a moment of silence for those members and colleagues we have lost since the 2015 business meeting. We encourage discussion from the floor.

 


Friday, October 21

9:00 AM–10:30 AM

Concurrent Platform Session D

48. Mapping Cancer Susceptibility Alleles

Ballroom A, West Building, Convention Centre

Moderators: Sanjay S. Shete, MD Anderson, Houston
  Meredith Yeager, DCEG, Natl Cancer Inst, Bethesda

 

189/9:00 Identification of novel susceptibility loci and genes for breast cancer risk: A large transcriptome-wide association study in 119,000 cases and 101,000 controls of European descent. L. Wu, J. Long, X. Guo, P. Kraft, R. Milne, K. Michailidou, J. Beesley, A. Dunning, P. Pharoah, J. Simard, G. Chenevix-Trench, D. Easton, W. Zheng, on behalf of the Breast Cancer Association Consortium.

190/9:15 A GWAS including 30,882 estrogen receptor negative or BRCA1 mutation-related breast cancer cases and 110,088 controls identifies 10 new susceptibility variants. R.L. Milne, K.B. Kuchenbaecker, K. Michailidou, J. Beesley, S. Kar, S. Lindström, S. Hui, A. Lemaçon, P. Soucy, A. Droit, G.D. Bader, P.D.P. Pharoah, F.J. Couch, D.F. Easton, P. Kraft, G. Chenevix-Trench, M. Garcia-Closas, M.K. Schmidt, A.C. Antoniou, J. Simard, Breast Cancer Association Consortium & Consortium of Investigators of Modifiers of BRCA1/2.

191/9:30 Prostate cancer meta-analysis from more than 143,000 men identifies 57 novel prostate cancer susceptibility loci. F. Schumacher, A. Amin Al Olama, S. I. Berndt, S. Benlloch, M. Ahmed, X. Sheng, D. F. Easton, F. Wiklund, P. Kraft, S. J. Chanock, B. E. Henderson, D. V. Conti, Z. Kote-Jarai, C. A. Haiman, R. A. Eeles, On behalf of ELLIPSE, PRACTICAL, CaPS, BPC3, PEGASUS.

192/9:45 Meta-analysis of genome-wide association data for 51,978 women identifies four new susceptibility loci for endometrial cancer. T.A. O'Mara, D.D. Buchanan, T. Dörk, P.A. Fasching, E.L. Goode, P. Hall, D. Lambrechts, R.J. Scott, E. Tham, J. Trovik, D.F. Easton, I. Tomlinson, A.B. Spurdle, D.J. Thompson, ECAC, BCAC.

193/10:00 Assessing pleiotropy among common cancers in the UK Biobank. J.D. Hoffman, R.E. Graff, M.N. Passarelli, J.S. Witte.

194/10:15 Risks of breast, ovarian and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers from a prospective cohort of 10,015 mutation carriers. A.C. Antoniou, K. Kuchenbaecker, D. Barnes, N. Andrieu, C. Nogues, M.J. Blom, C. Engel, D. Goldgar, K. Kast, F. van Leeuwen, R.L. Milne, T. Mooij, K.A. Phillips, M.B. Terry, J.L. Hopper, M. Rookus, D.F. Easton, International BRCA1/2 Carrier Cohort Study, Breast Cancer Family Registry, kConFab.


Friday, October 21

9:00 AM–10:30 AM

Concurrent Platform Session D

49. The Genetics of Type 2 Diabetes and Glycemic Traits

Ballroom B, West Building, Convention Centre

Moderators: Struan F.A. Grant, Children's Hosp Philadelphia
  Kyle J. Gaulton, Univ Oxford, UK

 

195/9:00 When is a coding variant association not a coding variant signal? A. Mahajan, on behalf of the ExT2D Exome Chip Consortium, for PROMIS, CHARGE, T2D-GENES/GoT2D, and DIAGRAM.

196/9:15 An integrative platform to uncover the mechanisms of the association of TCF7L2 and Type 2 Diabetes. M. Nobgrea, D. R. Sobreira, S. Strobel, N. Sinnott-Armstrong, M. Claussnitzer.

197/9:30 Large-scale association study of predicted gene expression implicates novel T2D genes. J.M. Torres, A. Barbeira, A. Morris, K. Shah, H. Wheeler, G.I. Bell, D. Nicolae, N.J. Cox, H. Im.

198/9:45 Multiple phenotypes applied to whole-exome sequence data to identify functional variants and implicate genes in metabolic disease. M.S. Udler, A.K. Manning, A. Mahajan, J.C. Florez, J. Flannick, on behalf of T2D-GENES, LUCAMP, SIGMA, and ESP.

199/10:00 Identification of a functional p.Thr280Met variant in RBPJL which associates with T2D in Pima Indians and potentially affects the established T2D locus CTRB1/2. A. Nair, J. Sutherland, P. Kumar, P. Piaggi, Y. Muller, M. Traurig, S. Kobes, R. Hanson, C. Bogardus, L. Baier.

200/10:15 Genetic variation modulates multiple dimensions of molecular phenotypes in T2D patients. A. Viñuela, J. Fernandez, A. Kurbasic, H. Krogh Pedersen, M.G. Hong, A.A. Brown, M. Abdalla, C. Howald, C. Groves, A. Mahajan, P.K. Davidsen, R. Gupta, C. Brorsson, K. Banasik, C. Prehn, A. Artati, M. Haid, M. Roßbauer, H. Grallert, J. Adamski, J.M. Schwenk, E. Pearson, S. Brunak, P.W. Franks, M.I. McCarthy, E. T. Dermitzakis, for the IMI DIRECT consortium.


Friday, October 21

9:00 AM–10:30 AM

Concurrent Platform Session D

50. Chromatin Architecture, Fine Mapping, and Disease

Ballroom C, West Building, Convention Centre

Moderators: Peng Jin, Emory Univ, Atlanta
  Bing Ren, UCSD, La Jolla

 

201/9:00 Rewiring of enhancer-gene interactions drives PLAU overexpression in the pathogenesis of Quebec Platelet Disorder. M.D. Wilson, M. Liang, A. Soomro, J.S. Waye, A.D. Paterson, G.E. Rivard, C.P.M. Hayward.

202/9:15 Capture Hi-C identifies compelling candidate causal genes and enhancers for multiple sclerosis in the 6q23 region. P. Martin, A. McGovern, K. Duffus, A. Yarwood, S. Schoenfelder, A. Barton, P. Fraser, J. Worthington, S. Eyre, G. Orozco.

203/9:30 Fine-mapping of obesogenic cis-regulatory eQTL variants using high resolution capture Hi-C. D.Z. Pan, K. Garske, M. Alvarez, C.K. Raulerson, K.L. Mohlke, M. Laakso, P. Pajukanta.

204/9:45 Regulatory activity of non-coding variants in multiple tissue and cell types at the VEGFA metabolic trait GWAS locus. J.P. Davis, S. Vadlamudi, C. Trevino, T.S. Roman, Y. Wu, M. Engle, J. Kuusisto, M. Civelek, A..J. Lusis, M. Laakso, K.L. Mohlke.

205/10:00 Epigenetic fine-mapping of cardiovascular disease loci in the liver. C. Brown, M. Caliskan, Y. Park, M. Trizzino, M. Beltrame, C. Radens, K. Wiles, S. Elwin, K. Olthoff, A. Shaked, D. Rader, B. Engelhardt.

206/10:15 Genetic determinants of chromatin accessibility predict variation in T cell activation and autoimmunity across human individuals. R. Gate, C. Cheng, D. Lituiev, M. Subramaniam, A. Siba, E.L. Aiden, I. Machol, M. Shamim, M. Beer, M. Tabaka, K. Hougen, C.J. Ye, A. Regev.


Friday, October 21

9:00 AM–10:30 AM

Concurrent Platform Session D

51. Inferring the Action of Natural Selection

Room 109, West Building, Convention Centre

Moderators: Melissa Wilson Sayres, Arizona State Univ, Tempe
  Srilakshmi Raj, Cornell Univ, Ithaca

 

207/9:00 Inference of dominance and selection coefficients from large-scale population data identifies recessive genes. D.J. Balick, D.M. Jordan, S. Sunyaev, R. Do.

208/9:15 Global shared natural selection for increased stature in recent human history. Y. Field, E.A. Boyle, N. Telis, Z. Gao, A. Bhaskar, J.K. Pritchard.

209/9:30 Population structure of UK Biobank and ancient Eurasians reveals adaptation at genes influencing blood pressure. K. Galinsky, P. Loh, S. Mallick, N.J. Patterson, A.L. Price.

210/9:45 Quantifying selection and demographic effects on quantitative genetic variation: An application to anthropomorphic traits. Y.B. Simons, G. Sella.

211/10:00 Estimating the selective effect of heterozygous protein truncating variants. C. Cassa, D. Weghorn, D. Balick, D. Jordan, D. Nusinow, K. Samocha, A. O'Donnell Luria, D. MacArthur, M. Daly, D. Beier, S. Sunyaev.

212/10:15 Negative selection in modern human populations involves synergistic epistasis. M. Sohail, O. Vakhrusheva, J.H. Sul, P. de Bakker, A. Kondrashov, S. Sunyaev.


Friday, October 21

9:00 AM–10:30 AM

Concurrent Platform Session D

52. The Many Twists of Single-gene Cardiovascular Disorders

Room 119, West Building, Convention Centre

Moderators: Daryl A. Scott, Baylor Col of Med, Houston
  Beth A. Kozel, Natl Heart Lung & Blood Inst, NIH, Bethesda

 

213/9:00 A molecular mechanism underlying the development of ventricular septal defects in individuals with 1p36 deletions. B. Kim, H.P. Zaveri, V.K. Jordan, A. Hernández-García, B. Fregeau, E.H. Sherr, D.A. Scott.

214/9:15 Phenotyping pipeline for bicuspid aortic valve with/without ascending aortic aneurysm highlights pathological relevance of ROBO4 to cardiovascular function. C.E. Woods, R. A. Gould, C.R. Moats, R.J. Rose, H.C. Dietz, A.S. McCallion, MIBAVA Leducq Consortium.

215/9:30 A rare pediatric Mendelian presentation of abdominal aortic aneurysm informs the predisposition for a common but complex cardiovascular disease. R.A. Gould, D.T. Au, M. Migliorini, G. MacCarrick, N.L. Sobreira, J.C. Lopez-Gutierrez, S.C. Muratoglu, D.K. Strickland, H.C. Dietz.

216/9:45 Loss-of-function mutations in the X-linked gene BGN cause a severe syndromic form of thoracic aortic aneurysms and dissections. B. Loeys, J.A.N. Meester, G. Vandeweyer, I. Pintelon, K. Waitzman, L. Young, L.W. Markham, J. Vogt, J. Richer, L. Beauchesne, S. Unger, A. Superti-Furga, E. Reyniers, A. Verstraeten, L. Van Laer.

217/10:00 Mutations in a novel cardiac specific exon of FLNA cause X-linked congenital heart disease. C. Preuss, S. Yang, F. Wünnemann, P. Chetaille, M. Samuels, H. Björck, P. Eriksson, S. Mohamed, G. Andelfinger.

218/10:15 The role of loss-of-function mutations on death and development of rejection after heart transplantation. J. van Setten, B.S. Cole, Y.R. Li, N. de Jonge, M.V. Holmes, C.C. Baan, O.C. Manintveld, A.M.A. Peeters, F. Dominguez, K.K. Khush, P. Garcia-Pavia, J.W. Rossano, R.A. de Weger, J.H. Moore, B. Keating, F.W. Asselbergs.


Friday, October 21

9:00 AM–10:30 AM

Concurrent Platform Session D

53. Friends or Foes? Interactions of Hosts and Pathogens

Room 207, West Building, Convention Centre

Moderators: Pui-Yan Kwok, UCSF
  Hong Li, Emory Univ, Atlanta

 

219/9:00 A complex structural variant at the glycophorin gene cluster is associated with strong protection against severe malaria in East Africa. G. Band, E. Leffler, K.A. Rockett, Q.S. Le, C.C.A. Spencer, D.P. Kwiatkowski, MalariaGEN.

220/9:15 Comparative genomics of innate immunity in human and non-human primates. J.C. Teixeira, L. Quintana-Murci.

221/9:30 Colorectal cancer mutational and transcriptome profiles shape the microbiome of the tumor microenvironment. R. Blekhman, M. Burns, E. Montassier, D. Knights.

222/9:45 GWAS of cellular and clinical traits reveals VAC14 regulates Salmonella invasion and typhoid fever susceptibility. D. Ko, M. Alvarez, S. Dunstan, P. Luo, L. Glover, S. Oehlers, E. Walton, L. Wang, D. Tobin.

223/10:00 Genetic control of RNA splicing contributes to inter-individual variation in transcriptional responses to bacterial infection. A.A. Pai, O. Tastet, J.C. Grenier, Y. Nedelec, V. Yotova, C.B. Burge, L.B. Barreiro.

224/10:15 An atlas of genomic variants connecting cellular host-pathogen traits to human infectious disease. L. Wang, D. Ko.


Friday, October 21

9:00 AM–10:30 AM

Concurrent Platform Session D

54. Novel Methods for Analyzing GWAS and Sequencing Data

Room 211, West Building, Convention Centre

Moderators: Dawei Li, Univ Vermont, Burlington
  Chris Cotsapas, Yale Sch Med, New Haven

 

225/9:00 Novel polygenic risk prediction using individual-level data and summary statistics for secondary traits. W. Chung, J. Chen, C. Chen, S. Lindstrom, P. Kraft, L. Liang.

226/9:15 Why real biological interactions are usually not detectable in genetic association analyses. N. Kodaman, S.M. Williams.

227/9:30 Testing rare-variant association without calling genotypes allows for systematic differences in sequencing between cases and controls. Y.J. Hu, P. Liao, H.R. Johnston, A.S. Allen, G.A. Satten.

228/9:45 Novel methodology to detect SNP association and heterogeneity in allelic effects between diverse populations via trans-ethnic meta-regression. A.P. Morris, R. Mägi, M. Horikoshi, T2D-GENES Consortium.

229/10:00 Efficiency and accuracy of fine-mapping using GWAS summary data. C. Benner, A. Havulinna, V. Salomaa, S. Ripatti, M. Pirinen.

230/10:15 Leveraging the diploid genome to increase power in *QTL studies. M. Subramaniam, N.A. Zaitlen, C.J. Ye.


Friday, October 21

9:00 AM–10:30 AM

Concurrent Platform Session D

55. From Gene Discovery to Mechanism in Neurological Disease

Room 221, West Building, Convention Centre

Moderators: Christelle Golzio, Inst Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), Illkirch, France
  Carol Saunders, Children's Mercy Hosp, Kansas City

 

231/9:00 De novo loss-of-function mutations in SON disrupt RNA-splicing of genes essential for brain development and metabolism, causing an intellectual disability syndrome. L.E.L.M. Vissers, J-H. Kim, D.N. Shinde, M.R.F. Reijnders, N.S. Hauser, R.L. Belmonte, G.R. Wilson, D.G.M. Bosch, P.A. Bubulya, V. Shashi, S. Petrovski, J.K. Stone, E.Y. Park, J.A. Veltman, M. Sinnema, C.T.R.M. Stumpel, J.M. Draaisma, J. Nicolai, H.G. Yntema, K.L. Lindstrom, B.B.A. de Vries, T. Jewett, S.L. Santoro, J. Vogt, K.K. Bachman, A.H. Seeley, A. Krokosky, C. Turner, L. Rohena, S. Tang, D. El-Khechen, M.T. Cho, K. McWalter, G. Douglas, B. Baskin, A. Begtrup, T. Funari, K. Schoch, A.P.A. Stegmann, S.J.C. Stevens, D-E. Zhang, D. Traver, X. Yao, D.G. MacArthur, H.G. Brunner, G.M. Mancini, R.M. Myers, T.M. Strom, D. Wieczorek, M. Hempel, F. Kortuem, F. Laccone, L.B. Owen, S-T. Lim, D.L. Stachura, E-Y.E. Ahn, University of Washington Center for Mendelian Genomics; The Deciphering Developmental Disorde.

232/9:15 Using predictive models to expand the locus heterogeneity of tRNA synthetase-related inherited disease. R. Meyer, S. Oprescu, A. Beg, A. Antonellis.

233/9:30 Establishing a phenotypic model of MBD5-Associated Neurodevelopmental Disorder (MAND) by utilization of patient-derived neural stem cells and RNA-seq. S.V. Mullegama, J.T. Alaimo, S.R. Williams, L. Chen, J.W. Innis, F..J. Probst, C. Haldeman-Englert, T. Ezashi, S.H. Elsea.

234/9:45 The contribution of de novo mutations in enhancers and ultra-conserved non-coding elements to severe developmental disorders in 8,000 children. P.J. Short, S. Gerety, J. McRae, E. Coomber, J.C. Barrett, M.E. Hurles, on behalf of the Deciphering Developmental Disorders study.

235/10:00 Unveiling microcephaly mechanisms associated with DNA repair disorders using induced pluripotent stem cells and cerebral organoids. F. Pirozzi, J. Ngo, T.H. Kim, K. Plona, Y. Chen, E. Gilmore, A. Wynshaw-Boris.

236/10:15 Early biomarkers and mechanisms of retinal degeneration identified in a mouse model of human mitochondrial dysfunction: The harlequin apoptosis-inducing factor hypomorph. K.A. Hill, T.C. MacPherson, A.M. Laliberte, A. Prtenjaca, E.A. Dolinar, J. Mayers, T. Privorozky, Y. Balboul, A. Bentley-De Sousa, A. Li, M. Edwards, I. Kisilevsky, S. Rajkarnikar, J.R.J. Thompson, B. Rubin, M.A. Bernards, C.M.L. Hutnik.


Friday, October 21

9:00 AM–10:30 AM

Concurrent Platform Session D

56. Genomes in the Clinic and Research: Patient-family-participant Perspectives

Room 302, West Building, Convention Centre

Moderators: Julianne M. O'Daniel, Univ North Carolina, Chapel Hill
  Stephanie M. Fullerton, Univ Washington, Seattle

 

237/9:00 Issues important to families considering exome sequencing. S. Adam, P.H. Birch, R.R. Coe, N. Bansback, M.B. Connolly, E. Toyota, M.J. Farrer, M.K. Demos, J.M. Friedman.

238/9:15 Parental expectations and attitudes towards receiving genomic results in healthy children. J.L. Williams, F.D. Davis, A.L. Fan, L. Bailey, K. Fultz, M.S. Williams, M.F. Murray, A.K. Rahm.

239/9:30 Healthcare outcomes and costs after genome sequencing among healthy adults: Results of a randomized controlled trial. J.L. Vassy, K.D. Christensen, E.F. Schonman, D. Dukhovny, P.M. Diamond, C.L. Blout, J. Oliver Robinson, J.B. Krier, M.F. Murray, A.L. McGuire, R.C. Green, for the MedSeq Project.

240/9:45 Beyond diagnostic yield – An economic perspective on the impact of whole exome sequencing (WES) in medical decision-making. T. Vrijenhoek, E.M. Middelburg, G.R. Monroe, K.L.I. van Gassen, A.M. Hövels, N.V. Knoers, G.W. Frederix.

241/10:00 Assessing the acceptability of genomic services for community health centers that provide care for under-served populations. K.A.B. Goddard, J.V. Davis, L. Jacob, C. McMullen, J.L. Holup, P. Foley, E.K. Cottrell, J.L. Schneider, B. Wilfond.

242/10:15 Enhancing diversity in genomic medicine research: Factors influencing enrollment and retention. J. Berg, E. Moore, E. Corty, M. Roche, Z. Girnary, B. Ania, J. O'Daniel, F-C. Lin, C. Rini, J. Evans, G. Henderson.


Friday, October 21

11:00 AM–1:00 PM

Concurrent Invited Session II

57. ASHG/ESHG Building Bridges Session: Navigating the Myriad Career Paths in Human Genetics

Room 119, West Building, Convention Centre

Moderators: Anthony Antonellis, ASHG 2016 Program Chair
  Joris Veltman, ESHG 2016 Program Chair

 

Modern day human genetics is a field of constant change, which has been driven by major breakthroughs in basic science and clinical research, and by tremendous advances in the technologies that serve these disciplines. Over the last decade, human genetics has expanded from the confines of traditional academic and biomedical environments into many additional sectors. As a result, our trainees require exposure to a vast array of experiences and skill sets to become effective members of the genetics community and to take advantage of the different career paths that are currently available. These issues complicate the design of training plans with respect to determining the specific skills that should be included and when and how they should be taught. Through the use of inspiring stories, this session will introduce current issues in training and career development and will elicit a discussion on how our field should move forward to prepare future generations of human geneticists. This "Building Bridges" session is the fifth in a continuing series conducted in conjunction with the European Society of Human Genetics.


Alison Gammie

Elizabeth Quinlan-Jones

Ethan Perlstein

Paul de Bakker

 

11:00 AM   Introduction. A. Antonellis. ASHG 2016 Program Chair.

11:05 AM   Preparing trainees for multiple career options in the biomedical research workforce. A. Gammie. NIGMS, NIH, Bethesda.

11:30 AM   Combining fetal and genomic medicine in clinical practice: The role of the specialist midwife. E. Quinlan-Jones. Birmingham Women’s Hosp. NHS Fndn Trust, Birmingham, UK.

11:55 AM   From postdoc to founder of a rare disease startup. E. Perlstein. Perlstein Lab PBC, San Francisco.

12:10 PM   Bridging continents and careers to bring human biology to medicines. P. de Bakker. Vertex Pharmaceuticals, Boston.

12:35 PM   Panel discussion. L. Brody, S. Faherty. NHGRI, NIH, Bethesda.


Friday, October 21

11:00 AM–1:00 PM

Concurrent Invited Session II

58. Applying Multi-omics to Complications of Solid-organ Transplantation

Room 221, West Building, Convention Centre

Moderators: Brendan J. Keating, Univ Pennsylvania, Philadelphia
  Pamala Jacobson, Univ Minnesota, Minneapolis

 

To date over 650,000 solid-organ transplants have been conducted in the United States with most recipients subjected to potent immunosuppression therapies (ISTs) for the remainder of their lives. While there have been considerable advances in graft clinical management and ISTs over the last two decades, the rates of acute rejection are still significant, and co-morbidities from ISTs such as new onset of diabetes after transplant (NODAT), nephrotoxicity and liver damage remain major clinical issues. With the increase in malaise such as chronic kidney disease and congestive heart failure, waiting lists for donor organs continue to expand above and beyond the pool of available organ donations. While HLA compatibility is recognized as being very important for graft survival, an increasing body of evidence shows that non-HLA allogenicity accounts for over twice that of HLA in kidney transplantations. Large inter-individual difference in the metabolism of tacrolimus, the most commonly prescribed IST, are also shown to have significant genetic underpinnings, with a single SNP in CYP3A5 accounting for 45% of tacrolimus blood levels, resulting in the recent implementation of genotype-guided clinical dosing. Despite the high mortality, comorbidities and monetary costs associated with transplantation, it has only recently become an active area for collaboration in genomics. Well-powered genome-wide association studies (GWAS) are now available from The International Genetics & Translational Research in Transplantation Network (iGeneTRAiN) which is conducting meta-analyses for various transplant-related phenotypes across >34,500 recipients/donors from 28 transplant studies across Europe and North America. A number of highly specific and sensitive non-invasive miRNA and mRNA biomarker panels for detection of sub-clinical rejection are also nearing clinical implementation.

 

11:00 AM   The International Genetics & Translational Research in Transplantation Network (iGeneTRAiN). P. Jacobson. Univ Minnesota, Minneapolis.

11:30 AM   The impact of HLA and non-HLA genomics in transplant rejection. F. W. Asselbergs. Univ Med Ctr, Utrecht, Netherlands.

12:00 PM   Detecting sub-clinical transplant rejection using non-invasive miRNA and mRNA signatures. B. J. Keating. Univ Pennsylvania, Philadelphia.

12:30 PM   Multi-omic approaches in transplantation. M. Snyder. Stanford Univ.


Friday, October 21

11:00 AM–1:00 PM

Concurrent Invited Session II

59. Beyond DNA Fingerprinting: Novel Developments in Forensics

Room 211, West Building, Convention Centre

Moderators: Suzanne M. Leal, Baylor Col Med, Houston
  Michael Nothnagel, Univ Cologne, Germany

 

Genetic fingerprinting has been a hallmark achievement in forensics, helping to identify victims and perpetrators and to resolve relationships between individuals among other applications, and has dominated the public image of forensics in the past decades. However, usage of genetic information in forensic applications has substantially widened in recent years and has enabled applications that go far beyond fingerprinting. In fact, forensics and human genetics share synergy where developments in one area find application in another and vice versa, e.g., scientific method development that assists both fields. A major focus of ongoing forensic research is the prediction of externally visible characteristics (EVC), which include age, appearance (e.g., hair, skin and eye color) and ancestry. One of the challenges that forensics faces is analysis of ultra-low-level, degraded and contaminated DNA samples. Furthermore, sequence based microbiome analysis opens new possibilities for estimating the time of death. These developments are largely unknown to researchers working in the field of human genetics, but deserve to be recognized. To foster interaction between the human genetics and forensics communities, this session covers the following four topics: 1) Analysis of ultra-low-level, degraded and contaminated DNA samples; 2) methylation-based predication of age; 3) genotype prediction of skin, hair and eye color and 4) post-mortem predictions using microbial community changes.

 

11:00 AM   Against all odds: Forensic evidence from ultra-low-level, degraded and contaminated samples. P. Gill. Norwegian Inst Publ Hlth, Oslo, Norway.

11:30 AM   Epigenetic clock and estimates of DNA methylation age. S. Horvath. UCLA.

12:00 PM   DNA prediction of eye, hair, and skin color for investigative purposes. M. Kayser. Erasmus Univ Med Ctr, Rotterdam, Netherlands.

12:30 PM   Microbial community change accurately predicts the postmortem interval. J. Metcalf. Univ Colorado, Boulder.


Friday, October 21

11:00 AM–1:00 PM

Concurrent Invited Session II

60. Evaluating Effectiveness of Traditional and Novel Methods of Genetic/Genomic Counselling

Room 109, West Building, Convention Centre

Moderators: Patricia H. Birch, Univ British Columbia, Vancouver, Canada
  Jehannine Austin, Univ British Columbia, Vancouver, Canada

 

This genetic counselling (GC) session presents novel technologies, contrasts them with face-to-face GC, and discusses a framework and tools to evaluate effectiveness of GC delivered through any method. Emerging genetic/genomic applications have the potential to overburden the health care system’s current GC capacity. In response to this challenge, novel GC delivery mechanisms such as interactive e-counselling are being developed to enhance or replace some functions of conventional face-to-face GC. It has been argued that leading-edge technologies can mitigate geographical barriers, linguistic challenges, low literacy and numeracy, cultural and socio-economic differences and learning disabilities, and that use of e-decision-support tools can enhance quality of decisions. We will provide examples of several such tools designed to support informed decision-making in a variety of circumstances. However, for maximal evidence-based impact, a conceptual framework is needed to contextualize these innovations, and careful, theory-based, controlled studies, with quantifiable goals, are needed to determine and compare the impact of these technologies to conventional GC. Though GC research has largely focused on measuring specific facets of GC such as decisional quality, satisfaction or knowledge, no single tool measures all potential benefits of GC (Payne et al 2008). However, one tool has been rigorously developed to measure “empowerment,” a construct believed to be of global importance in GC. We present a conceptual framework for evidence-based GC research. We will discuss the tools that are currently available to evaluate GC, examine existing data, provide several examples of outcomes research in the clinical setting, and identify knowledge gaps.

 

11:00 AM   Educational technologies and genetic counselling in population genetic screening. S. A. Metcalfe. Royal Children's Hosp, Parkville, Australia.

11:30 AM   Using technology to meet patients' information needs in genetic counseling. K. A. Kaphingst. Huntsman Cancer Inst, Salt Lake City.

12:00 PM   A conceptual framework to categorize genetics service delivery outcomes and implications for research. H. Zierhut. Univ Minnesota, Minneapolis.

12:30 PM   Using data collected by patient-reported outcome measures for continuous quality improvement in medical genetics. M. McAllister. Cardiff Univ Sch Med, UK.


Friday, October 21

11:00 AM–1:00 PM

Concurrent Invited Session II

61. Clinical Spotlight: Gene Discovery, Genetic Counseling, and Clinical Care of Patients with Inherited Retinal Diseases

Room 302, West Building, Convention Centre

Moderators: Daniel C. Koboldt, Washington Univ, St. Louis
  Anand Swaroop, Natl Eye Inst, NIH, Bethesda

 

Inherited retinal diseases (IRDs) comprise a heterogeneous group of retinal degenerations, including retinitis pigmentosa, choroideremia, Leber congenital amaurosis (LCA), and other dystrophies. These disorders exhibit remarkable genetic heterogeneity as well; mutations in numerous genes can cause retinal diseases that exhibit dominant, recessive, or X-linked patterns of inheritance. The catalogue of pathogenic mutations and disease-associated genes for IRDs has grown considerably over the past two decades, fueled by both technological advances (i.e., next-generation sequencing) and well-established genetic testing programs. However, our knowledge of the molecular mechanisms linking pathogenic mutations to distinct clinical phenotypes has advanced relatively slowly. There remains a pressing need for innovative approaches to functionally validate genetic discoveries, and to incorporate that information into patient counseling and clinical care. This session brings together a diverse panel of experts in gene discovery, molecular characterization, genetic counseling, and treatment for inherited retinal diseases. Together, they will provide an overview of the current state of research in IRDs and use it as a context to discuss the best practices for transforming genetic discoveries into personalized precision medicine.

 

11:00 AM   Gene discovery and mutation detection in families with dominant retinitis pigmentosa. S. P. Daiger. Univ Texas Hlth Sci Ctr, Houston.

11:30 AM   Integrating genetic testing into the inherited retinal disease clinic. K. E. Branham. Kellogg Eye Ctr, Univ Michigan, Ann Arbor.

12:00 PM   Functional validation and genetic intervention for retinal disease genes. V. Sheffield. Univ Iowa Carver Col Med, Iowa City.

12:30 PM   From gene discovery to clinical trials for inherited retinal diseases. E. Pierce. Massachusetts Eye & Ear Infirmary, Boston.


Friday, October 21

11:00 AM–1:00 PM

Concurrent Invited Session II

62. Genome Editing: What Implications and Obligations Does this Emerging Technology Create?

Ballroom A, West Building, Convention Centre

Moderators: James C. O'Leary, Genet Alliance, Washington, DC
  Han G. Brunner, Maastricht Univ Med Ctr, Netherlands

 

Genome editing techniques have become both more precise and simple to perform, giving scientists the ability to alter targeted genetic sequences in both somatic and germline cells. Fears of designer babies, gene drives, and genetic discrimination, once relegated to science fiction, are now being seriously debated in the international scientific community. This session addresses the urgent need to delineate roles and responsibilities in order to promote sustainable research and clinical practice guided by proportionate regulation and based on public trust. Speakers will address priorities and limitations to research and clinical applications, ethical, legal, and social issues, models of governance, and patient and public perceptions. Representatives from ASHG and ESHG committees will share how each professional society is approaching these issues and will highlight similarities and differences to the regulatory approach being taken in North America and Europe.

 

11:00 AM   Genome editing for the understanding and treatment of diseases: Scientific and clinical implications. K. Musunuru. Univ Pennsylvania, Philadelphia.

11:30 AM   Hope and caution: The public's perception of genome editing technology. S. F. Terry. Genet Alliance, Washington, DC.

12:00 PM   Genome editing: The role of ESHG in establishing guidance. G. de Wert. Maastricht Univ, Netherlands.

12:30 PM   ASHG policy statement on human germline genome editing: Advancing research and global governance. Y. Bombard. Univ Toronto and St Michael's Hosp, Toronto, Canada.


Friday, October 21

11:00 AM–1:00 PM

Concurrent Invited Session II

63. How Natural Selection Shapes the Modern Human Genome: Methods and Examples

Ballroom B, West Building, Convention Centre

Moderators: Wendy Wong, Inova Translational Med Inst, Falls Church
  Min Zhang, Purdue Univ, West Lafayette

 

The prohibitive cost of sequencing has traditionally prevented researchers from performing population scale genomic research in humans. The rapid advancement in sequencing technology has made it feasible for researchers to perform comparative studies to detect natural selection in human populations with adequate power; however, it also introduces more complexity and challenges regarding how we mine such rich data. In this session, we will hear success stories in detecting adaptive selection of humans to the local environment by analytical comparative genomics methods. For instance, we will hear about how the EPAS1 gene has shown signature for adaptive selection by two of our speakers in two separate studies of different populations (Tibetan and Himalayan) of high altitudes. We will further demonstrate how we discovered this particular haplotype being selected in Tibetans as an example of genetic introgression from archaic humans. It has been estimated that each individual modern human genome carries thousands of damaging polymorphic variants, and potentially a lot more that are weakly deleterious. Finally, we will hear the latest developments on how we use patterns of haplotype sharing in modern humans to estimate the strength-purifying of natural selection. The tools and algorithms developed for these studies will also be discussed.

 

11:00 AM   Genomic evidence of human physiological adaptation. R. Nielsen. UC Berkeley.

11:30 AM   Classic selective sweeps in humans: How can we find more and when should we believe them? C. Tyler-Smith. Wellcome Trust Sanger Inst, Hinxton, UK.

12:00 PM   Gaining insight into natural selection by ancestral recombination graph inference. A. Siepel. Simons Ctr for Quantitative Biol, Cold Spring Harbor Lab.

12:30 PM   Direct and indirect measurement of disease-related selection on rare pathogenic variants. G. McVean. Wellcome Trust Ctr for Human Genet, Oxford, UK.


Friday, October 21

11:00 AM–1:00 PM

Concurrent Invited Session II

64. Innovative Approaches to Co-ordinated Genomics Education for all Healthcare Professionals in England

Room 207, West Building, Convention Centre

Moderators: Anneke Seller, Hlth Educ England, Birmingham, UK
  Susan L. Hill, NHS England, London, UK

 

A key aim of England's 100,000 Genomes Project is to create a new genomic medicine service for the National Health Service (NHS). The Health Education England Genomics Education Programme (GEP) exists to ensure NHS staff have the knowledge, skills and experience to deliver a world-leading personalised medicine service that allows patients to benefit from advances in genomics. The GEP is taking a co-ordinated national approach with two main aims: wide scale workforce transformation that will prepare the current NHS workforce to integrate genomics and ensure the right training to deliver the future workforce. This session will describe the scope of genomics developments in England, including the 100,000 Genomes Project, NHS Genomic Medicine Centres, the network of Training & Education Leads and the strategic implementation of the associated educational framework. We will present exemplars showcasing the comprehensive and innovative approach including: Development of a national network of universities to deliver a Genomic Medicine Master's and CPD programme in which students will have access to the 100,000 Genomes Project data for research; development of accredited training pathways for emergent fields (e.g., Clinical Bioinformatics) and re-shaping established training pathways (e.g., undergraduate medical education); development of online resources to support these developments and raise awareness; and educating consenters outside the genetics clinic. We will present data on our methodology and engagement with subject matter experts, course uptake and evaluations to demonstrate our impact and effectiveness and describe our approach to pedagogic research. We will also explore the new structures for international collaborations in education and training.

 

11:00 AM   The Genomics Education Programme: The strategic approach to genomics education for all healthcare professionals. S. L. Hill. NHS England, London, UK.

11:30 AM   New curricula and tools for the assessment of competence for healthcare professionals in genomics. A. Seller. Hlth Educ England, Birmingham, UK.

12:00 PM   Educating consenters outside the genetics clinic. E. Thomas. Queen Mary Univ London, UK.

12:30 PM   Development and implementation of an innovative genomic medicine master's. E. V. Davison. Hlth Educ England, Birmingham, UK.


Friday, October 21

11:00 AM–1:00 PM

Concurrent Invited Session II

65. Structural Genomics: Integrating Analysis of Chromosome Conformation in Disease and Diagnosis

Ballroom C, West Building, Convention Centre

Moderators: Cynthia C. Morton, Brigham & Women's Hosp, Harvard Med Sch, Boston
  Cinthya J. Zepeda-Mendoza, Brigham & Women's Hosp, Harvard Med Sch, Boston

 

With the exploration of chromatin structure through diverse microscopy and 3C-derived technologies, a variety of organizational units of the chromatin fiber at the sub-chromosomal and chromosomal scale have been discovered. The current diversity of chromatin conformations highlights the role that 3D architecture plays in the functionality of cells and reflects the complexity that exists within the nuclear components. Increasing knowledge of the contribution of chromatin architecture in diverse diseases is now available, and the list of potential pathogenic position effects is expanding. An exemplar illustration of this contribution is found in the recent study of diverse limb malformations by Lupiáñez et al. (Cell 161(5):1012-25, May 21, 2015). The present session focuses on presentation and discussion of current findings in chromatin architecture-disease associations, the technology behind it, and how topological information can be explored and used to predict pathogenic effects. An in-depth discussion of the integration of these results will follow, especially in the interpretation of structural variants of unknown significance in the clinical setting.

 

11:00 AM   The 3D chromatin architecture and long-range control of gene expression. B. Ren. Ludwig Cancer Res UC San Diego, La Jolla.

11:30 AM   Genome engineering of chromosome conformation. K. Seungsoo. Univ Washington, Seattle.

12:00 PM   Chromatin architecture: How structural variations result in disease. D. G. Lupiáñez. Max Planck Inst for Molec Genet, Res Group Devel & Disease, Berlin, Germany.

12:30 PM   In silico prediction of positional effects of human balanced chromosome rearrangements. C. J. Zepeda-Mendoza. Brigham & Women's Hosp, Harvard Med Sch, Boston.


Friday, October 21

4:30 PM–5:50 PM

66. Featured Plenary Abstract Session III

Ballroom ABC, West Building, Convention Centre

Moderators: Anthony Antonellis, ASHG 2016 Program Chair
  Heather Mefford, ASHG 2016 Program Committee

 

243/4:30 Aneuploidy and cancer predisposition caused by mutations in genes controlling chromosome segregation. N. Rahman, S. Yost, B. de Wolf, S. Hanks, M. Clarke, A. Zachariou, E. Ramsay, H. Wylie, S. Seal, E. Ruark, M.U. Rashid, G.J.P. Kops.

244/4:50 Discovery and dissection of regulatory elements of the Mendelian disease gene HPRT1 using programmed CRISPR/Cas9 guide pairs for multiplexed deletion scanning. M. Gasperini, G. Findlay, A. McKenna, C. Lee, J. Milbank, J. Shendure.

245/5:10 Discovery and challenges in low-pass whole genome sequencing of over 140,000 individuals from throughout China. X. Jin, on behalf of the Chinese Millionome Consortium.

246/5:30 Functional studies using Drosophila melanogaster reveal pervasive epistasis and common mechanisms for copy-number variant genes. S. Girirajan, L. Pizzo, M. Jensen, E. Huber, P. Patel, K. Vadodaria, A. Kubina, S. Yennawar, J. Iyer, M.D. Singh.


Friday, October 21

5:55 PM–6:10 PM

67. ASHG Arno Motulsky-Barton Childs Award for Excellence in Human Genetics Education Presentation

Ballroom ABC, West Building, Convention Centre

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

Introduction: Larry Brody, NIH/NHGRI

Recipient:
David Valle

David Valle, MD
Henry J. Knott Professor and Director, McKusick-Nathans Institute of Genetic Medicine
Professor, Department of Pediatrics and Department of Molecular Biology and Genetics, Opthalmology and Biology, Johns Hopkins University School of Medicine

As longtime Director of the Predoctoral Training Program in Human Genetics at Johns Hopkins, Dr. Valle has been involved in the education of more than 400 graduate students. He also helped develop and implement "Genes to Society," a revised curriculum for medical students, and has trained more than 40 graduate students and postdocs in his own laboratory. In addition, Dr. Valle co-directs the McKusick Short Course in Human and Mammalian Genetics and Genomics at the Jackson Laboratory, an annual two-week program for students from around the world. He edited three editions of The Metabolic Basis of Inherited Disease, and since 2001 has been the senior editor of the online version of Scriver's Metabolic and Molecular Bases of Inherited Disease.

 


Friday, October 21

6:10 PM–6:25 PM

68. ASHG Mentorship Award Presentation (New for 2016)

Ballroom ABC, West Building, Convention Centre

The ASHG Mentorship Award, new this year, recognizes ASHG members who have shown a sustained pattern of exemplary mentorship at the graduate student, postdoctoral, residency, or fellowship level.

Introduction: Max Muenke, NHGRI

Recipient:
Elaine H. Zackai, MD
Elaine Zackai

Professor of Pediatrics, Children's Hospital of Philadelphia
Professor of Pediatrics in Human Genetics and Professor of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania

After completing a residency in pediatrics and a fellowship in medical genetics, Dr. Zackai has held faculty and hospital appointments at CHOP and the University of Pennsylvania, where she has focused on diagnosis, dysmorphology, and applied clinical research responding to real-world situations. Her former trainees credit her dedication to students, leadership by example, compassion for patients, and rigorous approach to diagnosis with inspiring them to successful careers in human genetics.

 


Friday, October 21

6:25 PM–6:40 PM

69. ASHG Advocacy Award Presentation

Ballroom ABC, West Building, Convention Centre

The ASHG Advocacy Award recognizes individuals or groups who have exhibited excellence and achievement in applications of human genetics for the common good.

Introduction: Yvonne Bombard, St. Michael's Hospital and University of Toronto

Recipients:
Senator James Cowan, Parliament of Canada
Senator James Cowan

Bev Heim-Myers, Canadian Coalition For Genetic Fairness
Bev Heim-Myers

For several years, Senator Cowan and Bev Heim-Myers, Chair of the Canadian Coalition for Genetic Fairness (CCGF) and CEO of the Huntington Society of Canada and the member organizations of CCGF, have led efforts to pass a law preventing genetic discrimination in Canada. First introduced in 2013, Bill S-201, the Genetic Non-Discrimination Act, would protect individuals from being required to undergo a genetic test, or disclose the results of a test, as a condition of acquiring a good or service or entering into a contractual agreement. It would also prohibit employers from requiring employees to undergo genetic testing or disclose testing results, or taking discriminatory action against employees who refuse to undergo genetic testing or reveal testing results. Finally, it would amend the Canadian Human Rights Act to prohibit discrimination on the grounds of genetic characteristics.

 


Friday, October 21

6:45 PM–7:05 PM

70. Remarks by Senator James Cowan, Parliament of Canada

Ballroom ABC, West Building, Convention Centre

James S. Cowan, QC, is a senator in the Parliament of Canada. For several years, Senator Cowan has led efforts in Parliament to pass a new law to prevent genetic discrimination in Canada. Earlier this year, Senator Cowan’s bill, the Genetic Non-Discrimination Act, was passed unanimously by the Senate of Canada. It is now before the House of Commons. Together with the Canadian Coalition for Genetic Fairness, Senator Cowan is the 2016 recipient of ASHG’s Advocacy Award. In his remarks, Senator Cowan will address why it is important for Canada to join the United States and other countries in establishing strong protections against genetic discrimination.

 


Saturday, October 22

9:00 AM–10:00 AM

Concurrent Platform Session E

71. Mapping Complex Traits in Ethnically Diverse Cohorts

Ballroom A, West Building, Convention Centre

Moderators: Sonja I. Berndt, NCI, Rockville
  Yun Li, Univ North Carolina, Chapel Hill

 

247/9:00 Novel genome-wide sequence variants influence antibody response to Epstein-Barr Virus in an African Population. N. Sallah, T. Carstensen, K. Wakeham, R. Bagni, N. Labo, M. Pollard, D. Gurdasani, K. Ekoru, C. Pomilla, E. Young, S. Fatumo, G. Asiki, A. Kamali, M. Sandhu, P. Kellam, D. Whitby, R. Newton, I. Barroso.

248/9:15 A CPT1A missense mutation associated with fatty acid metabolism and reduced height in Greenlanders. L. Skotte, A. Koch, V. Yakimov, S. Zhou, B. Søborg, M. Andersson, S.W. Michelsen, J.E. Navne, J.M. Mistry, P.A. Dion, M.L. Petersen, M.L. Børresen, G.A. Rouleau, F. Geller, M. Melbye, B. Feenstra.

249/9:30 Evolution of hypertension: Understanding population differences - Insights from population genomic data. H. Schaschl, T. Göllner, M. Fieder.

250/9:45 Whole-genome sequencing study of serum peptide levels: The Atherosclerosis Risk in Communities study. P.S. de Vries, B. Yu, E.V. Feofanova, G.A. Metcalf, M.R. Brown, A.L. Zeigham, R.A. Gibbs, E. Boerwinkle, A.C. Morrison.


Saturday, October 22

9:00 AM–10:00 AM

Concurrent Platform Session E

72. From Phenotypes to Gene Discovery

Ballroom B, West Building, Convention Centre

Moderators: Peter N. Robinson, Jackson Lab for Genomic Med, Farmington
  Anne O'Donnell-Luria, Boston Children's Hosp

 

251/9:00 A massively scalable phenotyping approach using social media for genetic studies. J. Yuan, A. Gordon, D. Speyer, D. Zielinski, R. Aufrichtig, J. Pickrell, Y. Erlich.

252/9:15 Partitioning phenotype-ancestry correlations. D.S. Park, J. Jeff, B. Glicksberg, G. Belbin, N. Abul-Husn, R.J. Loos, J.H. Cho, E. Kenny, N. Zaitlen.

253/9:30 Marked high rate of multiple pathogenic variants in patients with Mendelian traits that show phenotypic expansion. E. Karaca, T. Harel, Z. Coban Akdemir, S.N. Jhangiani, Y. Bayram, D. Muzny, E. Boerwinkle, R.A. Gibbs, J.R. Lupski.

254/9:45 Translational deep phenotyping for clinical genomics. T. Groza, T. Roscioli, M. Cowley, G. Baynam, H. Dawkins, M. Haendel, C. Mungall, D. Smedley, P.N. Robinson, M.E. Dinger, A. Zankl.


Saturday, October 22

9:00 AM–10:00 AM

Concurrent Platform Session E

73. Whole-exome and Whole-genome Sequencing: From Disease Gene Discovery to Diagnosis

Ballroom C, West Building, Convention Centre

Moderators: Michael Friez, Greenwood Gen Ctr
  Yaping Yang, Baylor Col Med, Houston

 

255/9:00 A whole exome sequencing (WES) rare variant association study of Multiple Sclerosis (MS) subtypes identifies a significant association between LIX1L and primary progressive MS (PPMS). P. Bronson, K.D. Nguyen, K. Estrada, K. Gutwin, I. Kockum, J. Hillert, S. John, T. Harris, A. Day-Williams.

256/9:15 Exome sequencing reveals novel candidate genes and potential oligogenic inheritance in patients with hypergonadotropic hypogonadism. Y. Bayram, S. Turan, Z. Aycan, T. Tos, B. Hacihamdioglu, Z. Coban Akdemir, S. Bas, Z. Atay, T. Guran, S. Abali, J.J. White, G. Yesil, E. Karaca, S.N. Jhangiani, D.M. Muzny, A. Bereket, R.A. Gibbs, J.R. Lupski, Baylor-Johns Hopkins Center for Mendelian Genomics.

257/9:30 Novel analytic approaches used to solve unsolved whole exome sequencing data. N. Sobreira, F. Schiettecatte, H. Ling, E. Pugh, D. Witmer, K. Hetrick, P. Zhang, K. Doheny, S.N. Jhangiani, Z.H. Coban Akdemir, J. Posey, V.R. Sutton, E. Karac, Y. Bayram, J.R. Lupski, A. Hamosh, D. Valle.

258/9:45 Low-pass whole-genome sequencing in clinical cytogenetics: A validated approach. Z. Dong, F. Chen, H. Wang, H. Jiang, K.W. Choy.


Saturday, October 22

9:00 AM–10:00 AM

Concurrent Platform Session E

74. The Clinical Impact of WES and WGS

Room 109, West Building, Convention Centre

Moderators: Cheryl Shuman, Hosp Sick Children, Toronto, Canada
  Jason D. Merker, Stanford Univ

 

259/9:00 Medical management differs for children following whole genome sequencing compared to chromosome microarray. R.Z. Hayeems, J. Bhawra, K. Tsiplova, N. Monfared, M.S. Meyn, S. Bowdin, D. Stavropoulos, C. Marshall, R. Basran, C. Shuman, S. Ito, I. Cohn, C. Hum, M. Girdea, M. Brudno, R.D. Cohn, W.J. Ungar.

260/9:15 The genetics clinic of the future: Towards implementation of whole genome sequencing in diagnostic practice. I.J. Nijman, S. van Lieshout, T. Bradley, P. van Zon, M. van Stralen, F. van Ruissen, D.M. van Beek, P. Neerincx, J. ten Hoeve, F. Baas, R. Sinke, B. Sikkema, F. Hogervorst, J.K. Ploos van Amstel, G.H. Schuring-Blom, M. Weiss, E.C. Cuppen, E.A. Sistermans.

261/9:30 Reanalyzing yearly whole-exome sequencing results: An 8% increase in diagnostic yield. J. Thevenon, P. Kuentz, S. Nambot, A.-L. Bruel, D. Lehalle, M. Assoum, N. Jean-Marçais, A. Masurel-Paulet, P. Callier, A.-L. Mosca-Boidron, S. El Chehadeh, C. Poé, T. Jouan, M. Chevarin, N. Gigot, J.-B. Rivière, M. Lefebvre, E. Tisserant, J.-F. Deleuze, Y. Duffourd, L. Faivre, C. Thauvin.

262/9:45 Risk, recommendation, and rationale: How primary care providers interpret and manage genome sequencing results. I.J. Richardson, J.K. Davis, C. Kirby, R.C. Green, P.A. Ubel, J.L. Vassy.


Saturday, October 22

9:00 AM–10:00 AM

Concurrent Platform Session E

75. Improvements on NGS for the Clinic

Room 119, West Building, Convention Centre

Moderators: Christa L. Martin, Geisinger Hlth Syst, Danville
  David A. Buchner, Case Western Reserve Univ, Cleveland

 

263/9:00 HiSeq X performance: Optimization for clinical applications. K. Walker, R. Sanghvi, Q. Wang, H. Doddapaneni, J. Hu, Z. Momin, J. Santibanez, J. Farek, A. English, W. Salerno, Y. Han, H. Dinh, E. Boerwinkle, R. Gibbs, D.M. Muzny.

264/9:15 DName barcodes allow absolute quality control of genetic test processes based on NGS. H. Cuppens, S. Dillen, M. Jaspers, K. Verleysen.

265/9:30 A curated database of 130,000 variants from more than 1,200 genomes: Challenges for the clinical laboratory. D.L. Perry, A.J. Coffey, J. Avecilla, M. Bennett, N. Burns, A. Chawla, B. Juan, J. Kakishita, A. Khouzam, E. Thorpe, R.J. Taft.

266/9:45 Improving gene annotation to facilitate identification of missing variants of clinical significance. A. Frankish, C.A. Steward, M-M. Suner, D. Pervouchine, B. Uszczynska, J-M. Gonzalez, S. Fitzgerald, D. Grozeva, K. Carss, P. Cossette, F. Hamdan, J. Michaud, R. Petryszak, E. Tapanari, M. Diekhans, B.A. Minassian, F.L. Raymond, R. Guigó.


Saturday, October 22

9:00 AM–10:00 AM

Concurrent Platform Session E

76. The Phenotypic Implications of Gene Dosage and Regulation

Room 207, West Building, Convention Centre

Moderators: Donald F. Conrad, Washington Univ Sch Med, St. Louis
  Athma A. Pai, MIT, Cambridge

 

267/9:00 5-hydroxmethylcytosine-mediated epigenetic dysregulation in cerebellar degeneration. B. Yao, H. Bao, L. Chen, L. Lin, M. Poidevin, S. Yang, X. Li, C. Stoyas, A. La Spada, F. Ayhan, L. Ranum, L. Duvick, H. Orr, Z. Zalewski, D. Nelson, H. Wu, P. Jin.

268/9:15 Predicting haploinsufficiency from epigenomics data enables discovery of novel risk genes of developmental disorders. Y. Shen, X. Han.

269/9:30 The majority of pathogenic copy number variations in congenital limb malformation affect non-coding regulatory elements. M. Spielmann, R. Flöttmann, B. Kragsteen, S. Geuer, M. Socha, L. Allou, A. Sowińska-Seidler, J. Wagner, A. Jamsheer, B. Oehl-Jaschkowitz, D. de Silva, I. Kurth, I. Maya, F. Santos, W. Hülsemann, E. Klopocki, R. Mountford, G. Bork, D. Horn, P. Lapunzina, D. Duboule, S. Mundlos.

270/9:45 Subcutaneous adipose eQTLs coincident with GWAS loci identify 140 candidate target genes for cardiometabolic traits. Y. Wu, M. Civelek, C.K. Raulerson, L.J. Scott, C. Pan, A. Ko, A. He, C. Tilford, C. Fuchsberger, A.E. Locke, H.M. Stringham, A.U. Jackson, N.K. Saleem, N. Narisu, P.S. Chines, J. Kuusisto, P. Gargalovic, T. Kirchgessner, P. Pajukanta, F.S. Collins, M. Boehnke, M. Laakso, A.J. Lusis, K.L. Mohlke.


Saturday, October 22

9:00 AM–10:00 AM

Concurrent Platform Session E

77. Biomarkers and Somatic Cancer Diagnostics

Room 211, West Building, Convention Centre

Moderators: Gordana Raca, Children's Hosp Los Angeles
  Heather Mason-Suares, Partners Personalized Med, Cambridge

 

271/9:00 Common pan-cancer pathways and gene sets can identify tumors across over 30 cancer types. F.C. Lamaze, M. Agbessi, J.C. Grenier, V. Bruat, P. Awadalla, PCAWG consortium.

272/9:15 Longitudinal next generation sequencing (NGS) of plasma cell-free DNA (cfDNA) during a phase 1 basket trial of targeted AKT inhibitor (AZD5363) reveals clinical correlates and emergent somatic mutations. J. Reichel, L. Smyth, J. Tang, F. Meng, J. Patel, S.D. Selcuklu, D. You, A. Samoila, S. Chandarlpaty, M. Berger.

273/9:30 Identification of biomarkers to personalize treatment after resection surgery for stage I adenocarcinoma. A. Clemenceau, P. Joubert, Y. Bossé.

274/9:45 Whole exome sequencing of metastatic colorectal and lung cancers: Advances and challenges in interpretation of somatic and germline variants. A. Ghazani, N. Oliver, J. St. Pierre, A. Garofalo, L. Sholl, N. Lindeman, J. Garber, S. Joffe, P. Jänne, S. Gray, L. Garraway, E. Van Allen, N. Wagle.


Saturday, October 22

9:00 AM–10:00 AM

Concurrent Platform Session E

78. Neuropsychiatric Diseases of the Young and Old

Room 221, West Building, Convention Centre

Moderators: Peristera Paschou, Purdue Univ, West Lafayette
  Tao Wang, Johns Hopkins Univ, Baltimore

 

275/9:00 ADHD risk loci identified by genome-wide association meta-analysis. D. Demontis, the iPSYCH-Broad ADHD Workgroup and the Psychiatric Genomics Consortium: ADHD Subgroup.

276/9:15 Genome- and phenome-wide study of “nail biting”: Not just a habit. C. Tian, J. Tung, D. Hinds.

277/9:30 Dysregulation of RNA splicing in developing brains increases risk for neuropsychiatric disease. Y. Li, T. Raj.

278/9:45 Patient-derived iPSC model of an ABCA7 deletion associated with Alzheimer disease. H.N. Cukier, S.P. Gross, B.W. Kunkle, B.N. Vardarajan, S. Rolati, K.L. Hamilton-Nelson, P.L. Whitehead, B.A. Dombroski, R. Lang, L.A. Farrer, M.L. Cuccaro, J.M. Vance, J.R. Gilbert, G.W. Beecham, E.R. Martin, R.M. Carney, R. Mayeux, G.D. Schellenberg, G.S. Byrd, J.L. Haines, M.A. Pericak-Vance, D.M. Dykxhoorn.


Saturday, October 22

9:00 AM–10:00 AM

Concurrent Platform Session E

79. Diverse Model Systems for Teasing Out the Molecular Basis of Disease

Room 302, West Building, Convention Centre

Moderators: Megan Y. Dennis, Univ California, Davis
  Santhosh Girirajan, Pennsylvania State Univ, University Park

 

279/9:00 iPS cells-based pathophysiological investigation for large subcutaneous hematomas in Ehlers-Danlos syndrome caused by CHST14/D4ST1 deficiency. T. Kosho, F. Yue, T. Era, J. Nakayama, T. Yamaguchi, N. Miyake, S. Mizumoto, S. Yamada, R. Kawamura, K. Wakui, T. Yoshizawa, Y. Takahashi, K. Matsumoto, T. Hirose, J. Minaguchi, K. Takehana, M. Uehara, J. Takahashi, M. Ishikawa, C. Masuda, S. Shimazu, Y. Nitahara-Kasahara, A. Watanabe, T. Okada, K. Matsumoto, Y. Nomura, Y. Kakuta, A. Hatamochi, Y. Fukushima, K. Sasaki.

280/9:15 A Drosophila melanogaster model of 16p11.2 deletion supports a complex cis and trans interaction model for neurodevelopmental disorders. M. Singh, J. Iyer, L. Pizzo, M. Jensen, P. Patel, E. Huber, S. Girirajan.

281/9:30 Lymphoproliferation due to Fas-ligand defects in cats. A potential model for autoimmune lymphoproliferative syndrome (ALPS). L.A. Lyons, D. Aberdein, J.S. Munday, B. Gandolfi, K.E. Dittmer, R. Malik, 99 Lives Consortium.

282/9:45 Knockdown of chromatin remodeling gene Cecr2 causes subfertility in both male and female mice, but by different mechanisms. H.E. McDermid, C.B. Weatherill, K. Rowel Lim, V.V. Nguyen, R.C. Humphreys, K.A. Norton.


Saturday, October 22

10:15 AM–11:30 AM

Concurrent Platform Session F

80. Studying Gene Expression and Genetic Variation in Cell Models

Ballroom A, West Building, Convention Centre

Moderators: Juliet D. French, QIMR Berghofer Med Res Inst, Brisbane, Australia
  Emmanouil Dermitzakis, Univ Geneva Med Sch, Switzerland

 

283/10:15 Common genetic variation drives molecular heterogeneity in human iPSCs. H. Kilpinen, A. Goncalves, D. McCarthy, A. Leha, D. Bensaddek, A.I. Lamond, R. Durbin, D..J. Gaffney, O. Stegle, on behalf of the HipSci Consortium.

284/10:30 Inter-individual variation in epigenetic marks between human induced pluripotent stem (iPS) cell lines. A.T. Filimon Goncalves, P. Danecek, A. Leha, H. Kilpinen, R. Durbin, O. Stegle, D. Gaffney, HipSci Consortium (http://www.hipsci.org/).

285/10:45 Gene expression and splicing differences across 250 cellular environments. F. Luca, A. Richards, A. Pai, D. Kurtz, G. Moyerbrailean, G. Davis, A. Alazizi, C. Harvey, N. Hauff, Y. Sorokin, X. Wen, R. Pique-Regi.

286/11:00 Human induced pluripotent stem cells: A powerful model to investigate inter-individual regulatory variation across cell types. N.E. Banovich, Y.I. Li, A. Raj, M.C. Ward, P.Y. Tung, J.E. Burnett, M. Myrthil, S.M. Thomas, C.L. Burrows, I. Gallego Romero, B.J. Pavlovic, J.K. Pritchard, Y. Gilad.

287/11:15 In vitro human neuronal differentiation validated as genomic model system to study major psychiatric illnesses. A.P.S. Ori, M.H.M. Bot, R.T. Molenhuis, L.M. Olde Loohuis, R.A. Ophoff.


Saturday, October 22

10:15 AM–11:30 AM

Concurrent Platform Session F

81. NGS: Integration, Saturation, and Interpretation

Ballroom B, West Building, Convention Centre

Moderators: Ryan Tewhey, Broad Inst, Cambridge
  Timothy Reddy, Duke Univ, Durham

 

288/10:15 Saturation genome editing to characterize thousands of mutations at the HPRT1 locus. G.M. Findlay, M.J. Gasperini, J. Shendure.

289/10:30 Using multiplex non-coding CRISPR deletion libraries to individually perturb every CTCF binding site in the human genome. S.K. Reilly, R. Tewhey, E.A. Brown, P.C. Sabeti.

290/10:45 Personalized medicine for neurometabolic disorders via an integrated ‘-omics’ approach. C. van Karnebeek, M. Tarailo-Graovac, A. Matthews, C. Shyr, J. Lee, D. Wishart, C. Ross, H. Vallance, G. Sinclair, R. Salvarinova, S. Stockler, L. Kluijtmans, G. Horvath, R. Wevers, W. Wasserman.

291/11:00 Semi-automated bioinformatics approach to exome/genome data analysis for diagnosis and discovery of neurometabolic disease. M. Tarailo-Graovac, A. Matthews, J.Y.A. Zhu, C. Shyr, G.A. Horvath, R. Salvarinova, C.J. Ross, J.J.Y Lee, S. Stockler-Ipsiroglu, R. Wevers, H. Vallance, G. Sinclair, C.D. van Karnebeek, W.W. Wasserman.

292/11:15 Massively parallel digital transcriptional profiling of single cells. G. Zheng, J. Terry, P. Belgrader, P. Ryvkin, Z. Bent, R. Wilson, S. Ziraldo, T. Wheeler, G. McDermott, M. Gregory, J. Shuga, L. Montesclaros, D. Masquelier, S. Nishimura, M. Schnall-Levin, C. Hindson, R. Bharadwaj, A. Wong, K. Ness, L. Beppu, J. Deeg, C. McFarland, K. Loeb, W. Valente, N. Ericson, E. Stevens, J. Radich, T. Mikkelsen, B. Hindson, J. Bielas.


Saturday, October 22

10:15 AM–11:30 AM

Concurrent Platform Session F

82. Mosaicism and Disease

Ballroom C, West Building, Convention Centre

Moderators: Laura K. Conlin, Children's Hosp Philadelphia
  Karen L. Swisshelm, Univ Colorado Denver Hlth Sci

 

293/10:15 Single nucleotide mutagenesis starts from two-cell cleavage-stage: Direct evidence from genome-wide analysis. K. Choy, Z. Dong, Y. Cao, F. Chen, H. Jiang.

294/10:30 PIK3CA-Related Overgrowth Spectrum (PROS) molecular spectrum and recommendations for testing among a novel series of 205 patients. P. Kuentz, Y. Duffourd, J. St-Onge, A. Sorlin, V. Carmignac, T. Jouan, J. Amiel, N. Bahi-Buisson, D. Bessis, O. Boute, A.-C. Bursztejn, C. Chiaverini, C. Coubes, A. Goldenberg, B. Isidor, L. Martin, A. Maruani, J. Mazereeuw-Hautier, C. Mignot, F. Morice-Picard, F. Petit, A. Phan, R. Touraine, M. Vincent, M. Willems, N. Marle, S. Hadj-Rabia, P. Vabres, J.-B. Rivière, L. Faivre.

295/10:45 Frequency of mosaicism in parents of children with early-onset epilepsy. C. Myers, Z. Thuesmunn, A. Muir, G. Hollingsworth, A. Schneider, G. Carvill, L. Sadleir, I. Scheffer, H. Mefford.

296/11:00 The contribution of post-zygotic mutations resulting in sequence and structural mosaicism to dominant developmental disorders. M.E. Hurles, C. Wright, J. Kaplanis, D. Rajan, A. Sifrim, D. King, DDD Study.

297/11:15 GNA11 and GNAQ post-zygotic mosaicism cause an overlapping spectrum of neurocutaneous disorders. V.A. Kinsler, A.C. Thomas, Z. Zeng, J-B. Rivière, R. O'Shaughnessy, L. Al-Olabi, J. St-Onge, D..J. Atherton, H. Aubert, L. Bagazgoitia, S. Barbarot, E. Bourrat, C. Chiaverini, W.K. Chong, Y. Duffourd, K. Forde, M. Glover, L. Groesser, S. Hadj-Rabia, H. Hamm, R. Happle, P. Kuentz, J-P. Lacour, I. Mushtaq, S. Polubothu, R. Waelchli, M. Wobser, E.E. Patton, P. Vabres.


Saturday, October 22

10:15 AM–11:30 AM

Concurrent Platform Session F

83. Gene Regulation and Cardiovascular Disease

Room 109, West Building, Convention Centre

Moderators: Cristen J. Willer, Univ Michigan, Ann Arbor
  Nabila Bouatia-Naji, INSERM UMR970 Paris Cardiovascular Research Center (PARCC), Paris, France

 

298/10:15 Characterizing functional regulatory variants in iPSC-derived human cardiomyocytes. P. Benaglio, C. DeBoever, H. Li, F. Drees, M. D’Antonio, H. Matsui, A. Arias, A. DAntonio-Chronowska, E. Smith, K. Frazer.

299/10:30 Discovery of adipose-specific GxBMI interactions on the regulation of gene expression. K.S. Small, C.A. Glastonbury, A. Vinuela, A. Buil, G.H. Halldorsson, G. Thorleifsson, H. Helgason, U. Thorsteindottir, K. Stefansson, E.T. Dermitzakis, T.D. Spector.

300/10:45 Functional fine-mapping of coronary artery disease risk variants. B. Liu, M. Pjanic, T. Nguyen, S. Montgomery, C. Miller, T. Quertermous.

301/11:00 Cardiometabolic variants in adipose tissue ATAC-seq peaks at GWAS loci with coincident adipose tissue eQTLs. M.E. Cannon, K.W. Currin, A. Safi, L. Song, Y. Wu, M. Civelek, M. Laakso, G.E. Crawford, K.L. Mohlke.

302/11:15 Integrative functional genomics identifies regulatory mechanisms at coronary artery disease loci. C.L. Miller, M. Pjanic, T. Wang, T. Nguyen, A. Cohain, J.D. Lee, L. Perisic, U. Hedin, R.K. Kundu, D. Majmudar, J.B. Kim, O. Wang, C. Betsholtz, A. Ruusalepp, O. Franzen, T.L. Assimes, S.B. Montgomery, E.E. Schadt, J.L.M. Bjorkegren, T. Quertermous.


Saturday, October 22

10:15 AM–11:30 AM

Concurrent Platform Session F

84. Novel Discoveries in Mendelian Disease

Room 119, West Building, Convention Centre

Moderators: Clement Y. Chow, Univ Utah, Salt Lake City
  Karen W. Gripp, DuPont Hospital for Children, Wilmington

 

303/10:15 GNB5 variants cause a novel multisystem syndrome associated with sinus bradycardia and intellectual disability. P. De Nittis, E.M. Lodder, C.D. Koopman, W. Wiszniewski, C. Fishinger Moura de Souza, N. Lahrouchi, N. Guex, V. Napolioni, F. Tessadori, T. de Boer, L. Beekman, E.A. Nannenberg, I. Ratbi, A.A.M Wilde, W.F. Simonds, M. Neerman-Arbez, V.R. Sutton, F. Kok, J.R. Lupski, G. Merla, C.R. Bezzina, J. Bakkers, A. Reymond.

304/10:30 Biallelic hypomorphic mutations in a linear deubiquitinase define otulipenia, an early-onset systemic autoinflammatory disease. Q. Zhou, X. Yu, E. Demirkaya, N. Deuitch, D. Stone, W. Tsai, H. Wang, Y. Park, A. Ombrello, T. Romeo, E. Remmers, J. Chae, M. Gadina, S. Ozen, M. Abinun, D. Kastner, I. Aksentijevich.

305/10:45 Characterization and successful treatment of a novel autosomal dominant immune dysregulatory syndrome caused by a JAK1 gain-of-function mutation. M.L. McKinnon, R.J. Ragotte, K.L. Del Bel, A. Saferali, S. Turvey.

306/11:00 Mutation spectrum of NOD2 in an early-onset inflammatory bowel disease cohort reveals recessive Mendelian inheritance as a main driver of Crohn’s Disease. J.E. Horowitz, N. Warner, J. Staples, R. Murchie, C. Van Hout, A. King, K. Fiedler, J.G. Reid, J.D. Overton, A.R. Shuldiner, A. Baras, F. Dewey, A. Griffiths, O. Gottesman, A. Muise, C. Gonzaga-Jauregui, Geisinger-Regeneron DiscovEHR Collaboration.

307/11:15 Homozygous BRCA1 truncation causes Fanconi Anemia. A. Seo, T. Walsh, N. Rosenfeld, M.K. Lee, O. Dgany, E. Levy-Lahad, A. Shimamura, M.-C. King, H. Tamary.


Saturday, October 22

10:15 AM–11:30 AM

Concurrent Platform Session F

85. Genetic Variation in Common Immune Disease

Room 207, West Building, Convention Centre

Moderators: Jeffrey C. Barrett, Sanger Inst, Hinxton/Cambridge, UK
  Dawn M. Waterworth, GlaxoSmithKline, King of Prussia

 

308/10:15 Whole genome sequencing and imputation in inflammatory bowel disease uncovers mechanisms for multiple therapeutically-relevant associations. K.M. de Lange, Y. Luo, L. Moutsianas, J.C. Lee, L. Jostins, C. Lamb, N. Kennedy, J.C. Mansfield, M. Parkes, C.A. Anderson, J.C. Barrett, UK Inflammatory Bowel Disease Genetics Consortium.

309/10:30 A functional genome-wide genomics approach identifies genetic variations that contribute to variability in innate immune responses. V.K. Magadi Gopalaiah, Y. Li, M. Oosting, S. Smeekens, M. Jaeger, R. Aguirre-Gamboa, T. Schoffelen, A.F.M. Jansen, M. van Deuren, J.W.M. van der Meer, R.J. Xavier, M.G. Netea, C. Wijmenga, Human Functional Genomics Project.

310/10:45 Assessment of the genetic basis of rosacea severity by genome-wide association study and expression analysis highlights immuno-inflammation and skin pigmentation as key mechanisms. J.L. Aponte, M.N. Chiano, L.M. Yerges-Armstrong, D.A. Hinds, C. Tian, A. Gupta, D. Rajpal, J. Freudenberg, M.G. Ehm, D.M. Waterworth.

311/11:00 Joint omics analysis connects human IgG N-glycosylation to multiple immunological loci. X. Shen, L. Klarić, M. Mangino, I. Trbojević-Akmačić, M. Pučić-Baković, I. Rudan, O. Polašek, C. Hayward, T.D. Spector, J.F. Wilson, G. Lauc, Y.S. Aulchenko.

312/11:15 Causal effects of protein biomarkers on immune diseases. A. Johansson, U. Gyllensten, S. Enroth.


Saturday, October 22

10:15 AM–11:30 AM

Concurrent Platform Session F

86. Methods for Variant Calling

Room 211, West Building, Convention Centre

Moderators: Gabor T. Marth, Eccles Inst Human Genetics, Univ Utah, Salt Lake City
  Elliott H. Margulies, Illumina, San Francisco

 

313/10:15 RUFUS: Accurate and sensitive reference free variant detection. A. Farrell, D. Lee, G. Marth.

314/10:30 A hybrid approach for de novo human genome sequence assembly, phasing, and detection of complex structural variation. Y. Mostovoy, M. Levy-Sakin, J. Lam, E.T. Lam, A.R. Hastie, P. Marks, J. Lee, C. Chu, C. Lin, Z. Džakula, H. Cao, S.A. Schlebusch, K. Giorda, M. Schnall-Levin, J.D. Wall, N.J.L. Meeks, K.C. Chatfield, C.R. Coughlin II, T.H. Shaikh, P. Kwok.

315/10:45 A hybrid approach combining next and third generation sequencing data for powerful structural variant detection. X. Fan, Z. Chong, L. Nakhleh, K. Chen, Human Genome SV Consortium.

316/11:00 De novo assembly of individual human haplotypes from diploid samples. D. Church, R. Abbas, A. Fehr, B. Galvin, S. Garcia, H. Heaton, P. Hardenbol, J. Herschleb, C. Jabara, M. Imielinski, S. Kyriazopoulou-Panagiotopoulou, V. Kumar, P. Marks, H. Ordonez, M. Pratt, P. Shah, A. Xu, N. Weisenfeld, I. Yousif, G. Zheng, M. Schnall-Levin, D. Jaffe.

317/11:15 Monovar: Single-nucleotide variant detection in single cells. H. Zafar, Y. Wang, L. Nakhleh, N. Navin, K. Chen.


Saturday, October 22

10:15 AM–11:30 AM

Concurrent Platform Session F

87. Diseases of the Nervous System

Room 221, West Building, Convention Centre

Moderators: Julie Jurgens, Johns Hopkins Univ, Baltimore
  William Law, Johns Hopkins Univ, Baltimore

 

318/10:15 RNA-seq analysis of Parkinson disease patient-derived dopaminergic neurons reveals disease specific genes and pathways across multiple time-points. K. Belle, S. Sivasankaran, A. Mehta, D. Van Booven, M. Seignon, J. Vance, D. Dykxhoorn.

319/10:30 RNA-seq analysis identifies phenotypic heterogeneity among ex vivo purified dopamine neurons and highlights their progressive temporal diversification. P.W. Hook, S.A. McClymont, L.A. Goff, A.S. McCallion.

320/10:45 Identification of genetic modifiers of the age onset of amyotrophic lateral sclerosis associated with the expanded GGGGCC repeats. H. Kim, H. Bao, B. Jiao, J.D. Glass, T. Wingo, P. Jin.

321/11:00 Biallelic mutations in the nuclear 3’ exonuclease, TOE1, cause Pontocerebellar Hypoplasia Type 7 and result in snRNA processing defects. A. Schaffer, R. Markmiller, V. Eggans, M. Zaki, S. Sathe, S. Grainger, B. Rosti, E. Van Nostrand, Z. Schlachetzki, E. Scott, L. Heckman, E. Dikoglu, R. Rosti, N. Akizu, A. Gregor, A. Guemez-Gamboa, N. Foulds, W. Dobyns, N. Chi, D. Traver, L. Spaccini, S. Bova, S. Gabriel, M. Gunel, E.M. Valente, E. Bennett, G. Yeo, F. Baas, J. Lykke-Andersen, J. Gleeson.

322/11:15 Identification of a 1.35 Mb insertion within the distal hereditary motor neuropathy locus (DHMN1) on chromosome 7q34-q36.2. M.L. Kennerson, A.P. Drew, A.N. Cutrupi, M.H. Brewer, G.A. Nicholson.


Saturday, October 22

10:15 AM–11:30 AM

Concurrent Platform Session F

88. Characterizing the Processes of Recombination and Mutation

Room 302, West Building, Convention Centre

Moderators: Justin M. Zook, National Inst Standards & Technol, Gaithersburg
  Priya Moorjani, Columbia Univ, New York

 

323/10:15 Direct measurement of the mutagenic impact of recombination through deep genome sequencing of 519 families. A. Quinlan, T. Sasani, B. Pedersen, R. Layer, A. Farrell, R. Collins, M. Stone, H. Brand, J. Glessner, J. An, D. Werling, S. Dong, M. Gilson, L. Smith, M. State, A. Willsey, X. He, J. Buxbaum, B. Devlin, K. Roeder, M. Daly, H. Coon, G. Marth, M. Talkowski, S. Sanders.

324/10:30 A greater meiotic gene conversion rate in females increases with age. B.V. Halldorsson, M.T. Hardarson, B. Kehr, U. Styrkarsdottir, A. Gylfason, G. Thorleifsson, F. Zink, Ad. Jonasdottir, As. Jonasdottir, P. Sulem, G. Masson, U. Thorsteinsdottir, A. Helgason, A. Kong, D. Gudbjartsson, K. Stefansson.

325/10:45 Parent-of-origin specific signatures of de novo mutations. C. Gilissen, J.M. Goldmann, W.S.W. Wong, M. Pinelli, T. Farrah, D. Bodian, A.B. Stittrich, L.E.L.M. Vissers, A. Hoischen, J.C. Roach, J.G. Vockley, J.A. Veltman, B.D. Solomon, J.E. Niederhuber.

326/11:00 Characterization of the STR mutation process at every locus in the genome. M. Gymrek, T. Willems, N. Patterson, D. Reich, Y. Erlich.

327/11:15 Identification of recurrent copy number variants associated with developmental brain disorders from whole exome sequencing of 47,859 participants in the DiscovEHR study. A.E. Hare-Harris, A. Moreno-De-Luca, E. Maxwell, L. Habegger, C. O'Dushlaine, S. McCarthy, J.D. Overton, J. Reid, A. Luncas, D. Kim, T.H. Nelson, S.A. Pendergrass, M. Ritchie, D.H. Ledbetter, C.L. Martin.


Saturday, October 22

12:00 PM–1:00 PM

89. ASHG Closing Plenary Symposium: Late Breaking Abstracts

Ballroom B, West Building, Convention Centre

Moderators: Anthony Antonellis, ASHG 2016 Program Chair
  Christian Gilissen, ASHG 2016 Program Committee

 

3398/12:00 TOPMed: Early insights from sequencing and analysis of 45,934 deep human genomes. G. Abecasis, P. Natarajan, G. Peloso, S. Lee, NHLBI Trans-Omics for Precision Medicine and TOPMed Anthropometry and Lipids Working Groups.

3399/12:20 Epigenomic profiling at high resolution reveals genetic regulatory signatures underlying islet gene expression and type 2 diabetes. A. Varshney, L.J. Scott, R. Welch, M.R. Erdos, P.S. Chines, N. Narisu, R.D.O. Albanus, P. Orchard, B.N. Wolford, R. Kursawe, S. Vadlamudi, M.E. Cannon, J. Didion, J. Hensley, A. Kirilusha, L.L. Bonnycastle, D.L. Taylor, R.M. Watanabe, K.L. Mohlke, M. Boehnke, F.S. Collins, S.C.J. Parker, M.L. Stitzel, NIH Intramural Sequencing Center (NISC) Comparative Sequencing Program.

3400/12:40 Exome sequencing of infant dried blood spots identifies three-quarters of metabolic disorders found by newborn screening, indicating limits to exomes in both newborn screening and diagnostic testing. A.N. Adhikari, Y. Wang, R. Gallagher, Y. Zou, U. Sunderam, J. Shieh, A. Chellappan, L. Bassaganyas, B. Cai, F. Chen, G. Freedman, B.A. Koenig, M. Kvale, D. Lee, D. Vaka, B. Zerbe, S.D. Mooney, R. Srinivasan, P.-Y. Kwok, J.M. Puck, S.E. Brenner, The NBSeq Project.