All Numbered Sessions Listing

Tuesday, October 17

4:30 PM–5:00 PM

1. ASHG Presidential Address: Checking, Balancing, and Celebrating Genetic Diversity

South Hall B, Level 1, Convention Center

Nancy Cox

Nancy J. Cox, ASHG 2017 President

Of all science, human genetics is no doubt most cognizant of the value of diversity. Quite literally, we, as a science and as a species, would not be here without it. So this year, join me in celebrating that diversity, as we revisit some of the classic human genetics discoveries in balancing selection. It seems like a particularly important time to remind ourselves of the value of having a really deep understanding of the all of the genetic diversity in human populations and how local adaptations to specific environments, past and present, now reach through to affect our risk to what is often termed diseases of western diet and lifestyle. As always, we have much more to learn. Technology advances are rapidly expanding our ability to catalog human variation, and a host of new kinds of -omics data and computational methods provide an ever better foundation for understanding how this genetic variation affects the entire spectrum of human phenotypes. New observations inevitably lead to a reconsideration of what we think we know, and new kinds of data expand the kinds of questions we can ask, and I will explore both of these facets with reference to balancing selection.

 


Tuesday, October 17

5:00 PM–5:15 PM

2. ASHG Victor A. McKusick Leadership Award Presentation and Lecture: Bringing Genetics to New Frontiers

South Hall B, Level 1, Convention Center

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: Brendan Lee, Baylor College of Medicine, Houston

Recipient:
Art Beaudet
Arthur L. Beaudet, MD, Baylor College of Medicine, Houston

In the 1980s, Dr. Beaudet and colleagues were the first to document uniparental disomy in humans. Later, they drew a key distinction between genetic and epigenetic diseases that both lead to altered expression of the same genes, and identified ways to study these and better understand the conditions they caused. Currently, Dr. Beaudet’s research focuses on neuronal carnitine deficiency as a risk factor for autism; the role of genomic imprinting in diseases; and prenatal genetic diagnosis based on fetal cells isolated from maternal blood.

 


Tuesday, October 17

5:15 PM–5:30 PM

3. ASHG Curt Stern Award Presentation and Lecture: The Ciliopathies: From Genes to Biological Molecules to Therapeutic Opportunities

South Hall B, Level 1, Convention Center

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

Introduction: Jim Lupski, Baylor College of Medicine, Houston

Recipient:
Nicholas Katsanis
Nicholas Katsanis, PhD, Duke University, Durham

Dr. Katsanis began his career studying Bardet-Biedl syndrome (BBS), leading the discovery of several BBS genes and the establishment of the ciliopathies as a discrete entity. His lab continues to investigate the molecular causes behind ciliary disorders, with emphasis on the signaling roles of cilia, the mechanisms behind how genes interact to cause rare genetic disorders, and possible treatments for these conditions. In 2009, he established the Center for Human Disease Modeling at Duke University, which aims to facilitate collaboration across disciplines and to develop physiologically relevant, scalable tools to study variation among human patient genomes.

 


Tuesday, October 17

5:30 PM–7:00 PM

4. Featured Plenary Abstract Session I

South Hall B, Level 1, Convention Center

Moderators: Peter C. Scacheri, ASHG 2017 Program Committee Chair
  Heather C. Mefford, ASHG 2017 Program Committee

 

1/5:30 Novel loci associated with skin pigmentation identified in African populations. N. Crawford, D. Kelly, M. Hansen, M. Holsbach Beltrame, S. Fan, S. Bowman, E. Jewett, A. Ranciaro, S. Thompson, S. Pfeifer, J. Jensen, S. Wata Mpoloka, G. Mokone, T. Nyambo, D. Wolde Meskel, G. Belay, H. Rothschild, Y. Zhou, M. Kovacs, M. Xu, E. Oceana, Y. Song, E. Eskin, K. Brown, M. Marks, S. Loftus, W. Pavan, M. Yeager, S. Chanock, S. Tishkoff.

2/5:50 An atlas of 8,342 mosaic structural variants reveals genetic drivers of clonal hematopoiesis. P. Loh, G. Genovese, R.E. Handsaker, H.K. Finucane, Y.A. Reshef, P. Palamara, B.M. Birmann, S.F. Bakhoum, S.A. McCarroll, A.L. Price.

3/6:10 An intronic ABCA7 tandem repeat affects Alzheimer’s disease, gene expression, and alternative splicing. A. De Roeck, L. Duchateau, J. Van Dongen, C. Van Broeckhoven, K. Sleegers, BELNEU Consortium.

4/6:30 Scalable computational quantification of gender representation and behavior at ASHG. N. Telis, E.C. Glassberg, C. Gunter, J.K. Pritchard.


Tuesday, October 17

7:15 PM–9:15 PM

5. Poster Talks

Room 330A, Level 3, Convention Center

Moderators: Beryl B. Cummings, ASHG 2017 Program Committee
  Olivia G. Corradin, ASHG 2017 Program Committee

 

This session gives you a sneak peek at some of the top-scoring posters across a variety of topics through rapid-fire presentations. The featured abstracts were chosen by the Program Committee and are marked by a microphone in the online program. Conversations with the presenters will continue at the Poster Sessions throughout the meeting. Light refreshments will be provided.

 

432F    Germline de novo mutation clusters arise during oocyte aging in genomic regions with increased double-strand break incidence. C. Gilissen, J.M. Goldmann, V.B. Seplyarskiy, W.S.W. Wong, T. Vilboux, D.L. Bodian, B.D. Solomon, J.A. Veltman, J.F. Deeken, J.E. Niederhuber.

442W    Ancestral disparities in genetic architecture of life course correlations between early growth and adulthood cardiometabolic disorders. F. Tekola Ayele, T. Workalemahu, A. Amare.

490W    Revealing transcriptome and methylome landscapes in a human oocyte by parallel sequencing. T. Lee, Y. Qian, J. Liao, L. Chi, G. Kong, C. Chung, T. Leung, K. Yip, K. Chow, W. Chan, T. Li.

527T    Maternal origin of familial 22q11.2 deletions negatively impacts FSIQ scores. D.E. McGinn, T.B. Crowley, M. Unolt, B.S. Emanuel, E.H. Zackai, E. Moss, B. Morrow, J. Vermeesch, A. Swillen, D.M. McDonald-McGinn.

545T    Fine-scale demography and behavior of male and female human geneticists. E. Glassberg, N. Telis, C. Gunter.

610W    WGS in pediatric neuroncology patients shows a preponderance of germline Mendelian disease gene mutations. M. Bainbridge, S. Nahas, L. Farnaes, D. Dimmock, D. Malicki, M. Bondy, S. Chowdhury, S. Kingsmore, J. Crawford, R. Wechsler-Reya.

814W    Clinical relevance of non-coding A-to-I RNA editing in multiple human cancers. T. Gu, A. Fu, M. Bolt, K. White.

992T    Integrative omics analysis of a cohort of 198 singletons with cerebral palsy. J. Gecz, CL. vanEyk, JL. Broadbent, K. Harper, A. Gardner, BW. Van Bon, MA. Corbett, A. MacLennan.

1184T    LabWAS: A catalog of real-world associations between genetic variants and lab values. J.A. Goldstein, L.A. Bastarache, P. Speltz, A. Gifford, D.M. Roden, J.C. Denny.

1452F    Drug side effects and adverse events are predicted by genetics of their intended targets. P.A. Nguyen, A. Deaton, P. Nioi, L.D. Ward.

1525W    Chromosomal integration of libraries of full-length mutant genes with associated barcode tags. X. Jia, V. Chen, M. Maksutova, S. Jayakody, R. Lemons, J. Kitzman.

1566F    Cis regulatory variation determines dynamic HLA-DQB1 allelic expression in response to T cell activation. M. Gutierrez-Arcelus, S. Hannes, N. Teslovich, Y. Luo, H.J. Westra, K. Slowikowski, D.A. Rao, J. Ermann, M.B. Brenner, S. Raychaudhuri.

1668F    Identification of genetically associated changes in 3D-chromatin architecture by leveraging haplotype information across a three-generation family. W.W. Greenwald, H. Li, P. Benaglio, A. Schmitt, Y. Qiu, B. Ren, M. D'Antonio, E.N. Smith, K.A. Frazer.

1716F    A mutation in MAL is associated with a neurodevelopmental condition characterized by central hypomyelination, cerebellar atrophy and developmental delay. M. Elpidorou, J.A. Poulter, J.H. Livingston, E. Sheridan, C.A. Johnson.

1745T    Changes of open chromatin regions reveal stage-specific transcriptional network dynamics in human iPSC-derived neurons. W. Moy, S. Zhang, H. Zhang, H. McGowan, J. Shi, C. Leites, A.R. Sanders, P.V. Gejman, J. Duan.

1882W    Mapping human airway smooth muscle cell transcriptional and epigenetic responses to asthma-promoting cytokines reveals enrichments for asthma-associated SNPs. E.E. Thompson, Q. Dang, B. Mitchell-Handley, K. Rajendran, S. Ram-Mohan, J. Solway, R. Krishnan, C. Ober.

1988T    The genetic architecture of osteoarthritis: Insights from UK Biobank. E. Zeggini, E. Zengini, K. Hatzikotoulas, I. Tachmazidou, J. Steinberg, S. Hackinger, U. Styrkarsdottir, D. Suveges, B. Killian, A. Gilly, T. Ingvarsson, H. Jonsson, G. Babis, U. Thorsteinsdottir, K. Stefansson, J. Wilkinson.

2336T    Adaptive eQTLs in human populations. M. Quiver, J. Lachance.

2347W    Partitioning heritability of low-frequency variants reveals relative strength of negative selection across functional annotations. S. Gazal, A. Ganna, A. Schoech, P.R. Loh, A. Gusev, T. Esko, A. Palotie, B.M. Neale, S. Sunyaev, H.K. Finucane, A.L. Price.

2519T    Constitutive supernumerary marker chromosomes are the chromothripsis remnant of the supernumerary chromosome present in trisomic embryos. N. Kurtas, L. Leonardelli, L. Xumerle, M. Delledonne, A. Brusco, K. Chrzaowska, A. Schinzel, S. Guerneri, E. Manolakos, S. Giglio, T. Liehr, O. Zuffardi.

2732T    High-throughput discovery of deleterious cardiac sodium channel variants. A. Glazer, B. Kroncke, K. Matreyek, T. Yang, D. Fowler, D. Roden.

2855T    Integrating eQTL data with GWAS summary statistics identifies novel genes and pathways associated with schizophrenia. C. Wu, W. Pan.

2992W    DESCEND: Expression distribution deconvolution in scRNA-seq and characterization of transcriptional bursting and expression dispersion. J. Wang, N. Zhang, M. Li, A. Raj, J. Murray.


Wednesday, October 18

9:00 AM–10:30 AM

Concurrent Platform Session A

6. Genetics of Vascular, Valvular, and Syndromic Disorders

Room 220B, Level 2, Convention Center

Moderators: Guillaume Lettre, Montreal Heart Inst, Canada
  Nabila Bouatia-Naji, INSERM/Paris Cardiovasc Res Ctr, France

 

5/9:00 Functional characterization of modifier loci for Marfan syndrome reveals novel therapeutic strategies. R.D. Wardlow, J.J. Doyle, A.J. Doyle, N.K. Wilson, D. Bedja, H.C. Dietz.

6/9:15 Transcriptome analysis of miRNA and mRNA in the PL/J mouse model of hypoxia-induced pulmonary arterial hypertension. K.T. Ikeda, P.T. Hale, M.W. Pauciulo, N. Dasgupta, M.K. Pandey, W.C. Nichols.

7/9:30 Mechanistic interrogation of a gene-by-environment interaction informs the pathogenesis and treatment of Mendelian aneurysm disorders. N.K. Wilson, J.J. Doyle, E. Gallo MacFarlane, R. Bagirzadeh, G. Yazdanifar, D. Bedja, S.K. Cooke, H.C. Dietz, MIBAVA Leducq Consortium.

8/9:45 Identification of a novel marker for valve maturation: Loss of ADAMTS19 function causes progressive valve disease in mice and men. F. Wünnemann, A. Ta-Shma, M-P. Tremblay, C. Preuss, P. van Vliet, S. Leclerc, E. Audain, S. Gerety, M. Hurles, W. Makalowski, O. Elpeleg, M-P. Hitz, G. Andelfinger, MIBAVA Leducq Consortium.

9/10:00 LTBP3 recessive mutations cause amelogenesis imperfecta as well as aortic diseases. D. Guo, E. Regalado, J. Chen, A. Pinard, C. Rigelsky, L. Zilberberg, E. Hostetler, S. Wallace, M. Bamshad, D. Nickerson, D. Rifkin, D. Milewicz, University of Washington Center for Mendelian Genomics, Seattle, WA.

10/10:15 Identification of an autosomal recessive form of Noonan Syndrome. J. Johnston, J.J. van der Smagt, J.A. Rosenfeld, A. Alswaid, E.H. Baker, G. Borck, J. Brinkmann, W. Craigen, V.C. Dung, L. Emrick, D.B. Everman, K.L. van Gassen, S. Gulsuner, M.H. Harr, M. Jain, K.A. Leppig, D.M. McDonald-McGinn, C.T.B. Ngoc, E.R. Roeder, R.C. Rogers, J.C. Sapp, A.A. Schäffer, D. Schanze, N.E. Verbeek, M.A. Walkiewicz, E.H. Zackai, M. Zenker, C. Zweier, B. Lee, L.G. Biesecker, Members of UDN.


Wednesday, October 18

9:00 AM–10:30 AM

Concurrent Platform Session A

7. Modeling Mega-cohorts: Insights and Innovation

Room 220F, Level 2, Convention Center

Moderators: Xiang Zhou, Univ Michigan, Ann Arbor
  Tamar Sofer, Univ Washington, Seattle

 

NOTE: Overflow seating for this session is available in Room 220D.

 

11/9:00 Novel insights into clinically relevant variation using the diverse sample populations of the PAGE study. E.P. Sorokin, G.M. Belbin, G.L. Wojcik, N. Abul-Husn, S. Bien, N. Zubair, P. Norman, G. Nadkarni, C. Hodonsky, J. Odgis, C. Avery, S. Buyske, T. Matise, J. Kocarnik, L. Hindorff, R. James, K.E. North, R. Loos, C. Haiman, C. Kooperberg, C. Carlson, C.D. Bustamante, C.R. Gignoux, E.E. Kenny, the Population Architecture using Genomics and Epidemiology (PAGE) study.

12/9:15 Common and rare variants associated with adult height: The Million Veteran Program. T.L. Assimes, J. Huang, J. Li, K. Cho, Y. Ho, Y. Sun, N. Sun, J.M. Gaziano, J. Concato, S. Pyarajan, S. Muralidhar, H. Hunter-Zinck, H. Zhao, P. Wilson, P. Tsao, E.R. Hauser, C.J. O'Donnell, on behalf of the VA Million Veteran Program.

13/9:30 Integrated inference that accurately identifies close relatives in > 1 million samples. W.-M. Chen, A. Manichaikul, J. Nguyen, S. Onengut-Gumuscu, S.S. Rich.

14/9:45 Using genotyped relatives of ungenotyped type 2 diabetes cases as proxy-cases in a cohort based genome-wide association study. B.N. Wolford, S. Lee, W. Zhou, J.B. Nielsen, L.G. Fritsche, M. Lin, H.M. Kang, M. Gabrieldsen, O. Holmen, K. Hveem, G.R. Abecasis, M. Boehnke, C.J. Willer.

15/10:00 Sparse linear mixed models for pedigrees with millions of individuals. T. Shor, D. Geiger, Y. Erlich, O. Weissbrod.

16/10:15 Personalized feedback on the genetic risk of common complex diseases: The potential of a large population-based biobank, and methodological challenges. K. Fischer, K. Läll, R. Mägi, T. Esko, L. Leitsalu, N. Tõnisson, A. Metspalu.


Wednesday, October 18

9:00 AM–10:30 AM

Concurrent Platform Session A

8. Genetics and Epigenetics in Mental Illness

Room 230C, Level 2, Convention Center

Moderators: Simon Gregory, Duke Univ, Durham
  Zachary Kaminsky, Johns Hopkins Univ, Baltimore

 

NOTE: Overflow seating for this session is available in Room 230A.

 

17/9:00 Landscape of allele-specific open chromatin in human iPSC-differentiated neurons and its implication for mental disorders. S. Zhang, W. Moy, H. Zhang, H. McGowan, J. Shi, C. Leites, A. Sanders, Z. Pang, P. Gejman, J. Duan.

18/9:15 Alternative splicing of brain-expressed transcripts distinguishes major adult psychiatric disorders. N. Akula, R. Kramer, Q. Xu, K. Johnson, S. Marenco, J. Apud, H. Rhodes, B. Harris, B.K. Lipska, F.J. McMahon.

19/9:30 Sexually dimorphic DNA methylation in human brain and relevance to psychiatric disorders. Y. Xia, R. Dai, K. Wang, Y. Xu, H. Li, J. Xi, C. Chen, C. Liu, the PsychENCODE Consortium.

20/9:45 Genome-wide methylomic analysis of neonatal blood from Danish twins discordant for mental illness. S. Weinsheimer, A. Starnawska, C.S. Hansen, A. Buil, J. Bybjerg-Grauholm, M. Bækvad-Hansen, D.M. Hougaard, T. Sparsø, M. Bertalan, P.B. Mortensen, C.B. Pedersen, T.M. Werge.

21/10:00 GWAS of the PTSD “re-experiencing” symptom cluster in the MVP sample, N>150,000. J. Gelernter, N. Sun, R. Pietrzak, Q. Lu, Y. Hu, B. Li, Q. Chen, K. Radhakrishnan, M. Aslan, K.H. Cheung, Y. Li, N. Rajeevan, F. Sayward, K. Harrington, K. Cho, J. Honerlaw, S. Pyarajan, R. Quaden, J.M. Gaziano, J. Concato, H. Zhao, M.B. Stein, on behalf of: Dept Veterans Affairs Cooperative Studies Program (#575B) & Million Veteran Program.

22/10:15 Identification of genome-wide significant shared genomic segments in large extended Utah families at high risk for completed suicide. H. Coon, T.M. Darlington, W.B. Callor, E. Ferris, A. Fraser, Z. Yu, N. Williams, S.E. Crowell, L. Jerominski, D. Cannon, K.R. Smith, B. Keeshin, A.V. Bakian, E. Christensen, N.J. Camp, D. Gray.


Wednesday, October 18

9:00 AM–10:30 AM

Concurrent Platform Session A

9. Genome Structure and Function: The Contribution of Mutations to Human Genetic Diversity, Disease, and Evolution

Room 230G, Level 2, Convention Center

Moderators: Christine R. Beck, Jackson Lab for Genomic Med, UConn Health, Farmington
  Clement Y. Chow, Univ Utah, Salt Lake City

 

NOTE: Overflow seating for this session is available in Room 230E.

 

23/9:00 Genetic associations of DNA replication timing inferred from deep sequencing of 106 human embryonic stem cell lines. Q. Ding, C. Charvet, C.J. Hsiao, X. Zhu, F.T. Merkle, R.E. Handsaker, S. Ghosh, K. Eggan, S.A. McCarroll, M. Stephens, Y. Gilad, A.G. Clark, A. Koren.

24/9:15 Mutational origins and pathogenic consequences of multinucleotide mutations in 6,868 trios with developmental disorders. J. Kaplanis, M.E. Hurles, on behalf of the DDD study.

25/9:30 Characterization of the noncoding regulatory landscape within human-specific duplicated regions. P. Carmona Mora, C.J. Shew, E. Ha, M.Y. Dennis.

26/9:45 Single-molecule mapping of complex genomic regions across 26 human populations reveals population specific variation patterns. P. Kwok, C. Chu, A. Hastie, E. Lam, A. Leung, L. Li, J. McCaffrey, M. Levy-Sakin, Y. Mostovoy, S. Pastor, A. Poon, R. Rajagopalan, J. Sibert, W. Wang, E. Young, H. Cao, T. Chan, K. Yip, M. Xiao.

27/10:00 Evolutionarily young LINE elements initiate recurrent DNA breaks forming different-sized CNVs via both NAHR and microhomology-mediated DNA replication mechanisms. P. Szafranski, E. Kośmider, J. Wambach, L. Currie, S. Parkash, G.K. Suresh, M.T. Harting, M.D. Weaver, A.M. Khan, N. Tatevian, A.M. Breman, C.A. Shaw, E. Popek, C.R. Beck, A. Gambin, P. Stankiewicz.

28/10:15 Human immune defense mechanisms drive rapid genome evolution in vaccinia virus. T. Sasani, K. Rogers-Cone, R. Layer, N. Elde, A. Quinlan.


Wednesday, October 18

9:00 AM–10:30 AM

Concurrent Platform Session A

10. Disease Gene Discovery Strategies

Room 310A, Level 3, Convention Center

Moderators: Han Brunner, Radboud Univ Med Ctr, Nijmegen, Netherlands
  Kristin Kernohan, Children's Hosp Eastern Ontario, Ottawa, Canada

 

NOTE: Overflow seating for this session is available in Room 331A.

 

29/9:00 Integrated sequence technology approaches to genomic diagnosis of birth defects. K. Meltz Steinberg, J. Wambach, D. Wegner, D.E. Baldridge, D. Spencer, F.S. Cole.

30/9:15 New strategies for analyzing exomes from patients with rare and unknown disorders. K. Schmitz-Abe, P. Agrawal.

31/9:30 The Human-Mouse Disease Connection (HMDC) Portal: Comparing mouse and human disease data to enable discovery. C. Smith, S. Bello, J. Kadin, J. Richardon, Mouse Genome Informatics Team.

32/9:45 Gene discovery via direct-to-family engagement using MyGene2. J.X. Chong, R. Cornejo, Jr., A.G. Shankar, A.E. Tattersall, D.A. Nickerson, M.J. Bamshad, University of Washington Center for Mendelian Genomics.

33/10:00 Initiative on Rare and Undiagnosed Diseases in Pediatrics (IRUD-P) in Japan: Recent achievement and statistics. Y. Matsubara, K. Hata, T. Kaname, K. Kosaki, IRUD-P consortium.

34/10:15 Contribution of novel disease gene discovery to clinical diagnosis and management. J.E. Posey, J.A. Rosenfeld, Z.H. Coban Akdemir, S. Jhangiani, T. Harel, M.K. Eldomery, A. Stray-Pedersen, I.K. Chinn, S. Lalani, P. Stankiewicz, M. Walkiewicz, P. Liu, M. Leduc, L. Meng, F. Xia, X. Wang, R. Xiao, C.A. Shaw, C.M. Eng, D. Muzny, R.A. Gibbs, E. Boerwinkle, V.R. Sutton, S.E. Plon, J.S. Orange, Y. Yang, J.R. Lupski.


Wednesday, October 18

9:00 AM–10:30 AM

Concurrent Platform Session A

11. Therapeutic Advances in Mendelian Disease

Room 310C, Level 3, Convention Center

Moderators: Susan Slaugenhaupt, Massachusetts Gen Hosp Simches Res Ctr, Cambridge
  Philip Beales, UCL Inst Child Health, London, UK

 

35/9:00 Shedding light into voltage-gated sodium channel associated neurodevelopmental disorders. D. Lal, J. Du, C. Dühring Fenger, E. Perez-Palma, A.J. Campbell, A. Allen, D. Baez-Nieto, H.R. Wang, J. Cottrell, F. Wagner, J.Q. Pen, H. Stammberger, I. Helbig, P. DeJonge, S. Weckhuysen, B. Sheidley, S. Zuberi, A. Poduri, S. McCarroll, A. Brunklaus, R.S. Møller, M. Daly, A. Palotie.

36/9:15 CFTR-targeted therapy for a subset of splice-site and nonsense variants that allow protein production. M.J. Pellicore, T.A. Evans, E. Davis, S.T. Han, A. McCague, A. Joynt, Z. Lu, Y. Akhtar, N. West, C. Merlo, K.S. Raraigh, P.R. Sosnay, C. Cotton, G.R. Cutting, N. Sharma.

37/9:30 Correlating CFTR function with key clinical features to inform targeted treatment of cystic fibrosis. A. McCague, S.T. Han, M. Atalar, M.J. Pellicore, T.A. Evans, E.F. Davis, N. Sharma, K.S. Raraigh, P.R. Sosnay, G.R. Cutting.

38/9:45 A CRISPR-C2c2 based therapy to target toxic RNA in microsatellite expansion diseases. N. Zhang, T. Ashizawa.

39/10:00 The first viable mouse model of cblC deficiency displays growth failure and reduced survival which are rescued by hydroxocobalamin and AAV gene therapy. J.L. Sloan, M.L. Arnold, N.P. Achilly, G. Elliot, P. Zerfas, V. Hoffman, C.P. Venditti.

40/10:15 ZFN-mediated in vivo genome editing results in continuous high levels of GLA activity and effective substrate reduction in Fabry mice. S. Pagant, M. Yasuda, M.W. Huston, T. Wechsler, S. St. Martin, M.C. Holmes, R.J. Desnick.


Wednesday, October 18

9:00 AM–10:30 AM

Concurrent Platform Session A

12. Detection and Impact of Mosaicism in Human Disease

Room 320, Level 3, Convention Center

Moderators: James T. Bennett, Univ Washington/Seattle Children's Hosp
  Gemma L. Carvill, Northwestern Univ, Chicago

 

41/9:00 Parental mosaicism for apparent de novo variants from exome sequencing of 10,000 trios. R. Torene, K. Arvai, Z. Zhang, E. Butler, D. McKnight, J. Juusola, K. Retterer.

42/9:15 Deep amplicon resequencing identified parental mosaicism for approximately 10% “de novoSCN1A mutations in Dravet Syndrome families and was capable of multiple validation of mosaicism. X. Yang, X. Xu, Q. Wu, Y. Dou, K. Wang, A.Y. Ye, A.U. Huang, Y. Zhang, L. Wei.

43/9:30 A clinical survey of mosaic variants in disease-causing genes detected by whole exome sequencing. M.J. Tokita, W. He, F. Vetrini, A.V. Dharmadhikari, J. Zhang, T. Sim, X. Ge, P. Ward, A. Braxton, S. Narayanan, M. Leduc, X. Wang, L. Meng, R. Xiao, W. Bi, F. Xia, M. Walkiewicz, C. Shaw, C. Eng, P. Stankiewicz, Y. Yang, P. Liu.

44/9:45 Mosaic EFTUD1 mutation causes Shwachman-Diamond syndrome through dysregulating ribosome assembly. S. Lee, C.H. Shin, C.R. Hong, J.-D. Kim, J.M. Ko, T.-J. Cho, S.-W. Jin, H.J. Kang, H.H. Kim, M. Choi.

45/10:00 Assessing the landscape of selfish de novo FGFR2 mutations in human testes. H.K. Ralph, G.J. Maher, Z. Ding, E. Giannoulatou, N. Koelling, S.J. McGowan, G. McVean, A.O.M. Wilkie, A. Goriely.

46/10:15 Genomewide association and inference of clonal mosaicism implicates germline variation in XPO1 as a driver of genome instability. Y. Jakubek, S. Vattathil, P. Auer, P. Scheet.


Wednesday, October 18

9:00 AM–10:30 AM

Concurrent Platform Session A

13. Pleiotropism and Penetrance in Cancer-causing Genes

Room 330A, Level 3, Convention Center

Moderators: Pengei Liu, Baylor Col Med, Houston
  Wenyi Wang, Univ Texas, MD Anderson Cancer, Houston

 

47/9:00 Cancer risk in neurofibromatosis 1 (NF1): Nation-wide, population-based Danish cohorts followed up to 3/4 century. J.J. Mulvihill, L. Kenborg, J.H. Olsen, J. Rosendahl-Østergaard, H. Hasle, A. Redzkina, S.A. Sørensen, J.F. Winther.

48/9:15 Looking beyond the lamppost: Population-based exome sequencing to ascertain prevalence and penetrance in the DICER1 syndrome, a rare tumor-predisposition disorder. U.L. Mirshahi, J. Kim, K. Manickam, M.F. Murray, D.J. Carey, D.R. Stewart, on behalf of the Geisinger-Regeneron DiscovEHR Collaboration.

49/9:30 Higher-than-expected population prevalence of potentially pathogenic germline TP53 variants in individuals unselected for cancer history. K.C. De Andrade, L. Mirabello, D.R. Stewart, E. Karlins, R. Koster, M. Wang, S.M. Gapstur, M.M. Gaudet, N.D. Freedman, M.T. Landi, N. Lemonnier, P. Hainaut, S.A. Savage, M.I. Achatz.

50/9:45 Large-scale phenome-wide scan in twins helps identify candidate variants associated with seborrheic keratosis. S. Hebbring, Z. Ye, J. Pathak, S. Kim, L. Bastarache, J. Mayer, J. Liu, Y. Cheng, S. Schrodi, J. Denny, M. Brilliant.

51/10:00 Oncogenic potential of germline mutations in the lysosomal storage disease-associated genes. J. Shin, D. Kim, Y. Koh, S. Yoon.

52/10:15 Coverage matters: High rate of promoter 1B deletions in a large APC testing cohort. A.J. Stuenkel, K. Jasperson, H. LaDuca, M. Richardson, S. Gutierrez, K. Blanco, L. Hoang, C. Espenschied.


Wednesday, October 18

9:00 AM–10:30 AM

Concurrent Platform Session A

14. Landscape of Cancer: Bioinformatic Analyses

Room 330C, Level 3, Convention Center

Moderators: Lisa Mirabello, Natl Cancer Inst, Rockville
  Daniel Schaid, Mayo Clinic, Rochester

 

53/9:00 Passenger mutations in 2500 cancer genomes: Overall molecular functional impact and consequences. M. Gerstein, S. Kumar, P. McGillivray, W. Myerson, L. Salichos, S. Li, A. Harmanci, J. Warrell, E. Khurana, A. Fundichely, C. Chan, C. Herrmann, M. Nielsen, X. Li, Y. Zhang.

54/9:15 The impact of PRDM9 expression on the cancer genomic rearrangement landscape. A. Ang Houle, M. Agbessi, V. Bruat, F. Lamaze, L. Stein, P. Awadalla, Pan-Cancer Analysis of Whole Genome Consortium.

55/9:30 Unlocking the genetic and molecular regulation of APOBEC mutagenesis in human cancers. A.R. Banday, A. Bayanjargal, K.I. Udquim, O.O. Onabajo, A. Obajemu, L. Prokunina-Olsson.

56/9:45 Accelerating pharmacogenomics discovery by imputing drug response in The Cancer Genome Atlas and beyond. P. Geeleher, Z. Zhang, F. Wang, R.F. Gruener, A. Nath, G. Morrison, R.L. Grossman, R.S. Huang.

57/10:00 Identifying and characterizing novel virus integrations in hepatocellular carcinoma genomes by virome-wide analysis of whole-genome sequencing data. X. Chen, A. Sulovari, C. Jian, D. Li.

58/10:15 SiFit: A method for inferring tumor trees from single-cell sequencing data under finite-site models. H. Zafar, A. Tzen, N. Navin, K. Chen, L. Nakhleh.


Wednesday, October 18

11:00 AM–12:30 PM

Concurrent Platform Session B

15. Screening Cancer Cohorts for Novel Germline Cancer Genes

Room 220B, Level 2, Convention Center

Moderators: Matthew Bainbridge, Rady Children's Hospital, San Diego
  Elaine Ostrander, NHGRI, Bethesda

 

59/11:00 Exome sequencing identifies de novo germline mutations in patients with early-onset cancer. Z.K. Stadler, J. Vijai, M. Ronemus, S. Topka, T. Thomas, B. Yamrom, I. Iossifov, D. Villano, D. Levy, J. Kendall, C. Tran, S. Mukherjee, A. Maria, M. Robson, D. Bajorin, R. Kobos, B. Kushner, M. Walsh, L. Saltz, D. Feldman, G. Bosl, L. Norton, S. Modak, M. Seandel, M. Wigler, K. Offit.

60/11:15 Discovery and prevalence of germline and somatic mutations in patients with advanced renal cell carcinoma in MSK-IMPACT cancer genes. S. Mukherjee, M.I. Carlos, Z. Stadler, J. Vijai, M. Walsh, A.G. Arnold, M. Sheehan, Y. Kemel, V. Ravichandran, Z. Shameer, D. Coskey, N. Pradhan, C. Stewart, A. Victor, A. Zehir, A. A. Hakimi, J.A. Coleman, C.H. Lee, D.R. Feldman, M.H. Voss, D.B. Solit, M.F. Berger, M. Ladanyi, D. Mandelker, L. Zhang, M. Robson, R.J. Motzer, K. Offit.

61/11:30 Rates and qualities of actionable and uncertain findings detected by eMERGE panel sequencing in 1155 colorectal cancer patients. A.S. Gordon, H. Zouk, K.A. Leppig, D. Carrell, J. Ralston, A. Scrol, L. Witkowski, H.L. Rehm, E.A. Rosenthal, D.R. Crosslin, E. Larson, G.P. Jarvik.

62/11:45 Cancer risks associated with known and putative predisposition gene mutations in a 341 gene panel sequenced on 10,000 individuals with advanced cancers. J. Vijai, P. Sreenivasan, S. Mukherjee, C. Bandlamudi, Y. Kemel, V. Ravichandran, Z. Shameer, S. Topka, N. Bense, D. Mandelkar, A. Zehir, L. Zhang, M. Walsh, K. Cadoo, Z. Stadler, B. Taylor, D. Solit, M. Robson, M. Berger, K. Offit.

63/12:00 Prevalence of mutations in a large series of clinically ascertained ovarian cancer cases tested on multi-gene panels compared to reference controls. J. Lilyquist, H. LaDuca, E. Polley, B. Tippin Davis, H. Shimelis, C. Hu, S.N. Hart, J.S. Dolinsky, F.J. Couch, D.E. Goldgar.

64/12:15 Genome-wide association study (GWAS) identifies 9 novel breast cancer loci from analyses accounting for subtype heterogeneity. H. Zhang, J. Lecarpentier, T.U. Ahearn, K. Michailidou, R.L. Milne, P. Kraft, J. Simard, P.D.P Pharoah, M. Schmidt, D. Easton, N. Chatterjee, M. Garcia-Closas, on behalf of the Breast Cancer Association Consortium.


Wednesday, October 18

11:00 AM–12:30 PM

Concurrent Platform Session B

16. Cancer Genetic Testing: Approaches, Barriers, and Psychosocial Impact

Room 220F, Level 2, Convention Center

Moderators: Jessica Everett, New York Univ Med Ctr
  Kathleen Blazer, City of Hope Comprehensive Cancer Ctr, Duarte

 

65/11:00 Using cancer status is better, simpler and more cost-effective than family history in determining breast cancer genetic testing eligibility. N. Rahman, A. Turnbull, A. George, A. Strydom, Z. Kemp.

66/11:15 Discovery of germline pathogenic mutations in hereditary cancer syndromes with whole genome, low-coverage variant imputation. H.P. Ji, S.U. Greer, O. Barad, I. Kela, Y. Waldman.

67/11:30 Population genetic testing for breast and ovarian cancer susceptibility. I. Campbell, S. Rowley, L. Devereux, D. Goode, S. McInerny, N. Grewal, A. Lee, A. Trainer, M-A. Young, N. Li, P. James.

68/11:45 BRCA population screening in unaffected Ashkenazi Jewish women: A randomized controlled trial of different pre-test strategies. E. Levy-Lahad, S. Lieberman, A. Tomer, A. Ben-Chetrit, O. Olsha, S. Levin, R. Beeri, A. Raz, A. Lahad.

69/12:00 Barriers and facilitators to genetic testing among a population-based sample of young Hispanic and non-Hispanic White breast cancer survivors. D. Cragun, A. Weidner, T. Pal.

70/12:15 Psychosocial outcomes of genetic counseling in a population based sample of Black breast cancer survivors. S.T. Vadaparampil, M. L. Kasting, D. Cragun, J.P. Kim, B. Augusto, J. Garcia, C.L. Holt, K. Ashing, C. Hughes-Halbert, T. Pal.


Wednesday, October 18

11:00 AM–12:30 PM

Concurrent Platform Session B

17. Advances in Association Analysis

Room 230C, Level 2, Convention Center

Moderators: Leyao Wang, Yale Univ, New Haven
  Ching-Ti Liu, Boston Univ

 

NOTE: Overflow seating for this session is available in Room 230A.

 

71/11:00 Methods for meta-analysis of multiple traits using GWAS summary statistics with an application to lipid traits. D. Ray, M. Boehnke.

72/11:15 Quantifying directional effects of transcription factor binding on polygenic disease risk using GWAS summary statistics. Y. Reshef, H. Finucane, D. Kelley, A. Gusev, J. Ulirsch, L. O'Connor, B. van de Geijn, P. Loh, S. Grossman, G. Bhatia, S. Gazal, P. Palamara, L. Pinello, N. Patterson, R. Adams, A. Price.

73/11:30 Tissue specific transcriptome prediction leveraging GTEx datasets and gene-level association mapping and fine-mapping. Z. Qi, Y. Guan.

74/11:45 New IDEAS for GWAS loci: Using genome segmentation to identify causal variants and tissues driving disease associations. Y. Zhang, K. Sieber, M.R. Nelson, C. Guo.

75/12:00 Rare variant association in non-coding sequence: An analysis of deep coverage whole genome sequences and blood lipids in 16,324 individuals. P. Natarajan, G.M. Peloso, S.M. Zekavat, M. Montasser, A. Ganna, M. Chaffin, W. Zhao, J. Bloom, J.R. O'Connell, S.E. Ruotsalainen, M. Alver, J.A. Perry, I.L. Surakka, T. Esko, S. Ripatti, A. Correa, B. Neale, G. Abecasis, B. Mitchell, S.S. Rich, J.G. Wilson, L.A. Cupples, J.I. Rotter, C.J. Willer, S. Kathiresan, NHLBI TOPMed Lipids Working Group.

76/12:15 Imaging-wide association study: Integrating imaging endophenotypes in GWAS. Z. Xu, C. Wu, .W. Pan.


Wednesday, October 18

11:00 AM–12:30 PM

Concurrent Platform Session B

18. Strategies for Variant Interpretation

Room 230G, Level 2, Convention Center

Moderators: Caroline Astbury, Cleveland Clinic, Columbus
  Lora Bean, Emory Univ, Atlanta

 

NOTE: Overflow seating for this session is available in Room 230E.

 

77/11:00 Integrated analysis of exome sequencing and metabolomic profiling improves sequence variant interpretation, classification and diagnosis. J.T. Alaimo, L. Hubert, M. Miller, H. Dai, R. Xiao, F. Xia, W. Bi, M. Leduc, M. Walkiewicz, V.R. Sutton, C.M. Eng, Q. Sin, S.H. Elsea, Y. Yang.

78/11:15 A CRISPR/Cas9 pipeline for functionally characterizing variants of uncertain significance in very early onset psychosis. C.F. Mavros, A.H.M. Ng, C.A. Brownstein, K.G.C. Leeper, P.F. Chen, E.D. Buttermore, R.J. Kleiman, J.P. Rodriguez, K. Graber, S.K. Tembulkar, C. Genetti, P.B. Agrawal, A.H. Beggs, G.M. Church, J. Gonzalez-Heydrich.

79/11:30 Analysis of variants of uncertain significance: Application of neoteric protein structural dynamics. P.S. Atwal, P.R. Blackburn, M.T. Zimmerman, T. Caulfield.

80/11:45 Next-Generation Mapping (NGM): A novel approach for genetic diagnosis of structural variants. H. Barseghyan, W. Tang, R. Wang, M. Almalvez, E. Segura, M. Bramble, A. Lipson, E. Douine, H. Lee, E. Delot, S. Nelson, E. Vilain.

81/12:00 A high frequency of previously reported pathogenic variants in nephropathy genes among healthy controls suggests potential for erroneous clinical interpretation of sequence variants for kidney disorders. H. Milo Rasouly, D.A. Fasel, R. Heyman-Kantor, A. Mitrotti, R. Westland, E. Groopman, S. Sanna-Cherchi, D. Goldstein, A. Gharavi.

82/12:15 Gene-specific allele frequency thresholds for benign evidence to empower variant interpretation. D. Qian, S. Li, B.A.J. Sarver, Y. Tian, A. Elliott, H.M. Lu, M.H. Black.


Wednesday, October 18

11:00 AM–12:30 PM

Concurrent Platform Session B

19. From Association to Function for Cardiometabolic Traits

Room 310A, Level 3, Convention Center

Moderators: Erik Ingelsson, Stanford Univ
  Ron Do, Icahn Sch Med, New York

 

83/11:00 Redrawing the map of blood pressure genes in a transcriptome-wide association study of over 301,000 participants in the Million Veterans Program and 145,000 from UK Biobank. D.R. Velez Edwards, T.L. Edwards, J. Hellwege, A. Giri, E. Torstenson, Y.V. Sun, P. Elliot, E. Evangelou, M. Caulfied, P.W.F. Wilson, P.S. Tsao, C.P. Kovesdy, K.A. Birdwell, C. O'Donnell, A. Hung, on behalf of the VA Million Veteran Program and The UK Biobank.

84/11:15 Insights to the population structure and genetic architecture of cardiometabolic traits in 20,029 Finnish exomes. C.W.K. Chiang, A.E. Locke, K.M. Steinberg, S. Service, H. Abel, A.S. Havulinna, C. Chiang, L. Stell, H.M. Stringham, A.U. Jackson, M. Pirinen, D. Ray, D.E. Larson, D.C. Koboldt, L.J. Scott, R.S. Fulton, J. Nelson, T.J. Nicholas, P. Yajnik, V. Ramensky, N.O. Stitziel, I.M. Hall, C. Sabatti, S. Ripatti, V. Salomaa, A. Palotie, M. Laakso, M. Boehnke, R.K. Wilson, N.B. Freimer.

85/11:30 The genetic etiology of metabolic traits in people of Hispanic/Latino ancestry: Large-scale meta-analysis of single variant effects and gene-based functionally oriented analyses in 35,000 Hispanic/Latino individuals. J.E. Below, L.E. Petty, M. Graff, X. Guo, Y. Hai, J. Yao, A. Manichaikul, C. Schurmann, C. Gao, D. Nousome, J.M. Mercader, X.Q. Wang, L.S. Emery, T. Sofer, C.L. Hanis, R. Loos, N.D. Palmer, J. McCormick, S. Fisher-Hoch, J.C. Florez, R. McKean-Cowdin, E.J. Parra, J.I. Rotter, K.E. North.

86/11:45 Identification and validation of novel regulatory genes for simultaneous lipid and blood glucose control in a large coronary artery disease (CAD) cohort using integrative RNA, DNA, metabolomics and clinical trait causal networks. A. Cohain, N.D. Beckmann, D. Jordan, G.M. Belbin, A. Ruusalepp, R. Do, J.LM. Bjorkegren, E.E. Schadt.

87/12:00 Functional annotation of common noncoding and rare coding variants in ANGPTL3. X. Wang, A. Raghavan, A.C. Vourakis, A.E. Sperry, W. Li, W. Lv, A.C. Chadwick, K. Musunuru.

88/12:15 Zebrafish larvae as a model system for high-throughput, image-based genetic screens in cardiometabolic diseases. M. den Hoed, A. Emmanouilidou, M. Bandaru, B. von der Heyde, T. Klingström, C. Wählby, P. Ranefall, A. Allalou, A. Larsson, E. Ingelsson.


Wednesday, October 18

11:00 AM–12:30 PM

Concurrent Platform Session B

20. Reproductive Genetics: Detection, Treatment, and Natural History of Errors

Room 310C, Level 3, Convention Center

Moderators: Katie Rudd, Lab Corp of America Holdings, Research Triangle Park
  Daniel Van Dyke, Mayo Clinic, Rochester

 

89/11:00 The landscape of chromosomal aberrations in in vitro fertilized preimplantation human embryos. S. Madjunkova, R. Abramov, R. Antes, V. Kuznyetsov, C. Librach.

90/11:15 Experience from the first live-birth derived from oocyte nuclear transfer as a treatment strategy for mitochondrial diseases. T. Huang, H. Liu, S. Luo, Z. Lu, A. Chávez-Badiolaa, Z. Liu, M. Yang, Z. Merhi, S. Silber, S. Munne, M. Konstantinidis, D. Wells, J. Tang, J. Zhang.

91/11:30 Non-invasive prenatal screening for single gene disorders in pregnancies with abnormal ultrasound findings or advanced paternal age. J. Li, Y. Feng, J. Sinson, H. Dai, X. Ge, G. Wang, H. Mei, A. Breman, A. Purgason, A. Pourpak, X. Wang, I. Van den Veyver, A. Beaudet, L. Wong, C. Eng, J. Zhang.

92/11:45 Cell-based noninvasive prenatal testing enables detection of benign and pathogenic copy number variants at much higher sensitivity than cell-free NIPT methods. L. Vossaert, A. Breman, J. Chow, L. U'Ren, Q. Wang, R. Salman, S. Qdaisat, A. Kim, X. Zhuo, E. Normand, C. Shaw, D. Henke, E. Chang, R. Seubert, J. Stilwell, E. Kaldjian, Y. Yang, I. Van den Veyver, A. Beaudet.

93/12:00 Individuals with monosomy X mosaicism (XO/XX) detected among 63,350 UK Biobank females appear asymptomatic of Turner syndrome. M.A. Tuke, K.S. Ruth, R.N. Beaumont, J. Tyrrell, S.E. Jones, H. Yaghootkar, C.L. Turner, M. Donohoe, A. Brooke, M. Collinson, R.M. Freathy, A.R. Wood, M.N. Weedon, T.M. Frayling, A. Murray.

94/12:15 Discernment in early childhood: Neurodevelopmental outcome and early hormonal therapy (EHT) in a large, prenatally diagnosed population of 47, XXY Boys. C. Samango-Sprouse, C. Keen, F. Mitchell, D. Sargsyan, L. Petrosyan, T. Sadeghin, A. Gropman.


Wednesday, October 18

11:00 AM–12:30 PM

Concurrent Platform Session B

21. Leveraging Human Knockouts to Understand Biology

Room 320, Level 3, Convention Center

Moderators: Marylyn Ritchie, Geisinger Hlth Sys, State College
  Laurent Francioli, Mass Gen Hosp, Boston

 

95/11:00 The spectrum of loss of function intolerance in the human genome. K.J. Karczewski, L.C. Francioli, K.E. Samocha, B.B. Cummings, D.P. Birnbaum, M.J. Daly, D.G. MacArthur, Genome Aggregation Database.

96/11:15 When are predicted loss-of-function (LOF) mutations not LOF mutations? Z. Coban Akdemir, J.J. White, Y. Bayram, S.N. Jhangiani, T. Gambin, E. Boerwinkle, R.A. Gibbs, C.M.B. Carvalho, J.R. Lupski.

97/11:30 Quantifying the impact of rare and ultra-rare coding variation across the phenotypic spectrum. A. Ganna, F.K. Satterstrom, S.M. Zekavat, I. Das, C. Churchhouse, J. Alfoldi, A.R. Martin, A.S. Havulinna, A. Byrnes, W.K. Thompson, P.R. Nielsen, K.J. Karczewski, M.I. Kurki, M.A. Rivas, N. Gupta, J. Flannick, V. Salomaa, C. Hultman, S. Ripatti, O. Kuismin, P. Bo Mortensen, D. MacArthur, M.J. Daly, P.F. Sullivan, A.E. Locke, A. Palotie, J.C. Florez, A.D. Børglum, S. Kathiresan, B.M. Neale, GoT2D/T2D-GENES, SIGMA, Helmsley IBD Exome Sequencing Project, FinMetSeq Consortium, iPSYCH-Broad.

98/11:45 Loss of function ABCC8 mutations in pulmonary arterial hypertension. W.K. Chung, M.S. Bohnen, L. Ma, N. Zhu, H. Qi, C. McClenaghan, C. Gonzaga-Jauregui, F.E. Dewey, J.D. Overton, J.G. Reid, A.R. Shuldiner, A. Baras, K.J. Sampson, U. Krishnan, E.B. Rosenzweig, Y. Shen, C.G. Nichols, R.S. Kass.

99/12:00 Completing a human gene knockout catalog through accurate phasing of 15K rare, deleterious compound heterozygous mutations in 61K exomes. J. Staples, N. Gosalia, E.K. Maxwell, C.G. Gonzaga-Jauregui, M.F. Murray, D. Carey, F.E. Dewey, O. Gottesman, G.R. DiscovEHR, L. Habeggar, J.G. Reid.

100/12:15 Distribution and clinical impact of human gene knockouts from 61,000 whole exome sequences in the DiscovEHR study. N. Gosalia, J. Staples, S. Balasubramanian, C. O'Dushlaine, V. Arunachalam, D.H. Ledbetter, M.D. Ritchie, D.J. Carey, J.D. Overton, J.G. Reid, T.M. Teslovich, N.S. Abul-Husn, L. Habegger, A.N. Economides, A. Baras, O. Gottesman, F.E. Dewey.


Wednesday, October 18

11:00 AM–12:30 PM

Concurrent Platform Session B

22. Detection and Interpretation of Structural Variation

Room 330A, Level 3, Convention Center

Moderators: Deanna Church, 10X Genomics, Pleasanton
  Rajiv C. McCoy, Univ Washington, Seattle

 

101/11:00 Linked-read whole-exome sequencing identifies a mosaic deletion at the NF1 locus resolving a previously intractable case of neurofibromatosis type 1. M. Gonzalez, R. Pellegrino, F. Mafra, J. Garifallou, C. Kaminski, L. Fang, K. Wang, K. Wimmer, S. Wenzel, C. Kao, H. Hakonarson.

102/11:15 K-mer based reference-free detection of family-private variants reveal the genetic complexity of HHT. A. Farrell, W. Wooderchak-Donahue, M. Velinder, A. Ward, P. Johnson, J. McDonald, P. Bayrak-Toydemir, G. Marth.

103/11:30 GRAPHITE: A computational framework for structural variation adjudication through graph remapping and visualization. A. Miller, D. Lee, G. Marth.

104/11:45 Making the most of targeted sequencing: Detecting CNVs and homozygous regions using off-target reads with SavvyCNV. M.N. Wakeling, E. De Franco, A.T. Hattersley, S. Ellard.

105/12:00 STIX: A scalable index for mining large whole-genome sequencing cohorts for reliable structural variant population allele frequency estimates. R.M. Layer, B.S. Pedersen, A.M. Quinlan.

106/12:15 Mapping and phasing of structural variation in patient genomes using nanopore sequencing. M. Cretu Stancu, M.J. van Roosmalen, I. Renkens, M. Nieboer, S. Middelkamp, J. de Ligt, G. Pregno, D. Giachino, G. Mandrile, J.E. Valle-Inclan, J. Korzelius, E. de Bruijn, E. Cuppen, M.E. Talkowski, T. Marschall, J. de Ridder, W.P. Kloosterman.


Wednesday, October 18

11:00 AM–12:30 PM

Concurrent Platform Session B

23. Neurodevelopmental Disorders: Causes and Mechanisms

Room 330C, Level 3, Convention Center

Moderators: Anne Goriely, MRC Weatherall Inst Molec Med, Oxford Univ, UK
  Ghayda Mirzaa, Seattle Children's Res Inst

 

107/11:00 Clinical experience with a reflex-based testing algorithm for neurodevelopmental disorders. L. Walters-Sen, J. Glass, E. Partack, E. Wakefield, L. Dyer, N. Leslie.

108/11:15 Defining the threshold for neurodevelopmental disorders in the context of the rare genetic background. L. Pizzo, M. Jensen, A. Polyak, J. Yoon, D. Pazuchanics, E. Huber, V. Kumar, S. Zeesman, K. Mannik, A. Reymond, P. Stankiewicz, O. Pichon, P. Prontera, A. Renieri, D. Amor, E. Sistermans, C. Schwartz, C. Romano, S.W. Cheung, J. Rosenfeld, J. Andrieux, S. Girirajan.

109/11:30 Mitochondrial dysfunction in Smith-Magenis syndrome reveals aberrant respiration. M.D. Fountain, S.V. Mullegama, J.P. Alaimo, C. Li, T. Donti, S.A. Behrendt-McLeroy, A. Besse, P.E. Bonnen, B.H. Graham, S.H. Elsea.

110/11:45 FDXR mutations cause sensorial neuropathies, a new mitochondrial Fe-S biogenesis disease. A. Paul, A. Drecourt, D. Dupin-Deguine, C. Vasnier, M. Oufadem, F. Petit, C. Masson, C. Bonnet, S. Masmoudi, I. Mosnier, L. Mahieu, D. Bouccara, J. Kaplan, G. Challes, C. Domange, F. Mochel, O. Sterkers, S. Gerber, P. Nitschke, C. Bole-Feysot, L. Jonard, S. Gherbi, I. Ben Aissa, S. Lyonnet, A. Rotig, A. Delahodde, S. Marlin.

111/12:00 De novo mutations in protein kinase genes CAMK2A and CAMK2B cause intellectual disability. S. Kury, G.M. van Woerden, T. Besnard, M.T. Cho, S. Sanders, H.A.F. Stessman, E.A. Sellars, J. Berg, J.L. Waugh, L. Robak, J.A. Bernstein, M. Deardorff, G.E. Hoganson, D.S. Johnson, T. Dabir, A. Sarkar, G. Lesca, P.A. Terhal, T.E. Prescott, D. Grange, A. Haeringen, C. Lam, G. Mirzaa, K. Helbig, J.A. Rosenfeld, P.B. Agrawal, S. Odent, S. Mercier, Y. Elgersma, S. Bezieau, CAMK2A/B Consortium.

112/12:15 De novo, deleterious sequence variants that alter the transcriptional activity of the homeoprotein PBX1 are associated with intellectual disability and pleiotropic developmental defects. A. Slavotinek, M. Risolino, M. Losa, M.T. Cho, K.G. Monaghan, D. Schneidman-Duhovny, S. Parisotto, J.C. Herkert, A.P.A Stegmann, K. Miller, N. Shur, J. Chui, E. Mueller, S.D. DeBrosse, J.O. Szot, G. Chapman, N.S. Pachter, D.S. Winlaw, B.A. Mendelsohn, H. Pedro, S.W. Dunwoodie, L. Selleri, J. Shieh.


Wednesday, October 18

4:15 PM–4:30 PM

24. ASHG William Allan Award Presentation and Lecture: Human Genetics: A Letter From Iceland

South Hall B, Level 1, Convention Center

The ASHG William Allan Award recognizes a scientist for substantial and far-reaching scientific contributions for 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: Mark J. Daly, Massachusetts General Hospital, Boston

Recipient:
Kári Stefánsson
Kári Stefánsson, MD, deCODE Genetics, Iceland

In 1996, Dr. Stefánsson founded deCODE Genetics with the vision of a large-scale population study in Iceland, a country with a relatively small, isolated, and homogenous population; a high-quality healthcare system; and extensive genealogical records. By engaging with the Icelandic population, deCODE has now collected DNA samples from more than 160,000 individuals and contributed greatly to public education about genetics in the country. Their work has inspired similar large-scale studies in other countries, including the UK Biobank and the United States’ All of Us initiative.

 


Wednesday, October 18

4:30 PM–4:35 PM

25. C.W. Cotterman Awards Presentation

South Hall B, Level 1, Convention Center

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.

 


Wednesday, October 18

4:35 PM–4:45 PM

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

South Hall B, Level 1, Convention Center

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 2017 Annual Meeting. This year’s 18 finalists will be acknowledged. See this year's finalists and semifinalists.

 


Wednesday, October 18

4:45 PM–5:00 PM

27. ASHG Arno Motulsky-Barton Childs Award for Excellence in Human Genetics Education Presentation and Lecture: Dysmorphology: Delineation to Determination

South Hall B, Level 1, Convention Center

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: Han G. Brunner, Radboud University, the Netherlands

Recipient:
Dian Donnai
Dian Donnai, MD, University of Manchester, UK

Dr. Donnai’s efforts in human genetics education have reached diverse audiences, including clinical geneticists, genetic counselors, students, and the public. Her research focuses on the underlying causes of developmental disorders in children; she founded an international dysmorphology conference series, regularly facilitates workshops in various countries and regards international networking as vital for rare disease research. She co-wrote New Clinical Genetics, a case-based textbook that is now in its third edition. She led a number of public engagement initiatives and believes dysmorphology/deep phenotyping/image analysis are essential components of modern clinical genomic practice.

 


Wednesday, October 18

5:00 PM–6:30 PM

28. Presidential Symposium: A Conversation with Bill Gates and Francis Collins

South Hall B, Level 1, Convention Center

Moderators: Nancy J. Cox, ASHG 2017 President
  Peter C. Scacheri, ASHG 2017 Program Committee Chair

 

The ASHG 2017 Presidential Symposium will feature speakers Bill Gates, Co-chair and Trustee of the Bill & Melinda Gates Foundation; and Francis Collins, Director of the U.S. National Institutes of Health. This 90-minute symposium will address global health and genomics in an informal, conversational format, with audience questions solicited ahead of time.

Symposium Description: We are starting to see the potential of genetic tools to move beyond applications in rare disease, to address problems affecting millions of people across the world. In his opening remarks, Mr. Gates will talk about the importance of understanding genetic contributors to health disparities and outcomes in global populations. He will also discuss the potential of new vaccines and cell- and drug-based therapies to transform the way we approach infectious disease. Dr. Collins will describe how advances in genomic technologies offer the promise of cures of a wide variety of human illnesses, from sickle cell disease to cancer, and how the vision of precision medicine can be pursued on a global scale.

Submit Your Questions: Audience question submission closed at noon on October 12. Thank you to those who submitted questions.

Security Considerations: Badges must be visible when entering this session. Attendees without badges will not be permitted entry. Bags larger than 12”x12”x6”, including meeting backpacks, are prohibited. To avoid waiting in long coat check lines, attendees are encouraged to check these items during lunch or leave them in their hotel rooms. Additional coat check stations will be located near the entrance to the session room. For those who wish to keep their items with them, the event will be live streamed in Rooms 220B, 220D, 220F, 230A, 230C, 230E, and 230G.

 


Thursday, October 19

9:00 AM–10:30 AM

Concurrent Platform Session C

29. Gene Discovery in Skeletal Phenotypes

Room 220B, Level 2, Convention Center

Moderators: Andrea Superti-Furga, Lausanne Univ Hosp, Switzerland
  Deborah Krakow, David Geffen Sch Med Los Angeles

 

113/9:00 Clinical relevance of systematic phenotyping and exome sequencing in patients with short stature. C.T. Thiel, N.N. Hauer, B. Popp, E. Schoeller, S. Schuhmann, K.E. Heath, A. Hisado-Oliva, P. Klinger, C. Kraus, U. Trautmann, M. Zenker, C. Zweier, A. Wiesener, R. Abou-Jamra, E. Kunstmann, D. Wieczorek, S. Uebe, F. Ferrazzi, C. Büttner, A.B. Ekici, A. Rauch, H. Sticht, H.-G. Dörr, A. Reis.

114/9:15 A low-frequency missense variant in SLC39A8 associated with idiopathic scoliosis. G. Haller, K. McCall, S. Jenkitkasemwong, C. Cruchaga, M. Harms, A. Goate, J. Morcuende, P. Giampietro, N. Miller, C. Wise, M. Knutson, M. Dobbs, C. Gurnett.

115/9:30 Mutations in fibronectin cause a subtype of spondylometaphyseal dysplasia with “corner fractures”. P.M. Campeau, C.S. Lee, H. Fu, N. Baratang, J. Rousseau, H. Kumra, V.R. Sutton, M. Niceta, A. Ciolfi, G. Yamamoto, D. Bertola, C.L. Marcelis, D. Lugtenberg, A. Bartuli, C. Kim, J. Hoover-Fong, N. Sobreira, R. Pauli, C. Bacino, D. Krakow, A. Kariminejad, M.T. McDonald, M. Aracena Alvarez, E. Lausch, A. Superti-Furga, J.T. Lu, D.H. Cohn, M. Tartaglia, B.H. Lee, D. Reinhardt.

116/9:45 Multiple gene discoveries in Robinow syndrome identify perturbation in the balance between Wnt signaling pathways in humans. C. Carvalho, J.J. White, J. Mazzeu, Z. Coban-Akdemir, Y. Bayram, V. Bahrambeigi, A. Hoischen, B. van Bon, A. Gezdirici, E. Gulec, F. Ramond, R. Touraine, M. Shinawi, E. Beaver, J. Heeley, J. Hoover-Fong, C. Durmaz, M. Duz, S. Price, B. Ferreira, A. Vianna-Morgante, S. Ellard, A. Parrish, K. Stals, J. Flores-Daboub, S. Jhangiani, R.A. Gibbs, H.A. Brunner, V.R. Sutton, J.R. Lupski.

117/10:00 Alterations in NFkB signaling contribute to the bone fragility in osteogenesis imperfecta type V. R. Marom, C. Lietman, A. Rajagopal, M. Jain, MM. Jiang, Y. Chen, E.M. Munivez, T.K. Bertin, R. Chen, B.H. Lee.

118/10:15 Whole genome sequencing of Atacama skeleton shows novel mutations linked with dysplasia. S. Bhattacharya, J. Li, A. Sockell, F. Bava, M. Kan, S. Chen, M. Avila-Arcos, X. Ji, N. Asadi, R. Lachman, H. Lam, C. Bustamante, A. Butte, G. Nolan.


Thursday, October 19

9:00 AM–10:30 AM

Concurrent Platform Session C

30. Repeats and Rearrangements: New Methods, Genes, and Mechanisms in Neurological Disease

Room 220F, Level 2, Convention Center

Moderators: Christelle Golzio, IGBMC, Illkirch, France
  Anna Lindstrand, Karolinska Inst, Stockholm, Sweden

 

119/9:00 Detection of long repeat expansions from PCR-free whole-genome sequence data. E. Dolzhenko, J.J.F.A. van Vugt, K. Ibáñez, G. Narzisi, M.A. Bekritsky, M. van Blitterswijk, A. Tucci, K.R. Smith, R. Rademakers, R. McLaughlin, W. Sproviero, A. Jones, A. Pittman, S. Morgan, O. Hardiman, A. Al-Chalabi, C. Shaw, K. Morrison, P.J. Shaw, C. Reeves, L. Winterkorn, N.S. Wexler, D.E. Housman, C. Ng, A. Li, R.J. Taft, L.H. van den Berg, D.R. Bentley, J.H. Veldink, M.A. Eberle, The US-Venezuela Collaborative Research Group.

120/9:15 A spinocerebellar ataxia mapping to the SCA37 locus is caused by a pentanucleotide ATTTC repeat insertion in the noncoding region of the DAB1 gene. J.R. Loureiro, A.I. Seixas, C. Costa, A. Ordóñez-Ugalde, H. Marcelino, C.L. Oliveira, J.L. Loureiro, A. Dhingra, E. Brandão, V.T. Cruz, A. Timóteo, B. Quintáns, G.A. Rouleau, P. Rizzu, A. Carracedo, J. Bessa, P. Heutink, J. Sequeiros, M.J. Sobrido, P. Coutinho, I. Silveira.

121/9:30 Identification of genetic modifiers of FXTAS by combining whole genome sequencing with fly genetics. H.E. Kong, J. Lim, E.G. Allen, D.J. Cutler, M.E. Zwick, S.L. Sherman, S.T. Warren, T.S. Wingo, P. Jin.

122/9:45 Dissecting the causal mechanism of X-linked dystonia-Parkinsonism by integrating genome and transcriptome assembly. R. Yadav, T. Aneichyk, W.T. Hendriks, D. Shin, D. Gao, C.A. Vaine, R.L. Collins, A. Stortchevoi, B. Curral, H. Brand, C. Hanscom, C. Antolik, M. Dy, A. Ragavendran, P. Acuña, C. Go, Y. Sapir, B. Wainger, D. Henderson, J. Dhakal, N. Ito, N. Weisenfeld, D. Jaffe, N. Sharma, X.O. Breakefield, L.J. Ozelius, D.C. Bragg, M.E. Talkowski.

123/10:00 Functional prioritization of Huntington's disease onset modifier genes in the HdhQ111/+ mouse. J. Loupe, T. Gillis, M. Kovalenko, J. Mysore, A. Nowell, R. Mauro Pinto, V. Wheeler, J. Gusella, J. Lee, M. MacDonald, GeM-HD Consortium.

124/10:15 Insights into the molecular pathogenesis of Huntington’s disease via multidimensional data analysis of the OVT73 sheep model. E.R. Mears, R.R. Handley, S.J. Reid, J.F. Gusella, M.E. MacDonald, S.R. Rudiger, S.C. Bawden, S. Patassini, P. Maclean, R. Brauning, H.J. Waldvogel, R.L.M. Faull, R.G. Snell.


Thursday, October 19

9:00 AM–10:30 AM

Concurrent Platform Session C

31. Secondary and Incidental Findings from WES/WGS

Room 230C, Level 2, Convention Center

Moderators: David Miller, Boston Children's Hosp
  Rachel Burnside, Lab Corp America, Durham

 

NOTE: Overflow seating for this session is available in Room 230A.

 

125/9:00 Evidence-based assessments of clinical actionability in the context of secondary findings: Updates from ClinGen’s Actionability Working Group. J.E. Hunter, E.M. Webber, K. Lee, K.R. Muessig, L.G. Biesecker, A.H. Buchanan, N. Lindor, C.L. Martin, J.M. O'Daniel, E.M. Ramos, A. Slovotinek, N. Sobreira, M.A. Weaver, M.S. Williams, J.P. Evans, K.A.B. Goddard.

126/9:15 Secondary (incidental) findings in whole exome and genome sequencing. A. Maksimovic, Z. Yüksel, A. M. Bertoli-Avella, O. Brandau, N. Nahavandi, A. Mohamed Saeed Al Shamsi, M. Alfadhel, M. A. Albalwi, N. Abbas Al-Sannaa, S. Kishore, P. Bauer, A. Rolfs.

127/9:30 Our experience with incidental findings in the CAUSES Research Clinic: A pediatric sequencing study in British Columbia. S. Adam, C. du Souich, A.M. Elliott, J.C. Mwenifumbo, C.D. van Karnebeek, T.N. Nelson, A.M. Lehman, J.M. Friedman.

128/9:45 Identification of secondary genetic variation in the HudsonAlpha CSER project. M.L. Thompson, C.R. Finnila, K.M. Bowling, S.M. Hiatt, M.D. Amaral, K.B. Brothers, K.M. East, D.E. Gray, J. Lawlor, W.V. Kelley, M. Neu, N.E. Lamb, E.J. Lose, C.A. Rich, S. Simmons, R.M. Myers, G.S. Barsh, E.M. Bebin, G.M. Cooper.

129/10:00 Frequency of pathogenic variants in Fanconi/BRCA pathway genes in ten thousand clinical exomes referred for non-cancer indications. S.E. Plon, A.K. Petersen, C.M. Eng, Y. Yang.

130/10:15 Secondary findings after virtual panels: A new frontier in incidental findings. E.D. Esplin, S. Yang, E. Haverfield, S. Aradhya, R.L. Nussbaum.


Thursday, October 19

9:00 AM–10:30 AM

Concurrent Platform Session C

32. Computational Methods for Causal Inference in Complex Traits

Room 230G, Level 2, Convention Center

Moderators: Lei Sun, Univ Toronto, Canada
  Nilah Ioannidis, Stanford Univ

 

NOTE: Overflow seating for this session is available in Room 230E.

 

131/9:00 Identification transcriptomic and epigenetic mediators in Alzheimer's disease: Bayesian inference and causal mediation analysis of regulatory programs in GWAS statistics. Y. Park, A. Sarkar, L. He, M. Kellis.

132/9:15 Identifying cis-mediators for trans-eQTLs across many human tissues using genomic mediation analysis. L.S. Chen, F. Yang, J. Wang, B. Pierce, GTEx consortium.

133/9:30 Casual inference in imaging-genetic data analysis. N. Lin, Z. Hu, R. Jiao, L. Luo, V. Calhoun, M. Xiong.

134/9:45 Gene x environment interactions and causal relationships between obesity and depression. T. Frayling, A.R. Wood, H. Yaghootkar, R. Beaumont, S.E. Jones, M.A. Tuke, K.S. Ruth, R.M. Freathy, A. Murray, M. Weedon, J. Tyrrell.

135/10:00 Large scale application of Mendelian randomization to electronic health records yields novel causal inferences. J.S. Weinstock, E.M. Schmidt, L.G. Fritsche, S. Kheterpal, C.M. Brummett, G.R. Abecasis.

136/10:15 Distinguishing genetic correlation from causation across 37 diseases and complex traits. L.J. O'Connor, A.L. Price.


Thursday, October 19

9:00 AM–10:30 AM

Concurrent Platform Session C

33. Microbiome, Variation, and Disease

Room 310A, Level 3, Convention Center

Moderators: Yu Wang, Univ of Michigan, Ann Arbor
  Alex Kotar, Emory Univ, Atlanta

 

137/9:00 Co-occurrence network modeling reveals disease-specific configurations of microbiome community structure across 2,500 twins. E.R. Davenport, T.D. Spector, R.E. Ley, A.G. Clark.

138/9:15 Biome-explainability: Quantifying microbiome-phenotype associations while accounting for host genetics. O. Weissbrod, D. Rothschild, E. Barkan, T. Korem, D. Zeevi, P. Costea, A. Godneva, I. Kalka, N. Bar, N. Zmora, D. Israeli, N. Kosower, G. Malka, B.C. Wolf, T. Avnit-Sagi, M. Lotan-Pompan, A. Weinberger, Z. Halpern, S. Carmi, E. Elinav, E. Segal.

139/9:30 Microbiome and host genetics in inflammatory bowel disease and irritable bowel syndrome. A. Zhernakova, A. Vich Vila, F. Imhann, V. Collij, S. Jankipersadsing, Z. Mujagic, T. Gurry, A. Kurilshikov, MJ. Bonder, X. Jiang, L. Franke, G. Dijkstra, E.A.M. Festen, R. Xavier, E.J. Alm, D. Jonkers, J. Fu, R.K. Weersma, C. Wijmenga.

140/9:45 Systematic analysis of association of blood circulating proteins with genome and microbiome. A. Kurilshikov, D. Zhernakova, T. Le, B. Atanasovska, M.J. Bonder, S. Sanna, R. Boer, F. Kuipers, L. Franke, C. Wijmenga, A. Zhernakova, J. Fu.

141/10:00 Population structure of the human gut microbiome across ethnically diverse sub-Saharan Africans. M.A. Rubel, M.E.B. Hansen, A.G. Bailey, J.R. Dave, A. Ranciaro, S.R. Thompson, M. Campbell, W.R. Beggs, S.W. Mpoloka, G. Mokone, M.M.M. Bolaane, T. Nyambo, F.D. Bushman, S.A. Tishkoff.

142/10:15 Inter-species variation in the gut microbiota controls host gene regulation in primates. R. Blekhman, A.L. Richards, A. Muehlbauer, A. Alazizi, M. Burns, A. Gomez, J. Clayton, K. Petrzelkova, C. Cascardo, R. Pique-Regi, F. Luca.


Thursday, October 19

9:00 AM–10:30 AM

Concurrent Platform Session C

34. Genetic Architecture of Neurological Traits

Room 310C, Level 3, Convention Center

Moderators: Megan Y. Dennis, Univ California Davis
  Stephanie L. Bielas, Univ Michigan Med Sch, Ann Arbor

 

143/9:00 Understanding the genetic architecture of migraine using a collection of 1,214 families from Finland. P. Gormley, M.I. Kurki, M.E. Hiekkala, K. Veerapen, P. Häppölä, A. Mitchell, D. Lal, P. Palta, I. Surakka, M.A. Kaunisto, E. Hämäläinen, P. Jousilahti, V. Salomaa, V. Artto, M. Färkkilä, H. Runz, M.J. Daly, B.M. Neale, S. Ripatti, M. Kallela, M. Wessman, A. Palotie.

144/9:15 A meta-analysis of genome-wide association studies identifies novel Parkinson’s disease risk loci. D. Chang, M. Nalls, I. Hallgrímsóttir, J. Hunkapiller, M. van der Brug, F. Cai, G. Kerchner, G. Ayalon, B. Bingol, M. Sheng, D. Hinds, T. Behrens, A. Singleton, T. Bhangale, R. Graham, International Parkinson’s Disease Genomics Consortium, UKDPDSBB, 23andMe Research Team.

145/9:30 Parkinson’s disease gene identification using differential gene expression analysis of iPSC generated neural stem cells. S. Kumar, J.E. Curran, D.M. Lehman, R. Duggirala, D. Glahn, J. Blangero.

146/9:45 Examining the genetic architecture of the human cortex: Results from the ENIGMA consortium GWAS meta-analyses of cortical thickness and surface area. S. Medland, on behalf of the The Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium.

147/10:00 Low frequency coding variation in CYP2R1 has large effects on Vitamin D level and risk of multiple sclerosis. D. Manousaki, T. Dudding, S. Haworth, Y. Hsu, C. Liu, C. Medina-Gomez, T. Voortman, N. van der Velde, H. Melhus, C. Robinson-Cohen, D.L. Cousminer, M. Nethander, L. Vandenput, R. Noordam, V. Forgetta, L. Lind, E.S. Orwoll, D.O. Mook-Kanamori, K. Michaelsson, B. Kestenbaum, C. Ohlsson, D. Mellstrom, L.C.P.G. de Groot, S.F.A. Grant, D.P. Kiel, M.C. Zillikens, F. Rivadeneira, S. Sawcer, N.J. Timpson, J. B. Richards.

148/10:15 Genome-wide association study: Pandemrix-induced narcolepsy in Sweden. M. Wadelius, N. Eriksson, H. Smedje, Q-Y. Yue, P.K.E. Magnusson, P. Hallberg, on behalf of Swedegene.


Thursday, October 19

9:00 AM–10:30 AM

Concurrent Platform Session C

35. High Throughput Functional Analysis of Enhancers and Variants

Room 320, Level 3, Convention Center

Moderators: Timothy Reddy, Duke Univ, Durham
  Ryan Tewhey, Jackson Lab, Bar Harbor

 

149/9:00 High-resolution dissection of regulatory function for millions of predicted enhancers in human. M. Kellis, X. Wang, L. He, S. Goggin, A. Saadat, M. Claussnitzer.

150/9:15 Measuring enhancer activity at the human genome scale: Comprehensive and quantitative assessment of steady-state and induced regulatory activity following glucocorticoid stimulation. G.D. Johnson, C.M. Vockley, L.C. Bartelt, N. Clark, S.M. Leichter, G.E. Crawford, T.E. Reddy.

151/9:30 An ultra-high resolution Capture-C promoter ‘interactome’ implicates causal genes at SLE GWAS loci. M.E. Johnson, E. Manduchi, C. Le Coz, M.E. Leonard, S. Lu, K.M. Hodge, N.D. Romberg, A. Chesi, A.D. Wells, S.F.A. Grant.

152/9:45 High throughput functional prioritization of candidate genes from large-scale sequencing and GWAS studies. P. Heutink, J. Taeger, E. Lara Flores, M. Bedi, N. Alves Fernandes, J. Simon-Sanchez, P. Rizzu, The International Parkinsons Disease Genomics Consortium (IPDGC).

153/10:00 Functional interrogation of common genetic variation uncovers regulators of hematopoiesis and therapeutic targets. S.K. Nandakumar, S.K. McFarland, L.M. Mateyka, J.C. Ulirsch, G.S. Cowley, X. Yang, J.G. Doench, D.E. Root, V.G. Sankaran.

154/10:15 High-throughput functional analysis of PTEN variants reveals genotype-phenotype relationships. T.L. Mighell, S. Evans, B.J. O'Roak.


Thursday, October 19

9:00 AM–10:30 AM

Concurrent Platform Session C

36. Genetic Architecture of Rare Variants Across Diseases

Room 330A, Level 3, Convention Center

Moderators: Alper Uzun, Women & Infants Hosp, Providence
  Di Zhang, Baylor Col Med, Houston

 

155/9:00 Population-wide whole-genome sequencing in a Greek isolate reveals rare variant burdens associated with multiple quantitative traits. A. Gilly, D. Suveges, K. Kuchenbaecker, L. Southam, K. Hatzikotoulas, T. Bjørnland, E.V.R. Appel, E. Casalone, G. Melloni, K.B. Kilian, N.W. Rayner, A.-E. Farmaki, E. Tsafantakis, M. Karaleftheri, G. Dedoussis, E. Zeggini.

156/9:15 Inferring compound heterozygotes from large-scale exome sequencing data. L.F. Francioli, M.H. Guo, K.J. Karczewski, B.B. Cummings, M. Lek, V. Thaker, M.J. Daly, J.N. Hirschhorn, D.G. MacArthur, Genome Aggregation Database.

157/9:30 Novel dual-indexing strategy enables high scale sample multiplexing and eliminates the impact of index-swapping on Illumina sequencers. M. Costello, M. Fleharty, S. Ferriera, T. Howd, J. Abreu, Y. Farjoun, T. Desmet, S. Dodge, N. Lennon, S. Gabriel.

158/9:45 Recessive coding variants make only a minor contribution to undiagnosed developmental disorders in the United Kingdom. H.C. Martin, W. Jones, J. McRae, D.R. Fitzpatrick, H.V. Firth, M. Hurles, J. Barrett, Deciphering Developmental Disorders Study.

159/10:00 Fine-scale structure of rare variants in 18K genomes from the TOPMed Consortium and its implications for study design. T. O'Connor, D. Harris, M. Kessler, A. Shetty, B. Mitchell, D. Taliun, D. Nickerson, R. Hernandez, G. Abecasis, TOPMed Consortium.

160/10:15 Large-scale identity-by-descent mapping discovers rare haplotypes of large effect. S. Shringarpure, D. Hinds, V. Vacic, S. Pitts, R. Gentleman, A. Auton, 23andMe Research Team.


Thursday, October 19

9:00 AM–10:30 AM

Concurrent Platform Session C

37. Non-coding Variation and Epigenetic Effects in Cancer

Room 330C, Level 3, Convention Center

Moderators: Liying Zhang, Memorial Sloan Kettering Cancer Ctr, New York
  Dawei Li, Univ Vermont, Burlington

 

161/9:00 Using induced pluripotent stem cells to identify downstream effects of genetic risk factors linked to cancer. M.J. Bonder, D. Seaton, B. Mirauta, H. Kilpinen, J. Korbel, O. Stegle, The HipSci consortium.

162/9:15 A spectrum of rare Mendelian to common GWAS variants underlying familial prostate cancer at 8q24. J. Smith, J. Breyer, W. Dupont.

163/9:30 Cis-regulatory drivers in chronic lymphocytic leukaemia and skin cancer. H. Ongen, O. Delaneau, M. Stevens, C. Howald, E.T. Dermitzakis.

164/9:45 Recurrently altered enhancers in colorectal cancer identify known and novel predisposition loci. S.A. Bien, A. Saiakhova, T.A. Harrison, C. Qu, J.R. Huyghe, H.M. Kang, G.R. Abeçasis, G. Casey, D.A. Nickerson, L. Hsu, S.B. Gruber, P. Scacheri, U. Peters, on behalf of GECCO, CCFR and CORECT.

165/10:00 Assessing the gene regulatory landscape in 1,188 human tumours. K. Lehmann, A. Brazma, C. Calabrese, S. Dentro, S. Erkek, N. Fonseca, A. Kahles, H. Kilpinen, J. Korbel, F. Liu, J. Markowski, G. Raetsch, RF. Schwarz, O. Stegle, L. Urban, P. Van Loo, S. Waszak, D. Wedge, Z. Zhang, PanCancer Analysis Working Group 3, PanCancer Analysis Working Group 8.

166/10:15 Sex-specific differences in expression dysregulation across The Cancer Genome Atlas studies. A.D. Skol, R. Dohn, E. Lipschultz, Z. Zhang, R.L. Grossman, B. E. Stranger.


Thursday, October 19

11:00 AM–12:30 PM

Concurrent Platform Session D

38. Neuromuscular Disease

Room 220B, Level 2, Convention Center

Moderators: Andrea Gropman, Children's National Med Ctr, Washington, DC
  Rossana Lucia Sanchez Russo, Emory Univ, Atlanta

 

167/11:00 Inherited nodopathies and defective axoglial interactions are responsible for arthrogryposis multiplex congenita. J. Melki, J. Maluenda, S. Xue, G. Ravenscroft, C. Manso, L. Quevarec, A. Vivanti, F. Marguet, M. Gut, I. Gut, M. Tawk, N.G. Laing, J. Devaux, B. Reversade, A. Laquérriere.

168/11:15 World’s largest gene-panel sequencing effort reveals genetic landscape of limb-girdle muscular dystrophies and potential multi-genic inheritance. B. Nallamilli, S. Chakravorty, L. Rufibach, M.P. Wicklund, M. Harms, T. Mozaffar, M. Hegde.

169/11:30 ATP1A1 represents a significant novel dominant Charcot-Marie-Tooth disease gene. A.P. Rebelo, L. Lassuthova, G. Ravenscroft, P. Lamont, M. Baxter, R. Ong, M. Davis, F. Manganelli, F. Tao, C. Saghira, L. Abreu, Y. Bai, D. Isom, N. Laing, B.O. Choi, P. Seeman, M. Shy, L. Santoro, S. Zuchner.

170/11:45 Rare variant burden analysis deciphers genetic architecture of inherited peripheral neuropathies. D.M. Bis, F. Tao, L. Abreu, P. Sleiman, H. Hakonarson, S. Zuchner, Inherited Neuropathy Consortium.

171/12:00 Pilot study of population-based newborn screening for spinal muscular atrophy in New York state. D.M. Kay, J.N. Kraszewski, C.F. Stevens, C. Koval, B. Haser, V. Ortiz, L. Cohen, R. Jain, S.P. Andrew, N.M. LaMarca, S. Dunaway Young, D.C. De Vivo, M. Caggana, W.K. Chung.

172/12:15 Recessive mutations in the fusiogenic protein myomaker cause Carey-Fineman-Ziter syndrome. S.A. Di Gioia, S. Connors, N. Matsunami, J. Cannavino, M.F. Rose, N.M. Gilette, P. Artoni, N.L. de Macena Sobreira, W.M. Chan, B.D. Webb, C.D. Robson, C. Van Ryzin, A. Ramirez-Martinez, P. Mohassel, T. Hartman, I.M. Hayes, D.M. Markie, A. Swift, P.S. Chines, C.E. Speck-Martins, F.S. Collins, E.W. Jabs, C.G. Bönnemann, E.N. Olson, J.C. Carey, S.P. Robertson, I. Manoli, E.C. Engle, Moebius Syndrome Research Consortium.


Thursday, October 19

11:00 AM–12:30 PM

Concurrent Platform Session D

39. Advances in the Genetics of Autoimmune Disease

Room 220F, Level 2, Convention Center

Moderators: Chris Cotsapas, Yale Sch Med, New Haven
  Soumya Raychaudhuri, Brigham & Women's Hosp/Broad Inst, Cambridge

 

173/11:00 Direct reconstruction of human genomes capturing highly divergent regions including MHC. N.I. Weisenfeld, P.N. Shah, V. Kumar, S. Williams, C. Catalanotti, N. Keivanfar, D.M. Church, D.B. Jaffe.

174/11:15 Full resolution HLA typing of 273 individuals from deep whole-genome sequencing data enables genetic studies of human 6p21.3. J. Reyna, N. Nariai, D. Jakubosky, E. Smith, K. Frazer.

175/11:30 The MHC Diversity in Africa Resource: A roadmap to understanding HLA diversity in Africa. M.O. Pollard, A.J. Mentzer, T. Porter, A.T. Dilthey, C. Pomilla, S. Peacock, N. Careb, S. Lule, A. Diarra, N. van Niekerk, on behalf of the MDAP Investigators.

176/11:45 GWAS of canker sores implicates Th-1 differentiation and signaling pathway and shared genetic architecture with inflammatory bowel disease. F. Sathirapongsasuti, S. Pitts, D. Hinds, V. Vacic, R. Gentleman.

177/12:00 Using exome sequencing to expand the genetic architecture of IBD. M. Daly, M. Rivas, C. Stevens, B. Avila, J. Koskela, T. Ahmad, G. Atzmon, S.R. Brant, J. Cho, M. Farkkila, A. Franke, B. Glaser, K. Kontula, S. Kugathasan, D. McGovern, A. Palotie, J. Rioux, T. Segal, H. Sokol, D. Turner, R.K. Weersma, H. Winter, R. Xavier.

178/12:15 Genotype and phenotype analyses revealed novel susceptibility genes and new clinical classification for psoriasis. B.-J. Feng, S. McCarthy, H. Li, K. Praveen, J. Walsh, J. Hawkes, M. Milliken, D.E. Goldgar, J.G. Reid, J.D. Overton, F. Dewey, C. Gonzaga-Jauregui, S.L. Guthery, K. Callis-Duffin, G.G. Krueger.


Thursday, October 19

11:00 AM–12:30 PM

Concurrent Platform Session D

40. Defining High Risk in Cancer

Room 230C, Level 2, Convention Center

Moderators: Nicola Camp, Univ Utah, Salt Lake City
  Sylvia Casadei, Univ Washington, Seattle

 

179/11:00 Functional characterization of BRIP1 missense alleles: Distinguishing cancer susceptibility alleles from benign polymorphisms. C. Moyer, J. Gillespie, R. Doberstein, J. Ivanovich, G.M. Collett, M. Harrell, E. Swisher, P.J. Goodfellow.

180/11:15 Functional characterization of variants of uncertain significance in BRCA2: Fifty shades of BRCA2 deficiency. R.L.S. Mesman, F.M.G.R. Calleja, G. Hendriks, P. Devilee, C.J. van Asperen, H. Vrieling, M.P.G. Vreeswijk.

181/11:30 Incorporation of tumor RNA expression data in pathogenicity classification of germline variants. C. Kesserwan, D. Hedges, S. Newman, K. Hamilton, R. Mcgee, E. Quinn, R. Nuccio, J. Valdez, M. Rusch, S. Foy, J. Nakitandwe, L. Harrison, A. Ouma, S. Hines-Dowell, S. Shurtleff, E. Azzato, D. Ellison, J. Downing, J. Zhang, K. Nichols.

182/11:45 Splicing mutation risk analysis in hereditary breast and ovarian cancer exomes. E.J. Mucaki, B.C. Shirley, S.N. Dorman, P.K. Rogan.

183/12:00 Early diagnosis of lung cancer: Identification of miRNAs in the blood as non-invasive biomarkers. L. Shi, B. Song, Z. Yi, W. Zhang.

184/12:15 Assessing the feasibility of using whole genome mate pair sequencing in detecting diagnostic/prognostic chromosomal abnormalities seen in patients with acute myeloid leukemia. U. Aypar, G. Vasmatzis, S. Johnson, J. Smadbeck, S. Smoley.


Thursday, October 19

11:00 AM–12:30 PM

Concurrent Platform Session D

41. Natural Selection on Human Phenotypes

Room 230G, Level 2, Convention Center

Moderators: Jedidiah Carlson, Univ Michigan, Ann Arbor
  Yair Field, Stanford Univ

 

185/11:00 Identifying complex traits under polygenic selection in the UK Biobank. X. Liu, P.R. Loh, L. O'Connor, A. Schoech, S. Gazal, A.L. Price.

186/11:15 Widespread signatures of negative selection in the genetic architecture of human complex traits. J. Zeng, R. de Vlaming, Y. Wu, M. Robinson, L. Lloyd-Jones, L. Yengo, C. Yap, A. Xue, J. Sidorenko, A. McRae, J. Powell, G. Montgomery, A. Metspalu, T. Esko, G. Gibson, N. Wray, P. Visscher, J. Yang.

187/11:30 High-throughput inference of pairwise coalescent times identifies signals of selection and enriched disease heritability. P. Palamara, J. Terhorst, Y. Song, A. Price.

188/11:45 Polygenic selection underlies evolution of brain structure volumes and behavioral traits. B.E. Stranger, E.R. Beiter, E.A. Khramtsova, C. Van Der Merwe, E.R. Chimusa, C. Simonti, D.J. Stein, J.A. Capra, J.A. Knowles, P. Straub, L.K. Davis.

189/12:00 An approximate full-likelihood coalescent method for detecting genomic sites under selection. A.J. Stern, R. Nielsen.

190/12:15 Fine-mapping the favored mutation in a positive selective sweep. A. Akbari, A. Iranmehr, M. Bakhtiari, S. Mirarab, V. Bafna.


Thursday, October 19

11:00 AM–12:30 PM

Concurrent Platform Session D

42. Consumers and Health Care Providers: Perspectives of Genetic Technology

Room 310A, Level 3, Convention Center

Moderators: Toni Pollin, Univ Maryland Sch Med, Baltimore
  Wendy Uhlmann, Univ Michigan, Ann Arbor

 

191/11:00 In their own words: Adolescent attitudes about deferring genetic testing for adult-onset conditions. A. Rahm, L. Bailey, O. D’Accordo, Y. Munishor, C. Miller, E. Davidson, L. Hercher, A.J. Young, K. Pulliam, H. Zhang, M. Dougherty, M. Williams.

192/11:15 International attitudes of genetics professionals toward human gene editing. A.J. Armsby, Y. Bombard, N.A. Garrison, B.L. Halpern-Felsher, K.E. Ormond.

193/11:30 Consent to genome sequencing in research: A randomized controlled trial comparing two consent interventions. E. Turbitt, P.P. Chrysostomou, A.R. Heidlebaugh, H.L. Peay, L.M. Nelson, B.B. Biesecker.

194/11:45 Beyond uncertainty: Experiences of patients who participate in variant of uncertain significance reclassification research. S. Makhnoon, L. Garrett, W. Burke, D. Bowen, B. Shirts.

195/12:00 Importance of returning research results to exome participant families. A. Warman, A. Incorvaia, M. Angrist, S. Katsanis.

196/12:15 Participant characteristics, motivations, healthcare utilization, and perceived utility in ostensibly healthy adults undergoing genome sequencing: Early findings from the PeopleSeq Consortium. E.S. Zoltick, M.D. Linderman, L.S. Pais, M.A. McGinniss, E. Ramos, M.P. Ball, G.M. Church, D.G.B. Leonard, S. Pereira, A.L. McGuire, T.C. Caskey, S.C. Sanderson, E.E. Schadt, S.D. Crawford, R.C. Green, The PeopleSeq Consortium.


Thursday, October 19

11:00 AM–12:30 PM

Concurrent Platform Session D

43. Gene Discovery and Functional Models of Intellectual Disability

Room 310C, Level 3, Convention Center

Moderators: Anne Slavotinek, UCSF
  Yaping Yang, Baylor Col Med, Houston

 

197/11:00 Recurrent de novo heterozygous mutations disturbing the GTP/GDP binding pocket of RAB11B cause intellectual disability and a distinctive brain phenotype. M.R.F. Reijnders, I.J.C. Lamers, H. Venselaar, A. Kraus, S. Jansen, L.B.A. de Vries, G. Houge, G. Aasland Gradek, J. Seo, M. Choi, J. Chae, S. Letteboer, S. van Beersum, S. Dusseljee, H.G. Brunner, D. Doherty, T. Kleefstra, R. Roepman.

198/11:15 Deficient activity of genes associated with amino acid metabolism underlies an autosomal recessive syndrome of microcephaly and hypomyelination. T. Nakayama, A. Al-Maawali, Q. Ouyang, J. Wu, D.J. Vaughan, M. El-Quessny, A. Rajab, S. Khalil, S. Niaz, M. Gul Butt, S. Imran Murtaza, A. Javed, H. Rashid Chaudhry, A.A. AlZahrani, P. Galvin-Parton, J. Weiss, M.R. Andriola, S.M. Amudhavalli, L. Cross, O. Baytas, K. Schmitz-Abe, K. Markianos, R.S. Hill, J.N. Partlow, B.J. Barry, M. Al-Saffar, A.J. Barkovich, E.M. Morrow, J. Ling, G.H. Mochida.

199/11:30 Apoptosis drives the pathogenicity in a Drosophila model of 3q29 deletion. M.D. Singh, E. Huber, L. Pizzo, B. Lifschutz, I. Desai, A. Kubina, S. Sunder, M. Jensen, S. Girirajan.

200/11:45 Dominant RORA variants cause an intellectual disability syndrome associated with epilepsy, autistic features or cerebellar ataxia. X. Latypova, C. Guissart, T.N. Khan, P. Rollier, K. Õunap, L. Schema, M. Cho, K. Retterer, G. Lesca, S. Pajusalu, M.H. Wojcik, H. Stamberger, T. Deconinck, S. Weckhuysen, P. De Jonghe, L. Al-Gazali, S. Sanders, S. Sasorith, N. Leboucq, F. Rivier, C.M. Freitag, A.G. Chiocchetti, S. Kjaergaard, N. Katsanis, S. Bézieau, M. Koenig, S. Küry, E.E. Davis, L. Pasquier.

201/12:00 PRESO1 mutations cause X-linked intellectual disability by disrupting dendritic spine morphogenesis. J. Piard, J.H. Hu, P. M. Campeau, S. Rzońca, H. Van Esch, E. Vincent, M. Han, E. Rossignol, J. Castaneda, J. Chelly, C. Skinner, V. Kalscheuer, R. Wang, E. Lemyre, J. Kosińska, P. Stawinski, J. Bal, D. Hoffman, C. Schwartz, L. Van Maldergem, T. Wang, P. Worley.

202/12:15 USP9X mutations cause a spectrum of neurodevelopmental disorders underpinned by a disruption of multiple signalling pathways that control brain development. L.A. Jolly, B.V. Johnson, R. Kumar, N. Dikow, A. Goldstein, S. Asher, P. VanHasselt, M. Perry, S. Mahmutoglu, S. Grøborg, P. Zwijnenburg, M. Weiss, C. Reis, M. Koenig, L. Pasquier, M. Lines, C. Keegan, C. Lopez-Otin, A. Fernández Jaén, H. Lefroy, B. Keren, M. Raynaud, S. Küry, M. Reijnders, T. Kleefstra, T. Pierson, T. Burne, M. Piper, S.A. Wood, J. Gecz.


Thursday, October 19

11:00 AM–12:30 PM

Concurrent Platform Session D

44. Polygenic Risk Scores and Genetic Correlation in Complex Disease

Room 320, Level 3, Convention Center

Moderators: Nilanjan Chatterjee, Johns Hopkins Univ, Baltimore
  Jennifer Brody, Univ Washington, Seattle

 

203/11:00 Polygenic risk scores identify novel relationships between complex traits. R.L. Kember, S. Damrauer, A. Small, M. Bucan, D. Rader.

204/11:15 Overtransmission of polygenic risk alleles for migraines in 2,048 Finnish trios. K. Veerapen, M.E. Hiekkala, P. Gormley, M.I. Kurki, A. Mitchell, H. Runz, P. Häppölä, P. Palta, E. Hämäläinen, M.A. Kaunisto, V. Arrto, M. Färkkilä, B. Neale, M. Daly, M. Wessman, M. Kallela, A. Palotie.

205/11:30 Association of polygenic risk scores for multiple cancers in a phenome-wide study: Results from The Michigan Genomics Initiative. L.G. Fritsche, S.B. Gruber, Z. Wu, E.M. Schmidt, S.E. Moser, V.M. Blanc, C.M. Brummett, S. Kheterpal, G.R. Abecasis, B. Mukherjee.

206/11:45 A powerful approach to estimating annotation-stratified genetic covariance using GWAS summary statistics. Q. Lu, B. Li, D. Ou, M. Erlendsdottir, R. Powles, T. Jiang, Y. Hu, D. Chang, C. Jin, W. Dai, Q. He, Z. Liu, S. Mukherjee, P. Crane, H. Zhao.

207/12:00 Phenotype connectivity map across human diseases derived from phenome-wide association study on 38,682 samples. A. Verma, L. Bang, J.E. Miller, Y. Zhang, M.T.M. Lee, D.J. Carey, M.D. Ritchie, S.A. Pendergrass, D. Kim, on behalf of the DiscovEHR collaboration.

208/12:15 Quantifying the shared genetic components of complex traits and Mendelian phenotypes. M. Kumar, V. Arboleda, H. Shi, N. Mancuso, B. Pasaniuc.


Thursday, October 19

11:00 AM–12:30 PM

Concurrent Platform Session D

45. Single Cell Omics Technologies

Room 330A, Level 3, Convention Center

Moderators: Stylianos Antonarakis, Univ Geneva Med Sch, Switzerland
  Yuchao Jiang, Univ North Carolina, Chapel Hill

 

209/11:00 Single cell transcriptome atlas of the mouse kidney reveals important cell diversity. J. Park, R. Shrestha, C. Qiu, A. Kondo, S. Li, K. Suszták.

210/11:15 Characterizing the landscape of somatic mutations in normal aging human tissues using a novel single-cell whole-genome sequencing approach. X. Dong, L. Zhang, M. Lee, A. Maslov, J. Vijg.

211/11:30 Dissecting the microenvironment of multiple tumor types using 5’ and 3’ single cell RNA-seq. S.C. Boutet, V. Giangarra, G.X.Y. Zheng, A.M. Barrio, L. Montecarlos, J. Lee, S. Marrs, K.J. Wu, P. Ryvkin, T. Mikkelsen, D.M. Church.

212/11:45 Scalable single-cell DNA methylation sequencing by combinatorial indexing. R. Mulqueen, D. Pokholok, S. Norberg, A. Fields, J. Shendure, C. Trapnell, B.J. O'Roak, Z. Xia, F. Steemers, A. Adey.

213/12:00 X chromosome inactivation in human single cells. C. Borel, M. Garieri, G. Stamoulis, E. Falconnet, P. Ribaux, F. Santoni, S.E. Antonarakis.

214/12:15 SAVER: Gene expression recovery for single cell RNA sequencing. M. Huang, J. Wang, E.A. Torre, H. Dueck, S.M. Shaffer, R. Bonasio, J.I. Murray, A. Raj, M. Li, N.R. Zhang.


Thursday, October 19

11:00 AM–12:30 PM

Concurrent Platform Session D

46. Sequencing in Neonatal and Pediatric Disorders

Room 330C, Level 3, Convention Center

Moderators: Erik Thorland, Mayo Clinic, Rochester
  Swaroop Aradhya, Invitae, Palo Alto

 

215/11:00 Clinical utility and cost effectiveness of rapid whole genome sequencing in the neonatal and pediatric intensive care unit. S. Chowdhury, S. Nahas, M. Bainbridge, S. Batalov, J. Cakici, S. Caylor, Y. Ding, L. Farnaes, J. Friedman, K. Gil, A. Hildreth, R. Hovey, L. Puckett, L. Salz, L. van der Kraan, N. Veeraraghavan, S. White, M. Wright, C. Yamada, N. Sweeney, D. Dimmock, S. Kingsmore.

216/11:15 Utility of exome sequencing for infants in intensive care units: Ascertainment of severe single-gene disorders and impact on medical management. L. Meng, M. Pammi, A. Saronwala, P. Magoulas, A. Ghazi, F. Vetrini, W. He, A. Dharmadhikari, C. Qu, X. Ge, M. Tokita, T. Santiago-Sim, H. Dai, H. Smith, M. Azamian, M. Wangler, D. Scott, J. Belmont, X. Wang, M. Leduc, R. Xiao, P. Liu, C. Shaw, M. Walkiewicz, W. Bi, F. Xia, B. Lee, C. Eng, Y. Yang, S. Lalani.

217/11:30 Clinical benefit of whole genome sequencing: A report on 300 families. A. Narravula, A.M. Bertoli-Avella, Z. Yüksel, O. Brandau, J. Balázs, J.M. Garcia-Aznar, C. Baldi, O. Paknia, M. Weber, M.E.R. Weiss, H. Yavuz, S. Franzenburg, K.K. Kandaswamy, D. Trujillano, N. Nahavandi, A. Al Shamsi, M. Alfadhel, M.A. Albalwi, N. Al-Sannaa, S. Kishore, P. Bauer, A. Rolfs.

218/11:45 The breadth of genomic variation detected by clinical whole genome sequencing: An iHope Program Cohort summary. E. Thorpe, A. Scocchia, J. McEachern, M.C. Jones, D. Masser-Frye, D. Henry, R. Ortiz, S.S. Ajay, M. Bennett, K. Bluske, C.M. Brown, N.J. Burns, A. Chawla, A.J. Coffey, M.L. Cremona, M. Eberle, V.G. Gainullin, A. Gross, R.T. Hagelstrom, W.L. Li, A. Malhotra, D.L. Perry, M. Rajan, V. Rajan, J.W. Belmont, D.R. Bentley, R.J. Taft, ICSL software development team; ICSL variant curation team.

219/12:00 Increased rates of diagnosis and precision medicine with genomic sequencing compared to chromosomal microarray: A meta-analysis of 19,714 infants and children with likely genetic diseases. D. Dimmock, M.M. Clark, Z. Stark, L. Farnaes, T.Y. Tan, S.M. White, S.F. Kingsmore.

220/12:15 An automated reanalysis pipeline for clinical exome data reveals novel diagnoses. S.W. Baker, J. Murrell, B. Krock, A. Santani.


Thursday, October 19

4:15 PM–6:15 PM

Concurrent Invited Session I

47. Analysis of Cancer Genome Variation Using Long-read Sequencing

Room 310A, Level 3, Convention Center

Moderators: Jeffrey Rosenfeld, Rutgers Cancer Inst NJ, New Brunswick
  Sara Goodwin, Cold Spring Harbor Lab, Woodbury

 

Long reads are changing our understanding of the human genome. With these reads of several kb and longer, short repeats can be spanned and full mRNAs can be sequenced. We are using these reads from sequencers including Pacific Biosciences and Oxford Nanopore to gain insight into the changes that occur in cancerous cells. These cells have rearranged genomes that lead to both altered gene expression and the expression of fusion transcripts. We will provide insights into these genomic changes as well as software for their analysis.

 

4:15 PM   Long read sequencing of tumor RNA and DNA to analyze fusions and amplicons. J. Rosenfeld. Rutgers Cancer Inst NJ, New Brunswick.

4:45 PM   Rapid structural event characterization of clinical cancer samples on the Oxford Nanopore MinION. S. Goodwin. Cold Spring Harbor Lab, Woodbury.

5:15 PM   Accurate and fast detection of complex and nested structural variations using long read technologies. F. Sedlazeck. Human Genome Sequencing Ctr, Baylor Col Med, Houston.

5:45 PM   Long read sequencing reveals a complex splicing isoform and fusion transcript repertoire in human breast cancer. J. Banchereau. Jackson Lab for Genomic Med, Farmington.


Thursday, October 19

4:15 PM–6:15 PM

Concurrent Invited Session I

48. Clinical Spotlight: VUS-busters: Cutting-edge Strategies for Interpreting Variants in Clinical and Research Sequencing

Room 330A, Level 3, Convention Center

Moderators: Daniel C. Koboldt, Nationwide Children's Hosp, Columbus
  Aaron Quinlan, Univ Utah, Salt Lake City

 

The adoption of exome and whole genome sequencing as frontline genetic tests has dramatically increased the speed and success rate of molecular diagnosis. These improvements should not only help end the diagnostic odyssey for many patients, but also allow faster intervention and genome-informed clinical care. Yet the task of interpreting exome- or genome-wide variants of possible clinical relevance remains daunting for clinical geneticists and genetic counselors. The sheer number of variants, many of which have an unknown significance, represents a significant bottleneck in the practice of genomic medicine. Furthermore, a majority of rare disease cases (60-75%) screened with these technologies fail to achieve a definitive diagnosis. This session brings together a diverse panel of experts in clinical genomic medicine to address issues of central importance to both researchers and clinicians. They will describe state-of-the-art approaches for alleviating the interpretation bottleneck, including aggregated genome databases, comprehensive variant annotation, and phenotype-driven analysis. They will also describe best practices for solving difficult-to-diagnose cases: disorders arising from unusual inheritance models, somatic and germline mosaicism, pathogenic noncoding variants, structural variants, and multifactorial genetic bases. Together, they will provide cohesive guidance for improving the speed and success of variant interpretation.

 

4:15 PM   Power of the people: Using large-scale, diverse reference databases to improve variant interpretation. A. O'Donnell-Luria. Boston Children's Hosp/Broad Inst, Boston.

4:45 PM   Identifying oligogenic causes of congenital heart disease. K. McBride. Nationwide Children's Hosp, Columbus.

5:15 PM   Novel analytic approaches used to solve unsolved whole exome sequencing data. N. Sobreira. Johns Hopkins Univ, Baltimore.

5:45 PM   Phenotype-driven analysis of exome and genome data. P. Robinson. Jackson Lab for Genomic Med, Farmington.


Thursday, October 19

4:15 PM–6:15 PM

Concurrent Invited Session I

49. Data Sharing, Analysis, and Tools to Catalyze Translation from Genomic to Clinical Knowledge

Room 330C, Level 3, Convention Center

Moderators: Benjamin Neale, Massachusetts Gen Hosp, Boston
  Noel Burtt, Broad Inst, Boston

 

With recent progress in high throughput technologies, we have made unprecedented strides in understanding the function of the genome and identifying thousands of loci robustly associated with complex traits and diseases. However, the translation of this information to actionable targets to improve human health has been much more challenging than anticipated. Public repositories such as dbGaP and others make these data broadly accessible to investigators. However, given the complex analytic and computational resources needed to turn raw data into useful formats, most of the data remain untapped. To take advantage of the full potential of these data and accelerate progress in human health, several efforts have been initiated to democratize access to knowledge and facilitate fluid sharing across all stakeholders. These include the Genomic Data Commons, the Global Alliance for Genomic Health working groups, Accelerating Medicines Partnership in T2D, and multiple public web portals that provide consumable knowledge. Speakers in this session will describe these efforts and the path forward.

 

4:15 PM   Serving genetic data and tools to the world. J. Flannick. Broad Inst, Boston.

4:45 PM   The EGA as a platform for effective data sharing of human genetic and phenotype data. T. Keane. EMBL-EBI, Hinxton, United Kingdom.

5:15 PM   Converting sequence data from over 140,000 people into rare disease diagnoses. D. MacArthur. Massachusetts Gen Hosp, Boston.

5:45 PM   Assessing the phenome-wide consequences of genetically regulated molecular traits. H. Im. Univ Chicago.


Thursday, October 19

4:15 PM–6:15 PM

Concurrent Invited Session I

50. Diversity Matters: Scientific and Ethical Strategies for Achieving Representation in Genomics

Room 230C, Level 2, Convention Center

Moderators: Nanibaa' A. Garrison, Seattle Children's Hosp
  Heather M. Highland, Univ North Carolina, Chapel Hill

 

A recent analysis of published genetic research studies has shown a persistent bias in including people of European ancestry, with only 19% of participants of non-European ancestry, most of whom are people of Asian ancestry; groups from other ancestries remain poorly represented. The underrepresentation of non-European populations poses problems for genomic research and translation to clinical care through missed opportunities to identify new genetic variants that are associated with disease risk, underpowered analyses due to low numbers of certain ethnic groups, and incorrect conclusions due to under-representation or misrepresentation of minority groups in genomic reference databases. This session will showcase the views of an interdisciplinary group of experts, including those with bioethics, genetic epidemiology, population genetics, and community engagement experience, who will discuss why achieving diversity in genomic research is critical from both a scientific and ethical standpoint. Key concepts include: ethical and just reasons for including more communities of color, genetic epidemiological rationales for understanding disease, population genetics reasons for understanding diseases and disparities across diverse populations, and the importance of community engagement in underrepresented communities.

 

4:15 PM   Aiming for equity: The ethical case for greater diversity in genomic research participation. S.M. Fullerton. Univ Washington Sch Med, Seattle.

4:45 PM   Improved strategies to leverage complex genetic architecture for trait mapping in diverse admixed populations. G.L. Wojcik. Stanford Univ Sch Med.

5:15 PM   Broadening diversity in genomic research to build better resources for medical genetics. E.E. Kenny. Icahn Sch Med at Mount Sinai, New York.

5:45 PM   Engagement, equity, and the promise of precision medicine. C.H. Wilkins. Vanderbilt Univ Med Ctr & Meharry Med Col, Nashville.


Thursday, October 19

4:15 PM–6:15 PM

Concurrent Invited Session I

51. Emerging Challenges in Complex Traits: One Locus, but Multiple Variants, Genes, and Tissues

Room 320, Level 3, Convention Center

Moderators: Benjamin F. Voight, Univ Pennsylvania Perelman Sch Med, Philadelphia
  Christopher D. Brown, Univ Pennsylvania Perelman Sch Med, Philadelphia

 

This session will describe emerging complexities that have arisen from the mechanistic characterization of loci responsible for complex trait variation in humans. Recent findings challenge the assumption that GWAS loci can be explained by a single causal variant affecting the expression of a single gene in a single tissue. Speakers will describe their work that demonstrates the existence of functional allelic and tissue heterogeneity and of regulatory mechanisms that target multiple genes at individual loci. These findings have implications for our understanding of complex disease mechanisms and for future therapeutic development.

 

4:15 PM   “There is a danger”: Emerging challenges for computational approaches to dissect complex trait associated loci. B.F. Voight. Univ Pennsylvania Perelman Sch Med, Philadelphia.

4:45 PM   Pleiotropic effects of complex trait variants implicate multiple genes in risk. M. Nobrega. Univ Chicago.

5:15 PM   Gene expression as a model and a tool for the dissection of complex trait mechanisms. C.D. Brown. Univ Pennsylvania Perelman Sch Med, Philadelphia.

5:45 PM   Functional studies uncover allelic heterogeneity of regulatory variation at complex trait loci. K. Mohlke. Univ North Carolina Chapel Hill.


Thursday, October 19

4:15 PM–6:15 PM

Concurrent Invited Session I

52. FACEing the Challenge: Advances in Our Understanding of Facial Development and Disease

Room 220B, Level 2, Convention Center

Moderators: Kerstin U. Ludwig, Univ Bonn, Germany
  Brian C. Schutte, Michigan State Univ, East Lansing

 

Human facial development is an orchestrated process characterized by evolutionary constraint and inter-individual variation, and results in each case in a unique facial appearance. Recent research has yielded important insights into molecular, genetic, and evolutionary aspects of facial development that lie between these poles of constraint and variation. In this session, speakers from diverse research disciplines will present recent developments in the field of facial development and disease. For normal facial development, knowledge from both the functional and genetic variation level will be presented, including recent developments in our understanding of human facial shape variation and evolution, the molecular pathways of palatogenesis, and novel approaches in induced pluripotent stem cell-derived cell systems. For facial malformations, examples from both Mendelian and multifactorial traits such as cancer will be presented to illustrate that craniofacial phenotypes represent a common comorbidity. Furthermore, the session will discuss the contribution of recent technological innovations to improved understanding of both syndromic and non-syndromic disorders, the manner in which ethnicity and subphenotype variation contribute to disease etiology, and the challenges that need to be overcome in order to translate genetic association findings into functional insights.

 

4:15 PM   Genetics of facial disorders: Is it that complex? K.U. Ludwig. Univ Bonn, Germany.

4:45 PM   Abnormal periderm development as a potential pathogenic mechanism for orofacial clefting. B.C. Schutte. Michigan State Univ, East Lansing.

5:15 PM   Face-to-face, linking cis-regulatory divergence to craniofacial evolution in human and chimpanzee. H.K. Long. Stanford Univ.

5:45 PM   The generation of variation and the developmental genetics of facial shape. B. Hallgrimsson. Univ Calgary, Canada.


Thursday, October 19

4:15 PM–6:15 PM

Concurrent Invited Session I

53. Novel Insights into Human Brain Evolution from Advanced Genomics

Room 230G, Level 2, Convention Center

Moderators: Simon E. Fisher, Max Planck Inst for Psycholinguistics, Nijmegen, Netherlands
  Evan Eichler, Univ Washington, Seattle

 

Dramatic advances in genomic technologies are shedding new light on the evolutionary origins of human-specific traits and how the relevant molecular pathways may be disturbed in related disorders. This session will showcase the extraordinary impact that cutting-edge molecular approaches are making on our understanding of the distinctive evolution, development, and functions of the human brain. Evan Eichler introduces the topic, showing how the latest sequencing methods help resolve the critical contributions of segmental duplications to the emergence of our species. Crucially, these genomic processes have at the same time put modern humans at high risk of neurodevelopmental disease, including autism, intellectual disability, and epilepsy. Next, Wieland Huttner describes how a sophisticated combination of comparative transcriptomics with functional analyses in model systems has identified human-specific genes, such as ARHGAP11B, that can be mechanistically linked to neocortical expansion. The third speaker, Fenna Krienen, discusses innovative work integrating spatial patterns of gene expression in the human neocortex with patterns of functional connectivity, as indexed by state-of-the-art neuroimaging. Her research uncovers a role for molecular modifications of upper cortical layers in the evolution of long-range connections in the human brain. Finally, Alex Pollen explains how his analyses of gene expression in single cells can be correlated with their position, morphology, and cellular behavior during development. This approach has highlighted species-specific changes in radial glia gene expression that may help uncover what makes us human, and yield novel windows into brain disorders.

 

4:15 PM   Human evolution and disease by segmental duplication. E. Eichler. Univ Washington, Seattle.

4:45 PM   The role of human-specific genes, notably ARHGAP11B, in neural stem cell amplification and neocortex expansion in development and evolution. W. Huttner. Max Planck Inst Molec Cell Biol & Genet, Dresden, Germany.

5:15 PM   Variation in gene expression across the human neocortex is associated with brain network organization. F. Krienen. Harvard Med Sch, Boston.

5:45 PM   Evolution and development of human neural stem cells. A. Pollen. UCSF.


Thursday, October 19

4:15 PM–6:15 PM

Concurrent Invited Session I

54. Rigor and Reproducibility in Genetic Research

Room 220F, Level 2, Convention Center

Moderators: Douglas F. Dluzen, Morgan State Univ, Baltimore
  Christoph Nowak, Uppsala Univ, Sweden

 

Scientific rigor and reproducibility are the cornerstones of basic and clinical genetics research. Both concepts must work in concert to ensure success in future research endeavors and maintain the public's trust in science, particularly in the era of "big data" and the increasing availability/affordability of genetic testing. Mounting evidence suggests that a significant portion of reported research cannot be reproduced outside the publishing lab, which has led to the so-called "reproducibility crisis" in science. This session addresses the need to discuss the factors contributing to the "reproducibility crisis" in genetic research, including study design, reporting of false positives, P-hacking, transparency in methodology and reporting of raw genetic data, bioethics, student training in genetic studies, and failure to replicate new findings published in high-impact journals. Speakers will discuss novel strategies and practical solutions for the urgent need to improve genetic research practices and study design, increase transparency and replication in the reported findings and methodologies in basic and clinical genetic research, and the appropriate use of statistical analysis for the interpretation of findings. A particular emphasis will be placed on the mentor-trainee relationship as a critical interaction during early-career training that can promote increased awareness of this problem and address these issues in an impactful way.

 

4:15 PM   Making genetics research more reproducible. D. Fanelli. Stanford Univ, Palo Alto.

4:45 PM   Genetic replication studies: Strategies to assess reproducibility. N. Perfito. Sci Exchange, Palo Alto.

5:15 PM   Setting the foundations: The path toward sustainable and comprehensive research training. A. Gammie. Natl Inst Gen Med Sci, Bethesda.

5:45 PM   What do rigor and reproducibility mean in the changing world of science communication? C. Gunter. Emory Univ, Atlanta.


Thursday, October 19

4:15 PM–6:15 PM

Concurrent Invited Session I

55. Solving the Unsolved: Systems to Facilitate the Discovery of Novel Rare Disease Genes from Genomic Sequencing

Room 310C, Level 3, Convention Center

Moderators: Heidi L. Rehm, Harvard Med Sch, Cambridge
  Kym Boycott, Children's Hosp of Eastern Ontario, Ottawa, Canada

 

This session will address the increasingly common challenge of exome and genome sequencing wherein the majority of patients lack a clear diagnosis after initial analysis. For such patients, finding just a single additional patient with a deleterious variant in the same gene and overlapping phenotype may provide sufficient evidence to causally implicate the gene, enabling a diagnosis for the patient. Multiple rare disease consortia have established services to facilitate such matching. To unify these efforts, an international collaboration called Matchmaker Exchange (MME) launched a federated platform to facilitate the identification of cases with similar phenotypic and genotypic profiles and harness the collective data across all of the participating databases. The MME enables queries of multiple matchmaker services without having to separately query all services or deposit data in each one. This session will present the work of several of the connected genomic matchmaking systems: DECIPHER, GeneMatcher, MyGene2, and PhenomeCentral. Speakers will focus on use cases, user communities (clinicians, researchers, patients), matching algorithms, lessons learned, successes, and the evolution of genomic matchmaking.

 

4:15 PM   A decade of genomic matchmaking using DECIPHER. M. Hurles. Wellcome Trust Sanger Inst, Cambridge, United Kingdom.

4:45 PM   Phenotypic and genomic matchmaking through PhenoDB and GeneMatcher. A. Hamosh. Johns Hopkins Univ Sch Med, Baltimore.

5:15 PM   PhenomeCentral & RareConnect: Clinician and patient rare disorder networks to enable broad data sharing. M. Brudno. Hosp for Sick Children & Univ Toronto, Canada.

5:45 PM   MyGene2: Radically open data sharing to accelerate the pace of gene discovery. M. Bamshad. Univ Washington & Seattle Children's Hosp.


Friday, October 20

9:00 AM–10:00 AM

Concurrent Platform Session E

56. Genomic Testing: A Focus on Results

Room 220B, Level 2, Convention Center

Moderators: Deborah Cragun, Univ South Florida, Tampa
  Daniel Riconda, Baylor Col Med, Houston

 

NOTE: Overflow seating for this session is available in Room 220D.

 

221/9:00 Returning carrier status from genomic sequencing in newborns: Early observations from the BabySeq Project. C.A. Genetti, G.E. VanNoy, S. Fayer, W. Betting, O. Ceyhan-Birsoy, K. Machini, J. Murry, M. Lebo, T. Yu, P.B. Agrawal, R.B. Parad, I.A. Holm, S. Pereira, A.L. McGuire, H.L. Rehm, R.C. Green, A.H. Beggs, The BabySeq Project.

222/9:15 Genetic screening for healthy individuals: Preliminary results from a medically actionable genetic screening panel. E. Haverfield, E.D. Esplin, S. Aguilar, K.E. Ormond, A. Hanson-Kahn, P. Atwal, S. Macklin, C. Sak, S. Bleyl, C. Fine, A. Lynch, R.L. Nussbaum, S. Aradhya.

223/9:30 Physicians’ perspectives on returning unsolicited genomic results to patients and health care providers. D.B. Pet, I.A. Holm, J.L. Willaims, M.F. Myers, L.L. Novak, K.B. Brothers, G.L. Wiesner, E. W. Clayton.

224/9:45 Non-inferiority of a web platform compared to in-person counselor return of carrier results: A randomized controlled trial. B.B. Biesecker, K.L. Lewis, K.L. Umstead, J.J. Johnston, E. Turbitt, K.P. Fishler, J.H. Patton, I.M. Miller, A.R. Heidlebough, L.G. Biesecker.


Friday, October 20

9:00 AM–10:00 AM

Concurrent Platform Session E

57. Exploring the Impact of Archaic Ancestry

Room 220F, Level 2, Convention Center

Moderators: Vanessa Romero, National Inst Genetics, Japan
  James Hicks, Washington Univ St. Louis

 

225/9:00 Neanderthal introgression reintroduced thousands of ancestral alleles lost in the out of Africa bottleneck. J. Capra, C. Simonti.

226/9:15 Quantifying the impact of Neanderthal gene flow on human phenotypes. C.R. Robles, A. Ganna, A. Gusev, D. Reich, S. Sankararaman.

227/9:30 Interpreting human genomic regions depleted of archaic hominin ancestry. A.B. Wolf, J.M. Akey.

228/9:45 Imputing ancient gene expression reveals significant differential expression in Neanderthal tissues. L.L. Colbran, P. Evans, E.R. Gamazon, N.J. Cox, J.A. Capra.


Friday, October 20

9:00 AM–10:00 AM

Concurrent Platform Session E

58. Data Sharing to Improve Genomic Variant Interpretation

Room 230C, Level 2, Convention Center

Moderators: Ross Rowsey, Mayo Clinic, Rochester
  Lisa Vincent, GeneDx, Inc., Gaithersburg

 

NOTE: Overflow seating for this session is available in Room 230E.

 

229/9:00 Resolving variant interpretation differences in ClinVar between 43 clinical laboratories. S. Harrison, J. Dolinsky, H. Rehm, ClinGen's Sequence Variant Inter-Laboratory Discrepancy Resolution Task Team.

230/9:15 An interlaboratory study of complex variant detection in clinical testing. S. Lincoln, J. Zook, R. Truty, S. Chowhurdy, A. Fellowes, S. Mahamdallie, M. Ferber, M. Cleveland, C. Huang, F. Tomson, E. Klee, W. DeSilva, S. Seal, S. Aradhya, R. Garlick, R. Nussbaum, N. Rahman, S. Kingsmore, M. Salit, B. Shirts.

231/9:30 The impact of sharing patient-derived data in ClinVar via GenomeConnect. J.M. Savatt, D.R. Azzariti, W.A. Faucett, M. Landrum, D.H. Ledbetter, C. Lese Martin, V. Rangel Miller, E. Palen, H. Rehm, J. Rhode, S. Turner, E. Rooney Riggs.

232/9:45 Efficacy of reanalyzing negative clinical WES data to identify new genes in intellectual disability/congenital anomalies. A. Bruel, S. Nambot, V. Quéré, M. Assoum, A. Vittobello, S. Moutton, N. Houcinat, D. Lehalle, N. Jean-Marçais, J. Thevenon, M. Chevarin, C. Poë, T. Jouan, P. Callier, A. Mosca-Boidron, E. Tisserand, C. Philippe, F. Tran Mau-Them, Y. Duffourd, L. Faivre, C. Thauvin-Robinet.


Friday, October 20

9:00 AM–10:00 AM

Concurrent Platform Session E

59. Congenital and Pediatric Heart Diseases

Room 230G, Level 2, Convention Center

Moderator: Wendy K. Chung, Columbia Univ, New York

 

233/9:00 The genetic architecture of pediatric cardiomyopathy. S. Ware, P. Dexheimer, S. Bhatnagar, A. Sridhar, J. Wilkinson, M. Tariq, J. Schubert, S. Colan, L. Shi, C. Canter, D. Hsu, S. Webber, D. Dodd, M. Everitt, P. Kantor, L. Addonizio, J. Jefferies, J. Rossano, E. Pahl, P. Rusconi, W. Chung, T. Lee, J. Towbin, A. Lal, E. Miller, H. Razoky, J. Czachor, L. Martin, B. Aronow, S. Lipshultz, Pediatric Cardiomyopathy Registry Study Group.

234/9:15 Congenital heart malformations in Sub-Saharan Africa and Asia: An exome sequencing study. P. Kruszka, S.I. Berger, S.K. Hong, A.A. Adeyemo, P. Tanpaiboon, E.N. Ekure, M. Muenke.

235/9:30 De novo noncoding mutations in congenital heart disease. F. Richter, S. Morton, J. Homsy, A. Kitaygorodsky, H. Qi, N. Patel, K. Manheimer, D.E. Dickel, A. Visel, I. Barozzi, M. Linderman, G. Hoffman, E.E. Schadt, D. Jordan, R. Do, D. McKean, J. Priest, J.R. Kaltman, D. Srivastava, J. Yost, M. Tristani-Firouzi, M. Brueckner, E. Goldmuntz, Y. Shen, W.K. Chung, J.G. Seidman, C.E. Seidman, B.D. Gelb, Pediatric Cardiac Genomics Consortium.

236/9:45 Congenital heart defects in Bainbridge Ropers syndrome. A. Srivastava, B. McGarth, R. K.C., Y.C. Tsan, C.E. Keegan, A. Helms, S.L. Bielas.


Friday, October 20

9:00 AM–10:00 AM

Concurrent Platform Session E

60. Transcriptomics in Complex Neurological/Neuropsychiatric Disease

Room 310A, Level 3, Convention Center

Moderators: Minerva Carrasquillo, Mayo Clinic, Jacksonville
  Dimitrios Avramopoulos, Johns Hopkins Univ, Baltimore

 

237/9:00 Multi-tissue transcriptome analysis reveals genetic mechanisms of neuropsychiatric traits. E.R. Gamazon, A. Zwinderman, N. Cox, D. Denys, E. Derks.

238/9:15 Genetically driven gene expression associated with nicotine dependence across ten brain regions reveals novel genes and brain regions. C.A. Markunas, D.B. Hancock, Y. Guo, G.W. Reginsson, R. Sherva, A. Loukola, C. Minica, N.C. Gaddis, S.M. Lutz, D.F. Gudbjartsson, K.A. Young, D.W. McNeil, B. Qaiser, P.A.F. Madden, L.A. Farrer, J. Vink, N.L. Saccone, M.C. Neale, H.R. Kranzler, M.L. Marazita, D.I. Boomsma, J. Gelernter, J. Kaprio, N. Caporaso, T.E. Thorgeirsson, J.E. Hokanson, L.J. Bierut, N. Cox, K. Stefansson, E.O. Johnson.

239/9:30 Using large scale brain eQTL meta-analysis from multiple RNA-sequencing cohorts to identify neurodegenerative and neuropsychiatric risk candidates. S.K. Sieberts, T. Perumal, M. Carrasquillo, M. Allen, J. Reddy, K. Dang, J. Calley, P.J. Ebert, A. Dobbyn, E. Stahl, N. Taner, L.M. Mangravite, AMP-AD Consortium eQTL Working Group and the CommonMind Consortium (CMC).

240/9:45 Transcriptome analysis implicates joint dysfunction of GABAergic interneurons and metabolism in schizophrenia. A. Norris, M.A. Kondo, A.E. Jaffe, X. Chen, A. Sawa, J. Pevsner.


Friday, October 20

9:00 AM–10:00 AM

Concurrent Platform Session E

61. Context Matters: Genes, Environment, and Sex (Part 1)

Room 310C, Level 3, Convention Center

Moderators: Timothy Frayling, Univ Exeter, Devon, UK
  William Bush, Case Western Reserve Univ, Cleveland

 

241/9:00 Multi-ancestry genome-wide association study incorporating gene-alcohol intake interactions identifies 18 new lipid loci. P.S. de Vries, M.R. Brown, A.R. Bentley, T.W. Winkler, A.T. Kraja, A.C. Morrison, CHARGE Gene-Lifestyle Interactions Working Group.

242/9:15 Gene x environment interactions in the UK Biobank study: Evidence that both physical inactivity and sleep inefficiency accentuate the genetic risk of obesity. A.R. Wood, S.E. Jones, Z. Kutalik, H. Yaghootkar, R. Beaumont, M.A. Tuke, K.S. Ruth, R.M. Freathy, A. Murray, M.N. Weedon, J. Tyrrell, T.M. Frayling.

243/9:30 Multi-ancestry genome-wide association study of gene × smoking interactions identifies novel lipid loci. A.R. Bentley, Y.J. Sung, M.R. Brown, C.N. Rotimi, L.A. Cupples, CHARGE Gene-Lifestyle Interactions Working Group.

244/9:45 Machine learning approaches to identify genetic and context-based differences in heart disease prediction between males and females. S. Raj, A.G. Clark, M. Sabuncu.


Friday, October 20

9:00 AM–10:00 AM

Concurrent Platform Session E

62. New Paradigms for Regulatory Variant Contribution to Disease Risk

Room 320, Level 3, Convention Center

Moderators: Emmanouil Dermitzakis, Univ Geneva, Switzerland
  Gosia Trynka, Sanger Inst, Cambridgeshire, UK

 

245/9:00 An expanded view of complex traits: From polygenic to omnigenic. Y. Li, E. Boyle, J. Pritchard.

246/9:15 Joint effects of regulatory and coding variants shape human genetic variation and disease risk. S.E. Castel, A. Cervera, F. Reverter, R. Guigo, I. Iossifov, A. Vasileva, T. Lappalainen.

247/9:30 Evidence of compensatory variations on the remaining allele of rare deletions. K. Popadin, E. Porcu, M. Lepamets, K. Mannik, M. Garieri, R. Magi, Z. Kutalik, A. Reymond.

248/9:45 Pleiotropic noncoding regulatory elements are under purifying natural selection. D. Radke, D.J. Balick, J. Sul, S. Akle, M. Maurano, R. Green, J. Stamatoyannopoulos, S. Sunyaev.


Friday, October 20

9:00 AM–10:00 AM

Concurrent Platform Session E

63. Gene Expression Studies of T2D

Room 330A, Level 3, Convention Center

Moderators: Adam Locke, Washington Univ St. Louis
  Steven Bray, LifeOmic, Morrisville

 

249/9:00 Parent-of-origin effects on gene expression in type 2 diabetes offspring trios. R.B. Prasad, G. Kovacs, A. Lindqvist, G. Hatem, A. Lessmark, P. Almgren, M. Vitai, N. Oskolkov, T. Singh, P. Vikman, M. Åkerlund, N. Wierup, I. Artner, L. Koranyi, L. Groop.

250/9:15 Identification of expression regulation mediating association loci for T2D through characterization of human pancreatic islets and β-cells. A. Viñuela, M. van de Bunt, A. Varshney, N. Oskolkov, P.E. MacDonald, L. Scott, M.L. Stitzel, C.J. Parker, for the InsPIRE consortium.

251/9:30 Transcriptome sequence analysis at single-cell resolution reveals depot-specific signatures in adipose tissue-derived stromal vascular fraction cells linked to metabolic diseases. J. Vijay, X. Shao, M-M. Simon, M-C. Vohl, A. Tchernof, E. Grundberg.

252/9:45 Transcriptomic profiling of the developing human islet and mechanisms of type 2 diabetes predisposition. M. Perez-Alcantara, M. van de Bunt, N. Beer, C. Honoré, M. Hansson, A. Gloyn, M. McCarthy.


Friday, October 20

9:00 AM–10:00 AM

Concurrent Platform Session E

64. Measuring Effects of Genetic Variants with High-Throughput Assays

Room 330C, Level 3, Convention Center

Moderators: Manolis Kellis, MIT, Cambridge
  Casey Romanoski, Univ Arizona, Tucson

 

253/9:00 The effect of genetic variation on promoter usage and enhancer activity. M. Garieri, O. Delaneau, F. Santoni, D. Mull, P. Carninci, E.T. Dermitzakis, S.E. Antonarakis, A. Fort.

254/9:15 Massively parallel reporter assays at the population scale: Quantifying the regulatory effect of non-coding variation in a large human cohort. S.J. Cunningham, G.D. Johnson, W.H. Majoros, C.M. Vockley, C. Guo, M.G. Hayes, W.L. Lowe Jr., T.E. Reddy.

255/9:30 Principles of gene regulation and noncoding variant function from hundreds of enhancer perturbations. J. Engreitz, C. Fulco, T. Jones, R. Anyoha, E. Perez, M. Kane, G. Munson, S. Grossman, E. Lander.

256/9:45 Identification of enhancer elements at multiple renal cancer susceptibility loci using a massively parallel reporter assay (MPRA). L. Machado Colli, L. Jessop, M.J. Machiela, J. Choi, T. Myers, M. Purdue, K. Brown, S.J. Chanock.


Friday, October 20

10:15 AM–11:15 AM

Concurrent Platform Session F

65. DNA Methylation

Room 220B, Level 2, Convention Center

Moderators: Weihua Guan, Univ Minnesota, Minneapolis
  Genevieve Housman, Univ Chicago

 

257/10:15 Discovery of unique disease- and gene-specific peripheral blood DNA methylation signatures allows molecular diagnosis and VUS classification in hereditary genetic syndromes. B. Sadikovic, L. Schenkel, C. Schwartz, K. Boycott, P. Ainsworth, E. Aref-Eshghi.

258/10:30 Variation in mitochondrial DNA copy number influences nuclear DNA methylation. C.A. Castellani, R.J. Longchamps, J.A. Sumpter, A. Tin, J.A. Lane, M.L. Grove, J. Bressler, J. Coresh, J.S. Pankow, M. Fornage, N. Pankratz, E. Boerwinkle, D.E. Arking, CHARGE Aging and Longevity Working Group.

259/10:45 RNAseq in 302 phased trios provides a high resolution map of genomic imprinting. A.J. Sharp, B. Jadhav, R. Monajemi, K.K. Gagalova, H.H.M. Draisma, T. Lappalainen, S. Castel, L. Franke, P.A.C. ‘t Hoen, S.M. Kielbasa, BIOS Consortium.

260/11:00 Genome-wide survey of parent-of-origin effects on DNA methylation identifies candidate imprinted loci in humans. G. Cuellar-Partida, C. Laurin, T. Gaunt, S. Ring, C. Relton, G.D. Smith, D.M. Evans.


Friday, October 20

10:15 AM–11:15 AM

Concurrent Platform Session F

66. Splicing in Complex Traits

Room 220F, Level 2, Convention Center

Moderators: Graham Johnson, Duke Univ, Durham
  Jill Moore, Univ Mass Med Sch, Worcester

 

261/10:15 Allele-specific expression improves local expression analysis of GWAS loci: Splicing of GSDMB identified for asthma in the human lungs. Z. Miao, A. Ko, P. Pajukanta.

262/10:30 Global transcriptomic analysis of human hematopoietic stem cells identifies alternative splicing of HMGA2 in mediating stem cell properties. M.H. Guo, M. Cesana, D. Cacchiarelli, L. Wahlster, S. Doulatov, L.T. Vo, B. Salvatori, C. Trapnell, K. Clement, P. Cahan, K.M. Tsanov, P.M. Sousa, J. Barragan, B. Tazon-Vega, F.M. Giorgi, A. Bolondi, A. Califano, J.L. Rinn, A. Meissner, J.N. Hirschhorn, G.Q. Daley.

263/10:45 Splice quantitative trait loci in human peripheral blood provide novel insight into the molecular determinants of COPD. A. Saferali, A. Lamb, M. Parker, J.H. Yun, R.P. Chase, B.D. Hobbs, H.M. Boezen, K. de Jong, E.K. Silverman, M.H. Cho, P.J. Castalidi, C.P. Hersh.

264/11:00 Multiple trait, gene expression, and splice junction associations at the cardiometabolic MADD-NR1H3 GWAS locus. C.K. Raulerson, A. Ko, M. Alvarez, T.S. Furey, M. Laakso, P. Pajukanta, K.L. Mohlke.


Friday, October 20

10:15 AM–11:15 AM

Concurrent Platform Session F

67. Ocular Development and Disease

Room 230C, Level 2, Convention Center

Moderators: Shay Ben-Shachar, Tel Aviv Med Ctr, Israel
  Daniah T. Beleford, UCSF

 

265/10:15 RERE is required for normal eye development in humans and mice. B. Kim, B. Freqeau, A. Hernandez-Garcia, V. Jordan, D. Stockton, M. Justice, E. Sherr, D. Scott.

266/10:30 Loss of ABCB5 leads to progressive visual loss due to sphingolipid accumulation in retinal pigment epithelium. G. Gonzalez, Y. Sasamoto, P. Banerjee, J. Akula, V. Poulaki, G. Berg, M.H. Frank, B.R. Ksander, N.Y. Frank.

267/10:45 CNIH4 and PMEL rare variants cause ocular pigment dispersion syndrome predisposing to pigmentary glaucoma. J.L. Wiggs, B.J. Fan, K. Allen, Q. Zhang, M.H. Kang, D.J. Rhee, D.S. Greenfield, R.K. Parrish, K. Linkroum, L.R. Pasquale, E.A. Pierce, C.J. Hammond, P.G. Hysi, N. Weisschuh, M.J. Simcoe, R.M. Leonhardt, R. Ritch.

268/11:00 Electronic health records elucidate complex relationships between genetics, the anatomy of the eye, and disease. C.R. Bauer, E.D.K. Cha, A.B. Paaby, D. Lavage, S.A. Pendergrass, on behalf of the DiscovEHR collaboration.


Friday, October 20

10:15 AM–11:15 AM

Concurrent Platform Session F

68. Blood Omics in Large Cohorts

Room 230G, Level 2, Convention Center

Moderators: Samuli Ripatti, Inst Molec Med Finland, Helsinki
  Mark J. Daly, Broad Inst, Cambridge

 

269/10:15 Powerful genome-wide association screening of serum metabolites in 10K individuals. A. Gallois, J. Mefford, A. Ko, M. Laakso, N. Zaitlen, P. Pajukanta, H. Aschard.

270/10:30 Genetic determinants of the human plasma proteome and their role in biology and disease. B.B. Sun, J.C. Maranville, J.E. Peters, C.S. Fox, R.M. Plenge, J. Danesh, H. Runz, A.S. Butterworth.

271/10:45 Trans-eQTL meta-analysis in over 30,000 blood samples identifies genes and pathways affected by disease-related genetic variants. U. Võsa, A. Claringbould, T. Esko, L. Franke, BIOS Consortium, eQTLGen Consortium.

272/11:00 An imputation-based approach for matching unknown signals across untargeted metabolomics datasets. Y.H. Hsu, C. Churchhouse, T. Esko, A. Metspalu, J.M. Mercader, C. Gonzalez, M.E. Gonzalez, J.N. Hirschhorn.


Friday, October 20

10:15 AM–11:15 AM

Concurrent Platform Session F

69. Genetics of Addictive Behaviors

Room 310A, Level 3, Convention Center

Moderators: Dana Hancock, RTI Intl, Research Triangle Park
  Howard Edenberg, Indiana Univ Sch Med, Indianapolis

 

273/10:15 First genome wide association study of Internet addiction revealed strong shared risk factors with psychosis. A. Haghighatfard, A. Ghaderi.

274/10:30 Genome-wide analyses of smoking behaviors in schizophrenia: Findings from the Psychiatric Genomics Consortium. R. Peterson, T. Bigdeli, K. Kendler, A. Fanous, Schizophrenia Working Group of the Psychiatric Genomics Consortium.

275/10:45 Genetic associations of maximum regular alcohol intake in the Million Veteran Program. J. Concato, N. Sun, Q. Lu, Y. Hu, B. Li, Q. Chen, M. Aslan, K. Radhakrishnan, K.H. Cheung, Y. Li, R. Pietrzak, N. Rajeevan, F. Sayward, K. Cho, K. Harrington, J. Honerlaw, S. Pyarajan, R. Quaden, J.M. Gaziano, H. Zhao, M.B. Stein, J. Gelernter, on behalf of the VA Million Veteran Program.

276/11:00 GWAS meta-analysis identifies > 200 novel loci for smoking and drinking addiction. Y. Jiang, the GWAS and Sequencing Consortia of Alcohol and Nicotine addiction.


Friday, October 20

10:15 AM–11:15 AM

Concurrent Platform Session F

70. Context Matters: Genes, Environment, and Sex (Part 2)

Room 310C, Level 3, Convention Center

Moderators: Beth Hauser, Duke Univ, Durham
  Karen Mohlke, Univ North Carolina, Chapel Hill

 

277/10:15 Multi-omics profiling for individualized precision wellness using blood and saliva. G.I. Mias.

278/10:30 Integrative personal omics profiling during periods of environmental stress. M. Snyder, W. Zhou, B. Piening, R. Sailani, K. Contrepois, H. Roest, S. Ahadi, S. Leopold, B. Hansen, M. Avina, V. Rao, T. Mishra, S. Rose, G. Gu, B. Lee, S. Chen, S. Rego, D. Perelman, B. Leopold, T. McLaughlin, E. Sodergren, G. Weinstock.

279/10:45 Sex-specific inbreeding depression in humans. D.W. Clark, P. K. Joshi, T. Esko, J.F. Wilson, on behalf of the ROHgen Consortium.

280/11:00 Whole-exome sequencing identifies sex-specific risk variation for Alzheimer's disease. B.W. Kunkle, K.L. Hamilton-Nelson, A.C. Naj, A.B. Kuzma, D. Lancour, M. Butkiewicz, J. Malamon, Y. Ma, G.W. Beecham, W.S. Bush, L.S. Wang, R. Mayeux, J.L. Haines, L.A. Farrer, G.D. Schellenberg, M.A. Pericak-Vance, E.R. Martin, The Consortium for Alzheimer's Sequencing Analysis (CASA).


Friday, October 20

10:15 AM–11:15 AM

Concurrent Platform Session F

71. Autism

Room 320, Level 3, Convention Center

Moderators: Hilary Coon, Univ Utah Sch Med, Salt Lake City
  Brian O'Roak, Oregon Hlth & Sci Univ, Portland

 

281/10:15 SPARK: A large-scale genomic resource of over 20,000 individuals with autism spectrum disorder. P. Feliciano, The SPARK Consortium.

282/10:30 The MSSNG Autism Spectrum Disorder Whole Genome Sequencing Resource. S. Walker, R.K.C Yuen, D. Merico, M. Bookman, J.L. Howe, B. Thiruvahindrapuram, R. Patel, J. Whitney, N. Deflaux, J. Bingham, Z. Wang, G. Pellecchia, J.A. Buchanan, C.R. Marshall, N. Hoang, S.L. Pereira, T. Paton, W. Van Etten, M. Szego, L.J. Strug, B.A. Fernandez, L. Zwaigenbaum, B.A. Knoppers, E. Anagnostou, P. Szatmari, W. Roberts, R.H. Ring, D. Glazer, M.T. Pletcher, S.W. Scherer.

283/10:45 Rare variants conferring risk for autism and ADHD identified by whole exome sequencing of dried bloodspots. F.K. Satterstrom, F. Lescai, D. Demontis, R.K. Walters, C. Stevens, J. Grauholm, J.B. Maller, D.M. Hougaard, T.M. Werge, P.B. Mortensen, B.M. Neale, A.D. Børglum, M.J. Daly, iPSYCH-Broad Consortium.

284/11:00 Clinical exome sequencing as a first tier clinical diagnostic test for individuals with developmental delay and autism spectrum disorder (ASD/DD). S.V. Mullegama, S.D. Klein, A.R. Lipson, H. Lee, S.P. Strom, E.D. Douine, W. W. Grody, E. Vilain, S.F. Nelson, J.A. Martinez-Agosto.


Friday, October 20

10:15 AM–11:15 AM

Concurrent Platform Session F

72. Clinical Genomics in Cancer

Room 330A, Level 3, Convention Center

Moderators: Sunita Setlur, Brigham & Women's Hosp, Boston
  Robert Klein, Icahn Sch Med Mount Sinai, New York

 

285/10:15 Methylation accurately predicts age of cancer onset in patients with Li Fraumeni syndrome. B. Brew, L. Erdman, T. Guha, A. Novokmet, A. Dorea, J. Berman, A. Shlien, D. Malkin, A. Goldenberg.

286/10:30 Pediatric Cancer Variant Pathogenicity Information Exchange (PeCan-PIE): A cloud-based platform for curating and classifying germline mutations in cancer-related genes. M.N. Edmonson, A. Patel, D. Hedges, Z. Wang, E. Rampersaud, S. Newman, X. Zhou, M.C. Rusch, C. McLeod, M.R. Wilkinson, C. Pepper, S.V. Rice, J. Becksfort, K.E. Nichols, L.L. Robison, J.R. Downing, J. Zhang.

287/10:45 NBN germline mutations are associated with pan-cancer susceptibility and show in vitro DNA damage response defects. S. Topka, M.F. Walsh, A. Maria, N. Pradhan, C. Stewart, D. Mandelker, L. Zhang, M. Berger, Z.K. Stadler, J. Petrini, M. Robson, J. Vijai, K. Offit.

288/11:00 The spectrum of MYC translocations and their effect on gene upregulation in a dataset of 527 multiple myeloma patients. A. Mikulasova, C.T. Ashby, R. G. Tytarenko, S. Deshpande, O.W. Stephens, E. Tian, P.H. Patel, C.P. Wardell, S. Roy Choudhury, G.H. Jackson, F.E. Davies, G.J. Morgan, B.A. Walker.


Friday, October 20

10:15 AM–11:15 AM

Concurrent Platform Session F

73. Transcriptomic Analysis of Genetic Variation and Disease

Room 330C, Level 3, Convention Center

Moderators: Graham McVicker, Salk Inst Biol Sci, La Jolla
  Margaret Taub, Johns Hopkins Univ, Baltimore

 

289/10:15 Integrative analysis of exome sequencing and gene expression data identify novel non-HLA mismatched variants associated with antibody mediated rejection in kidney transplant. S. Pineda, T. Sigdel, A. Jackson, M. Sarwal, M. Sirota.

290/10:30 Leveraging molecular QTL to understand the genetic architecture of diseases and complex traits. F. Hormozdiari, S. Gazal, B. Geijn, H. Finucane, C. Ju, P. Loh, X. Liu, L. O'Connor, A. Gusev, E. Eskin, A. Price.

291/10:45 Integrating transcriptome sequencing from Mendelian disease patients and healthy controls enhances genetic variant interpretation. B. Cummings, J.L. Marshall, K.J. Karczewski, F. Zhao, B. Weisburd, The. GTEX Consortium, S. Donkervoort, L. Waddell, S. Sandaradura, G. O'Grady, E. Oates, J. Dowling, S.T. Cooper, C. Bonnemann, D.G. MacArthur.

292/11:00 Transcriptomic analysis of CD4+, CD8+, and CD14+ cells in newly diagnosed multiple sclerosis patients. K. Kim, E.L. Eggers, S.J. Caillier, S.L. Hauser, J.R. Oksenberg, S.E. Baranzini.


Friday, October 20

1:00 PM–2:15 PM

74. ASHG Business Meeting

Room 220F, Level 2, Convention Center

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 last business meeting. We encourage discussion from the floor.

 


Friday, October 20

2:30 PM–4:30 PM

Concurrent Invited Session II

75. ASHG/ESHG Building Bridges: Zika: From Virus to Host Response to Vector Control

Room 220B, Level 2, Convention Center

Moderators: Peter C. Scacheri, ASHG 2017 Program Committee Chair
  Joris Veltman, ESHG 2017 Program Chair

 

Since the emergence of the Zika virus from Africa as a truly global problem several years ago, biologists, epidemiologists, clinicians, and public health specialists have been scrambling to understand the nature, transmission, distribution, and health-related implications of this vector-borne pathogen. In this session, specialists from diverse fields will examine several aspects of the Zika epidemic, including the evolution and distribution of the virus, host response, the pathogen’s role in birth defects, and attempts at control through vaccine development.

 

2:30 PM   Introduction.

2:35 PM   Genomic epidemiology traces Zika virus evolution and spread in the Americas. B.L. MacInnis. Broad Inst, Cambridge.

2:55 PM   Zika virus: Update on a new cause of birth defects. S.A. Rasmussen. CDC, Atlanta.

3:15 PM   Host response to Zika virus infection. P. F. Vasconcelos. Inst Evandro Chagas, Brazil.

3:35 PM   Vaccine development. E.T.A. Marques. Univ Pittsburgh.

3:55 PM   Panel Discussion.


Friday, October 20

2:30 PM–4:30 PM

Concurrent Invited Session II

76. Biology at Single Cell Resolution: Understanding Cell-type-specific Responses in Development and Disease

Room 320, Level 3, Convention Center

Moderators: Sumantra Chatterjee, Johns Hopkins Univ Sch Med, Baltimore
  Loyal A. Goff, Johns Hopkins Univ Sch Med, Baltimore

 

Recent advances in sequencing and analysis techniques have made studying various molecular events at single cell resolution an increasingly robust and popular method. But the greatest impact of such studies will be on understanding the effects of genetic changes on the cellular fates, which play a critical role in normal development as well as lead to disorders. As the human genetics community rapidly moves towards understanding the functional consequences of various changes in our genome, it will be important to study that consequence at the level where the effects are first felt: the individual cell. In this session, we will present a brief outline of the potential and the challenges of single cell genomics technologies, its dynamic beginnings, its exciting future, and most importantly, the lessons we have learnt in this journey so far. We will discuss work looking at single cell transcriptomic, genomic, and epigenomic data from both disease and non-disease models to get a very broad perspective of how changes at the cellular level impact the broader discernible phenotype and how cell fate decisions are driven by very specific gene signatures in particular cellular subtypes that are different from their neighboring cells. We also show how disrupting critical genes involved in a specific process leads to distinct effects across different subsets of cells in a tissue, and why understanding these discrete effects will lead to a better understanding of normal developmental processes as well as reveal the complexity of cellular response in disease.

 

2:30 PM   Cell-type-specific responses in genetic disorders: Single cell reconstruction of neurogenesis defects in Kabuki Syndrome 1. L.A. Goff. Johns Hopkins Univ Sch Med, Baltimore.

3:00 PM   Single cell transcriptomics to study the emergence of the simian primitive syncytium and human embryo development. L. Kaye. Jackson Lab, Farmington.

3:30 PM   Cellular level consequences of loss of Ret signaling in Hirschsprung disease: Disease phenotype at single cell resolution. S. Chatterjee. Johns Hopkins Univ Sch Med, Baltimore.

4:00 PM   Chromatin accessibility dynamics during myogenesis at single-cell resolution. C. Trapnell. Univ Washington, Seattle.


Friday, October 20

2:30 PM–4:30 PM

Concurrent Invited Session II

77. Clinical Spotlight: Translational Genomics: Psychological and Health Behavior Research Outcomes

Room 330C, Level 3, Convention Center

Moderator: Barbara B. Biesecker, NHGRI/NIH, Bethesda

 

This session on translational genomics focuses on psychological wellbeing and health care utilization following receipt of results from genome sequencing, and discussion of key outcomes from a review of randomized controlled trials returning genetic test results. Data from an NIH genome-sequencing consortium representing findings from multiple studies analyzed in aggregate will be presented. We will discuss outcomes from return of both primary and secondary findings that may help to inform assessments of clinical utility of genome sequencing conducted for a variety of pursuits. Four presenters will contribute data: 1. Psychological outcomes, of primary findings; 2. Cost effectiveness and health care utilization of secondary findings; 3. Patient characteristics that predict uptake of genome sequencing results; and 4. Outcomes of randomized controlled trials comparing the effectiveness of delivery modes and interventions to enhance clinical outcomes.

 

2:30 PM   Twenty five years of randomized controlled trials in return of genetic testing and counseling: Effective delivery modes and interventions. B.B. Biesecker. NHGRI/NIH, Bethesda.

3:00 PM   Psychological outcomes of genome sequencing: Results from the CSER Consortium analyses. S. Gray. City of Hope, Duarte.

3:30 PM   Patient characteristics that may impede decisions to learn results from genome sequencing: Evidence from a large NIH cohort study. W.M. Klein. NCI/NIH, Rockville.

4:00 PM   Health care utilization outcomes of genome sequencing: Results from the CSER Consortium analyses. D. Veenstra. Univ Washington, Seattle.


Friday, October 20

2:30 PM–4:30 PM

Concurrent Invited Session II

78. Dosage-sensitive Sex-linked Genes: Role in Aneuploidy and Cancer

Room 230C, Level 2, Convention Center

Moderators: Christine M. Disteche, Univ Washington, Seattle
  Carolyn Brown, Univ British Columbia, Vancouver, Canada

 

A conserved set of genes with copies on the X/Y chromosomes in mammals have persisted in many species. These dosage-sensitive genes are engaged in critical functions such as transcription, translation, chromatin structure, splicing, and ubiquitination. The X-linked copy of these genes often escapes X inactivation, preserving two expressed copies in females and one X-linked and a Y-linked copy in males. However, expression between X-linked and Y-linked genes differ, leading to sex differences, which can be observed in early development prior to hormonal influence, as well as in acquired diseases such as cancer. These genes are essential for survival of human embryos, as shown in 45,X embryos in which X/Y genes are haploinsufficient. Over 99% of 45,X embryos die during development and those that survive may be either mosaic for a normal XX or XY line or have adapted to the aneuploidy via epigenetic mechanisms. This session aims to bring together experts on sex-linked dosage sensitive genes and their role in constitutional sex chromosome aneuploidy and in disease such as cancer. By the end of the session, the audience should appreciate the role of specific X/Y genes in sex differences and in the regulation of the epigenetic landscape of cells.

 

2:30 PM   Breaking the silence: Genes that escape X-chromosome inactivation. C. Brown. Univ British Columbia, Vancouver, Canada.

3:00 PM   Role of X/Y genes in early development and in sex chromosome aneuploidy. C.M. Disteche. Univ Washington, Seattle.

3:30 PM   Genome-wide epigenetic effects of sex chromosome aneuploidy. C. Gravholt. Aarhus Univ Hosp, Denmark.

4:00 PM   Sex differences in cancer and the role of X/Y genes. A.A. Lane. Harvard Med Sch, Boston.


Friday, October 20

2:30 PM–4:30 PM

Concurrent Invited Session II

79. High-throughput Sequencing of Adaptive Immune Receptors: Insights into Disease Mechanisms and Treatment

Room 310A, Level 3, Convention Center

Moderators: Ronald Hause, Juno Therapeutics, Inc, Seattle
  James Crowe, Vanderbilt Univ, Nashville

 

The adaptive immune system plays a central role in many disease processes, including autoimmunity, cancer, transplant rejection, and pathogen defense. The key effectors of adaptive immunity are B- and T-lymphocytes, which undergo somatic DNA rearrangements to generate extremely diverse collections of cell-surface receptors. These receptors constitute a person’s “immune repertoire”; collectively, they can bind virtually any foreign antigen. It has been challenging to characterize the receptors of large numbers of B cells and T cells until recently, when modern DNA sequencing technologies were adapted for use on these highly polymorphic loci. High-throughput repertoire sequencing has enabled investigators to survey the adaptive immune system at unprecedented depth, leading to advances in immunology, therapeutic development, and clinical practice. This session will begin with a broad overview of the field, its recent successes, and its future challenges. Subsequent presentations will illustrate the role of immune repertoire sequencing in finding biomarkers for cancer immunotherapy, developing new vaccines, and comparing adaptive immune responses across different human tissues.

 

2:30 PM   High-throughput immune repertoire sequencing: A powerful tool for studying the adaptive immune system. B. Howie. Adaptive Biotechnologies Corp, Seattle.

3:00 PM   T-cell receptor sequencing to identify biomarkers of patient response to anti-PD-L1 therapy for cancer. S. Funt. Mem Sloan Kettering Cancer Ctr, New York.

3:30 PM   Leveraging immunosequencing for improved vaccine development and antibody therapies for viruses. J. Crowe. Vanderbilt Univ, Nashville.

4:00 PM   Repertoire sequencing of T cells in multiple human tissues provides insights into adaptive immune protection against herpes simplex virus type 2. C. Posavad. Univ Washington & Fred Hutchinson Cancer Res Ctr, Seattle.


Friday, October 20

2:30 PM–4:30 PM

Concurrent Invited Session II

80. Illuminating Somatic Mutations in Neurological Development and Disease

Room 310C, Level 3, Convention Center

Moderators: Amy C. Lossie, Natl Inst on Drug Abuse/NIH, Bethesda
  Geetha Senthil, Natl Inst Mental Hlth/NIH, Rockville

 

Somatic mutations encompass changes to the genome that occur after fertilization. These sequence changes or copy number alterations include SNVs, tandem repeat changes, CNVs, transposable elements (e.g., LINE1, Alu, and SVA elements), mitochondrial mutations, mitotic mis-segregation, DNA replication errors, and changes induced by double strand breaks. Somatic mutations are well-characterized in cancer, and emerging studies have documented the occurrence of LINE1 activation, SNVs, activity-induced double strand breaks, and mitochondrial mutations in various regions of the brain. In this session, Haig Kazazian will provide an overview of somatic mutations in human disease. This will be followed by Michael Lodata, who will talk about SNVs in human cerebral cortical neurons and show how these mutations can trace neuronal lineages and showcase that transcription-induced damage could shape human phenotypes. The third speaker will be Scott Kennedy, who will focus on the role of mitochondrial mutations in Alzheimer's disease. Dr. Kennedy's group has shown an increase in C to T transitions in the regulatory D loop in the hippocampus or parietal lobe of people with Alzheimer's, suggesting that replication errors, not oxidative damage, are inducing these somatic changes. Ryan Stott will end the session with a talk on the discovery that activity-induced double strand breaks in immediate early genes are necessary for neuronal function. These talks highlight the potential of somatic mutations to drive neurological development and disease.

 

2:30 PM   Somatic mosaicism in medical genetics. H. Kazazian. Johns Hopkins Univ, Baltimore.

3:00 PM   Somatic mutations reflect developmental and transcriptional histories in human neurons. M.A. Lodato. Boston Children's Hosp.

3:30 PM   Absence of oxidative DNA damage-induced somatic mutations in human mitochondrial DNA in aging and neurodegeneration. S.R. Kennedy. Univ Washington Med, Seattle.

4:00 PM   Activity-induced DNA breaks in learning and disease. R.T. Stott. Massachusetts Inst Technol, Cambridge.


Friday, October 20

2:30 PM–4:30 PM

Concurrent Invited Session II

81. Layers of Complexity: Dissecting the Etiology of Mendelian Diseases Characterized by Extreme Heterogeneity

Room 330A, Level 3, Convention Center

Moderators: Anthony Antonellis, Univ Michigan, Ann Arbor
  Stephan Züchner, Univ Miami Miller Sch Med

 

A major challenge facing human genetics is characterizing the clinical, locus, and allelic heterogeneity of inherited disease. This is particularly important with respect to clinically evaluating patients, counseling families, and characterizing disease-causing alleles. One inherited disease with vast heterogeneity is Charcot-Marie-Tooth disease (CMT). CMT composes a class of peripheral neuropathies mainly characterized by muscle weakness and sensory loss in the distal extremities. To date, approximately 100 loci have been implicated in CMT and dozens of unique, disease-causing lesions have been identified at each locus. Furthermore, patients with CMT display a wide array of disease severity even among patients carrying a molecularly indistinguishable mutation. For example, patients with CMT who carry a 1.4 Mb duplication CNV containing the PMP22 locus (CMT1A) have ages of onset ranging from the first decade to the sixth decade of life and can be mildly affected, requiring little assistance with mobility, or severely affected, requiring a wheelchair; these observations indicate that genetic and environmental factors modify the disease phenotype. During the past decade, great advances have been made in defining the locus and allelic heterogeneity of human inherited disease. However, challenges still remain in refining patient phenotypes, counseling affected families, identifying disease-modifying factors, and characterizing disease pathogenesis. This session brings together clinicians and basic scientists, who will use CMT and other inherited disorders to present current methods for studying disease heterogeneity. Importantly, this session will serve as a paradigm for studying any human disease characterized by clinical, locus, and allelic heterogeneity.

 

2:30 PM   From phenotype to genotype and back: Modular phenotyping in the genomic era. R. Schüle. Univ Tübingen, Tuebingen, Germany.

3:00 PM   Genetic analysis in the age of next-generation sequencing: Navigating challenges and communicating with the patient population. S.M. Feely. Univ Iowa, Iowa City.

3:30 PM   Genetic modifier studies of peripheral neuropathies. S. Züchner. Univ Miami Miller Sch Med.

4:00 PM   Molecular signatures of rare variants that explain phenotypic diversity. J.R. Lupski. Baylor Col Med, Houston.


Friday, October 20

2:30 PM–4:30 PM

Concurrent Invited Session II

82. Metabolomic Perspectives in a Genomic Era: Garrod's Inborn Errors and Warburg's Theory of Cancer

Room 220F, Level 2, Convention Center

Moderator: Stephen H. Tsang, Columbia Univ Med Ctr, New York

 

In the current era of precision medicine, we have identified a large number of genetic variants in patients with various diseases. Yet, a patient's genetic code alone cannot universally explain their condition. It is the interplay between genomics, proteomics, and metabolomics from which phenotypes arise. The mechanisms by which genomic variations exert their phenotypic effects can be revealed through the study of the metabolome in the relevant target human cells. By definition, metabolites are substances required for, or produced by, the biochemical reactions of metabolism in living organisms; thus, a metabolome is all of the metabolites produced by a single organism. Like the proteome, the metabolome is closely tied to an organism's genome but is also influenced by which genes are transcribed as well as what materials the cell can obtain from its environment. The metabolome lies at the intersection of the genome and the environment and is malleable to epigenetic influences, making it an ideal target for studying disease states and developing potential therapeutics that will be efficacious regardless of which mutation(s) produce a patient's condition. In this session, forerunners in this field will present developments in metabolomics research and its utility for clinical interventions in cases of congenital disorders and cancer. Specifically, they will discuss strategies for interrogating the abundance of metabolites, performing metabolite profiling, and using this information to assess the dynamic state of the cell in relation to both health and disease.

 

2:30 PM   Metabolic pathway selection to support in cell proliferation. M. Vander Heiden. Koch Inst at MIT, Cambridge.

3:00 PM   Understanding metabolic phenotypes in human cancer. R.J. DeBerardinis. UT Southwestern, Dallas.

3:30 PM   A metabolic ecosystem in the eye. J.B. Hurley. Univ Washington, Seattle.

4:00 PM   The metabolome, urea cycle, and small molecule therapy. B. Lee. Baylor Col Med, Houston.


Friday, October 20

2:30 PM–4:30 PM

Concurrent Invited Session II

83. Using Controls from External Studies: Issues, Methods, and Successes

Room 230G, Level 2, Convention Center

Moderator: Sarah A. Gagliano, Univ Michigan, Ann Arbor

 

This trainee-organized session will start off with a talk on study design: given a set budget, determine the number of cases to include to maximize power for densely genotyped or sequencing-based studies with available controls from a different study, termed external controls. The second speaker will speak on a method (which is currently being extended to include sequencing-based data) to determine ancestry in order to match external controls to the study's participants. The third speaker will discuss an application of incorporating external controls into a case-control GWAS study on ischemic stroke, and extensions of this work such as the use of exome chip external data for rare variant analysis. The fourth speaker will talk more broadly about an issue that arises when independent studies incorporate sets of external controls from the same sources: how to deal with shared controls in meta-analysis for genotype or sequencing-based data, with extensions to correlated effect sizes.

 

2:30 PM   Increasing power for case-control studies by incorporating genetic data from population based studies. P. Yajnik. Univ Michigan, Ann Arbor.

3:00 PM   Leveraging external controls for powerful and accurate GWAS through model-based allele frequency estimates in ancestry-matched controls. D. Chen. Broad Inst, Boston.

3:30 PM   Combining cases and publicly-available controls for discovery of common disease loci through genome-wide association testing. S.L. Pulit. Univ Med Ctr Utrecht, The Netherlands & Big Data Inst, Oxford, UK.

4:00 PM   A general framework for meta-analyzing dependent studies with overlapping subjects in association mapping. D. Duong. UCLA.


Friday, October 20

4:45 PM–5:00 PM

84. ASHG Mentorship Award Presentation and Lecture: Double Happiness: The Duty and Joy of Life-long Mentoring

South Hall B, Level 1, Convention Center

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

Introduction: Sanjay I. Bidichandani, University of Oklahoma

Recipient:
John Mulvihill
John J. Mulvihill, MD, University of Oklahoma Health Sciences Center

Dr. Mulvihill has founded multiple successful genetics training programs across the country – including the NIH Interinstitute Medical Genetics Training Program, the Department of Human Genetics at the University of Pittsburgh, and the Section of Pediatric Genetics at OUHSC – and has personally mentored trainees across fields and career stages through these and other programs. His research has focused on the genetics of human cancer, particularly late genetic and reproductive effects in cancer survivors and germ cell mutagenesis.

 


Friday, October 20

5:00 PM–5:15 PM

85. ASHG Advocacy Award Presentation and Lecture: Genetics and Society: Advocating for and with Science

South Hall B, Level 1, Convention Center

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

Introduction: Joann Boughman, University System of Maryland

Recipients:
Edward McCabe
Edward R. B. McCabe, MD, PhD
Distinguished Professor Emeritus and Inaugural Mattel Executive Endowed Chair,
Department of Pediatrics, UCLA School of Medicine
Inaugural Physician-in-Chief, UCLA Mattel Children’s Hospital
Former Chief Medical Officer, March of Dimes

Dr. McCabe began his career studying inherited metabolic diseases and developing screening techniques for genetic conditions. As Executive Chair of Pediatrics at UCLA, he established multiple medical and research centers, and chaired the HHS Secretary’s Advisory Committees on Genetic Testing and on Genetics, Health and Society. More recently, at the March of Dimes Foundation, he worked to prevent prematurity, birth defects, and infant mortality, advocating successfully for the Newborn Screening Saves Lives Reauthorization Act, the FDA’s approval of voluntary fortification of corn masa flour with folic acid, and the Frank R. Lautenberg Chemical Safety for the 21st Century Act.

 


Friday, October 20

5:15 PM–5:30 PM

86. ASHG Early Career Award Presentation and Lecture: Using Large Scale Genomic Databases to Improve Disease Variant Interpretation

South Hall B, Level 1, Convention Center

The ASHG Early Career Award, new this year, recognizes the contributions of genetics and genomics scientists in their first 10 years as an independent investigator.
Introduction: Mark J. Daly, Massachusetts General Hospital, Boston

Recipient:
Daniel MacArthur
Daniel G. MacArthur, PhD, Massachusetts General Hospital/Harvard Medical School, Broad Institute of MIT and Harvard, Boston

Dr. MacArthur’s research focuses on the use of large-scale genomic technologies and resources to improve the diagnosis of rare diseases. As part of this effort, he and his colleagues developed the Exome Aggregation Consortium database and website, a resource that has collected and analyzed exome sequences from more than 60,000 individuals, and its successor, the Genome Aggregation Database. These resources are used widely in the genetics community and have contributed to many collaborative gene discovery projects.

 


Friday, October 20

5:30 PM–7:00 PM

87. Featured Plenary Abstract Session II

South Hall B, Level 1, Convention Center

Moderators: Erica E. Davis, ASHG 2017 Program Committee
  Daniel Doherty, ASHG 2017 Program Committee

 

293/5:30 The contribution of rare variants, polygenic risk, and novel candidate genes to the hereditary risk of breast cancer in a large cohort of breast cancer families. N. Li, S. Rowley, D. Goode, L. Devereux, S. McInerny, N. Grewal, A. Lee, M. Wong-Brown, R. Scott, A. Trainer, K. Gorringe, P. James, I. Campbell.

294/5:50 The Model Organisms Screening Center for the Undiagnosed Diseases Network. M.F. Wangler, S. Yamamoto, M. Westerfield, J. Postlethwait, H. Bellen.

295/6:10 Modeling and therapeutic testing of leukodystrophies in 3D human cortical spheroids. Z. Nevin, M. Madhavan, E. Shick, K. Allan, P. Tesar.

296/6:30 Direct assessment of unexpectedly abundant paternal sperm mosaicism allows for the quantification of recurrence risk in autism. M.W. Breuss, M. Kleiber, R.D. George, D. Antaki, K.N. James, L.L. Ball, O. Hong, D. Musaev, A. Nguyen, O. Devinsky, J. Sebat, J.G. Gleeson.


Saturday, October 21

8:30 AM–9:30 AM

Concurrent Platform Session G

88. Functional Analyses of Cancer Genes

Room 220B, Level 2, Convention Center

Moderators: Sean Tavtigian, Huntsman Cancer Inst, Salt Lake City
  Michael Dean, Natl Cancer Inst, Gaithersburg

 

297/8:30 Expression quantitative trait loci of primary melanocytes facilitate identification of melanoma susceptibility genes. T. Zhang, J. Choi, M. Kovacs, S. Loftus, M. Xu, W. Pavan, K. Brown.

298/8:45 The landscape of chromatin activity in renal cell carcinoma reveals thousands of germline regulatory variants with somatic interactions. A. Gusev, M. Freedman.

299/9:00 Prognostic signature from DNA methylation and corresponding gene expression predicts survival of oral squamous cell carcinoma. S. Shen, G. Wang, Q. Shi, R. Zhang, Y. Zhao, D. Christiani, Y. Wei, F. Chen.

300/9:15 Epigenetic modifications of innate immunity genes impact early-stage non-small cell lung cancer survival: An integrative analysis of epigenome and transcriptome in Caucasian population. R. Zhang, Y. Wei, Y. Guo, E. Loehrer, Z. Liu, L. Liang, A. Shafer, Z. Wang, P. Tejera, S. Shen, S. Salama, T. Fleischer, M. Bjaanæs, A. Karlsson, M. Planck, F. Chen, J. Staaf, A. Helland, M. Esteller, X. Lin, D. Christiani.


Saturday, October 21

8:30 AM–9:30 AM

Concurrent Platform Session G

89. Modelling Candidate Disease Variants in Cellular and Animal Models

Room 220F, Level 2, Convention Center

Moderators: Katherina Walz, Univ Miami
  Michael Wangler, Baylor Col Med, Houston

 

301/8:30 An epigenetic switch confers pleiotropic risk for bone mineral density and hyperglycaemia. N.A. Sinnott-Armstrong, I.S. Sousa, E. Rendina-Ruedy, R. Sallari, X. Chen, S.E. Nitter Dankel, G. Mellgren, A. Guntur, D. Karasik, H. Hauner, C. Rosen, D.P. Kiel, Y.-H. Hsu, M. Claussnitzer.

302/8:45 Rare GREB1L mutations contribute to the genetic heterogeneity of congenital kidney malformations. K. Khan, S. Sanna-Cherchi, R. Westland, P. Krithivasan, F. Lorraine, H.M. Rasouly, I.L. Pediaditakis, I. Ionita-Laza, D.A. Fasel, K. Kiryluk, M. Bodria, E.A. Otto, M.G. Sampson, C.E. Gillies, A. Mitrotti, L. Gesualdo, V. Tasic, A. Latos-Bielenska, G.S. Makar, F. Hildebrandt, J.V. Wijk, M. Saraga, F. Scolari, D.B. Goldstein, G.M. Ghigger, A. Materna-Kiryluk, R.P. Lifton, N. Katsanis, E.E. Davis, A.G. Gharavi.

303/9:00 Mutations in the mitochondrial ribosomal protein MRPS22 lead to XX gonadal dysgenesis. A. Chen, D. Tiosano, H. Baris, Y. Bayram, T. Guran, A. Mory, L. Kulnane, C. Hodges, Z. Akdermir, S. Turan, S. Jhangiani, C. Hoppel, H. Salz, J. Lupski, D. Buchner.

304/9:15 Mutations of CDC14A are associated with nonsyndromic deafness DFNB32 or HIIMS, hearing impairment infertile male syndrome. A. Imtiaz, I. Belyantseva, A. Berirl, C. Fenollar-Ferrer, R. Bashir, A. Bouzid, U. Shaukat, I. Bukhari, H. Azaiez, K. Booth, K. Kahrizi, A. Maqsood, E. Wilson, T. Fitzgerald, A. Tlili, R. Olszewski, A. Rehman, M. Starost, A. Waryah, M. Hoa, L. Dong, R. Morell, R. Smith, S. Riazuddin, S. Masmoudi, K. Kindt, S. Naz, T. Friedman.


Saturday, October 21

8:30 AM–9:30 AM

Concurrent Platform Session G

90. Cerebral Palsy and Epilepsy

Room 230C, Level 2, Convention Center

Moderators: Donna Martin, Univ Michigan Med Ctr, Ann Arbor
  Kameryn Butler, Emory Univ, Atlanta

 

305/8:30 Discovery of cerebral palsy genes through trio-based whole exome sequencing in cryptogenic individuals. S. Bakhtiari, S.C. Jin, X. Zeng, M. Corbett, S. Padilla-Lopez, B. Norton, H. Magee, C. van Eyk, R.P. Lifton, K. Bilguvar, A.H. MacLennan, J. Gecz, M.C. Kruer.

306/8:45 Debunking the cerebral palsy (CP)-birth asphyxia myth: Frequent genomic etiologies for CP identified by exome sequencing. A. Moreno-De-Luca, A. Gonzalez-Mantilla, S.M. Myers, J. Reid, J. Overton, D.H. Ledbetter, C.L. Martin, on behalf of the DiscovEHR collaboration.

307/9:00 Why West: Comparative analysis of age, etiology, genes and molecular pathways in infants who do and do not develop spasms. S. Chakravorty, S. Koh, R.P. Saneto, Z.M. Grinspan, J.E. Sullivan, E.C. Wirrell, R.A. Shellhaas, J.R. Mytinger, W.D. Gaillard, E.H. Kossoff, I. Valencia, K.G. Knupp, C. Wusthoff, C. Keator, N. Ryan, T. Loddenkemper, C.J. Chu, E.J. Novotny Jr., J. Coryell, M. Hegde, A.T. Berg.

308/9:15 Epilepsy: Whole exome sequencing of 6K cases and 14k controls confirms a significant role for ultra-rare deleterious coding variants. D. Howrigan, on behalf of the Epi25k Consortium.


Saturday, October 21

8:30 AM–9:30 AM

Concurrent Platform Session G

91. Diverse Approaches to the Genetics of T2D

Room 230G, Level 2, Convention Center

Moderators: Jennifer Below, Univ Texas Hlth Sci Ctr, Houston
  Alisa Manning, Massachusetts Gen Hosp/Broad Inst, Cambridge

 

309/8:30 TOPMed whole genome sequence association analysis of type 2 diabetes. J. Wessel, J. Brody, B. Hidalgo, A. Manning, on behalf of the Trans-Omics for Precision Medicine (TOPMed) Program, Diabetes Working Group.

310/8:45 Eighteen novel loci associated with type-2 diabetes in multi-ethnic analyses involving 484,989 individuals. J. Lee, D. Miller, J. Huang, J. Lynch, S. Damrauer, Y. Sun, T. Assimes, J. Lee, K. Cho, S. Muralidhar, Q. Shao, S. DuVall, K. Lee, D. Rader, M. Gaziano, J. Concato, P. Tsao, C. O’Donnel, K. Chang, J. Meigs, P. Wilson, P. Reaven, L. Phillips, D. Saleheen.

311/9:00 Discovery and fine-mapping of type 2 diabetes susceptibility loci across ethnically diverse populations. A. Mahajan, H. Kitajima, X. Sim, M.CY. Ng, W. Zhang, J.E. Below, D. Taliun, K.J. Gaulton, A.P. Morris, on behalf of the DIAMANTE Consortium.

312/9:15 Inverting the problem: Environmental signal maximization in type 2 diabetes using genetic correction. J. Blangero, J.M. Peralta, J.E. Curran, S. Williams-Blangero.


Saturday, October 21

8:30 AM–9:30 AM

Concurrent Platform Session G

92. Population-based Diagnostic Sequencing

Room 310A, Level 3, Convention Center

Moderators: Steven Harrison, Partners Healthcare Personalized Med, Cambridge
  Carol Saunders, Children's Mercy Hosp, Kansas City

 

313/8:30 Design and implementation of a sequencing panel for eMERGE Phase III. L. Witkowski, M.V. Harden, E. Kudalkar, M.S. Leduc, L.M. Mahanta, E. Hynes, L.J. Babb, M.J. Bowser, C. Graham, C-F. Lin, S.B. Baxter, S.B. Gabriel, S.J. Aronson, M.S. Lebo, B.H. Funke, N.J. Lennon, H.L. Rehm, H. Zouk.

314/8:45 Genomic sequencing results from the first 100 newborns sequenced in the BabySeq Project. O. Ceyhan-Birsoy, K. Machini, J. Murry, M.S. Lebo, S. Fayer, C. Genetti, T.S. Schwartz, G.E. VanNoy, T.W. Yu, P.B. Agrawal, R.B. Parad, I.A. Holm, A. McGuire, R.C. Green, A.H. Beggs, H.L. Rehm.

315/9:00 Precision medicine screening using whole genome sequencing, whole body imaging and noninvasive functional diagnostics. C.Y.-C. Hou, P. Brar, D. Karow, A. Kahn, N. Shah, V. Lavrenko, H.C. Yu, A.M. Dale, L. Guo, T.J. Jonsson, B.M. Wittmann, I. Bartha, S. Ramakrishnan, A. Bernal, J. Brewer, W.H. Biggs, A. Telenti, B.A. Perkins, C.T. Caskey, J.C. Venter.

316/9:15 Five years of clinical whole genome sequencing in asymptomatic individuals: Insights and future directions. M. Cremona, V. Gainullin, R. Hagelstrom, W. Li, J. Avecilla, M. Bennett, K. Bluske, C. Brown, N. Burns, A. Chawla, A. Coffey, ICSL Curation Team, B. Juan, A. Malhotra, M. Mcginniss, F. Mullen, M. Rajan, V. Rajan, E. Ramos, A. Scocchia, S. Ajay, M. Eberle, ICSL past and present members, D. Perry, D. Bentley, R. Taft.


Saturday, October 21

8:30 AM–9:30 AM

Concurrent Platform Session G

93. Identification and Function of Enhancers

Room 310C, Level 3, Convention Center

Moderator: Christopher Brown, Univ Penn, Philadelphia

 

317/8:30 Genetic analysis of enhancer RNA (eRNA) variation in human population. H. Kwak, K. Kristjánsdóttir, H.M. Kang.

318/8:45 Intra- and inter-chromosomal chromatin interactions mediate genetic effects on gene expression. O. Delaneau, K. Popadin, M. Zazhytska, K. Kumar, G. Ambrosini, A. Gschwind, C. Borel, D. Marbach, D. Lamparter, S. Bergmann, P. Bucher, S. Antonarakis, A. Reymond, E. Dermitzakis.

319/9:00 From mammals to fish and back again: Discovering new regulators of early cardiac development. M.D. Wilson, X. Yuan, M. Song, P. Devine, B.G. Bruneau, I.C. Scott.

320/9:15 Genomic variation modulates islet regulatory landscape: Application of islet-specific deep learning model. A. Wesolowska-Andersen, M. Thurner, J. Torres, J. Fernandez, M. McCarthy, A. Mahajan, A.L. Gloyn, M. McCarthy.


Saturday, October 21

8:30 AM–9:30 AM

Concurrent Platform Session G

94. Genetic Associations for Behavioral Phenotypes

Room 320, Level 3, Convention Center

Moderators: Ece Uzun, Warren Alpert Med Sch Brown Univ, Providence
  Dongnhu Truong, Yale Univ, New Haven

 

321/8:30 Genome-wide association study of chronotype in 355,728 individuals identifies 106 genetic variants influencing circadian rhythms in humans. S.E. Jones, J.M. Lane, V. van Hees, J. Tyrrell, R.N. Beaumont, K.S. Ruth, M.A. Tuke, H. Yaghootkar, Y. Hu, R.M. Freathy, A. Murray, K.V. Allebrandt, P.R. Gehrman, D.A. Lawlor, M.K. Rutter, R. Saxena, T.M. Frayling, A.R. Wood, D.A. Hinds, M.N. Weedon, the 23andMe Research Team.

322/8:45 Genetic associations of low sleep hours in a sample of >130,000 subjects from the Million Veteran Program. H. Zhao, N. Sun, Q. Lu, Y. Hu, B. Li, Q. Chen, M. Aslan, K. Radhakrishnan, K.H. Cheung, Y. Li, R. Pietrzak, N. Rajeevan, F. Sayward, K. Cho, K. Harrington, J. Honerlaw, S. Pyarajan, R. Quaden, J.M. Gaziano, J. Concato, M.B. Stein, J. Gelernter, on behalf of the VA Million Veteran Program.

323/9:00 Functional consequences of genetic loci associated with IQ in a meta-analysis of 87,740 individuals. J.R.I. Coleman, J. Bryois, H. Gaspar, P. Jansen, J. Savage, N. Skene, R. Plomin, J. Hjerling-Leffler, P.F. Sullivan, D. Posthuma, G. Breen.

324/9:15 Large-scale genetic study of risk tolerance and risky behaviors identifies 29 new loci and reveals shared genetic influences. J.P. Beauchamp, R. Karlsson Linnér, P. Biroli, M.A. Fontana, E. Kong, F. Meddens, R. Wedow, D.J. Benjamin, P.D. Koellinger, Social Science Genetic Association Consortium.


Saturday, October 21

8:30 AM–9:30 AM

Concurrent Platform Session G

95. Host-pathogen Interactions in the Genetics of the Immune System

Room 330A, Level 3, Convention Center

Moderator: Hanna Ollila, Stanford Univ

 

325/8:30 Profiling immunoglobulin repertoires by RNA sequencing across 8555 samples from 53 GTEx tissues. H. Yang, S. Mangul, I. Mandric, N. Strauli, D. Montoya, J. Rotman, W. Van Der Wey, J. Ronas, B. Statz, A. Zelikovsky, R. Spreafico, S. Shifman, N. Zaitlen, M. Rossetti, M. Ansel, E. Eskin.

326/8:45 Genome-wide analysis of transcriptional and cytokine response variability in activated human immune cells. S. Kim-Hellmuth, M. Bechheim, B. Puetz, P. Mohammadi, J. Schumacher, V. Hornung, T. Lappalainen.

327/9:00 Multi-omics and deep-phenotyping integration predicts cytokine response to pathogens. Y. Li, O. B. Bakker, R. Aguirre-Gamboa, S. Sanne, M. Oosting, S. Smeekens, M. Jaeger, S. Withoff, R.J. Xavier, L.A.B. Joosten, V. Kumar, M.G. Netea, C. Wijmenga.

328/9:15 Tensor decomposition for myeloid and brain tissue gene expression identifies neurodegenerative disease associated trans-eQTLs. S. Ramdhani, T. Raj.


Saturday, October 21

8:30 AM–9:30 AM

Concurrent Platform Session G

96. Investigating the Role of Non-coding Variants in Disease

Room 330C, Level 3, Convention Center

Moderators: Pradeep Natarajan, Broad Inst, Cambridge
  Yang Li, Univ Chicago 

 

329/8:30 Predicting splicing directly from sequence using a neural network model of splice site competition. D.A. Knowles, Y.I. Li, K.K. Fahr, J.K. Pritchard.

330/8:45 Prioritizing functional rare variants: The impact of rare variation on alternative splicing. B.J. Strober, J. Davis, M. Grove, Y. Kim, P. Parsana, E. Tsang, J. Merker, S. Montgomery, A. Battle.

331/9:00 Investigating non-coding variants: Characterizing potential disease causing variants on microRNA binding sites. C. Lau, T. Frisby, N. Balanda, M. Malicdan, B. Pusey, W. Gahl, D. Adams.

332/9:15 Annotating pathogenic non-coding variants in genic regions. S. Gelfman, Q. Wang, K.M. McSweeney, Z. Ren, F. La-Carpia, M. Halvorsen, K. Schoch, F. Ratzon, E.L. Heinzen, M.J. Boland, S. Petrovski, D.B. Goldstein.


Saturday, October 21

9:45 AM–10:45 AM

Concurrent Platform Session H

97. Transcriptome-wide Association Studies

Room 220B, Level 2, Convention Center

Moderators: Hae Kyung Im, Univ Chicago
  Alexander Gusev, Harvard Univ, Cambridge

 

333/9:45 Joint imputation of gene expression in 44 tissues identifies context-specific associations for complex traits. Y. Hu, M. Li, Q. Lu, S. Muchnik, J. Wang, H. Zhao.

334/10:00 Transcriptome-wide association studies are vulnerable to false positives due to co-regulation. M. Wainberg, N. Sinnott-Armstrong, D. Knowles, D. Golan, H. Tang, M. Rivas, A. Kundaje.

335/10:15 Meta-prediction of gene expression levels from genotypes across multiple tissues and datasets. A. Liu, H. M. Kang.

336/10:30 Variant-sensitive prediction of RNA expression using convolutional neural networks. M. Abdalla, M. Abdalla, C.C. Holmes, M.I. McCarthy.


Saturday, October 21

9:45 AM–10:45 AM

Concurrent Platform Session H

98. Improved Interpretation of Missense Variants

Room 220F, Level 2, Convention Center

Moderators: James Ware, Imperial College London, UK
  Kaitlin Samocha, Wellcome Trust Sanger Inst, Hinxton, UK

 

337/9:45 Aggregation of population-based genetic variation over protein domain homologues strongly improves diagnostic prediction of missense variants. L. Wiel, H. Venselaar, J.A. Veltman, G. Vriend, C. Gilissen.

338/10:00 De novo missense mutation clustering identifies candidate neurodevelopmental disorder genes. S.H. Lelieveld, L. Wiel, H. Venselaar, R. Pfund, G. Vriend, J.A. Veltman, H.G. Brunner, L.E.L.M. Vissers, C. Gilissen.

339/10:15 Missense mutations disrupting the ATPase domain of CHD3 cause a novel neurodevelopmental syndrome with intellectual disability, macrocephaly and impaired speech and language. L. Snijders Blok, J. Rousseau, J. Twist, S. Ehresmann, L. Faivre, J. Thevenon, M. Assoum, L. Rodan, C. Nowak, J. Douglas, K.J. Swoboda, M.A. Steeves, I. Sahai, C.T.R.M. Stumpel, P. Wheeler, M. Willing, E. Fiala, A. Kochhar, W.T. Gibson, A.S.A. Cohen, R. Agbahovbe, J. Rankin, I.J. Anderson, S. Skinner, R. Louie, H. Warren, A. Afenjar, R. Lewandowski, J. Propst, M. Choi, J.H. Chae, S. Price, M. Cho, C. Zweier, A. Reis, M. Bialer, C. Moore, M. Swinkels, E.H. Brilstra, G.R. Monroe, G. van Haaften, R. Newbury-Ecob, the DDD study, L. .D. Shriberg, P. Deriziotis, T. Kleefstra, H.G. Brunner, M. Takaku, J.D. Roberts, R.M. Petrovich, S. Machida, H. Kurumizaka, P.A. Wade, S.E. Fisher, P.M. Campeau.

340/10:30 Findings from the Critical Assessment of Genome Interpretation, a community experiment to evaluate phenotype prediction. G. Andreoletti, R.A. Hoskins, J. Moult, S.E. Brenner, CAGI Participants.


Saturday, October 21

9:45 AM–10:45 AM

Concurrent Platform Session H

99. Big Data Approaches in Support of Population Studies

Room 230C, Level 2, Convention Center

Moderators: Hilary Finucane, Broad Inst, Cambridge
  Nicholas Timpson, Univ Bristol, UK

 

NOTE: Overflow seating for this session is available in Room 230A.

 

341/9:45 Development of a pipeline to support translational research: Incorporating multiple data sources to select genetic pharmacomimetics and implement PheWAS in UK Biobank. K. Song, M. Chiano, B.H. Dessailly, A. Pandey, T. Johnson, M.G. Ehm, M.R. Nelson, J.C. Whittaker, R.A. Scott, L.M. Yerges-Armstrong.

342/10:00 Big data distributed system for phenome and genome management and analysis in a large health system. X. Liu, W.S.W. Wong, P. Kothiyal, W. Zhu, F. Zhou, S. Gao, S. Madhappan, L. Smith, H. Hunter, A. Black, J.F. Deeken, J.E. Niederhuber.

343/10:15 A wellness study of 108 individuals using dense, dynamic, personal data clouds. A. Magis, N.D. Price, J.C. Earls, G. Glusman, R. Levy, C. Lausted, D.T. McDonald, U. Kusebauch, C.L. Moss, Y. Zhou, S. Qin, R.L. Moritz, K. Brogaard, M. Conomos, G.S. Omenn, J.C. Lovejoy, L. Hood.

344/10:30 Statistical methods and computational algorithms to enable robust and efficient cloud-scale joint variant calling of >60,000 deeply sequence genomes. H. Kang, J. LeFaive, A. Tan, C. Scheller, T. Blackwell, G. Abecasis.


Saturday, October 21

9:45 AM–10:45 AM

Concurrent Platform Session H

100. Novel Genetic and Environmental Contributions to Cancer Risk

Room 230G, Level 2, Convention Center

Moderators: Bryony Thompson, Univ Utah, Huntsman Cancer Inst, Salt Lake City
  Aniko Sabo, Baylor Col Med, Houston

 

345/9:45 Assessing the effect of a range of modifiable risk factors on overall cancer risk: A Mendelian randomization study. J. Ong, J. An, G. Chenevix-Trench, P. Gharahkhani, S. MacGregor.

346/10:00 Evaluating cancer risk in children with non-chromosomal birth defects: A population-based registry linkage study and family-based genetic analysis. S. Sisoudiya, H.E. Danysh, M.E. Scheurer, A. Brown, A. Sabo, S.E. Plon, P.J. Lupo.

347/10:15 Capture-recapture method gives estimate of the number of families in Central Ohio with Lynch syndrome. B.H. Shirts, J.M.O. Ranola, R. Pearlman, H. Hampel.

348/10:30 Identification of novel breast cancer risk genes using a gene-based analysis of regulatory variants. J. Beesley, M. Ferreira, W. Shi, F. Al-Ejeh, P. Kraft, W. Zheng, A. Antoniou, D.F. Easton, G. Chenevix-Trench, on behalf of BCAC and CIMBA.


Saturday, October 21

9:45 AM–10:45 AM

Concurrent Platform Session H

101. Neurological Disorders: Chromatin in the Spotlight

Room 310A, Level 3, Convention Center

Moderators: Alexandre Reymond, Univ Lausanne, Switzerland
  Harrison Brand, Massachusetts Gen Hosp, Boston

 

349/9:45 Germline heterozygous mutations in KDM3B cause a syndrome with intellectual disability and short stature. I.J. Diets, K. Baltrunaite, E. Waanders, M.R.F. Reijnders, R. Pfundt, S. Bergevoet, A. Vulto-van Silfhout, G. Beunders, J. Thevenon, L. Perrin, B. Keren, A. Afenjar, C. Nava, S. Bartz, B. Peri, N. Verbeek, K. van Gassen, H. Brunner, B. van der Reijden, V. Hwa, T. Kleefstra, N. Hoogerbrugge, A. Dauber, R.P. Kuiper, M. Jongmans.

350/10:00 De novo germline variants in Histone 3 Family 3A (H3F3A) and Histone 3 Family 3B (H3F3B) associated with a severe neurodegenerative disorder with unique functional effect different from somatic mutations. E.J. Bhoj.

351/10:15 Haploinsufficiency of the chromatin-remodeling bromodomain PHD finger transcription factor BPTF leads to developmental delay, microcephaly, and dysmorphic features. P. Stankiewicz, T.N. Khan, P. Szafranski, L. Slattery, J.A. Bernstein, C.W. Brown, B. Bostwick, H. Streff, S. Rednam, S. Scollon, K.L. Bergstrom, D.W. Parsons, S.E. Plon, M.W. Vieira, C.R.D.C. Quaio, W.A.R. Baratela, J.C. Acosta Guio, R. Armstrong, S.G. Mehta, C.A. Bacino, R. Xiao, A.M. Breman, J.L. Smith, M.E. Hurles, N. Katsanis, E.E. Davis, Y. Yang.

352/10:30 Germline mutations on the histone H4 core cause a developmental syndrome by affecting DNA damage response and cell cycle control. G. van Haaften, F. Tessadori, J. Giltay, J. Hurst, M. Massink, K. Duran, H.R. Vos, R.M. van Es, D.D.D. Study, R. Scott, K. van Gassen, J. Bakkers.


Saturday, October 21

9:45 AM–10:45 AM

Concurrent Platform Session H

102. Enhancers and Human Disease

Room 310C, Level 3, Convention Center

Moderator: Bing Yao, Emory Univ Sch Med, Atlanta

 

353/9:45 Pathogenic and therapeutic epigenetic modulation of a novel super-enhancer at the TGFB2 locus in systemic sclerosis. J.Y. Shin, H.C. Dietz.

354/10:00 Multiple functional variants at the 13q14 risk locus for osteoporosis regulate RANKL expression through long-range super-enhancer. D.L. Zhu, X.F. Chen, N.N. Wang, B.J. Lu, Y. Rong, T.L. Yang.

355/10:15 Protein-mediated 3D genome architecture in human B cells by HiChIP. Y. Fu, R. Pelikan, C. Lareau, M. Aryee, J. Kelly, P. Gaffney.

356/10:30 Integration of chromosomal interactions with local adipose gene expression identifies obesity genes beyond GWAS. D.Z. Pan, K.M. Garske, A. Ko, Y.V. Bhagat, M. Alvarez, J. Boocock, C.K. Raulerson, C.A. Glastonbury, K.S. Small, J.S. Sinsheimer, K.L. Mohlke, M. Laakso, P. Pajukanta.


Saturday, October 21

9:45 AM–10:45 AM

Concurrent Platform Session H

103. The Genetics of Obesity

Room 320, Level 3, Convention Center

Moderator: Jennifer Mulle, Emory Univ, Atlanta

 

357/9:45 Asprosin: Using genetics to discover a novel orexigenic hormone. C. Duerrschmid, Y. He, C. Wang, J. Bournat, Y. Xu, A. Chopra.

358/10:00 Novel mutations in ADCY3 cause severe, monogenic obesity in humans. S. Saeed, A. Bonnefond, F. Tamanini, M.U. Mirza, J. Manzoor, Q.M. Janjua, S.M. Din, J. Gaitan, A. Milochau, E. Durand, E. Vaillant, A. Haseeb, F.D. Graeve, I. Rabearivelo, O. Sand, G. Queniat, R. Boutry, D.A. Schott, H. Ayesha, M. Ali, T.A. Butt, T. Rinne, C. Stumpel, A. Abderrahmani, J. Lang, M. Arslan, P. Froguel.

359/10:15 Common and rare variants associated with body mass index (BMI) among multi-ethnic veterans: The Million Veteran Program. J. Huang, J.J. Lee, N. Sun, Y.L. Ho, K. Cho, Y. Sun, J. Lynch, T. Assimes, S. Muraldihar, J.M. Gaziano, J. Concato, P. Tsao, P. Wilson, K.M. Chang, C.J. O'Donnell, D. Saleheen, for the VA Million Veteran Program.

360/10:30 Promoter or enhancer activation by CRISPRa rescues haploinsufficiency caused obesity. N. Matharu, S. Rattanasopha, L. Maliskova, Y. Wang, A. Hardin, C. Vaisse, N. Ahituv.


Saturday, October 21

9:45 AM–10:45 AM

Concurrent Platform Session H

104. Advancing Drug Discovery by Genetic Analysis in Large Cohorts

Room 330A, Level 3, Convention Center

Moderator: Dana Crawford, Case Western Reserve Univ, Cleveland

 

361/9:45 Genome-wide analysis of UK Biobank to aid drug discovery in a consortium of pharmaceutical companies. M.R. Nelson, A. Day-Williams, R.A. Scott, S. Glass, N. Smaoui, Z. Ding, C. Franklin, C. Vangjeli, M. Weale, S. John, M.G. Ehm, A. Holden, G. McVean, C. Spencer, Genomics Resources Consortium.

362/10:00 Pharmacogenetic testing in the Veterans Health Administration: Recommendations from the VA Clinical Pharmacogenetics Subcommittee. A. Stone, J.T. Callaghan, M.A. Mendes, V.M. Pratt, R. Przygodzki, M.T. Scheuner, S.A. Schichman, J.L. Vassy, for the VA Clinical Pharmacogenetics Subcommittee.

363/10:15 Phenome-wide association studies (PheWAS) across large “real-world” population cohorts support drug target selection. D. Diogo, C. Tian, C. Vangjeli, C. Spencer, C. Franklin, M. Weale, M. Alanne-Kinnunen, H. Mattsson, E. Kilpeläinen, R. Samuli, M. March, D. Reilly, M-P. Reeve, J. Hutz, N. Bing, S. John, D. MacArthur, M. Daly, H. Hakonarson, V. Salomaa, A. Palotie, D. Hinds, P. Donnelly, R. Plenge, A. Day-Williams, C. Fox, H. Runs.

364/10:30 Large-scale PheWAS in UK Biobank: A paradigm shift in genetic evaluation of prospective and existing drug targets. L.M. Yerges-Armstrong, K. Song, M. Chiano, B.H. Dessailly, A. Pandey, T. Johnson, M.G. Ehm, M.R. Nelson, J.C. Whittaker, R.A. Scott.


Saturday, October 21

9:45 AM–10:45 AM

Concurrent Platform Session H

105. Regulation of Gene Expression in Metabolic and Vascular Tissues

Room 330C, Level 3, Convention Center

Moderators: Jane Francisca Ferguson, Vanderbilt Univ, Nashville
  Sylvia Nuernberg, Univ Pennsylvania Perelman Sch Med, Philadelphia

 

365/9:45 Discovering cell-specific regulatory networks using natural genetic variation. C. Romanoski, L. Stolze, M. Whalen.

366/10:00 Genetic and epigenetic regulation of gene expression in the human liver. M. Caliskan, J. Segert, S. Rao, M. Trizzino, Y. Park, K.M. Olthoff, A. Shaked, D.J. Rader, B.E. Engelhardt, C.D. Brown.

367/10:15 Interaction between two promoter/enhancer variants in CYP7A1: Robust effect on hepatic mRNA expression and association with lipids and risk of CAD and diabetes. D. Wang, K. Hartmann, M. Seweryn, W. Sadee.

368/10:30 Functional regulatory mechanism of smooth muscle cell-restricted LMOD1 coronary artery disease locus. C. Miller, V. Nanda, T. Wang, M. Pjanic, B. Liu, T. Nguyen, T. Quertermous, N. Leeper.


Saturday, October 21

11:00 AM–1:00 PM

106. Featured Plenary Abstract Session III and Late-Breaking Abstract Talk

South Hall B, Level 1, Convention Center

Moderators: Kiran Musunuru, ASHG 2017 Program Committee
  Hua Tang, ASHG 2017 Program Committee

 

369/11:00 Molecular diagnostics of Mendelian disorders via RNA sequencing. H. Prokisch, D.M. Bader, C. Mertes, R. Kopajtich, G. Pichler, A. Iuso, T.B. Haack, E. Graf, T. Schwarzmayr, C. Terrile, E. Koňaříková, B. Repp, P. Lichtner, C. Leonhardt, B. Funalot, A. Donati, V. Tiranti, A. Lombes, C. Jardel, D. Gläser, R.W. Taylor, D. Ghezzi, J.A. Mayr, A. Rötig, P. Freisinger, F. Distelmaier, T.M. Strom, T. Meitinger, J. Gagneur, L.S. Kremer.

370/11:20 Massively parallel reporter assays combined with cell-type specific expression quantitative trait loci profiling identified a functional melanoma risk variant in HIV-1 inhibitor gene, MX2. J. Choi, T. Zhang, M. Makowski, A. Vu, M. Kovacs, L. Colli, M. Xu, N. Lam, S. Chanock, S. Loftus, W. Pavan, M. Vermeulen, K. Brown.

371/11:40 Integrative analysis of loss-of-function variants in clinical and genomic data reveals novel genes associated with cardiovascular traits. B.S. Glicksberg, L. Amadori, N.K. Akers, K. Sukhavasi, O. Franzén, L. Li, G.M. Belbin, K. Shameer, M.A. Badgeley, K.W. Johnson, B. Readhead, B.J. Darrow, E.E. Kenny, C. Betsholtz, R. Ermel, J. Skogsberg, A. Ruusalepp, E.E. Schadt, J.T. Dudley, H. Ren, J.C. Kovacic, C. Giannareli, S.D. Li, J.L.M. Björkegren, R. Chen.

372/12:00 Phenomewide association study of life course health events: Analyzing 50 years of hospitalization, prescription drug use and death data. S. Ripatti, A. Havulinna, T. Kiiskinen, P. Helkkula, H. Hautakangas, P. Häppölä, S. Ruotsalainen, J. Koskela, M. Kurki, I. Surakka, M. Perola, M. Kallela, V. Salomaa, B. Neale, M. Pirinen, H. Laivuori, E. Widén, M. Daly, A. Palotie.

3022/12:20 A multi-hit de novo mutation model for idiopathic simplex autism. T.N. Turner, B.P. Coe, D.E. Dickel, K. Hoekzema, B.J. Nelson, M.C. Zody, Z.N. Kronenberg, F. Hormozdiari, A. Raja, L.A. Pennacchio, R.B. Darnell, E.E. Eichler.