Session Listing

Tuesday, October 6

4:30 PM–5:00 PM

1. ASHG Presidential Address: All in the Family – or “Gee our old LaSalle ran great”

Hall F, Level 1, Convention Center

The notion of family is seminal in human genetics for many reasons: the inheritance and genetic basis of traits is discerned from family patterns; arguments about heritability and nature versus nurture are derived from studies of family relationships; population genetic structure and social diversity are determined by patterns of mate choice; genetic information is typically delivered in the context of families. The classic 1970’s sitcom “All in the Family” broke new ground as it documented social changes occurring at the time, often leaving the family patriarch Archie Bunker at a loss. “All in the Family” has given way to “Modern Family” in our time, a show that documents further diversification of the classic family unit, including increasing intermarriage and gay couples. Definitions of family are evolving and expanding, as are definitions of race and gender. Our society of geneticists can also be considered a family, one that is large, diverse and specialized. At the same time, genomic technologies such as NIPT, whole genome sequencing and genome editing are advancing to the point of imminent common use in clinical practice. These dramatic shifts both in society and technology are pushing the boundaries of our experience, creating both challenges and opportunities, in research and clinical practice. Archie Bunker was often ill prepared to deal with the impact of modernity. Are we?


Tuesday, October 6

5:00 PM–6:45 PM

2. Presidential Symposium: Genetic Epidemiology at Scale: High Throughput Genomics Linked to Large Scale EHR Systems

Hall F, Level 1, Convention Center

Moderator: Neil Risch, ASHG 2015 President

The past decade has witnessed the development of large electronic health record (EHR) based cohorts linked to genomic information, primarily genome-wide genotyping. The power of such cohorts to produce novel genetic associations has been amply demonstrated. Currently and in the near future, resources such as the Kaiser Permanente Research Program on Genes, Environment and Health; the UK Biobank; the VA Million Veteran Program; and others are making available genetic data linked to comprehensive EHR-based clinical outcomes and traits on over a million people. At the same time, the President of the United States and the Director of NIH are spearheading a new Precision Medicine Initiative (PMI) to create a cohort of a million individuals that will support research into precision medicine and its clinical application. This symposium will provide an update on the latest developments of the PMI, and discussions of the various genetic, genomic, and epidemiological characteristics of this and other existing cohorts. Large EHR-based cohorts provide an unprecedented opportunity, and the goal is to maximize their utility for future research into the genetic and environmental origins of common diseases, their risk factors, prevention, and treatment.

Francis Collins
NIH, Bethesda

David Hunter
Harvard T.H. Chan
Sch Publ Hlth, Boston

Naomi Wray
Univ Queensland,

Marylyn Ritchie
Geisinger Hlth System,
Penn State Univ

Introduction. Neil Risch. UCSF.
The U. S. Precision Medicine Initiative. Francis Collins. NIH, Bethesda.
Personalized medicine, an epidemiological perspective. David Hunter. Harvard T.H. Chan Sch Publ Hlth, Boston
Studying genetic variation in large cohorts. Naomi Wray. Univ Queensland, Australia.
‘Omics and electronic health records - a dynamic duo. Marylyn Ritchie. Geisinger Hlth System, Penn State Univ


Wednesday, October 7

8:45 AM–9:45 AM

3. ASHG/ESHG Building Bridges: Barriers and Drivers for the Implementation of Clinical Sequencing: An International Discussion

Hall F, Level 1, Convention Center

Moderators: Chris Gunter, ASHG 2015 Program Chair
  Joris Veltman, ESHG 2016 Program Chair

ASHG logoESHG logo

Through the “Building Bridges” series, both the American and European Societies of Human Genetics have committed to discussion of important issues affecting their members. At ASHG 2015, this plenary session is a discussion with meeting attendees about perceptions of clinical sequencing in the US and the EU. Our speakers will cover the regulation of next-generation sequencing testing by the US FDA and implementation of sequencing in large cohort projects, as well as legislative proposals in the EU to restrict genetic testing and the community response to them.

8:45 AM: Introduction.

8:50 AM: Perspectives.

Philippos Patsalis
Cyprus Inst.
Neurology Genet

Elizabeth Mansfield
Silver Spring

David Barton
Our Lady’s
Children’s Hosp,
Dublin, Ireland

Wendy Chung
Columbia Univ,
New York

Philippos Patsalis. Cyprus Inst. Neurology Genet.
Elizabeth Mansfield. OIR/CDRH/FDA, Silver Spring.
David Barton. Our Lady’s Children’s Hosp, Dublin, Ireland.
Wendy Chung. Columbia Univ, New York.

9:15 AM: Discussion.

This “Building Bridges” session is the third in a continuing series conducted in conjunction with the European Society of Human Genetics.


Wednesday, October 7

9:50 AM–10:30 AM

4. Featured Plenary Abstract Session I

Hall F, Level 1, Convention Center

Moderator: Chris Gunter, 2015 Program Chair

1/9:50 Massively parallel experimental analysis of missense mutations in BRCA1 for interpreting clinical variants of uncertain significance. L. M. Starita, M. Islam, J. Gullingsrud, S. Fields, J. D. Parvin, J. Shendure.

2/10:10 Matrix metallopeptidase 21 (MMP21) is mutated in human heterotaxy and is an essential determinant of vertebrate left-right asymmetry. J. Amiel, G. C. Gabriel, F. Bajolle, M. Tsang, H. Liu, A. Noll, L. D. Smith, S. Lyonnet, L. de Pontual, S. A. Murray, D. Bonnet, S. F. Kingsmore, J. Amiel, P. Bouvagnet, C. W. Lo, C. T. Gordon.

Wednesday, October 7

11:00 AM–1:00 PM

Concurrent Invited Sessions I

5. Building the Genetic and Genomic Atlas of Gynecologic Health

Holiday Ballroom 1, 2nd Floor, Hilton Baltimore Hotel

Moderators: Cecilia M. Lindgren, Broad Inst Harvard & MIT, Boston
  Stacey Missmer, Harvard Univ, Boston

This will be the first comprehensive scientific session around the genetics and genomics of gynecologic health to be presented at the ASHG Annual Meeting. Endometriosis, polycystic ovary syndrome (PCOS), and uterine fibroids are highly prevalent gynecologic pathologies that underlie the most common indications for gynecologic interventions worldwide: pelvic pain, menorrhagia, and infertility. These conditions, as well as the ubiquitous impact of menarchal and menopausal timing on women's health, demand the focus of complex disease and evolutionary geneticists. The primary focus of the proposed session will be on clinical characterization, data generation, analysis and results, including implications for the specific diseases and traits, for gene discovery and for biologic and clinical utility. We have brought together leaders in the field to discuss their experiences in applying a wide array of strategies for variant, gene and pathway discoveries, as well as a dissection of pleiotropy for these disorders and traits. Each of the invited speakers will discuss the significant advances made in genetic and genomic discovery (with a particular focus on novel and late-breaking findings as of October 2015), the challenges of and insights into phenotype classification and diagnosis of these conditions, and the broader biologic and clinical implications of these efforts.


11:00 AM   Genetics of menarche and menopause reveal diverse biologic pathways. J. M. Murabito. Boston Univ Sch Med, Framingham.

11:30 AM   Genetics and genomics of polycystic ovary syndrome (PCOS). C. M. Lindgren. Broad Inst Harvard & MIT, Boston.

12:00 PM   Endometriosis: Genomics meets phenomics. K. Zondervan. Wellcome Trust Ctr for Human Genet, Oxford, United Kingdom.

12:30 PM   From GWAS to therapy in uterine leiomyomata. C. Morton. Harvard Univ, Boston.

Wednesday, October 7

11:00 AM–1:00 PM

Concurrent Invited Sessions I

6. Cancer Genetics in the Genomics Era

Hall F, Level 1, Convention Center

Moderators: Daniel C. Koboldt, Washington Univ, St. Louis
  Adam S. Kibel, Brigham & Women, Boston

High-throughput sequencing has fundamentally changed the field of human genetics, particularly in how we study genetic diseases like cancer. Candidate gene approaches – sequencing genes of interest in cancer genetics cohorts – have uncovered many rare pathogenic mutations predisposing individuals to certain cancer types, and GWAS efforts have implicated hundreds of genes with small to moderate effects on risk. Yet these loci collectively explain only a fraction of the heritability of cancer, suggesting that many genes remain to be discovered. The availability of large cancer genetics cohorts, combined with the unbiased discovery power of whole genome and exome sequencing, now empowers a comprehensive search for inherited factors (rare and common SNPs, indels, and structural variants) influencing cancer predisposition. Moreover, the ever-growing catalogues of tumor genome sequences – such as those created by the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) – enable integrated analyses of germline variation with somatic mutation data across tumor types (i.e. pan-cancer analysis). In this session, we will describe progress in identifying new cancer genes, and highlight some of the challenges faced in the analysis and interpretation of large-scale cancer sequencing data in the genomics era. Topics that will be explored include: • Cellular and developmental origins of pediatric cancer • Key findings of pan-cancer analysis efforts • Computational pipelines to analyze large-scale sequencing data • Opportunities for leveraging existing cancer genomics datasets • Strategies for integrative analysis of germline and somatic variants • Correlation of germline/somatic variation to clinical features such as tumor subtype.


11:00 AM   Somatic mutations in pediatric solid tumors and identification of druggable pathways. M. A. Dyer. St Jude Children’s Res Hosp, Memphis.

11:30 AM   Computational approaches for large-scale cancer genetics. L. Ding. Washington Univ, St Louis.

12:00 PM   Germline studies of the Pan-Cancer Analysis of Whole Genomes (PCAWG). J. Korbel. European Molec Biol Lab (EMBL), Heidelberg, Germany.

12:30 PM   The somatic origins of cancer revealed through integrated pan-cancer analysis. J. Stuart. UC Santa Cruz.

Wednesday, October 7

11:00 AM–1:00 PM

Concurrent Invited Sessions I

7. Epilepsy Genetics: Exomes, Mechanisms, and Interventions

Room 327, Level 3, Convention Center

Moderators: Miriam H. Meisler, Univ Michigan, Ann Arbor
  Heather C. Mefford, Univ Washington, Seattle

Epilepsy is a common, heterogeneous disorder with an overall incidence of approximately 1/1000. Exome sequencing has revealed the important role of de novo mutations in non-familial epilepsy. Early Infantile Epileptic Encephalopathy (EIEE) is a catastrophic disorder that includes seizures, developmental delay, intellectual disability and susceptibility to sudden death (SUDEP). The session will begin with an overview of high throughput exome sequencing of individuals with EIEE. Well established functional assays in transfected cells and knock-in mice have been applied to investigate the effects of many de novo ion channel mutations. Both gain-of-function and loss-of-function mechanisms have been identified. Hot-spots for recurrent mutations have been identified, and intergenic interactions have been demonstrated in crosses between mice with knock-in mutations. Analysis of patient-derived iPSC cell lines has revealed the effect of patient mutations on firing patterns of re-programmed neurons and cardiomyocytes, providing indications for clinical intervention. Drug screening in a zebrafish model of SCN1A mutation has identified lead compounds for development of novel therapies. Epilepsy research has thus incorporated a broad range of genetic approaches. The rapid progress in this field demonstrates the increasing impact of genetic research on treatment of genetic disease.


11:00 AM   Exome sequencing in epilepsy. H. C. Mefford. Univ Washington, Seattle.

11:30 AM   Functional effects of sodium channel mutations. M. H. Meisler. Univ Michigan, Ann Arbor.

12:00 PM   Re-programmed neurons and cardiomyocytes from patient iPSCs. L. L. Isom. Univ Michigan, Ann Arbor.

12:30 PM   High throughput drug discovery in a zebrafish model. S. C. Baraban. UC, San Francisco.

Wednesday, October 7

11:00 AM–1:00 PM

Concurrent Invited Sessions I

8. Human Phenotypes for Researchers, Clinicians and Patients

Room 318/321, Level 3, Convention Center

Moderator: Jonathan Haines, Case Western Reserve Univ, Cleveland

“Phenotype” means different things to different people and the definition may be affected by context. In biology, “phenotype” generally refers to the collection of observable traits of an organism, comprising its morphology; its physiology at the level of the cell, the organ, and the body; and its behavior, comprising even characteristics such as the gene expression profiles in response to environmental cues. In medicine, “phenotype” is commonly used to describe some deviation from normal morphology, physiology, or behavior, and combinations of phenotypes are used to make clinical diagnoses and prescribe treatment. Biomedical research, including genomic and epidemiologic studies, are now impacting clinical practice, and precise, consistent phenotypes are essential for investigators and clinicians to effectively communicate across all stages of the “bench to bedside” continuum. This session addresses what phenotype means in different contexts, the impact of how the phenotype is collected, and why phenotypes are integral to biomedical research and clinical practice. "What is a phenotype?" presents resources, context and approaches to acquiring phenotypic data. "How do we collect phenotypes?" presents options for collecting phenotypic data and suggestions for increasing consistency and collaboration. "Why are phenotypes important?" demonstrates the importance of consistent phenotypes to substantiate clinical genetics. "Who is involved?" underscores the growing involvement of patients in phenotype development. To facilitate discussion across the broad spectrum of "phenotype", the four presentations will be limited to 20 minutes (plus 5 minutes for questions) with a 20 minute general discussion session at the end.


11:00 AM   What is a phenotype? It depends…. A. Kho. Northwestern Univ, Chicago.

11:30 AM   How do we collect phenotypes? Common measures facilitate collaborative research. C. McCarty. Essentia Inst for Rural Hlth, Duluth.

12:00 PM   Why are phenotypes important? Using phenotypes to support genomic interpretation and discovery. H. Rehm. Partners Lab for Molec Med & Harvard Med Sch, Cambridge.

12:30 PM   Who is involved? Phenotypes as measures for research participants. J. O'Leary. Genetic Alliance.

Wednesday, October 7

11:00 AM–1:00 PM

Concurrent Invited Sessions I

9. Looking Beyond the Genes: Non-coding Mutations and 21st Century Disease Genetics.

Ballroom I, Level 4, Convention Center

Moderators: Malte Spielmann, Max Planck Inst for Molec Genet, Berlin, Germany
  Sumantra Chatterjee, Johns Hopkins Univ Sch Med, Baltimore

High-throughput genomic technologies are revolutionizing human genetics. So far the focus has been on the 1.5% of the genome that is coding, in spite of the fact that the great majority of genomic variants fall outside the coding regions. While whole genome sequencing studies have failed to identify coding mutations in 40% of the cases, there is evidence from recent efforts to annotate the non-coding sequence that over 80% of the genome is biochemically active. In this session, we review the recent advances in the identification of non-coding mutations and structural variations that influence gene regulation and their consequences for human disease. We show that mutations and structural variations outside of the coding genome can interfere with normal gene regulation by disrupting the regulatory landscape. Therefore, the regulatory landscape of the genome has also to be taken into consideration when investigating the pathology of human disease. Topics that will be explored include primary research results from leading groups in this field; discovery of cis regulatory elements, model systems to analyze non-coding mutations, in particular CRISPR-Cas, whole genome sequencing, and data analysis; and the broader implications of these efforts for biology and human genetics.


11:00 AM   Deletion studies of distant-acting enhancers uncover their functions in human biology and disease processes. A. Visel. Genomics Div, Lawrence Berkeley Natl Lab, Berkeley.

11:30 AM   The influence of structural variation on genomic integrity and gene regulation. M. Spielmann. Max Planck Inst for Molec Genet, Berlin, Germany.

12:00 PM   The enhancer mutation problem: Figuring out phenotype based on genotype. N. Ahituv. UC San Francisco.

12:30 PM   Functional consequences of common non-coding polymorphisms in Hirschsprung disease. S. Chatterjee. Johns Hopkins Univ Sch Med, Baltimore.

Wednesday, October 7

11:00 AM–1:00 PM

Concurrent Invited Sessions I

10. Maternal Age and Recombination: Risks to Aneuploidy

Room 309, Level 3, Convention Center

Moderators: Ross Rowsey, Washington State Univ, Pullman
  Louise Newnham, Univ Sussex, Brighton, United Kingdom

As a species, humans face a unique challenge to reproduction. For reasons not completely understood, we have an extraordinarily high rate of aneuploidy, with ~10% of clinically recognized pregnancies having a fetus with too many or too few chromosomes. The origin of the chromosome error has been widely studied, and two key risk factors have been identified: advanced maternal age and abnormal recombination. However, the etiology of aneuploidy remains a complex puzzle that we do not fully understand. Over the past few years, studies in both humans and model organisms have provided insight into factors that are key components of the generation of aneuploidy. While advanced maternal age remains a key risk factor because of the ever increasing average maternal age, abnormal recombination also is critical to understand, as every adequately studied human trisomy has been associated with abnormal recombination. In this session, we will discuss new findings helping us understand the recombination process, as well as the use of new technologies that are increasing our understanding of nondisjunction.


11:00 AM   Human ‘MeioMaps’: Genome-wide meiotic recombination and chromosome segregation outcomes in individual human oocytes. L. Newnham. Univ Sussex, Brighton, United Kingdom.

11:30 AM   Recombination initiation maps in human individuals. F. Pratto. Natl Inst Hlth, Bethesda.

12:00 PM   Maintaining centromere identity in the mammalian oocyte. E. M. Smoak. Univ Pennsylvania, Philadelphia.

12:30 PM   Multiple routes to maternal age-related aneuploidy. R. Rowsey. Washington State Univ, Pullman.

Wednesday, October 7

11:00 AM–1:00 PM

Concurrent Invited Sessions I

11. Mendelian Disorders of the Epigenetic Machinery: Genetic Disorders with Epigenetic Consequences.

Room 307, Level 3, Convention Center

Moderators: Hans T. Bjornsson, McKusick-Nathans Inst Genet Med, Johns Hopkins Univ, Baltimore
  Sharon E. Smith, Boston Children's Hosp, Boston

In the last several years a number of genetic defects involving various components of the epigenetic machinery have been uncovered. These Mendelian disorders of the epigenetic machinery are genetic disorders expected to have widespread epigenetic consequences. All these disorders lead to neurological dysfunction, either intellectual disability (majority) or progressive adult onset neurological phenotypes (DNMT1). In many ways, the study of this group of disorders offers a unique opportunity to understand the complex interactions of genetics and epigenetics in development and disease. Furthermore, given the inherent flexibility of epigenetic modifications, there are some emerging therapeutic possibilities on the horizon. In this session, we will describe current progress in exploring the pathogenic sequence in these disorders using high throughput methods, the discovery of relevant target genes, and the use of agents to modify epigenetic marks in an effort to ameliorate ongoing problems relating to defective epigenetic regulation.


11:00 AM   Kabuki syndrome: a potentially treatable cause of intellectual disability. H. T. Bjornsson. McKusick-Nathans Inst Genet Med, Johns Hopkins Univ, Baltimore.

11:30 AM   ATR-X syndrome: How defects of a chromatin remodeler lead to alpha thalassemia. R. Gibbons. Univ Oxford, John Radcliffe Hosp, Oxford, United Kingdom.

12:00 PM   MBD5-associated intellectual disability: A methyl-binding protein that regulates target gene expression affecting circadian, developmental, and neurological pathways. S. H. Elsea. Baylor Col Med, Houston.

12:30 PM   Defects of the maintenance methyltransferase DNMT1 lead to progressive neurological phenotypes in association with global hypomethylation. C. Klein. Mayo Clin, Rochester.

Wednesday, October 7

11:00 AM–1:00 PM

Concurrent Invited Sessions I

12. Policy Challenges Affecting Clinical Integration of Next-Generation Sequencing: Advancing Toward Resolution

Holiday Ballroom 4, 2nd Floor, Hilton Baltimore Hotel

Moderators: Mary A. Majumder, Baylor Col Med, Houston
  Robert Cook-Deegan, Duke Univ, Durham

New policy approaches are needed to facilitate appropriate integration of next-generation sequencing (NGS) into clinical care. In particular, realizing the full potential benefit of this technology requires attention to challenges in three critical policy domains: oversight of the quality of tests and related services; intellectual property; and coverage and reimbursement. In this session, we begin by reviewing the results of the final phase of an innovative modified Delphi process with a broad group of stakeholders, which focused on identifying the three highest priority policy challenges related to clinical integration of NGS and assessing possible approaches to addressing these challenges. Building on this foundation, experts in the three policy domains will offer up-to-the-minute summaries of developments of interest to the genomics community in their respective areas of expertise and suggest strategies for attempting to resolve the policy challenges they believe pose the greatest barriers to clinical integration of NGS.


11:00 AM   Barriers to clinical integration of next-generation sequencing and possible policy solutions: Results of an expert panel policy Delphi exercise. D. Messner. Ctr for Med Technol Policy, Baltimore.

11:30 AM   Next-generation sequencing: What is the appropriate regulatory framework? G. Javitt. DLA Piper LLP, Washington, DC.

12:00 PM   Proprietary databases: Gaining traction on an “intractable” problem. R. Cook-Deegan. Duke Univ, Durham.

12:30 PM   Addressing reimbursement challenges for next-generation sequencing. P. Deverka. American Institutes for Res, Chapel Hill.

Wednesday, October 7

11:00 AM–1:00 PM

Concurrent Invited Sessions I

13. Secure, Efficient, and Scalable Computational Genetics via Summary Statistics

Room 316, Level 3, Convention Center

Moderators: Noah Zaitlen, UCSF, San Francisco
  Nancy J. Cox, Univ Chicago

Computational methods for identifying new risk loci, training risk prediction models, and fine-mapping causal variants from summary statistics of genome-wide association studies are playing an increasingly important role in the human genetics community. This is due to two significant advantages when working with summary statistics as opposed to full genotype data. First, summary statistic-based methods are generally orders of magnitude faster than their genotype-based counterparts. The rapidly increasing size of existing and planned cohorts into the hundreds of thousands is causing computational bottlenecks for some standard analyses. Second, analyses of summary statistics are often a necessity since access to individual-level data is complicated by privacy and other issues. Indeed, high impact journals now require summary statistics to be publicly released as part of the publication process. In this session we will cover a range of methods that leverage summary statistics from GWAS and meta-analysis efforts to gain further insight into the biology of complex traits and to facilitate the translation of this knowledge into actionable targets to improve the health of people.


11:00 AM   Fully powered polygenic prediction using summary statistics. A. Price. Harvard Sch Publ Hlth, Boston.

11:30 AM   Mining GWAS summary statistics for insight into shared disease mechanisms. J. K. Pickrell. New York Genome Ctr, New York.

12:00 PM   Integrative approaches for multi-ethnic fine-mapping of known risk loci. B. Pasaniuc. UCLA, Los Angeles.

12:30 PM   Tissue-specific imputed transcriptome based gene level association test using summary statistics. H. Im. Univ Chicago.

Wednesday, October 7

11:00 AM–1:00 PM

Concurrent Invited Sessions I

14. When You Know You've Found the One: Fine-Mapping GWAS Hits to a Single Variant

Ballroom III, Level 4, Convention Center

Moderators: Jeffrey C. Barrett, Wellcome Trust Sanger Inst, Hinxton, United Kingdom
  Mark J. Daly, Massachussetts Gen Hosp, Boston

Following up GWAS hits has been a major focus of complex disease geneticists in recent years. A number of papers have described general biological pathways or overall enrichments in functional genomics annotations, but often have assumed that GWAS will rarely be able to pinpoint exact causal variants. In this session we show that a range of approaches, including fine-mapping with very large sample sizes (which separate SNPs in high LD), or samples from multiple ethnicities (which have different LD patterns) can often identify one, or only a few, likely causal variants. We will also present experimental approaches, including cell-specific functional enrichment, massively parallel reporter assays and CRISPR/Cas9 genome editing, that can help narrow the search for causal variants. All four talks will focus on unpublished data, in addition to reviewing the literature.


11:00 AM   Large scale fine-mapping in inflammatory bowel disease. J. C. Barrett. Wellcome Trust Sanger Inst, Hinxton, United Kingdom.

11:30 AM   Trans-ancestry approaches to fine-mapping GWAS loci. K. L. Mohlke. Univ North Carolina, Chapel Hill.

12:00 PM   The right cells in the right place. G. Trynka. Wellcome Trust Sanger Inst, Hinxton, United Kingdom.

12:30 PM   High throughput experimental fine-mapping of individual variants. K. Musunuru. Harvard Stem Cell Inst, Cambridge.

Wednesday, October 7

2:30 PM–4:30 PM

Concurrent Platform Session A

15. Update on Breast and Prostate Cancer Genetics

Ballroom I, Level 4, Convention Center

Moderators: Melinda Aldrich, Vanderbilt Univ, Nashville
  Marc Tischowitz, Univ Cambridge, UK

3/2:30 Meta-analysis of OncoArray, iCOGS, and GWAS data for more than 220,000 women identifies more than 50 novel breast cancer susceptibility loci. K. Michailidou, S. Lindstrom, J. Dennis, D. J. Hunter, Z. Wang, S. Chanock, J. Simard, P. Kraft, D. F. Easton, on behalf of BCAC, DRIVE, and PERSPECTIVE.

4/2:45 Exome sequencing to identify new genes underlying early-onset breast cancer susceptibility. D. Koboldt, K. Kanchi, J. Ivanovich, R. Fulton, I. Borecki, P. Goodfellow, R. Wilson, E. Mardis.

5/3:00 Five independent 6q25 breast cancer risk variants regulate ESR1 and RMND1 and display genotype-phenotype correlations. S. Edwards, A. Dunning, K. Michailidou, K. Kuchenbaecker, D. Thompson, J. French, J. Beesley, C. Healy, S. Kar, K. Pooley, E. Dicks, D. Barrowdale, N. Sinnott-Armstrong, R. Cowper-Sallari, K. Hillman, S. Kaufmann, H. Sivakumaran, M. Moradi Marjaneh, E. Lopez-Knowles, M. Dowsett, P. Pharoah, J. Simard, P. Hall, M. Garcia-Closas, C. Vachon, G. Chenevix-Trench, A. Antoniou, D. Easton.

6/3:15 Breast cancer risk at the 5p12 locus is mediated through chromatin looping and regulation of FGF10 and MRPS30. M. Ghoussaini, J. French, K. Michailidou, S. Nord, J. Beesley, J. Dennis, K. Hillman, S. Kaufmann, E. Dicks, S. Ahmed, M. Maranian, C. S. Healey, C. Baynes, C. Luccarini, M. Bolla, J. Wang, V. N. Kristensen, P. D. P. Pharoah, G. Chenevix-Trench, D. F. Easton, A. M. Dunning, S. L. Edwards, Breast Cancer Assn Consortium.

7/3:30 Cross-cancer genome-wide pleiotropy analysis based on GAME-ON and GECCO across five common cancers: Lung, ovary, breast, prostate, and colon cancer. R. J. Hung, G. Fehringer, P. Kraft, C. A. Hiaman, P. Pharoah on behalf of OCAC, R. Eeles on behalf of PRACTICAL, N. Chatterjee, D. Seminara, S. Chanock, F. Schumacher, S. Lindström, K. Stefansson, D. C. Christiani, H. Shen, K. Shiraishi, A. Takahashi, AABC. AAPC, JAPC, LABC, LAPC, Y. Bosse, M. Obeidat, M. L. Freedman, U. Peters on behalf of GECCO, S. Gruber on behalf of CORET, C. I. Amos on behalf of TRICL/ILCCO, T. A. Sellers on behalf of FOCI, D. Easton on behalf of BCAC, D. J. Hunter on behalf of DRIVE, B. E. Henderson on behalf of ELLIPSE, Genetic Associations and Mechanisms in Oncology (GAME-ON) Network.

8/3:45 Common genetic variants modify breast and prostate cancer risks for male BRCA1 and BRCA2 mutation carriers: Implications for risk prediction. G. Chenevix-Trench, J. Lecarpentier, K. Kuchenbaecker, K. Offit, F. Couch, J. Simard, M. Thomassen, R. Schmutzler, G. Chenevix-Trench, D. Easton, A. C. Antoniou, on behalf of CIMBA.

9/4:00 Whole exome sequencing in 75 high-risk families identifies eight previously unknown prostate cancer susceptibility genes. D. M. Karyadi, M. S. Geybels, E. Karlins, B. Decker, L. McIntosh, S. Kolb, S. K. McDonnell, S. Middha, L. M. FitzGerald, M. S. DeRycke, D. J. Schaid, S. N. Thibodeau, J. L. Stanford, E. A. Ostrander.

10/4:15 Population and evolutionary genomics of prostate cancer-associated variants: Implications for health disparities in men of African descent. J. Lachance, C. Hanson, M. E. B. Hansen, S. A. Tishkoff, T. R. Rebbeck.

Wednesday, October 7

2:30 PM–4:30 PM

Concurrent Platform Session A

16. Switching on to Regulatory Variation

Ballroom III, Level 4, Convention Center

Moderators: Gosia Trynka, Sanger Inst, Hinxton, UK
  Yang Li, Stanford Univ

11/2:30 Integrative approaches for large-scale transcriptome-wide association studies. A. Gusev, A. Ko, H. Shi, G. Bhatia, W. Chung, B. W. J. H. Penninx, R. Jansen, E. J. C. de Geus, D. I. Boomsma, F. A. Wright, P. F. Sullivan, E. Nikkola, M. Alvarez, M. Civelek, A. J. Lusis, T. Lehtimaki, M. Kahonen, I. Seppala, O. T. Raitakari, J. Kuusisto, M. Laakso, A. L. Price, P. Pajukanta, B. Pasaniuc.

12/2:45 Improved identification of the genetic basis of disease by integrated analysis of RNA-seq together with whole-genome and exome-based sequencing data. D. W. Craig, S. Szelinger, A. M. Claasen, I. Schrauwen, R. F. Richholt, M. De Both, B. E. Hjelm, S. Rangasamy, A. L. Siniard, A. L. Courtright, M. J. Huentelman, V. Narayanan.

13/3:00 Comprehensive transcriptome analysis using synthetic long read sequencing reveals molecular co-association and conservation of distant splicing events. H. Tilgner, F. Jahanbani, M. Rasmussen, M. Snyder.

14/3:15 Comprehensive genome and transcriptome structural analysis of a breast cancer cell line using PacBio long read sequencing. M. Nattestad, K. Ng, S. Goodwin, T. Baslan, J. Gurtowski, F. Sedlazeck, E. Hutton, E. Tseng, J. Chin, T. Beck, Y. Sundaravadanam, M. Kramer, E. Antoniou, J. Hicks, M. Schatz, W. R. McCombie.

15/3:30 Tissue-specific transcriptome-wide networks reflect joint regulation of alternative splicing and gene expression. A. Saha, Y. Kim, D. Knowles, S. Mostafavi, A. Battle, The GTEx Consortium.

16/3:45 Massively parallel quantification of the regulatory effects of non-coding variation reveals functional variants associated with fetal adiposity. C. Guo, C. M. Vockley, W. H. Majoros, M. Nodzenski, D. M. Scholtens, M. G. Hayes, W. L. Lowe, T. E. Reddy.

17/4:00 Detection of trans and cis splicing QTLs through large scale cancer genome analysis. K. Lehmann, A. Kahles, C. Kandoth, N. Schultz, O. Stegle, G. Rätsch.

18/4:15 The landscape of X inactivation across human tissues: From single cells to population sequencing. T. Tukiainen, A. Villani, M. Rivas, A. Kirby, D. DeLuca, R. Satija, A. Byrnes, J. Maller, T. Lappalainen, A. Regev, N. Hacohen, K. Ardlie, D. MacArthur, The GTEx Project Consortium.

Wednesday, October 7

2:30 PM–4:30 PM

Concurrent Platform Session A

17. Shedding Light into the Dark: From Lung Disease to Autoimmune Disease

Room 307, Level 3, Convention Center

Moderators: Martin Tobin, Univ Leicester, UK
  Tonu Esko, Children's Hosp Boston

19/2:30 The contribution of the cysteinyl leukotriene 1 (CysLT1) gene and other genetic loci to atopic asthma in the Tristan da Cunha population. M. D. Thompson, J. Stankova, M. Clunes, G. E. Rovati, D. E. Cole, M. C. Maj, V. Capra, D. L. Duffy.

20/2:45 Utilizing an African specific genotyping array for a large-scale GWAS for asthma in African Americans. H. R. Johnston, N. Rafaels, D. Hu, D. Torgerson, S. Chavan, J. Gao, G. Abecasis, M. Hansen, R. Mathias, Z. S. Qin, K. Barnes, Y. J. Hu, CAAPA Consortium.

21/3:00 Integration of genome-wide association data and human protein interaction networks identifies a gene sub-network underlying childhood-onset asthma. Y. Liu, M. Brossard, C. Sarnowski, P. Margaritte-Jeannin, F. Llinares, A. Vaysse, M. H. Dizier, E. Bouzigon, F. Demenais, and GABRIEL asthma consortium.

22/3:15 The utility of real world data for performing genetic target validation: TRPV4 and lung edema. D. Waterworth, L. Warren, M. Hurle, D. Behm, J. Pulley, E. Bowton, J. Denny, D. Sprecher, M. Ehm.

23/3:30 Quantifying heritability explained in inflammatory bowel disease using 18,000 GWAS and 9,000 next generation sequencing data. Y. Luo, K. de Lange, UK. IBD Genetics Consortium, C. A. Anderson, J. C. Barrett.

24/3:45 The X-factor of complex disease: Methods, software, and extensive application for studying the X chromosome in association studies. A. Keinan, on behalf of the XWAS Consortium.

25/4:00 Imputation of low-frequency variants identifies novel Alzheimer's disease loci in the IGAP Consortium. B. Kunkle, B. Grenier-Boley, B. W. Kunkle, M. Vronskaya, V. Chouraki, M. Butkiewics, S. V. Van der Lee, R. Sims, A. M. Toglehofer, J. Jakobsdottir, B. Dombroski, O. Valladeres, J. Bis, E. R. Martin, R. Mayeux, L. A. Farrer, C. Duijn, J. L. Haines, P. Holmans, J. C. Lambert, J. Williams, S. Seshadri, P. Amouyel, G. D. Schellenberg, M. Pericak-Vance, For The IGAP Consortium.

26/4:15 A new locus of genetic resistance to severe malaria is associated with a locus of ancient balancing selection. G. Band, on behalf of the MalariaGEN consortium.

Wednesday, October 7

2:30 PM–4:30 PM

Concurrent Platform Session A

18. Addressing the Difficult Regions of the Genome

Room 309, Level 3, Convention Center

Moderators: Stephen Lincoln, Invitae, San Francisco
  Jennifer Lee, Greenwood Genet Ctr

27/2:30 Long read single-molecule real-time (SMRT) full gene sequencing of cytochrome P450 2D6 (CYP2D6). Y. Yang, W. Qiao, R. Sebra, G. Mendiratta, A. Gaedigk, R. Desnick, S. Scott.

28/2:45 An NGS-based carrier screen for congenital adrenal hyperplasia with 95% detection rate. D. Muzzey, M. R. Theilmann, K. M. D'Auria, H. H. Lai, C. S. Chu, I. S. Haque, E. A. Evans, H. P. Kang, J. R. Maguire.

29/3:00 Supplemental CNV analysis in NGS genepanel data in a diagnostic setting. J. J. Saris, R. van Minkelen, M. A. van Slegtenhorst, H. T. Brüggenwirth, L. H. Hoefsloot.

30/3:15 The application of the CNVSeq method for whole genome copy number variant detection. A. Tzika, P. Roberts, S. Hewitt, C. Watson, L. Crinnion, D. Bonthron.

31/3:30 Detection of relevant pharmacogenomic variants and CYP2D6 copy number using a highly multiplexed next generation sequencing assay. F. C. L. Hyland, M. Manivannan, S. C. Chen, T. Chen, T. Hartshorne, M. Anderson, G. Liu.

32/3:45 Next-generation sequencing-based genetic testing of autosomal dominant polycystic kidney disease. P. C. Wu, Y. H. Yang, T. W. Kao, J. W. Huang, T. S. Chu, P. L. Chen.

33/4:00 A method for detecting intragenic copy number changes of BRCA1 and BRCA2 using next-generation sequencing data. P. J. B. Sabatini, K. Chun.

34/4:15 DNA combing as a first-tier genetic testing for facioscapulohumeral dystrophy type 1: A cohort of 155 patients. R. Owen, F. Z. Boyar, X. J. Yang, B. H. Nguyen, V. Sulcova, P. Chan, Y. Liu, A. Anguiano, C. M. Strom.

Wednesday, October 7

2:30 PM–4:30 PM

Concurrent Platform Session A

19. Statistical Genetics: Complex Phenotypes, Complex Solutions

Room 316, Level 3, Convention Center

Moderators: Andrew DeWan, Yale Univ, New Haven
  Kristel Van Steen, Univ of Liege, Belgium

35/2:30 Pitfalls in development of statistical methods for rare variant association studies. G.T. Wang, D. Zhang, Z. He, D. Hang, B. Li, SM. Leal.

36/2:45 Ignoring pleiotropy bias in Mendelian randomization with polygene scores can easily lead to incorrect inferences about causality. C. M. Astley, M. Kals, T. Esko, J. N. Hirshhorn, K. Fischer.

37/3:00 Mendelian randomization provides evidence for a causal effect of low vitamin D on multiple sclerosis risk: Results from the Kaiser Permanente MS Research Program. B. Rhead, M. Gianfrancesco, A. Mok, X. Shao, H. Quach, L. Shen, A. Bernstein, C. Schaefer, L. F. Barcellos.

38/3:15 Contrasting regional architectures of schizophrenia and other complex diseases using fast variance components analysis. P. Loh, G. Bhatia, A. Gusev, H. K. Finucane, B. K. Bulik-Sullivan, S. J. Pollack, T. R. de Candia, S. H. Lee, N. R. Wray, K. S. Kendler, M. C. O'Donovan, B. M. Neale, N. Patterson, A. L. Price, Schizophrenia Working Group of the Psychiatric Genomics Consortium.

39/3:30 Multivariate analysis of whole exome sequence data identifies rare variants with pleiotropic effects on obesity-related metabolic traits in 31,000 participants of the Regeneron Genetics Center – Geisinger MyCode collaborative project – DiscovEHR. S. Mukherjee, C. O’Dushlaine, C. V. Hout, S. Bruse, J. B. Leader, D. N. Hartzel, J. Staples, S. Hamon, J. Overton, J. G. Reid, A. Baras, D. J. Carey, H. L. Kirchner, M. D. Ritchie, S. A. Pendergrass, M. Murray, D. H. Ledbetter, O. Gottesman, F. Dewey, A. R. Shuldiner.

40/3:45 Quantifying penetrance in a dominant disease gene using large population control cohorts. E. V. Minikel, S. M. Vallabh, M. Lek, K. O. Estrada, K. E. Samocha, J. F. Sathirapongsasuti, C. Y. McLean, J. Y. Tung, L. P. C. Yu, M. J. Daly, D. G. MacArthur, Exome Aggregation Consortium.

41/4:00 Evaluation of the regional variability of missense constraint in 60,000 exomes. K. E. Samocha, M. Lek, D. G. MacArthur, B. M. Neale, M. J. Daly, Exome Aggregation Consortium.

42/4:15 MARV: A novel method and software tool for genome-wide multi-phenotype analysis of rare variants. M. Kaakinen, R. Mägi, K. Fischer, M.-R. Järvelin, AP. Morris, I. Prokopenko.

Wednesday, October 7

2:30 PM–4:30 PM

Concurrent Platform Session A

20. Think Globally, Act Locally: Copy Number Variation

Room 318/321, Level 3, Convention Center

Moderators: Patricia M. Miron, UMass Mem Med Ctr, Worcester
  Azra Ligon, Brigham and Women's Hosp, Boston

43/2:30 Association of copy number variations with decreased cognitive phenotypes and fitness in unselected populations. A. Reymond, R. Magi, A. Mace, B. Cole, A. Guyatt, H. Shihab, A. Maillard, H. Alavere, A. Kolk, A. Reigo, E. Mihailov, L. Leitsalu, A. M. Ferreira, M. Nõukas, A. Teumer, E. Salvi, D. Cusi, M. McGue, W. G. Iacono, T. R. Gaunt, J. S. Beckmann, S. Jacquemont, Z. Kutalik, N. Pankratz, N. Timpson, A. Metspalu, K. Mannik.

44/2:45 The role of transcription in mammalian cell copy number variant formation. S. Park, M. F. Arlt, S. Rajendran, M. T. Paulsen, R. Beroukhim, M. Ljungman, T. E. Wilson, T. W. Glover.

45/3:00 Quantitative functional studies using Drosophila melanogaster identify dosage-sensitive and sex-specific effects of neurodevelopmental genes. L. Pizzo, P. Patel, L. Pizzo, K. Vadodaria, Q. Wang, A. Kubina, S. Yennawar, R. Pandya, S. Girirajan.

46/3:15 Single-cell analysis reveals that endogenous retrotransposons generate somatic mosaicism in neuronal and non-neuronal cells. J. A. Erwin, A. C. Paquola, T. Singer, C. Quayle, T. Bedrosian, A. Muotri, R. Lasken, F. G. Gage.

47/3:30 Evolution and structural diversity of the complement factor H related gene cluster. S. Cantsilieris, L. Harshman, N. Janke, E. E. Eichler.

48/3:45 Repetitive DNA at CNV breakpoints is susceptible to gross chromosomal rearrangement. K. Rudd, K. E. Hermetz, Y. Nishida, Y. Zhang, N. Saini, K. S. Lobachev.

49/4:00 A potential role for the linker for activation of T-cells (LAT) in the neuroanatomical phenotype of the 16p11.2 BP2-BP3 CNVs. M. N. Loviglio, M. Leleu, T. Arbogast, K. Mannik, G. Giannuzzi, J. Beckmann, J. Rougemont, S. Jacquemont, N. Katsanis, C. Golzio, A. Reymond, 16p11.2 Consortium.

50/4:15 Paired-duplications mark cryptic inversions and are a common signature of complex structural variation that is misclassified by chromosomal microarray. H. Brand, R. L. Collins, C. Hanscom, J. A. Rosenfeld, V. Pillalamarri, M. R. Stone, F. Kelley, T. Mason, L. Margolin, S. Eggert, E. Mitchell, J. C. Hodge, J. F. Gusella, S. J. Sanders, M. E. Talkowski.

Wednesday, October 7

2:30 PM–4:30 PM

Concurrent Platform Session A

21. Recent Advances in the Genetic Basis of Neuromuscular and Other Neurodegenerative Phenotypes

Holiday Ballroom 1, 2nd Floor, Hilton Baltimore Hotel

Moderators: Megan Dennis, UC Davis
  Marina Kennerson, ANZAC Res Inst, Concord, Australia

51/2:30 RNA sequencing of a mouse model of spinal muscular atrophy reveals tissue-wide changes in splicing of U12-dependent introns in genes involved in cell cycle, intracellular trafficking, and neuronal function. T. K. Doktor, Y. Hua, H. S. Andersen, S. Brøner, A. R. Krainer, B. S. Andresen.

52/2:45 BAC transgenic model of C9ORF72 ALS/FTD. Y. Liu, A. Pattamatta, T. Zu, T. Reid, L. P. W. Ranum.

53/3:00 Altered RNA processing in ALS4. C. Grunseich, I. X. Wang, J. Watts, T. Lanman, G. Ramrattan, Z. Zhu, D. Bakar, A. B. Schindler, E. Hartnett, K. H. Fischbeck, V. G. Cheung.

54/3:15 A recurrent mutation in KCNA2 in complicated autosomal dominant spastic paraplegia: An expansion of the channelopathy spectrum and a novel disease mechanism. K. L. Helbig, U. B. S. Hedrich, A. C. Teichmann, J. Hentschel, D. N. Shinde, W. A. Alcaraz, S. Tang, C. Jungbluth, S. L. Dugan, R. Schüle, H. Lerche, J. R. Lemke.

55/3:30 Mouse resources for comparative Mendelian genomics. L. Reinholdt, H. Fairfield, A. Srivastava, R. Liu, A. Lakshminarayana, B. Harris, S. Karst, M. Berry, P. Ward-Bailey, C. Byers, A. Czechanski, W. Martin, K. Cheng, L. Goodwin, J. Morgan, D. Bergstrom.

56/3:45 Activation of the DNA damage response in an induced model of spinal muscular atrophy. M. Jangi, H. Li, X. Yang, P. Cullen, A. Thai, M. Liu, C. Fleet, C. F. Bennett, F. Rigo, A. R. Krainer, C. Roberts, N. Allaire, C. Sun, J. P. Carulli, J. F. Staropoli.

57/4:00 Recessive mutations in the UGO1-like protein SLC25A46 cause an optic atrophy. T. Huang, S. Zuchner, J. Dallman, V. Carelli, A. Abrams, R. Hufnagel, A. Rebelo, C. Zanna, N. Patel, M. Gonzalez, I. Campeanu, L. Griffin, S. Groenewald, A. Strickland, F. Tao, F. Speziani, L. Abreu, R. Schüle, L. Caporali, C. Morgia, A. Maresca, R. Liguori, R. Lodi, Z. Ahmed, K. Sund, X. Wang, L. Krueger, Y. Peng, C. Prada, C. Prows, K. Bove, E. K. Schorry, A. Antonellis, H. H. Zimmerman, O. A. Abdulrahma.

58/4:15 Neuronal aneuploidy and associated apoptosis in familial and sporadic frontotemporal lobar degeneration indicate that FTLD, like Alzheimer’s disease and Niemann-Pick C1, is a cell cycle disorder. H. Potter, J. Caneus, A. Granic, D. Dickson.

Wednesday, October 7

2:30 PM–4:30 PM

Concurrent Platform Session A

22. Neuropsychiatric Diseases of Childhood

Holiday Ballroom 4, 2nd Floor, Hilton Baltimore Hotel

Moderators: Peristera Paschou, Democritus Univ Thrace, Alexandroupoli, Greece
  Jennifer Mulle, Emory Univ, Atlanta

59/2:30 Results from the largest GWAS of autism spectrum disorder to date. J. Grove, The iPSYCH-SSI-Broad/MGH collaboration and Psychiatric Genomics Consortium Autism Working Group.

60/2:45 De novo likely gene disrupting mutations and genic copy number variants increase the risk for Tourette’s Disorder. T. V. Fernandez, R. A. King, J. Xing, A. J. Willsey, A. Dietrich, J. A. Tischfield, G. A. Heiman, M. W. State, The TIC Genetics Collaborative Group.

61/3:00 Rare copy number variants implicate neuronal cell adhesion molecules in Tourette Syndrome. A. Huang, D. Yu, L. Davis, C. Mathews, P. Paschou, N. Freimer, J. Scharf, G. Coppola, TSA International Consortium for Genomics, and the GTS GWAS Replication Initiative.

62/3:15 Whole exome sequencing with simultaneous analysis of both parents has a high diagnostic yield for patients with epilepsy and neurodevelopmental disorders. M. Stosser, T. Brandt, K. Retterer, J. Juusola, G. Richard, S. Suchy, D. McKnight.

63/3:30 Gene discovery and high-throughput resequencing of candidate genes in epileptic encephalopathies. C. T. Myers, J. M. McMahon, A. Schneider, R. K. Møller, G. L. Carvill, I. E. Scheffer, H. C. Mefford, Epi4K Consortium.

64/3:45 Loss-of-function mutations in SLC12A5 encoding the potassium-chloride co-transporter KCC2 in epilepsy of infancy with migrating focal seizures. T. Stödberg, A. McTague, A. Ruiz, H. Hirata, J. Zhen, P. Long, I. Farabella, E. Meyer, A. Kawahara, G. Vassallo, S. Stivaros, M. Bjursell, H. Stranneheim, S. Tigerschiöld, B. Persson, I. Bangash, K. Das, D. Hughes, N. Lesko, J. Lundeberg, R. Scott, A. Poduri, I. Scheffer, H. Smith, P. Gissen, S. Schorge, M. Reith, M. Topf, D. Kullmann, R. Harvey, A. Wedell.

65/4:00 Functional analysis of GRIN2A mutations in childhood epileptic encephalopathies. L. Addis, L. R. Vidler, D. A. Collier, D. K. Pal, D. Ursu.

66/4:15 Hyperexcitability of neurons and cardiomyocytes in a mouse model of SCN8A epileptic encephalopathy. J. L. Wagnon, C. R. Frasier, L. F. Lopez-Santiago, Y. Yuan, J. Hull, Y. Bao, M. H. Meisler.

Thursday, October 8

9:00 AM–10:30 AM

23. Distinguished Speakers Symposium: The Art and Science of Science Communication

Hall F, Level 1, Convention Center

Moderator: Chris Gunter, ASHG 2015 Program Chair

In 2015, doing great science is often not enough. We need to be able to effectively communicate our scientific processes and findings to multiple audiences in order to win funding and public support. This symposium features three trailblazers in science communication, working through multiple media sources to engage people with the exciting and challenging stories of human genetics. Our speakers will be Ed Yong, one of the best science journalists working today and author of the blog “Not Exactly Rocket Science”; Liz Neeley, executive director of The Story Collider and architect of science outreach strategies based on public engagement data; and Andrea Downing, patient and data sharing advocate and creator of an online community around BRCA findings.

E. Yong
Science Writer

L. Neeley
The Story Collider

A. Downing
Advocate and Writer


9:00 AM   Introduction. C. Gunter. Marcus Autism Ctr, Emory Univ Sch of Med, Children’s Healthcare of Atlanta.

9:10 AM   “Nobody has to read this crap”, or Why science journalism is not science communication and why that matters. E. Yong. Science Writer.

9:35 AM   The stories we tell ourselves about science communication. L. Neeley. The Story Collider.

10:00 AM   ePatients and the power of a connected community. A. Downing. Advocate and Writer.

Thursday, October 8

2:30 PM–4:30 PM

Concurrent Platform Session B

24. Going All In: Experimental Characterization of Complex Trait Loci

Ballroom I, Level 4, Convention Center

Moderators: Casey Brown, Univ Penn, Philadelphia
  Barbara Stranger, Univ Chicago

67/2:30 Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing glaucoma-related endophenotypes. A. Iglesias Gonzalez, H. Springelkamp, A. Mishra, T. Aung, C.-Y. Cheng, J. E. Craig, C. J. Hammond, M. Hauser, A. W. Hewitt, R. Höhn, C. C. W. Klaver, A. J. Lotery, D. A. Mackey, L. R. Pasquale, N. Pfeiffer, A. C. Viswanathan, J. L. Wiggs, T.-Y. Wong, C. M. van Duijn, S. MacGregor, International Glaucoma Genet Consortium.

68/2:45 The genomic region harboring the type 2 diabetes presumed causal variant within TCF7L2 forms long-range functional connections with ACSL5. M. E. Johnson, Q. Xia, A. Chesi, B. T. Johnston, S. Lu, E. F. Rappaport, P. Huang, A. D. Wells, G. A. Blobel, S. F. A. Grant.

69/3:00 Genome-wide association studies identify RAB38 and HS6ST1 associated with albuminuria in diabetes. A. Teumer, on behalf of the CKDGen Consortium.

70/3:15 Chromosome interaction analysis of risk loci in related autoimmune diseases reveals complex, long-range promoter interactions implicating novel candidate genes. P. Martin, A. McGovern, G. Orozco, K. Duffus, A. Yarwood, S. Schoenfelder, N. Cooper, A. Barton, C. Wallace, P. Fraser, J. Worthington, S. Eyre.

71/3:30 A rare A2ML1 variant confers susceptibility to otitis media and causes changes in the middle ear microbiome. R. L. P. Santos-Cortez, C. M. Chiong, M. R. T. Reyes-Quintos, M. L. C. Tantoco, X. Wang, A. Acharya, I. Abbe, A. P. Giese, J. D. Smith, E. K. Allen, B. Li, E. M. Cutiongco-de la Paz, M. C. Garcia, E. G. D. V. Llanes, P. J. Labra, N. J. Ajami, J. F. Petrosino, G. T. Wang, K. A. Daly, J. Shendure, M. J. Bamshad, D. A. Nickerson, J. A. Patel, S. Riazuddin, M. M. Sale, T. Chonmaitree, Z. M. Ahmed, G. T. Abes, S. M. Leal, University of Washington Ctr for Mendelian Genomics.

72/3:45 Systems genetics approach unravels the molecular mechanisms underlying lung function variation and uncovers novel therapeutic targets for COPD. M. Obeidat, Y. Nie, K. Hao, Y. Bossé, M. Laviolette, D. Nickle, D. Postma, W. Timens, S. Gharib, L. Wain, M. Artigas, M. Tobin, I. Hall, S. London, D. Sin, P. Paré, SpiroMeta, CHARGE and Lung eQTL Consortia.

73/4:00 Fine-mapping and molecular assays identify multiple functional variants at the ANGPTL8 HDL-C GWAS locus. M. E. Cannon, C. K. Raulerson, Q. Duan, Y. Wu, A. Ko, P. Pajukanta, M. Laakso, Y. Li, K. L. Mohlke.

74/4:15 Functional analyses of type 2 diabetes-associated loci provides mechanistic insight into genetic susceptibility. E. A. O'Hare, L. M. Yerges-Armstrong, J. A. Perry, A. R. Shuldiner, N. A. Zaghloul.

Thursday, October 8

2:30 PM–4:30 PM

Concurrent Platform Session B

25. Powering Up Complex Trait Genetics

Ballroom III, Level 4, Convention Center

Moderators: Barbara Engelhardt, Princeton Univ.
  Benjamin Neale, Broad Inst, Cambridge

75/2:30 Integrative tissue-specific functional annotations in the human genome provide novel insights on many complex traits and improve replication rates in genome wide association studies. Q. Lu, R. Powles, Q. Wang, J. He, H. Zhao.

76/2:45 A general analytical framework to identify pathogenic genes underlying complex diseases. P. Shooshtari, C. Cotsapas.

77/3:00 metaCCA: Summary statistics-based multivariate meta-analysis of genome-wide association studies using canonical correlation analysis. A. Cichonska, J. Rousu, P. Marttinen, A. J. Kangas, P. Soininen, T. Lehtimäki, O. T. Raitakari, M. R. Järvelin, V. Salomaa, M. Ala-Korpela, S. Ripatti, M. Pirinen.

78/3:15 A systematic analysis of differential pathway architectures in diverse functional genomics networks for large-scale prediction of pathways from GWAS and exome-sequencing projects. J. D. Mercer, S. Rosenbluh, A. Liberzon, J. Grabarek, D. Thompson, T. Eisenhaure, S. Carr, J. Jaffe, J. Boehm, A. Tsherniak, A. Subramanian, R. Narayan, T. Natoli, T. Liefeld, B. Wong, J. Bistline, T. Li, S. Calvo, Y. Li, J. Mesirov, N. Hacohen, A. Regev, K. Lage.

79/3:30 Identifying genetically-driven clinical phenotypes using linear mixed models. J. D. Mosley, J. S. Witte, S. J. Hebbring, E. K. Larkin, L. Bastarache, C. M. Shaffer, J. H. Karnes, C. M. Stein, J. C. Denny, D. M. Roden.

80/3:45 Genetic validation and application of pathway-based annotation for unknown signals in untargeted metabolomics. Y. H. Hsu, T. Esko, T. H. Pers, A. Metspalu, J. N. Hirschhorn.

81/4:00 Quantifying uncertainty in heritability estimation using linear mixed models. R. Schweiger, E. Halperin.

82/4:15 Genotype imputation with millions of reference samples. B. L. Browning, S. R. Browning.

Thursday, October 8

2:30 PM–4:30 PM

Concurrent Platform Session B

26. Hereditary Cancer Genes: Old and New

Room 307, Level 3, Convention Center

Moderators: Angela Brooks-Wilson, Canada's Michael Smith Genome Sci Ctr, Vancouver, Canada
  Douglas Stewart, NCI/NIH, Rockville

83/2:30 Germline mutations in cancer-predisposition genes in 1,120 children with cancer: A report from the Pediatric Cancer Genome Project. J. Zhang, M. Walsh, G. Wu, M. Edmonson, T. Gruber, J. Easton, D. Hedges, X. Ma, X. Zhou, D. Yergeau, M. Wilkinson, B. Vandor, X. Chen, R. McGee, S. Hines-Dowell, R. Nuccio, E. Quinn, S. Shurtleff, M. Rusch, J. Becksfort, M. Weaver, L. Ding, E. Mardis, R. Wilson, C.-H. Pui, A. Gajjar, D. Ellison, A. Pappo, K. Nichols, J. Downing, St. Jude/Washington Univ Pediatric Cancer Genome Project.

84/2:45 Germline variants among unselected patients enrolled in a tumor/normal cancer genomic sequencing project identifies a high percentage with inherited risk. V. M. Raymond, J. N. Everett, E. M. Stoffel, J. W. Innis, Y. M. Wu, D. R. Robinson, P. Vats, R. J. Lonigro, R. Mody, A. M. Chinnaiyan.

85/3:00 Somatic TP53 mutations detected in germline testing: The importance of phenotypic correlation in cancer predisposition testing. J. N. Weitzel, K. R. Blazer, H. LaDuca, B. Nehoray, T. Slavin, T. Pesaran, C. Rybak, I. Solomon, M. Neil-Swiller, E. Chao.

86/3:15 ChIP-Seq analysis of lymphocytes from Li-Fraumeni patients reveals the drastic impact on p53 DNA binding of heterozygous TP53 mutations associated with early-onset cancers. T. Frebourg, Y. Zerdoumi, R. Lanos, A. Bouzelfen, F. Charbonnier, G. Bougeard, J.-M. Flaman.

87/3:30 Tumour risks and genotype-phenotype-proteotype analysis of 800 patients with germline mutations in the succinate dehydrogenase subunit genes SDHB, SDHC, and SDHD. E. R. Maher, K. A. Andrews, L. Vialard, D. B. Ascher, D. E. V. Pires, N. Bradshaw, T. Cole, F. Lalloo, M. McConachie, P. J. Morrison, V. Murday, S. M. Park, Y. Wallis, D. Goudie, R. S. Lindsay, C. G. Perry, L. Izatt, E. R. Woodward, SDH-UK Consortium.

88/3:45 A parent-of-origin effect impacts the phenotype in low penetrance retinoblastoma families segregating the p.Arg661Trp mutation of RB1. C. Houdayer, P. Eloy, C. Dehainault, M. Sefta, I. Aerts, L. Lumbroso le Rouic, D. Stoppa Lyonnet, F. Radvanyi, G. Millot, M. Gauthier Villars.

89/4:00 Germline and somatic inactivating SMARCA4 mutations in small cell carcinoma of the ovary, hypercalcemic type (SCCOHT): Diagnostic and therapeutic implications. P. Ramos, P. Ramos, H. Yin, A. N. Karnezis, Y. Wang, M. L. Russell, D. W. Craig, V. L. Zismann, A. Sekulic, B. E. Weissman, D. G. Huntsman, J. M. Trent.

90/4:15 Common variants in MMP20 at 11q22.2 predispose to 11q deletion and impact neuroblastoma risk. X. Chang, L. McDaniel, C. Hou, M. Diamond, K. Thomas, J. Li, Y. Guo, F. Mentch, H. Qiu, C. Kim, S. Diskin, P. Sleiman, E. Attiyeh, J. Maris, H. Hakonarson.

Thursday, October 8

2:30 PM–4:30 PM

Concurrent Platform Session B

27. Advances in Epigenetics: What Would Waddington Say?

Room 309, Level 3, Convention Center

Moderators: Reid Alisch, Univ Wisconsin, Madison
  Terry Furey, UNC Chapel Hill

91/2:30 Epigenetic and transcriptional dysregulation of oxytocin receptor (Oxtr) in Tet1 methylcytosine dioxygenase deficient mouse brain. A. J. Towers, XL. Li, A. L. Bey, P. Wang, S. K. Siecinski, S. Xu, X. Cao, L. J. Duffney, YH. Jiang.

92/2:45 GWAS meta-analysis identifies susceptibility loci for epigenetic age acceleration in human cerebellum. A. Lu, E. Hannon, M. Levine, K. Hao, E. Crimmins, A. Kozlenkov, K. Lunnon, J. Miller, S. Dracheva, S. Horvath.

93/3:00 Methylomic aging as a window on lifestyle impact: Tobacco and alcohol alter the rate of biological aging. M. V. Dogan, S. R. H. Beach, M. K. Lei, C. E. Cutrona, M. Gerrard, F. X. Gibbons, R. L. Simons, G. H. Brody, R. A. Philibert.

94/3:15 A survey of DNA methylation polymorphism in the human genome identifies environmentally responsive co-regulated networks of epigenetic variation. R. Joshi, P. Garg, C. Watson, A. Sharp.

95/3:30 A novel predictive model of sexual orientation using epigenetic markers. T. C. Ngun, W. Guo, N. M. Ghahramani, K. Purkayastha, D. Conn, F. J. Sanchez, S. Bocklandt, M. Zhang, C. M. Ramirez, M. Pellegrini, E. Vilain.

96/3:45 RNF12 is essential for X-inactivation in female mouse embryonic stem cells, is required for female mouse development, and might be a target for future therapies to treat X-linked disorders in females: Evidence from a mouse knockout model. S. Barakat, J. Gribnau.

97/4:00 Deep learning the relationship between chromatin architecture, chromatin state, and transcription factor binding. A. Kundaje, C. S. Foo, J. Israeli, A. Shrikumar, J. Buenrostro, A. Schep, W. Greenleaf.

98/4:15 Inter-planetary systems biology reveals differences in twin astronauts at the genetic, epigenetic, transcriptional, and epitranscriptomic levels. C. Mason.

Thursday, October 8

2:30 PM–4:30 PM

Concurrent Platform Session B

28. Adult-onset Neuropsychiatric Disease

Room 316, Level 3, Convention Center

Moderators: Dan Arking, Johns Hopkins, Baltimore
  Nora Urraca, Le Bonheur Children's Hosp, Memphis

99/2:30 Vitamin D and risk of multiple sclerosis: A Mendelian randomization study. L. E. Mokry, S. Ross, O. S. Ahmad, V. Forgetta, G. Davey Smith, A. Leong, C. M. T. Greenwood, J. B. Richards.

100/2:45 Genome-wide interaction study of Parkinson disease and vitamin D deficiency implicates immune system pathways. W. K. Scott, L. Maldonado, G. W. Beecham, E. R. Martin, M. L. Evatt, J. C. Ritchie, J. L. Haines, C. P. Zabetian, H. Payami, M. A. Pericak-Vance, J. M. Vance, L. Wang.

101/3:00 DNAJC6 mutations associated with early-onset Parkinson’s disease. S. Olgiati, M. Quadri, M. Fang, J. P. M. A. Rood, J. A. Saute, H. F. Chien, C. G. Bouwkamp, J. Graafland, M. Minneboo, G. J. Breedveld, J. Zhang, F. W. Verheijen, W. Mandemakers, A. J. W. Boon, J. A. Kievit, L. B. Jardim, E. R. Barbosa, C. R. M. Rieder, K. L. Leenders, J. Wang, V. Bonifati.

102/3:15 A novel protein aggregation mechanism triggered by translation of cryptic amyloidogenic elements in the 3' UTR of neurofilament genes. A. Rebelo, A. Abrams, E. Cottienne, A. Horga, M. Gonzalez, A. Sanchez-Mejias1, L. Matilde, H. Houlden, J. Blake, C. Woodward, M. Sweeney, J. Holton, M. Hanna, J. Dallman, M. Auer-Grumbach, M. Reilly, S. Zuchner.

103/3:30 Identification of a founder mutation in ABCA7 in a Belgian cohort of Alzheimer's disease patients. K. Sleegers, E. Cuyvers, T. Van den Bossche, A. De Roeck, C. Van Cauwenberghe, S. Vermeulen, M. Mattheijssens, K. Peeters, S. Engelborghs, M. Vandenbulcke, R. Vandenberghe, P. P. De Deyn, C. Van Broeckhoven, BELNEU Consortium.

104/3:45 SORL1 rare variants: A major risk factor for familial early onset Alzheimer disease. G. Nicolas, C. Charbonnier, D. Wallon, O. Quenez, C. Bellenguez, B. Grenier-Boley, S. Rousseau, A.-C. Richard, A. Rovelet-Lecrux, K. Le Guennec, D. Bacq, J.-G. Garnier, R. Olaso, A. Boland, V. Meyer, J.-F. Deleuze, P. Amouyel, H.-H. Munter, G. Bourque, M. Lathrop, T. Frebourg, R. Redon, L. Letenneur, J.-F. Dartigues, E. Génin, J.-C. Lambert, D. Hannequin, D. Campion.

105/4:00 Loss-of-function mutations in TBK1 are a frequent cause of frontotemporal dementia and amyotrophic lateral sclerosis in Belgian and European cohorts. M. Cruts, I. Gijselinck, S. Van Mossevelde, J. van der Zee, A. Sieben, B. Heeman, S. Engelborghs, M. Vandenbulcke, R. Vandenberghe, P. De Jonghe, P. Cras, P. De Deyn, J.-J. Martin, M. Cruts, BELNEU Consortium, EU EOD Consortium.

106/4:15 The C9orf72 repeat expansion modulates onset age of FTD-ALS through increased DNA methylation and transcriptional downregulation. M. Cruts, I. Gijselinck, S. Van Mossevelde, J. van der Zee, A. Sieben, S. Engelborghs, J. De Bleecker, A. Ivanoiu, O. Deryck, D. Edbauer, M. Zhang, B. Heeman, E. Rogaeva, P. De Jonghe, P. Cras, J.-J. Martin, P. P. De Deyn, C. Van Broeckhoven, BELNEU Consortium.

Thursday, October 8

2:30 PM–4:30 PM

Concurrent Platform Session B

29. The Ever-Changing Chromosome

Room 318/321, Level 3, Convention Center

Moderators: Natalia Leach, Integrated Genetics/Lab Corp, Westborough
  Athena Cherry, Stanford Univ

107/2:30 Missed connections: Failure to recombine is a common feature of human oogenesis. T. Hassold, H. Maylor-Hagen, J. Gruhn, P. Hunt.

108/2:45 An isogenic trisomic-disomic model system using cells from people with mosaic Down syndrome unmasks trisomy 21 associated increases in age-related chromosomal instability and telomere shortening. K. Rafferty, C. Charalsawadi, C. Jackson-Cook.

109/3:00 Runs of homozygosity (ROH) reveal correction of chromosomal imbalances during fetal development. A. L. Penton, D. Segal, R. Burnside, P. Papenhausen.

110/3:15 Genomic imbalances in fetuses and patients with congenital heart malformation. I. Maya, S. Kahana, T. Tenne, S. Jakobson, J. Yeshaya, M. Shohat, L. Basel-Vanagaite.

111/3:30 The role of copy number losses in non-syndromic cleft lip and palate. L. A. Harney, B. W. Darbro, A. Long, J. Standley, R. A. Cornell, J. C. Murray, J. R. Manak.

112/3:45 Interchromosomal core duplicons drive recurrent complex inversions within the chromosome 8p23.1 region. K. Mohajeri, C. D. Campbell, J. Huddleston, B. Nelson, C. R. Catacchio, M. Ventura, E. E. Eichler.

113/4:00 Characterization of mosaic chromothripsis in the human germline by chromosomal microarray and whole genome sequencing. F. Quintero-Rivera, C. Redin, N. Dorrani, J. A. Martinez-Agosto, M. E. Talkowski.

114/4:15 Mechanistic insights of complex insertional translocations. S. Gu, C. M. B. Carvalho, B. Yuan, W. Bi, A. Patel, S. W. Cheung, J. R. Lupski.

Thursday, October 8

2:30 PM–4:30 PM

Concurrent Platform Session B

30. Connecting the Dots: Hard and Soft Tissue Syndromes

Holiday Ballroom 1, 2nd Floor, Hilton Baltimore Hotel

Moderators: Anne Slarotinek, UCSF
  Nathaniel Robin, Univ Alabama Birmingham

115/2:30 Pathogenesis, risk stratification, and management of pregnancy-associated aortic dissection in Marfan syndrome and related connective tissue disorders. M. L. Russo, G. L. MacCarrick, E. Sparks, H. C. Dietz, J. P. Habashi.

116/2:45 Williams-Beuren syndrome as an epigenetic disease: Association of GTF2IRD1 with chromatin silencing complexes. P. Carmona-Mora, F. Tomasetig, C. P. Canales, A. Alshawaf, M. Dottori, J. I. Young, R. Barres, E. C. Hardeman, S. J. Palmer.

117/3:00 Pseudoxanthoma elasticum: Expanding ABCC6 mutation database and pathogenicity test of missense mutations by zebrafish mRNA rescue. S. Raftari, H. Vahidnezhad, L. Youssefian, A. Mirzaei, M. Daneshpazhouh, M. Salehi, H. R. Mahmoudi, Q. Li, J. Uitto.

118/3:15 Comparison of phenotypic features associated with TGFBR1 and TGFBR2 mutations: Results of the Montalcino Aortic Consortium. G. Jondeau, J. Ropers, E. Regalado, A. Braverman, A. Evangelista, G. Teixedo, J. De Backer, L. Muino Mosquera, S. Naudion, C. Zordan, T. Morisaki, H. Morisaki, Y. Von Kodolitsch, S. Dupuis-Girod, S. A. Morris, R. Jeremy, S. Odent, M. Langeois, M. Spentchian, M. Aubart, C. Boileau, R. Pyeritz, D. Milewicz, Montalcino Aortic Consortium.

119/3:30 Variations in non-coding regions of TGFβ3, CDH2, and IRF6, affecting their expression, show association with cleft lip and palate (CL±P). P. Kumari, S. K. Singh, R. Raman.

120/3:45 Natural history of dermatan 4-O-sulfotransferase 1 (D4ST1)-deficient Ehlers-Danlos Syndrome (DDEDS): From an international collaborative clinical study by the International Consortium for EDS. T. Kosho, D. Syx, T. Van Damme, H. Morisaki, H. Kawame, T. Sonoda, Y. Hilhorst-Hofstee, A. Maugeri, N. Voermans, R. Mendoza-Londono, K. Wierenga, P. Jayakar, K. Ishikawa, T. Kobayashi, Y. Aoki, S. Watanabe, T. Ohura, M. Kono, K. Mochida, T. Morisaki, N. Miyake, M. Malfait.

121/4:00 Cbx3 and its role in craniofacial development: Zebrafish as a model system for testing dysmorphology candidate genes. H. E. Edelman, C. Woods, J. E. Hoover-Fong, A. S. McCallion.

122/4:15 Cerebro-costo-mandibular syndrome revisited: Phenotype and outcome of twenty molecularly confirmed individuals. D. C. Lynch, M. Tooley, E. J. Bhoj, E. G. Lemire, B. N. Chodirker, J. P. Taylor, D. K. Grange, E. H. Zackai, E. P. Kirk, J. Hoover-Fong, L. Fleming, R. Savarirayan, S. F. Smithson, A. M. Innes, J. S. Parboosingh, F. P. Bernier.

Thursday, October 8

2:30 PM–4:30 PM

Concurrent Platform Session B

31. Genetics/Genomics Education: From Pupils to Parents

Holiday Ballroom 4, 2nd Floor, Hilton Baltimore Hotel

Moderators: Arti Pandya, UNC Chapel Hill
  Karen Weissbecker, Tulane Univ, New Orleans

123/2:30 Development of the GLASS: Genetics Literacy Assessment for Secondary Schools. R. J. Okamura, S. S. Lee, B. Bowling, K. E. Ormond.

124/2:45 New tool for measuring genetic variation knowledge among health professionals. K. Abdallah, M. Moss, J. Jenkins, K. Calzone, S. Sellers, V. Bonham.

125/3:00 Knowledge and attitudes of medical residents and fellows working in various hospitals of the United States of America, on genetic testing for disease specific biomarkers and knowledge of precision medicine. S. Ghavimi, H. Azimi, P. Sealy.

126/3:15 Evolution from expository to open inquiry learning to improve genetic literacy. T. C. Tatum Parker, D. Karge-Galik.

127/3:30 Evaluation of a web-based decision aid for people considering the APOE genetic test for Alzheimer’s risk. D. T. Zallen, M. Ekstract, G. I. Holtzman, K. Y. Kim, S. M. Willis.

128/3:45 Introduction of population based NGS expanded carrier screening in the Netherlands. K. M. Abbott, M. Viel, M. Veldhuis, M. Plantinga, T. Dijkhuizen, J. Schuurmans, I. van Langen, R. Sinke.

129/4:00 Preconception genome sequencing and patient choice: The psychosocial impact of adverse results. T. L. Kauffman, M. Gilmore, P. Himes, E. Morris, Y. Akkari, L. Amendola, J. Davis, M. O. Dorschner, G. Jarvik, M. Leo, C. McMullen, D. Nickerson, C. Pak, S. Punj, J. A. Reiss, J. Schneider, C. S. Richards, D. K. Simpson, A. L. Rope, P. Robertson, B. Wilfond, K. A. B. Goddard, CSER consortium and NextGen study team.

130/4:15 Economic impact of genome sequencing for preconception carrier screening: The time costs for genetic counseling. P. Himes, F. L. Lynch, M. J. Gilmore, E. M. Morris, J. A. Reiss, T. L. Kauffman, C. McMullen, J. V. Davis, M. C. Leo, J. L. Schneider, K. A. B. Goddard, B. Wilfond.

Thursday, October 8

5:00 PM–7:00 PM

Concurrent Platform Session C

32. Human-wide Association Studies: More Genotypes, More Phenotypes, More Diverse Populations

Ballroom I, Level 4, Convention Center

Moderators: Ron Do, Icahn Sch of Med, New York
  Mariaelisa Graff, UNC Chapel Hill

131/5:00 Phenome-wide association study provides biologic insights into the etiology of age-related macular degeneration. M. Brilliant, J. Mayer, J. Liu, W. Lee, B. Hoch, S. Schrodi, J. Joyce, A. Ikeda, S. Hebbring.

132/5:15 Complex diseases are associated with variation in Mendelian genes: A phenome-wide study using Human Phenotype Ontology and a population genotyped on the Exome BeadChip. L. A. Bastarache, J. Mosely, T. Edwards, R. Carroll, H. Mo, L. Wiley, W. Wei, J. Denny.

133/5:30 PheWAS study using research participants’ self-reported data provides insight into Th17/IL-17 pathway. M. G. Ehm, J. L. Aponte, S. F. Cook, S. Ghosh, A. Gupta, D. A. Hinds, C. G. Lariminie, L. Li, T. Johnson, C. Tian, S. C. Zelt, D. Rajpal, D. M. Waterworth.

134/5:45 Functional variant PheWAS in 30,000 exomes using EHR-extracted laboratory measures in the Geisinger Health System MyCode - Regeneron Genetics Center Collabrative Project DiscovEHR. A. Verma, J. Leader, S. Dudek, J. R. Wallace, C. Dushlaine, C. Van Hout, L. Haebagger, A. Lopex, F. E. Dewey, O. Gottesman, J. Overton, J. G. Reid, A. Baras, A. R. Shuldiner, D. J. Carey, J. L. Kirchner, D. H. Ledbetter, M. D. Ritchie, S. A. Pendergrass.

135/6:00 Exome-wide study identifies loci displaying pleiotropic associations with multiple cardiometabolic traits in continental Africans. F. Tekola-Ayele, A. Adeyemo, A. R. Bentley, A. P. Doumatey, J. Zhou, G. Chen, D. Shriner, C. Adebamowo, J. Achaempong, J. Oli, O. Fasanmade, T. Johnson, A. Amoah, K. Agyenim-Boateng, B. A. Eghan Jr., D. Ngare, C. N. Rotimi.

136/6:15 Trans-ethnic meta-analysis reveals novel loci and effector genes for kidney function in diverse populations. A. Morris, A. Mahajan, J. Haessler, Y. Okada, A. Stilp, J. Whitfield, C. Laurie, N. Franceschini.

137/6:30 How low can you go: Cohort-wide 1x whole genome sequencing in a Greek isolate reveals multiple quantitative trait signals. A. Gilly, L. Southam, R. Moore, A.-E. Farmaki, J. Schwartzentruber, P. Danecek, E. Tsafantakis, G. Dedoussis, E. Zeggini.

138/6:45 Whole genome sequencing increase the power to detect trait-associated rare variants shifted towards high frequencies in the Sardinian island population. C. Sidore, M. Zoledziewska, F. Danjou, F. Busonero, A. Maschio, E. Porcu, A. Mulas, C. Chiang, G. Pistis, M. Steri, S. Naitza, M. Pitzalis, J. Marcus, R. Nagaraja, A. Angius, J. Novembre, S. Sanna, D. Schlessinger, G. Abecasis, F. Cucca.

Thursday, October 8

5:00 PM–7:00 PM

Concurrent Platform Session C

33. Decoding Variants in Coding Regions

Ballroom III, Level 4, Convention Center

Moderators: Shamil Sunyaev, Brigham & Women's Hosp, Boston
  Kym Boycott, Children's Hospital of Eastern Ontario, Univ Toronto, Ottawa, Canada

139/5:00 Phased annotation of protein-coding variants across 60,706 human exomes. A. J. Hill, B. Cummings, K. J. Karczewski, M. Lek, D. G. MacArthur, Exome Aggregation Consortium (ExAC).

140/5:15 Meta-analysis of more than 2,100 trios reveals novel genes for intellectual disability. C. Gilissen, S. H. Lelieveld, M. R. F. Reijnders, R. Pfiundt, H. Yntema, P. de Vries, B. A. de Vries, T. Kleefstra, M. Nelen, J. A. Veltman, H. G. Brunner, C. Vissers.

141/5:30 Assessing the pathogenicity of insertion and deletion variants with the Variant Effect Scoring Tool. C. Douville, D. L. Masica, P. D. Stenson, D. N. Cooper, D. Gygax, R. Kim, M. Ryan, R. Karchin.

142/5:45 Deep genetic connection between cancer and developmental diseases. H. Qi, C. Dong, K. Wang, Y. Shen.

143/6:00 Characterizing ribosome readthrough in humans. J. Moore, Z. Weng.

144/6:15 A comprehensive methodology for assessing variant-specific gene dysfunction in the context of non-disease-associated genomes. L. Silver, J. L. Larson, A. J. Silver, C. Borroto, B. Spurrier, R. M. Lim, N. Delaney, L. M. Silver.

145/6:30 A massively parallel pipeline to clone DNA variants and examine molecular phenotypes of human disease mutations. H. Yu.

146/6:45 Gene discovery in Mendelian diseases. D. Vuzman, N. Y. Frank, N. Stitziel, S. Chopra, S. R. Sunyaev, R. L. Maas, Brigham Genomic Medicine Program (BGMP).

Thursday, October 8

5:00 PM–7:00 PM

Concurrent Platform Session C

34. The Real Next Gen: Reproductive Genetics

Room 307, Level 3, Convention Center

Moderators: Urvashi Surti, Univ Pittsburgh
  Brynn Levy, Columbia Univ Med Ctr, New York

147/5:00 An important role for rare loss-of-function variants in spermatogenic failure. R. George, J. Hughes, L. Brown, L. Lin, D. Koboldt, R. Fulton, R. Oates, S. Silber, R. Wilson, D. Page.

148/5:15 Complex mitotic-origin aneuploidy in human embryos: Genetic risk factors and fertility consequences. R. C. McCoy, Z. Demko, A. Ryan, M. Banjevic, M. Hill, S. Sigurjonsson, M. Rabinowitz, H. B. Fraser, D. A. Petrov.

149/5:30 Expanding non-invasive prenatal testing to include microdeletions and segmental aneuploidy: Cause for concern? T. Sahoo, M. N. Strecker, N. Dzidic, S. Commander, M. K. Travis, C. Doherty, K. Hovanes.

150/5:45 NLRP2: A paternally-imprinted gene implicated in innate immunity and blastocyst development has a major gene effect on endometriosis. K. Ward, R. Chettier, P. Farrington, H. Albertsen.

151/6:00 Investigation of DNA variants responsible for pre-eclampsia. R. McGinnis, F. Dudbridge, D. Lawlor, J. Kemp, C. Franklin, N. Williams, On behalf of the InterPregGen Consortium.

152/6:15 Ancestry matched genome-wide association study identifies variants associated with spontaneous preterm birth. M. Sirota, J. Toung, W. Sikora-Wohfeld, C. R. Gignoux, C. D. Bustamante, G. Shaw, H. O'Brodovich, D. Stevenson, A. J. Butte.

153/6:30 Large scale genome-wide association study for birth weight identifies 13 novel loci and reveals genetic links with a variety of adult metabolic and anthropometric traits. M. Horikoshi, F. R. Day, J. R. B. Perry, J.-J. Hottenga, R. Li-Gao, M. N. Kooijman, R. Beaumont, N. M. Warrington, N. J. Timpson, Early Growth Genetics (EGG) Consortium.

154/6:45 Assessing genetic counsellors’ use of shared decision-making. P. H. Birch, A. V. Port-Thompson, S. Adam, F. Legaré, J. M. Friedman.

Thursday, October 8

5:00 PM–7:00 PM

Concurrent Platform Session C

35. Genetic Problems of the Heart, Aorta, and Valves

Room 309, Level 3, Convention Center

Moderators: Elizabeth K. Speliotes, Univ Michigan, Ann Arbor
  Tim Assimes, Stanford Univ Sch Med

155/5:00 Mutations in DCHS1 cause mitral valve prolapse. D. Milan, R. Durst, K. Sauls, M. Talkowski, J. J. Schott, x. Jeunemaitre, A. Hagege, R. A. Levine, R. A. Norris, S. Slaugenhaupt.

156/5:15 ROBO-SLIT mutations predispose individuals to bicuspid aortic valve with ascending aortic aneurysm. R. A. Gould, H. Aziz, A. Kumar, C. Preuss, C. Woods, N. Sobreira, H. Ling, S. A. Mohamed, A. Franco-Cereceda, G. Andelfinger, A. S. McCallion, P. Eriksson, L. V. Laer, B. L. Loeys, H. C. Dietz, MIBAVA Foundation Leducq.

157/5:30 Genetic, developmental, and paracrine interactions in the complex pathogenesis of heritable aneurysm conditions. E. Gallo MacFarlane, J. P. Habashi, Y. Chen, D. Bedja, H. C. Dietz.

158/5:45 Discovery of novel genes underlying congenital heart defects driven by analysis of 4,593 exomes from affected families. A. Sifrim, M.-P. Hitz, S. Al Turki, A. Wilsdon, J. McRae, T. Singh, B. Thienpont, J. Breckpot, K. Setchfield, F. Bu'Lock, A. K. Manickaraj, A. V. Postma, S. Omer, J. Bentham, S. Bhattacharya, C. Cosgrove, H. Watkins, H. Abdul-Khaliq, H.-H. Kramer, O. Tokan, U. Bauer, P. Daubeney, R. Abu-Sulaiman, K. Devriendt, S. Mital, B. Keavney, J. Goodship, S. Klaassen, D. Brook, M. E. Hurles, UK10K Consortium, Deciphering Developmental Disorders Study.

159/6:00 A rare missense variant in the B-type natriuretic peptide gene NPPB is associated with increased risk for incident heart failure. P. Salo, A. Havulinna, P. Jousilahti, V. Salomaa, M. Perola.

160/6:15 Meta-analysis of exome chip variants identifies rare and common variants associated with electrocardiographic left ventricular mass. G. Kosova, N. Verweij, P. van der Harst, C. Newton-Cheh, on behalf of the CHARGE Consortium EX-EKG working group.

161/6:30 Investigating the effects of coding variants on QT and JT intervals utilizing data from 95,626 individuals. N. A. Bihlmeyer, J. A. Brody, D. E. Arking, N. Sotoodehnia, CHARGE Consortium EX EKG Working Group.

162/6:45 HUNTing for susceptibility genes for myocardial infarction with whole genome sequencing. C. Willer, O. Holmen, H. Zhang, E. Schmidt, W. Zhou, J. Chen, G. Abecasis, M. Boehnke, R. Mills, H. M. Kang, K. Hveem.

Thursday, October 8

5:00 PM–7:00 PM

Concurrent Platform Session C

36. Methods Matter: Approaches for Genomic Analysis

Room 316, Level 3, Convention Center

Moderators: Kees Albers, Radboud UMC, Nijmegen, Netherlands
  Melissa Gymrek, MIT, Cambridge

163/5:00 In silico predictive modelling of CRISPR/Cas9 guide efficiency. J. Listgarten, I. Smith, M. Hegde, J. Doench, N. Fusi.

164/5:15 A novel algorithm for estimating shared haplotype segments using rare genetic variants. P. Albers, M. McCarthy, G. McVean.

165/5:30 PADRE: Pedigree Aware Distant Relationship Estimation. J. E. Below, J. Staples, D. J. Whitherspoon, L. B. Jorde, U. W. C.M.G., D. A. Nickerson, C. D. Huff.

166/5:45 Haplotype phasing using cluster graphs. D. C. Aguiar, L. T. Elliott, Y. W. Teh, B. E. Engelhardt.

167/6:00 Fine-mapping cellular trait QTLs with RASQUAL and ATAC-seq. N. Kumasaka, A. Knights, D. Gaffney.

168/6:15 A phenotype-aware approach to the prioritization of coding and non-coding rare disease variants. D. Smedley, J. Jacobsen, C. Mungall, N. Washington, S. Kohler, S. E. Lewis, M. Haendel, P. N. Robinson.

169/6:30 Subclonal hierarchy inference from somatic mutations: Automatic reconstruction of cancer evolutionary trees from multi-region next generation sequencing. N. Niknafs, V. Beleva-Guthrie, DQ. Naiman, R. Karchin.

170/6:45 A powerful new method based on mutual information to simultaneously test for additive, dominance, and interaction effects. A. I. Young, F. Wauthier, P. Donnelly.

Thursday, October 8

5:00 PM–7:00 PM

Concurrent Platform Session C

37. Clinical Genetics: From Sequence to Mechanism

Room 318/321, Level 3, Convention Center

Moderators: Katrina Dipple, UCLA
  Helga Toriello, Spectrum Hlth, Grand Rapids

171/5:00 A new ciliopathy protein complex directing assembly of the IFT machinery is implicated in OFD syndrome and other ciliopathies. C. Thauvin-Robinet, AL. Bruel, M. Toriyama, C. Lee, S. P. Taylor, I. Duran, D. H. Cohn, J. M. Tabler, K. Drew, M. R. Kelley, S. Kim, T. J. Park, D. Braun, G. Pierquin, A. Biver, K. Wagner, A. Malfroot, I. Panigrahi, H. A. Al-Lami, Y. Yeung, Y. J. Choi, L. Faivre, JB. Rivière, J. Chen, K. J. Liu, E. M. Marcotte, F. Hildebrandt, D. Krakow, P. K. Jackson, J. B. Wallingford.

172/5:15 Differential regulation of glucose homeostasis and β-cell mass in Bardet-Biedl Syndrome and Alstrom Syndrome. S. Lodh, T. L. Hostelley, C. C. Leitch, E. A. O'Hare, N. A. Zaghloul.

173/5:30 Loss-of-function mutations in IFIH1 predispose to severe viral respiratory infections in children. S. Asgari, LJ. Schlapbach, S. Anchisi, C. Hammer, I. Bartha, PJ. McLaren, T. Junier, D. Garcin, J. Fellay.

174/5:45 A novel (epi)genotype-specific and histotype-targeted tumor surveillance protocol in Beckwith-Wiedemann Syndrome based on cancer data meta-analysis. G. Ferrero, M. Gregnanin, C. Molinatto, G. Baldassarre, S. Russo, A. Riccio, G. B. Ferrero.

175/6:00 A recurrent mosaic mutation of SMO (Smoothened) causes Curry-Jones syndrome. S. R. F. Twigg, Y. Zhou, K. A. Miller, S. J. McGowan, J. Taylor, J. Craft, J. C. Taylor, A. F. Brady, J. Clayton-Smith, C. L. Clericuzio, C. J. Curry, W. B. Dobyns, D. K. Grange, D. Horn, R. B. Hufnagel, M. C. Jones, I. K. Temple, A. O. M. Wilkie.

176/6:15 The genetics of emphysema: Mutations in telomere genes uncover a distinct genetic etiology and common mechanism for pathogenesis. S. E. Stanley, C. D. Applegate, M. Armanios.

177/6:30 High frequency of VACTERL association in Fanconi Anemia. B. P. Alter, S. A. Savage, N. Giri.

178/6:45 De novo deletions and truncating mutations in USP9X cause a recognizable ID syndrome with multiple congenital abnormalities in females. M. R. F. Reijnders, V. Zachariadis, B. Latour, G. M. Mancini, C. M. A. van Ravenswaaij-Arts, H. E. Veenstra, B. M. Anderlid, S. Wood, A. S. Brooks, H. Malmgren, M. Vreeburg, V. R. Sutton, Z. Stark, J. Gecz, L. Jolly, C. Gilissen, R. Pfundt, T. Kleefstra, R. Roepman, A. Nordgren, H. G. Brunner.

Thursday, October 8

5:00 PM–7:00 PM

Concurrent Platform Session C

38. Clinical Impact of Genetic Variation

Holiday Ballroom 1, 2nd Floor, Hilton Baltimore Hotel

Moderators: Marshall Summar, Children's Natl Med Ctr, Washington, DC
  Howard McLeod, Moffitt Cancer Center, Tampa

179/5:00 Genome-wide association study of olanzapine pharmacokinetics. K. L. Bigos, R. M. Haynes, D. Chen, D. R. Weinberger.

180/5:15 Concurrent direct human leukocyte antigen (HLA) genotyping and genome-wide association study (GWAS) reveal major genetic determinants of anti-thyroid drug-induced agranulocytosis. P. Chen, S. Shih, P. Wang, C. Fann, W. Yang, T. Chang.

181/5:30 EuDAC: Genome-wide association study of drug-induced agranulocytosis in Europe. M. Wadelius, N. Eriksson, L. Ibañez, E. Bondon-Guitton, R. Kreutz, A. Carvajal, M. Lucena, E. Sancho Ponce, J. Martin, T. Axelsson, Q.-Y. Yue, P. K. Magnusson, P. Hallberg, on the behalf of EuDAC.

182/5:45 The impact of genetics on drug efficacy and implications for future research. M. R. Nelson, T. Johnson, L. Warren, A. R. Hughes, S. L. Chissoe, C.-F. Xu, D. M. Waterworth.

183/6:00 Regulatory variants other than VKORC1 -1639 G>A may explain the effect on warfarin dose. M. Cavalli, N. Eriksson, G. Pan, H. Nord, S. J. Connolly, M. D. Ezekowitz, S. Yusuf, L. Wallentin, M. Wadelius, C. Wadelius.

184/6:15 Assessing the clinical impact of ethnicity-specific pharmacogenetic allele variation in over 100,000 patients with biobank-linked electronic medical records. N. Gonzaludo, T. J. Hoffmann, D. K. Ranatunga, C. Schaefer, N. Risch, P. Y. Kwok.

185/6:30 Efficacy of whole genome sequencing over a lifetime: Medically actionable genomic mutations in 300 patients. M. He, M. Brilliant.

186/6:45 Genetic variation in STAT4 predicts response to interferon-α therapy for HBeAg-positive chronic hepatitis B. D. Jiang, X. Wu, J. Qian, X. P. Ma, J. Yang, Z. Li, R. Wang, L. Sun, F. Liu, P. Zhang, X. Zhu, J. Wu, K. Chen, L. Zheng, D. Lu, L. Yu, Y. Liu, J. Xu.

Thursday, October 8

5:00 PM–7:00 PM

Concurrent Platform Session C

39. Mendel and Beyond: Looking through Genome Sequences

Holiday Ballroom 4, 2nd Floor, Hilton Baltimore Hotel

Moderators: Suleyman Gulsuner, Univ Washington, Seattle
  Ashleigh Schaffer, UC San Diego

187/5:00 The search for Mendelian genes (MG) using whole exome sequencing (WES): Lessons learned from analysis of >5,000 cases. N. Sobreira, S. Jhangiani, F. Schiettecatte, C. Boehm, K. Doheny, T. Gambin, Z. Akdemir, D. Muzny, R. Gibbs, E. Boerwinkle, W. Wiszniewski, J. Lupski, A. Hamosh, D. Valle.

188/5:15 Discovery of novel dominant and recessive causes of severe developmental disorders, in coding and non-coding sequences. M. Hurles, The Deciphering Developmental Disorders (DDD) Study.

189/5:30 Defining variation sensitive regions in genes associated with disease. A. N. Abou Tayoun, S. H. Al Turki, M. S. Lebo, H. L. Rehm, S. S. Amr.

190/5:45 Individual clinical variation, beyond monogenic disease: The aggregation of pathogenic variant alleles in a personal genome. J. E. Posey, T. Harel, J. A. Rosenfeld, P. Liu, Z. Niu, F. Xia, R. E. Person, M. Walkiewicz, D. M. Muzny, C. M. Eng, E. Boerwinkle, A. L. Beaudet, S. E. Plon, R. A. Gibbs, Y. Yang, J. R. Lupski.

191/6:00 99 Lives Cat Genome Sequencing Initiative: Discovery of feline models for human diseases - every life counts. L. A. Lyons, E. K. Creighton, H. C. Beale, M.-C. W. Lee, B. Gandolfi, 99 Lives Cat Consortium.

192/6:15 Post-zygotic point mutations are an underrecognized source of novel genomic variation. R. Acuna-Hidalgo, M. P. Kwint, T. Bo, M. van de Vorst, M. Pinelli, J. A. Veltman, A. Hoischen, L. E. L. M. Vissers, C. Gilissen.

193/6:30 The hunt for rare disease diagnosis: Utilization of social media, model organisms, and pathway analysis in pediatric exome sequencing. A. I. Nesbitt, E. Denenberg, Z. Yu, S. W. Baker, K. B. Pechter, E. Dechene, H. Dubbs, E. Bedoukian, A. Wilkens, L. Medne, X. Ortiz-Gonzale, E. Zackai, I. Krantz, M. Deardorff, A. Santani.

194/6:45 Improving diagnosis and furthering gene discovery through recruitment of clinical whole exome sequencing cases into research. Z. H. Coban Akdemir, M. K. Eldomery, T. Gambin, T. Harel, A. Stray-Pedersen, S. Penney, J. A. Rosenfeld, S. N. Jhangiani, D. M. Muzny, F. Xia, Y. Yang, C. M. Eng, S. E. Plon, V. R. Sutton, A. L. Beaudet, E. Boerwinkle, R. A. Gibbs, J. R. Lupski.

Friday, October 9

8:45 AM–9:00 AM

40. Gruber Genetics Prize Award Presentation and Rosalind Franklin Award Announcement

Hall F, Level 1, Convention Center

The Gruber Genetics Prize is awarded annually by The Gruber Foundation to a leading scientist, or up to three, in recognition of groundbreaking contributions to any realm of genetics research. The recipients will be presented with a gold laureate pin and will share the $500,000 unrestricted cash award. The Gruber lecture, “CRISPR-Cas9 Genome Editing: Origins and Development of a Revolutionary Technology,” will be given on Friday, October 9 from 1:00-1:45 pm in Ballroom I/II, Level 4 of the Baltimore Convention Center.


Emmanuelle Charpentier, PhD, Helmholtz Centre for Infection Research in Braunschweig, Germany

Jennifer Doudna, PhD, of the University of California, Berkeley, CA

The official citation to the Prize states: The Gruber Foundation proudly presents the 2015 Genetics Prize to Charpentier and Doudna for establishing a framework for universal genome editing. They discovered that the bacterial enzyme Cas9 is an endonuclease that cuts DNA at sites specified by a guide RNA, and defined biochemically the components required for this reaction. They showed that the sequence of the guide RNA could be modified to target the endonuclease to virtually any site. This provided the mechanism by which bacteria acquire immunity to specific viral infections, allowed introduction of specific mutations at desired sites, and provided the means to transfer efficient Cas9-directed break, repair, and editing to any cell type. This method has broadly enabled genome editing for uses in basic biology, medicine, biotechnology, and agriculture.

Rosalind Franklin Young Investigator Award: Every three years, the Rosalind Franklin Young Investigator Award is presented to two young women geneticists. One award is for research in genetics of humans and other mammals, and one award is for research in genetics of other model organisms. Funded by The Gruber Foundation, the award is administered by the American Society of Human Genetics and the Genetics Society of America. The awards are for career development and are $75,000 over three years. Winners of the Rosalind Franklin Award are in their first three years in an independent faculty level position in any area of genetics. The recipients of the 2016-2018 Rosalind Franklin Young Investigator Awards are listed below and will also be recognized.


Carolyn McBride, Princeton University

Maria Barna, PhD, Stanford University

Dr. McBride, the 2016 recipient in genetics of non-mammalian organisms, combines neurocience, evolutionary biology, genomics, and field work to understand the genetic bases of mosquito behavior. Dr. Barns, the 2016 recipient in human and mammalian genetics, uses mouse genetics to understand how ribosomes process information to create proteins for different types of cells and tissues. The Rosalind Franklin Award committee also gives honorable mention to Rachel Dutton, PhD, of the University of California, San Diego, for her work on the genetic mechanisms of formation of microbial communities in cheese; and Elizabeth Murchison, PhD, of Cambridge University for her work on transmissible cancers in dogs and Tasmanian devils.


Friday, October 9

9:00 AM–9:30 AM

41. ASHG William Allan Award Presentation

Hall F, Level 1, Convention Center

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

Introduction: Gene S. Fisch, CUNY/Baruch College


Kay E. Davies, DPhil
Dr. Lee’s Professor of Anatomy, Department of Physiology, Anatomy and Genetics, and Associate Head of the Medical Sciences Division
Director of the Medical Research Council Functional Genomics Unit, University of Oxford, UK

Dr. Davies led early research into Duchenne Muscular Dystrophy (DMD). In the 1980s, her research group identified genetic markers that allow prenatal diagnosis and carrier status determination of DMD, and mapped the gene coding for DMD to a specific location on the X chromosome. They also described the gene’s size and genetic deletions associated with disease, including a very large deletion of the gene coding for dystrophin found in a patient with mild disease. Follow-up research showed that in mice, introducing the dystrophin gene could prevent disease progression, which pioneered the development of dystrophin “minigenes” to treat DMD in people.

Dr. Davies’ work also led to the characterization of the protein utrophin, a relative of dystrophin. Working in mice, her group showed that increasing utrophin levels could prevent disease, developed drugs that do so, and began pursuing these as an approach to treat DMD in humans. Unlike some existing therapeutics, this strategy would be applicable to all patients. Her laboratory also uses mouse models to study other neurogenetic diseases, such as schizophrenia and ALS, with a focus on genes that affect the course of disease and clinical outcomes.

A longtime member of ASHG, Dr. Davies served on the Society’s Board of Directors from 2011-2013 and currently chairs its Nominating Committee. She has published 384 peer-reviewed papers, won numerous awards, and delivered several special lectures at various institutions.

Recent Recipients: Stuart H. Orkin (2014); Aravinda Chakravarti (2013); Uta Francke (2012); John M. Opitz (2011); Jurg Ott (2010)


Friday, October 9

9:30 AM–9:45 AM

42. The ASHG Arno Motulsky-Barton Childs Award for Excellence in Human Genetics Education

Hall F, Level 1, Convention Center

The ASHG Award for Excellence in Human Genetics Education was established to recognize those who have made significant contributions of exceptional quality and great importance to human genetics education. Individually and together, each of this year’s three recipients is an accomplished geneticist and educator. Over the years, they have taught regularly as well as run their own laboratories, and have been involved in program development and/or mentoring at various levels.

Introduction: Peter Byers, University of Washington


Robert L. Nussbaum, MD
Chief Medical Officer, Invitae
Clinical Professor of Medicine (Volunteer), University of California, San Francisco

Roderick R. McInnes, CM, MD, PhD
Director of the Lady Davis Institute at the Jewish General Hospital and Alva Chair in Human Genetics, Canada
Research Chair in Neurogenetics, and Professor of Human Genetics and Biochemistry
McGill University, Montreal, Canada

Huntington F. Willard, PhD
President and Director, Marine Biological Laboratory, Woods Hole
Professor of Human Genetics, University of Chicago

Dr. Nussbaum has worked on elucidating the genetic basis of disease, including the heritable forms of Parkinson disease, Lowe syndrome, and choroideremia. He has taught medicine and human genetics in various capacities over the years, from genetic counseling programs to medical school curricula to a publicly available online course for medical professionals. He served on the AJHG Editorial Board from 1987-1989; was a member of multiple ASHG committees since 1990, including a year as Chair of the Program Committee in 1992; belonged to the Society’s Board of Directors from 1992-1996; and was its President in 2004.

Dr. McInnes has contributed to scientific understanding of retina and eye development, as well as retinal degeneration, and currently, his laboratory focuses on neuronal processes. He has served on numerous educational committees since the 1970s, launched a training program for clinician-scientists, and taught genetics and provided guidance at the medical and graduate levels. Dr. McInnes has served on several ASHG committees since 1989, including a year as Chair of the Nominating Committee in 2000, and was an AJHG Associate Editor from 1994-1996. He was also a member of the ASHG Board of Directors from 2004-2007 and again from 2009-2012, and was the Society’s president in 2010.

Dr. Willard’s research has focused on the structure and function of chromosomes and genomes. Since the early 1980s, he has developed and directed educational programs at the medical, graduate, and undergraduate levels in human genetics, genomics, and computational biology. He has also co-edited several editions of the reference textbook Genomic and Personalized Medicine. Since 1986, Dr. Willard has served on various ASHG committees, including chairing the Nominating Committee in 1987 and 2006 and chairing the Program Committee in 1994, and was an AJHG Associate Editor from 1989-1991. He was a member of the ASHG Board of Directors from 1994-1996 and again from 2000-2003, and was the Society’s president in 2001. In addition, he received the ASHG William Allan Award in 2009.

Since 2001, Drs. Nussbaum, McInnes, and Willard have collaboratively authored the sixth, seventh, and eighth editions of the human genetics textbook Genetics in Medicine. Nearly 60 genetics education programs worldwide currently use the textbook, in levels ranging from undergraduate to graduate and professional study, and in diverse contexts including medical, nursing, public health, speech and language, and dental programs.

Recent Recipients: Suzanne B. Cassidy (2014); Jessica G. Davis (2013); Alan Emery (2012); Giovanni Romeo (2011); Thomas D. Gelehrter (2010)


Friday, October 9

9:45 AM–10:00 AM

43. ASHG Victor A. McKusick Leadership Award Presentation

Hall F, 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: David Valle, Johns Hopkins University


Charles Scriver, MD
Alva Professor Emeritus of Human Genetics, and Professor of Pediatrics, Biochemistry (Associate), Biology (Honorary), and Human Genetics at McGill University, Montreal, Canada

Dr. Scriver, a clinician-scientist who has dedicated his career to discovering, training, treating, and educating the public about inherited metabolic and other genetic diseases, has worked at McGill University for more than 50 years, having founded the deBelle Laboratory for Biochemical Genetics in 1961.

Early in his career, Dr. Scriver encountered a recurrent seasonal epidemic in Quebec that affected infants and children with Vitamin D deficiency. Along with colleagues, he instituted a combination of epidemiological, regulatory, economic, political, demographic, and cultural approaches to address the problem. Over the following years, he studied inborn errors of metabolism in the newly created deBelle Laboratory, where he identified a variety of inborn errors affecting enzymes, metabolic pathways, and membrane transport systems. He also helped develop pediatric genetic screening programs for high school students, which were shown to have lasting effects on personal and public health in Quebec. In addition, he helped implement a province-wide newborn screening program for phenylketonuria and hypothyroidism.

In addition to promoting public health, Dr. Scriver has been a leader in human genetics education and research. He served as lead editor of the 6th, 7th, and 8th editions of The Metabolic and Molecular Bases of Inherited Disease and is currently an emeritus editor of its online edition. He developed a Quebec-wide database tracking the incidence of genes that cause metabolic disorders, and since the 1980s, has advocated for the sharing of information to move genetics research forward.

A member of ASHG since the 1960s, he was part of its Committee on Genetic Services from 1975-1979, chaired its Awards Committee from 1979-1980, and chaired its Editorial Committee from 1985-1987. He also belonged to the Society’s Board of Directors from 1971-1974 and from 1985-1988, including a year as President in 1986. In addition, he has served as president of the Canadian Society for Clinical Investigation (1975), the Society for Pediatric Research (1976), the Society for the Study of Inherited Metabolic Diseases (UK) (1988), and the American Pediatric Society (1995).

Recent Recipients: David Valle (2014); Kurt Hirschhorn and Rochelle Hirschhorn (2013); Francis Collins (2012); Leon E. Rosenberg (2011); Charles J. Epstein (2010)


Friday, October 9

10:00 AM–10:15 AM

44. ASHG Curt Stern Award Presentation

Hall F, 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: Elaine Ostrander, NHGRI


Leonid Kruglyak, PhD
Professor of Human Genetics and Professor of Biological Chemistry, University of California, Los Angeles
Investigator, Howard Hughes Medical Institute

Dr. Kruglyak’s research has focused on understanding how genes interact with each other and the environment to influence traits. As a postdoc in the mid-1990s, he developed algorithms for the computer program GENEHUNTER, which allowed complex calculations of genetic linkage to be carried out on personal computers and quickly became a standard tool for mapping complex disease genes. Over the next decade, he authored key papers predicting the number of genetic markers required for GWAS in humans, and pioneered the field of genetics of global gene expression (eQTL analysis). In recent years, his laboratory has focused on using genomic technology to establish S. cerevisiae and C. elegans as model organisms to study complex genetic variation.

A member of ASHG since 1999 and AAAS Fellow since 2007, Dr. Kruglyak has received many awards, including a James S. McDonnell Centennial Fellowship in Human Genetics and a Burroughs Wellcome Fund Innovation Award in Functional Genomics. In 2007, ISI Thomson Scientific named Dr. Kruglyak a Highly Cited Researcher in Molecular Biology and Genetics, and as of 2015, his work has been cited over 40,000 times.

Recent Recipients: Goncalo R. Abecasis and Mark J. Daly (2014); John V. Moran (2013); Jay Shendure (2012); David Altshuler (2011); Vivian G. Cheung (2010)


Friday, October 9

10:15 AM–10:30 AM

45. ASHG Advocacy Award Presentation

Hall F, Level 1, Convention Center

The ASHG Advocacy Award, new in 2015, honors individuals or groups who have exhibited excellence and achievement in applications of human genetics for the common good, in areas such as facilitating public awareness of genetics issues, promoting funding for biomedical research, and integrating genetics into health systems.

Introduction: Michael Watson, Executive Director, American College of Medical Genetics and Genomics


R. Rodney Howell, MD
Professor in the Department of Pediatrics, Chairman Emeritus of Pediatrics, and Member of the Hussman Institute for Human Genomics
University of Miami Leonard M. Miller School of Medicine

Dr. Howell has led varied efforts to leverage biomedical and genetic advances to improve public health. He has held leadership positions with the Muscular Dystrophy Association since the 1980s, in which roles he advocated for research and improved care of people with muscular dystrophy and other neuromuscular diseases. He has also been heavily involved in implementing newborn genetic screening in the United States, leading a 2003 federal expert panel through standardizing screening protocols across the country, which led to the expansion of screening programs the following year. From 2003 to 2011, he led the congressionally mandated Advisory Committee on Heritable Disorders of Newborns and Children. In this role, he advised policymakers on pediatric genetic testing, including newborn screening, and established evidence-based processes that the Committee continues to use.

In addition, Dr. Howell has shown leadership in his own scientific and medical communities. From 1984-1986, he chaired the ASHG Genetics Services Committee. He was elected an AAAS Fellow in 1996 and has served on the Board of Directors for the American College of Medical Genetics and Genomics (ACMG) Foundation since 1992, including ten years as its president from 2003-2012. He was also a member of the ACMG Board of Directors from 1991-2012, serving as its President from 1999-2000.

For these achievements and others, Dr. Howell has received numerous awards, including Lifetime Achievement Awards from the Duke University Medical Alumni Association (2007) and from ACMG (2012), as well as the March of Dimes Colonel Harland D. Sanders Lifetime Achievement Award in Genetics (2013). In 1989, the University of Texas Medical School launched the R. Rodney Howell MD Lectureship in Medical Genetics in his honor, and in 2012, the Newborn Foundation/Newborn Coalition established the R. Rodney Howell Award in Newborn Health, naming Dr. Howell as its first recipient. In 2013, to commemorate the 30th anniversary of the Federal Rare Disease Act, he was named one of 30 Rare Disease Heroes by the U.S. FDA.


Friday, October 9

2:15 PM–4:15 PM

Concurrent Platform Session D

46. Hen's Teeth? Rare Variants and Common Disease

Ballroom I, Level 4, Convention Center

Moderators: Mingyao Li, Univ Penn, Philadelphia
  Jason Flannick, Broad Inst, Boston

195/2:15 Rare variants are a large source of heritability for gene expression patterns. R. Hernandez, D. Vasco, L. Uricchio, C. Ye, N. Zaitlen.

196/2:30 Haplotypes of common SNPs explain a large fraction of the missing heritability of complex traits. G. Bhatia, A. Gusev, P. Loh, BJ Vilhjálmsson, S. Ripke, S. Purcell, E. Stahl, M. Daly, TR de Candia, MC O'Donovan, SH Lee, N. Wray, BM Neale, MC Keller, NA Zaitlen, B. Pasaniuc, J. Yang, AL Price, Schizophrenia Working Group of the Psychiatric Genomics Consortium.

197/2:45 Estimating the respective contributions of human and viral genetic variation to HIV control. I. Bartha, P. McLaren, C. Brumme, R. Harrigan, A. Telenti, J. Fellay.

198/3:00 Rare and low-frequency coding variants contribute independently to human stature variation. M. C. Medina Gomez, E. Marouli, M. Graff, K. S. Lo, K. Lu, C. Schurmann, H. M. Highland, N. Heard-Costa, C. M. Lindgren, D. Liu, I. B. Borecki, J. N. Hirschhorn, R. J. F. Loos, T. M. Frayling, F. Rivadeneira, G. Lettre, P. Deloukas, On behalf of the BBMRI, the GOT2D, the CHARGE, and the GIANT Consortia.

199/3:15 Imputation of rare variants from the new Haplotype Reference Consortium identifies associations missed by 1000 Genomes. A. R. Wood, R. Beaumont, D. Hernandez, M. Nalls, J. R. Gibbs, S. Bandinelli, M. N. Weedon, A. Murray, A. Singleton, D. Melzer, L. Ferrucci, T. M. Frayling, Haplotype Reference Consortium.

200/3:30 Imputing genotypes of the Haplotype Reference Consortium into the haplotypes of a large case control study of age-related macular degeneration. L. G. Fritsche, S. Das, G. R. Abecasis, International AMD Genomics Consortium.

201/3:45 Whole-genome sequencing and genotype imputation across 35,000 individuals further defines the genetic architecture of inflammatory bowel disease. C. A. Anderson, on behalf of the UK IBD Genetics Consortium.

202/4:00 The next wave of autism gene discovery by targeted sequencing of thousands of patients. H. Stessman, B. Xiong, T. Wang, K. Hoekzema, L. Vives, N. Janke, C. Lee, B. Coe, R. Bernier, E. Eichler.

Friday, October 9

2:15 PM–4:15 PM

Concurrent Platform Session D

47. The Zen of Gene and Variant Assessment

Ballroom III, Level 4, Convention Center

Moderators: Shashikant Kulkarni, Washington Univ, St. Louis
  Yaping Yang, Baylor Col of Med, Houston

203/2:15 Allele frequency distribution of pathogenic sequence variants in ExAC and the implications for clinical genetic testing. Y. Kobayashi, S. Yang, A. McMurry, J. Garcia, S. Lincoln, K. Nykamp, S. Topper.

204/2:30 Classifying variants detected by whole genome sequencing of a healthy population: The good, the bad, and the ugly. S. Punj, Y. Akkari, M. O. Dorschner, D. A. Nickerson, G. P. Jarvik, L. M. Amendola, D. K. Simpson, A. Rope, J. Reiss, K. Kennedy, D. I. Quigley, C. Harding, J. Berg, T. Kauffman, M. Gilmore, P. Himes, B. Wilfond, K. A. B. Goddard, C. S. Richards.

205/2:45 Exploring the landscape of pathogenic genetic variation in the ExAC population database: Insights of relevance to variant classification. S. Gardner (Equal Contribution), W. Song (Equal Contribution), H. Hovhannisyan, W. Chen, A. Natalizio, K. Bogdanova, K. Weymouth, I. Thibodeau, S. Letovsky, A. Willis, N. Nagan.

206/3:00 Assessing the clinical validity of genes implicated in hereditary pheochromocytoma/paraganglioma and pancreatic cancer using the ClinGen framework. R. Ghosh, A. Buchanan, N. T. Strande, E. R. Riggs, S. S. Dwight, T. P. Sneddon, C. L. Martin, J. S. Berg, M. J. Ferber, K. Offit, K. L. Nathanson, S. E. Plon.

207/3:15 Assessment of Mendelian disorders among three Bronx, New York populations using ACMG criteria. G. diSibio, K. Upadhyay, P. Meyer, B. Baskovitch, C. Oddoux, H. Ostrer.

208/3:30 Frequency of cardiovascular secondary findings on whole-exome sequencing and utilization in familial testing. R. Tousignant, A. A. Singleton, B. Friedman, K. Retterer, G. Richard, D. Macaya.

209/3:45 Homozygous and compound heterozygous mutations in FBN1, unusual situations in molecular diagnosis of Marfan syndrome. P. Arnaud, N. Hanna, M. Aubart, B. Leheup, S. Dupuis-Girod, M.-A. Delrue, D. Lacombe, O. Milleron, M. Langeois, M. Spentchian, L. Gouya, G. Jondeau, C. Boileau.

210/4:00 Clinician perspectives on inconclusive genetic test results for osteogenesis imperfecta in children with unexplained fractures: Are families at risk if they engage in parental testing for VUS? E. Youngblom, M. L. Murray, P. H. Byers.

Friday, October 9

2:15 PM–4:15 PM

Concurrent Platform Session D

48. New Genes and Mechanisms in Developmental Disorders and Intellectual Disabilities

Room 307, Level 3, Convention Center

Moderators: Donna Martin, Univ Michigan, Ann Arbor
  Heather C. Mefford, Univ Washington, Seattle

211/2:15 Biallelic loss of human CTNNA2, encoding α-N-catenin, links ARP2/3-mediated actin regulation to neuronal migration. A. E. Schaffer, A. O. Caglayan, N. Al-Sanaa, H. Y. Al-Abdulwahed, R. O. Rosti, B. Copeland, S. T. Baek, E. Scott, M. S. Zaki, G. M. H. Abdel-Salam, T. Ben-Omran, A. Karimenejad, H. Kayserili, F. Mojahedi, M. Kara, N. Cai, J. Silhavy, E. Yosunkaya, B. A. Barshop, B. Kara, R. Nachnani, H. Megahed, F. Incecik, S. Danda, I. Miller, W. B. Dobyns, S. Gabriel, K. Bilguvar, M. Gunel, J. G. Gleeson.

212/2:30 Missense mutations in the middle domain of DNM1L cause infantile encephalopathy in humans and peroxisomal and mitochondrial defects in Drosophila and humans. L. Robak, Y. Chao, F. Xia, M. Koenig, C. Bacino, F. Scaglia, M. Wangler.

213/2:45 Mosaic and constitutional mutations of MTOR cause a spectrum of developmental brain disorders from focal cortical dysplasia to diffuse megalencephaly. G. Mirzaa, C. Campbell, N. Solovieff, L. Jansen, A. Timms, V. Conti, C. Adasm, E. Boyle, S. Collins, G. Ishak, S. Poliachik, S. Gunter, R. Leary, S. Mahan, M. Doerschner, S. Jhangiani, D. Muzny, E. Boerwinkle, R. Gibbs, J. Lupski, J. Shendure, R. Saneto, E. Novotny, W. Sellers, L. Murphy, M. Morrissey, J. Ojemann, R. Guerrini, W. Winckler, W. Dobyns.

214/3:00 MTIF2 mutations cause a novel disorder of mitochondrial translation. S. B. Pierce, R. Ganetzky, J. A. Foster, D. Xu, S. Wakefield, N. Sondheimer, S. P. Yang.

215/3:15 Overexpression of the chromosome 21 gene ATP5O results in enteric hypoganglionosis: The missing link between Down Syndrome and Hirschsprung disease? R. K. Chauhan, R. Lasabuda, Z. Azmani, H. C. van der Linde, A. S. Brooks, S. Edie, R. H. Reeves, A. J. Burns, I. T. Shepherd, R. M. W. Hofstra.

216/3:30 Mutations in PPP2R5D are a novel cause of intellectual disability, macrocephaly, hypotonia, and autism. L. B. Henderson, L. Shang, M. T. Cho, C. T. Fong, K. M. Haude, N. Shur, J. Lundburg, N. Hauser, J. Carmichael, J. Innis, J. Schuette, Y. W. Wu, S. Asaikar, M. Pearson, L. Folk, K. Retterer, K. G. Monaghan, W. K. Chung.

217/3:45 To elucidate the genetic of recessive cognitive disorders: 104 novel genes identified using deep sequencing. H. Najmabadi, H. Hu, Z. Fattahi, L. Musante, S. S. Abedini, M. Hosseini, F. Larti, M. Mohseni, P. Jamali, M. Beheshtian, F. Mojahedi, T. F. Wienker, K. Kahrizi, H. H. Ropers.

218/4:00 Variants in TAF1 are associated with a new syndrome with severe intellectual disability and characteristic dysmorphic features. G. J. Lyon, J. A. O'Rawe, Y. Wu, A. Rope, P. Y. Au, K. Kosma, C. Smith, S. Kitsiou-Tzeli, J. Schuette, F. Martinez, C. Orellana, M. Rosello, S. Oltra, A. Caro-Llopis, L. Jimenez Barrón, J. Swensen, H. Fang, D. Mittelman, C. Keegan, R. Robison, E. Yang, J. Parboosingh, K. Wang, J. Parboosingh, V. Kalscheuer, M. Hammer, M. Kousi, E. Davis, N. Katsanis, E. Wang.

Friday, October 9

2:15 PM–4:15 PM

Concurrent Platform Session D

49. Statistical Genetics: Networks, Pathways, and Expression

Room 309, Level 3, Convention Center

Moderators: Dajiang Liu, Penn State Univ, Hershey
  Brooke Fridley, Univ Kansas Med Ctr, Kansas City

219/2:15 A pathway-centric approach to rare variant association analysis. T. G. Richardson, N. J. Timpson, C. Campbell, T. R. Gaunt.

220/2:30 PolyTest: A novel method for joint analysis of genome-wide association studies and functional annotations. D. Golan, A. Raj, K. Gaulton, S. Jain, D. Calderon, Y. Field, T. Raj, J. Pritchard.

221/2:45 Sex-specific gene co-expression networks. B. E. Engelhardt, C. Gao, C. D. Brown.

222/3:00 Detection of master regulatory SNPs in expression and methylation quantitative trait loci studies. J. Shi, W. Wheeler, A. Battle, S. Mostavi, X. Zhu, M. M. Weissman, J. B. Potash, S. B. Montgomery, N. E. Caporaso, M. T. Landi, D. F. Levinson.

223/3:15 Proper use of allele-specific expression improves statistical power for cis-eQTL mapping with RNA-seq data. Y. J. Hu, W. Sun, J. Y. Tzeng, C. M. Perou.

224/3:30 Tensor decomposition uncovers trans eQTL networks in the multi-tissue EuroBATS study. J. Marchini, V. Hore, A. Vinuela, A. Buil, M. McCarthy, K. Small.

225/3:45 Integrative genome-wide gene expression and metabolomics networks in pregnant women identify Vitamin D variants associated with incident preeclampsia cases. J. Lasky-Su, A. Sharma, C. Clish, A. Litonjua, S. Weiss, IMPACT.

226/4:00 Are genetic interactions influencing gene expression in humans evidence for biological epistasis or statistical artifacts? A. Fish, J. A. Capra, W. S. Bush.

Friday, October 9

2:15 PM–4:15 PM

Concurrent Platform Session D

50. Going Platinum: Building a Better Genome

Room 316, Level 3, Convention Center

Moderators: Deanna Church, Personalis, Inc, Menlo Park
  Fiona Cunningham, EMBL-EBI Wellcome Trust

227/2:15 Building a platinum assembly from single haplotype human genomes generated from long molecule sequencing. K. Meltz Steinberg, T. A. Graves-Lindsey, V. A. Schneider, R. S. Fulton, J. Chin, M. Kremitzki, W. C. Warren, D. M. Church, E. E. Eichler, R. K. Wilson.

228/2:30 Building a better human genome reference and targeting structure using single molecule technologies. R. Sebra, M. Pendleton, A. Pang, A. Ummat, O. Franzen, T. Rausch, A. Stütz, W. Stedman, T. Anantharaman, A. Hastie, H. Dai, M. Fritz, H. Cao, A. Cohain, G. Deikus, L. Newman, S. Scott, A. Uzilov, R. Durrett, S. Blanchard, R. Altman, C. Chin, E. Paxinos, J. Korbel, R. Darnell, W. McCombie, P. Kwok, C. Mason, E. Schadt, A. Bashir.

229/2:45 Genome in a bottle: You may have sequenced, but how well did you do? J. M. Zook, H. Parikh, M. Salit, Genome in a Bottle Consortium and Global Alliance for Genomics and Health.

230/3:00 An accurate read mapper for graph genomes. W. Lee, K. Ghose, V. Semenyuk, D. Kural, R. Brown, A. Jain, B. Murray, B. Pollex, J. Browning, A. Stachyra, F. Sung.

231/3:15 Anchored pseudo-de novo assembly of human genomes identifies extensive sequence variation in unmapped sequence reads. K. H. Brown, J. J. Faber-Hammond.

232/3:30 A diploid personal human genome reference from diverse sequence data: A model for better genomes. K. C. Worley, Y. Liu, D. S. T. Hughes, S. C. Murali, R. A. Harris, A. C. English, O. A. Hampton, C. R. Beck, Y. Han, M. Wang, H. Doddapaneni, C. L. Kovar, W. J. Salerno, S. Richards, J. Rogers, J. R. Lupski, D. M. Muzny, R. A. Gibbs.

233/3:45 Genome-wide copy number detection using a hybrid clinical NGS assay. J. Harris, G. Bartha, S. Luo, A. Patwardhan, S. Garcia, S. Chervitz, M. Morra, D. Church, J. West, R. Chen.

234/4:00 A reference panel of common CNVs and SVs identified from high depth sequencing data on over 2000 samples of European ancestry. M. A. Bekritsky, J. O'Connell, S. S. Ajay, M. A. Eberle.

Friday, October 9

2:15 PM–4:15 PM

Concurrent Platform Session D

51. Cancer Genetic Mechanisms

Room 318/321, Level 3, Convention Center

Moderators: Marc Greenblatt, Univ Vermont, Burlington
  Stacey Edwards, QIMR Berghofer Med. Res. Ctr.

235/2:15 Integrative analysis of five cancer GWAS meta-analyses with eQTLs and splice QTLs from relevant normal tissues in GTEx proposes causal regulatory processes and genes for cancer risk. A. V. Segrè, D. S. DeLuca, T. Sullivan, E. Gelfand, S. B. Gruber, G. Casey, D. J. Hunter, B. Henderson, T. Sellers, C. I. Amos, D. G. MacArthur, S. Lindstroem, P. Kraft, A. Kristin, G. Getz, The GTEx Consortium, GAME-ON Network, CORECT, DRIVE, ELLIPSE, FOCI and TRICL Consortia.

236/2:30 Mutations in a promoter of APC cause a syndrome of gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) without colorectal involvement. G. Chenevix-Trench, J. Li, S. Healey, H. Sivakumaran, J. French, S. Edwards, K. Nones, N. Waddell, P. Pichurin, P. Hulick, K. J. Hamman, U. Rudloff, K. Calzone, J. J. Waterfall, D. Huntsman, P. Meltzer, D. Neklason, D. Goldgar, F. Carneiro, C. Kiraly-Borri, L. Schofield, D. Worthley, N. Lindor, G. Suthers, I. Schrader.

237/2:45 TNS1 mutations and gastrointestinal stromal tumors and defective mitochondria in the blistery (Tns1 knockout) D. melanogaster. F. Faucz, T. Silva, S. Reincke, A. Sen, R. Cox, M. Miettienen, S. Lo, J. Carney, C. Stratakis.

238/3:00 Exome sequencing provides evidence of pathogenicity for genes implicated in the development of colorectal cancer. E. A. Rosenthal, B. H. Shirts, L. Amendola, C. Gallego, M. Horike-Pyne, P. D. Robertson, P. H. Byers, C. Nefcy, D. Veenstra, F. Hisama, R. Bennett, M. O. Dorschner, D. Nickerson, D. Crosslin, R. Nassir, N. Zubair, T. Harrison, U. Peters, G. P. Jarvik.

239/3:15 Recurrent acquisition of super enhancer function drives druggable oncogenic expression programs in colorectal cancer. A. J. Cohen, O. Corradin, A. Saiakhova, C. F. Bartels, J. M. Luppino, G. Dhillon, I. M. Bayles, L. Beard, L. Myeroff, S. D. Markowitz, P. C. Scacheri.

240/3:30 Genomic landscape of colorectal tumors shapes the microbiome of the tumor microenvironment. R. Blekhman, M. Burns, E. Montassier, D. Knights.

241/3:45 PRKACA defects and adrenal tumors: Human and animal studies and gene dosage effects. P. Salpea, A. Angelousi, B. Yuan, F. R. Faucz, I. Levy, B. Delemer, S. Hieronimus, B. Feve, F. Kelestimur, G. Raverot, J. Bertherat, J. R. Lupski, M. Serpe, C. A. Stratakis.

242/4:00 CLIC5: A new transcriptional target of ETV6 in childhood acute lymphoblastic leukemia. B. Neveu, C. Richer, K. Lagacé, P. Cassart, M. Lajoie, J. F. Spinella, D. Sinnett.

Friday, October 9

2:15 PM–4:15 PM

Concurrent Platform Session D

52. Target Practice: Therapy for Genetic Diseases

Holiday Ballroom 1, 2nd Floor, Hilton Baltimore Hotel

Moderators: Joseph Shieh, UCSF
  Ken Huttner, Novartis, Cambridge

243/2:15 Towards personalized cellular adoptive immunotherapy targeting tumor specific neo-antigens in microsatellite unstable colorectal cancers. T. Frebourg, M. Hamieh, H. Kora, D. Tougeron, B. Mlecnik, G. Bindea, H. K. Angell, T. Fredriksen, N. Elie, E. Fauquembergue, A. Drouet, J. Leprince, J. Benichou, J. Mauillon, F. Le Pessot, R. Sesboüé, T. Frebourg, J. Galon, J.-B. Latouche.

244/2:30 Functional correction of dwarfism in a mouse model of achondroplasia using the tyrosine kinase inhibitor NVP-BGJ398. D. Komla Ebri, E. Dambroise, I. Kramer, C. Benoist-Lasselin, N. Kaci, P. Busca, G. Prestat, F. Barbault, D. Graus-Porta, A. Munnich, M. Kneissel, F. Di Rocco, M. Biosse-Duplan, L. Legeai-Mallet.

245/2:45 Potential AAV5 gene therapy for MPS IIIB mice brain. S. H. Kan, S. Q. Le, Q. D. Bui, P. I. Dickson.

246/3:00 Quantitative cell image-based high content screening identifies brain permeable small molecules that rescue peroxisome assembly defects in cells from patients with Zellweger spectrum disorder. N. Huang, P. K. Dranchak, A. Flores, C. Argyriou, R. Luo, X. Wang, E. N. Oliphant, A. B. Moser, R. MacAruther, C. Hsu, J. Inglese, N. E. Braverman, J. G. Hacia.

247/3:15 The Fibrodysplasia Ossificans Progressiva mutation ACVR1R206H causes disease by allowing the receptor ACVR1 to respond to Activin A. A. N. Economides, S. J. Hatsell, V. Idone, D. M. Alessi Wolken, L. Huang, H. J. Kim, L. Wang, X. Wen, K. C. Nannuru, J. Jimenez, L. Xie, G. Makhoul, R. Chernomorsky, D. D'Ambrosio, R. A. Corpina, C. Schoenherr, K. Feeley, H. Nistala, P. B. Yu, G. D. Yancopoulos, A. J. Murphy.

248/3:30 Necroptosis in Niemann-Pick Disease, type C1: A potential therapeutic target. A. C. Cougnoux, C. V. Cluzeau, J. M. Picache, C. A. Wassif, S. M. Cologna, F. D. Porter.

249/3:45 Clinical, molecular, and metabolomic studies reveal targets for therapy and new mechanisms of pathology in Barth Syndrome. H. Vernon, R. Thompson, B. DeCroes, R. McClellan, K. Mercier, W. Pathmasiri, S. Dhungana, J. Carlson, S. McRitchie, S. Sumner, Y. Sandlers.

250/4:00 Modulating ryanodine receptors by dantrolene attenuated neuropathic phenotype in Gaucher Disease mice. B. Liou, V. Inskeep, Y. Peng, R. Li, G. A. Grabowski, Y. Sun.

Friday, October 9

2:15 PM–4:15 PM

Concurrent Platform Session D

53. The Real World: Translating Sequencing into the Clinic

Holiday Ballroom 4, 2nd Floor, Hilton Baltimore Hotel

Moderators: Joon-Ho Yu, Univ Washington, Seattle
  Jen McCormick, Mayo Clinic, Rochester

251/2:15 A large-scale survey conducted by the eMERGE Network of patient perspectives on broad consent and data sharing in biospecimen research. M. E. Smith, S. Sanderson, N. Mercaldo, A. Antommaria, S. A. Aufox, M. Brilliant, K. Brothers, M. B. Claar, E. W. Clayton, J. J. Connolly, P. Conway, M. Fullerton, N. A. Garrison, H. Hakonarson, C. R. Horowitz, G. P. Jarvik, D. Kaufman, T. Kitchner, R. Li, E. Ludman, C. McCarty, J. B. McCormick, M. Myers, K. E. Nowakowski, J. Schildcrout, M. J. Shrubsole, S. Stallings, J. L. Williams, S. Ziniel, I. A. Holm.

252/2:30 Adolescents’ opinions on disclosure of non-actionable secondary findings in whole exome sequencing. S. B. Hufnagel, L. J. Martin, A. Cassedy, R. J. Hopkin, A. H. Antommaria.

253/2:45 Responses of primary care physicians to unsolicited secondary findings about Lynch Syndrome. K. D. Christensen, M. T. Scheuner, J. E. Garber, H. L. Rehm, R. C. Green.

254/3:00 The return of whole exome sequencing results in a pediatric cancer setting: What is being said? S. Scollon, L. B. McCullough, K. Bergstrom, R. A. Kerstein, D. W. Parsons, S. E. Plon, R. L. Street Jr.

255/3:15 Communication and management of genomic sequencing results by non-geneticist physicians. J. Krier, C. Blout, D. Lautenbach, J. Vassy, J. Oliver Robinson, M. Helm, K. Lee, M. Murray, R. Green.

256/3:30 Impact of genome sequencing on the medical care of healthy adults. J. L. Vassy, K. D. Christensen, D. Dukhovny, C. L. Blout, J. Oliver Robinson, J. B. Krier, M. F. Murray, A. L. McGuire, R. C. Green, for the MedSeq Project.

257/3:45 Short-term costs of integrating genome sequencing into clinical care: Preliminary results from the MedSeq Project. K. Christensen, K. C. Christensen, J. L. Vassy, D. R. Azzariti, C. Lu, H. L. Rehm, A. L. McGuire, R. C. Green, for the MedSeq Project.

258/4:00 Incorporation of whole genome sequencing results into the electronic medical record: Attitudes of MedSeq Project participants. C. L. Blout, J. O. Robinson, A. L. McGuire, P. M. Diamond, K. D. Christensen, L. Jamal, R. C. Green, for the MedSeq Project.

Friday, October 9

4:30 PM–6:30 PM

Concurrent Platform Session E

54. Changing Landscape of Genomic Testing

Ballroom I, Level 4, Convention Center

Moderators: Lora Bean, Emory Univ, Atlanta
  Belinda Chong, VCGS, MCRI, Parkville, Australia

259/4:30 Contributions of "healthy genomes" to expand our understanding of Mendelian conditions. D. L. Perry, J. Kakishita, A. Khouzam, E. Thorpe, E. Ramos, V. M. Raymond, A. Chawla, A. Livengood, S. Chowdhury, T. M. Hambuch.

260/4:45 Large scale analysis of interracial differences in genetic polymorphisms of CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 in the U.S. population. H. Yao, J. M. Harrington, T. Hsieh, T. Y. Jacobson, M. S. Shumaker, J. A. Byers, M. Nakano, C. J. Sailey, W. Mo.

261/5:00 Protein truncating mutations in the ARID2 gene are associated with a novel neurodevelopmental disorder. B. E. Friedman, L. Shang, M. T. Cho, K. Retterer, L. Folk, J. Humberson, L. Rohena, A. Sidhu, S. Saliganan, A. Iglesias, P. Vitazka, J. Juusola, W. K. Chung.

262/5:15 Molecular diagnoses of acute hepatic porphyrias: Comparisons of mutation positive results for various physician specialties. H. Naik, D. Doheny, J. Overbey, R. Srinivasan, R. J. Desnick, Porphyrias Consortium of the NIH Rare Diseases Clinical Research Network.

263/5:30 Utility of whole genome sequencing for detection of newborn screening disorders in a population cohort of 1696 neonates. D. L. Bodian, E. Klein, R. K. Iyer, W. S. W. Wong, P. Kothiyal, D. Stauffer, K. C. Huddleston, A. D. Gaither, I. Remsburg, A. Khromykh, R. L. Baker, G. L. Maxwell, J. G. Vockley, J. E. Niederhuber, B. D. Solomon.

264/5:45 Diagnostic utility of whole genome sequencing as an alternative to chromosomal microarray analysis in pediatric medicine. D. J. Stavropoulos, R. Jobling, D. Merico, S. Bowdin, N. Monfared, M. S. Meyn, M. Girdea, M. Szego, R. Zlotnik-Shaul, B. Thiruvahindrapuram, G. Pellecchia, T. Nalpathamkalam, M. Brudno, C. Shuman, R. Hayeems, C. Carew, R. Erickson, R. A. Leach, P. N. Ray, R. D. Cohn, S. W. Scherer, C. R. Marshall.

265/6:00 Panel testing for familial breast cancer: Tension at the boundary of research and clinical care. I. Campbell, E. Thompson, S. Rowley, N. Li, S. McInerny, L. Devereux, M. Wong-Brown, A. Trainer, M. Mitchell, R. Scott, P. James, Lifepool.

266/6:15 Yield of pathogenic/likely pathogenic variants in women with breast cancer undergoing hereditary cancer panel testing. L. M. Andolina, R. Nusbaum, L. R. Susswein, S. R. Solomon, K. S. Hruska, R. T. Klein.

Friday, October 9

4:30 PM–6:30 PM

Concurrent Platform Session E

55. Making Connections: From DNA Looping to eQTLs and Tissue-specific Regulation

Ballroom III, Level 4, Convention Center

Moderators: Nadav Ahituv, UCSF
  Tony Capra, Vanderbilt Univ, Nashville

267/4:30 Extremely high resolution 3D maps of human and mouse genomes across lineages and during differentiation reveal principles of chromatin looping. S. Rao, M. Huntley, N. Durand, E. Stamenova, I. Bochkov, J. Robinson, A. Sanborn, I. Machol, A. Omer, E. Lander, E. Lieberman Aiden.

268/4:45 Identifying the transcription factors mediating enhancer–target gene regulation in the human genome. Y.-C. Hwang, P. P. Kuksa, B. D. Gregory, L.-S. Wang.

269/5:00 Cell-free DNA comprises an in vivo nucleosome footprint that informs its tissue(s)-of-origin. M. W. Snyder, M. Kircher, A. J. Hill, J. Shendure.

270/5:15 Discovery of dendritic cell sub-populations in human blood by single cell RNA-sequencing. A. C. Villani, R. Satija, C. Ford, M. Griesbeck, W. Li, P. De Jager, A. Regev, N. Hacohen.

271/5:30 Mapping expression quantitative trait loci to identify insulin resistance, obesity, and Type 2 diabetes genes in African Americans. S. Das, S. Sajuthi, N. Sharma, J. Chou, J. Calles, J. Demons, S. Rogers, L. Ma, N. Palmer, D. McWilliams, J. Beal, M. Comeau, K. Williams, L. Menon, E. Kouba, D. Davis, J. Byers, M. Burris, S. Byerly, L. Easter, D. Bowden, B. Freedman, C. Langefeld.

272/5:45 Inferring causal relationships between gene expression and complex traits using Mendelian randomization (MR). Y. Park, I. McDowell, G. Gliner, B. F. Voight, B. E. Engelhardt, C. D. Brown, Genotype Tissue Expression (GTEx) Project Consortium.

273/6:00 Detection and interpretation of genome structural variation in GTEx samples. C. Chiang, R. M. Layer, R. P. Smith, A. J. Scott, A. B. Wilfert, . The GTEx Project Consortium, D. F. Conrad, I. M. Hall.

274/6:15 Mapping genetic and epigenetic factors influencing human hippocampal gene expression. P. Hoffmann, H. Schulz, A.-K. Ruppert, S. Herms, K. Pernhorst, C. Wolf, N. Karbalai, D. Czamara, A. J. Forstner, A. Woitecki, B. Pütz, A. Hilmer, N. Fricker, H. Vatter, B. Müller-Myhsok, M. M. Nöthen, T. Sander, A. Becker, P. Hoffmann, S. Cichon.

Friday, October 9

4:30 PM–6:30 PM

Concurrent Platform Session E

56. Novel Genes, Novel Regulators, and Monogenic Diseases

Room 307, Level 3, Convention Center

Moderators: Ozge Birsoy, Partners Healthcare, Brigham and Women's Hosp of Mass Gen Hosp, Cambridge
  Ayse Begum Tekinay, Bilkent Univ, Ankare, Turkey

275/4:30 Identification of major genetic modifiers of vascular disease in Marfan Syndrome mice. A. Doyle, J. Doyle, R. Wardlow, N. Wilson, D. Bedja, M. Lindsay, J. Habashi, L. Myers, K. Braunstein, S. Bachir, N. Huso, O. Squires, B. Rusholme, A. George, M. Caulfield, D. Judge, H. Dietz.

276/4:45 Novel genetic modifiers of retinitis pigmentosa identified by exploiting natural variation in Drosophila. C. Y. Chow, M. Wolfner, A. G. Clark.

277/5:00 Identification of a novel mutation for Perrault syndrome in the mitochondrial rRNA chaperone ERAL1. A. S. Plomp, I. A. Chatzispyrou, S. Guerrero, R. Ofman, M. A. M. M. Mannens, R. J. A. Wanders, J. N. Spelbrink, R. H. L. Houtkooper, M. Alders.

278/5:15 The molecular pathology of a large cohort of individuals with inherited retinal disease, determined through whole genome sequencing. K. J. Carss, G. Arno, M. Erwood, E. Dewhurst, J. Stephens, K. Stirrups, S. Ashford, C. Penkett, S. Hull, S. Lawrence, A. T. Moore, M. Michaelides, W. H. Ouwehand, A. R. Webster, F. L. Raymond, NIHR BioResource-Rare Diseases Consortium.

279/5:30 Vibration-induced urticaria due to aberrant mast cell degranulation caused by a mutation in ADGRE2. S. E. Boyden, A. Desai, G. Cruse, M. L. Young, H. C. Bolan, L. M. Scott, A. R. Eisch, R. D. Long, C. R. Lee, C. L. Satorius, A. J. Pakstis, A. Olivera, E. Chouery, A. Mégarbané, M. Medlej-Hashim, K. K. Kidd, D. L. Kastner, D. D. Metcalfe, H. D. Komarow.

280/5:45 Mutations in the unfolded protein response regulator ATF6 cause the cone dysfunction disorder achrom. S. Tsang, D. Zobor, W.-C. Chiang, N. Weisschuh, I. Gonzalez Menendez, S. Chang, S. C. Beck, M. Garcia Garrido, V. Sothilingam, M. W. Seeliger, F. Stanzial, E. Heon, A. Vincent, J. Beis, T. M. Strom, G. Rudolph, S. Roosing, A. I. den Hollander, F. P. M. Cremers, I. Lopez, H. Ren, A. T. Moore, A. R. Webster, M. Michaelides, R. K. Koenekoop, E. Zrenner, R. J. Kaufman, S. H. Tsang, B. Wissinger, J. Lin.

281/6:00 Mutations in the MET proto-oncogene cause osteofibrous dysplasia and alter the regulation of periosteal osteogenesis. C. A. Wise, M. J. Gray, P. Kannu, S. Sharma, S. P. Robertson, The International Genetics of Osteofibrous Dysplasia Research Group.

282/6:15 MIPEP mutations cause autosomal recessive mitochondrial dysfunction with left ventricular non-compaction, hypotonia, and infantile death. M. K. Eldomery, Z. C. Akdemir, J. A. Rosenfeld, R. Medikonda, L. C. Burrage, A. A. Shamsi, S. Penney, T. Gambin, S. N. Jhangiani, H. H. Zimmerman, D. M. Muzny, X. Wang, P. Ramachandran, L. J. Wong, E. Boerwinkle, R. A. Gibbs, S. E. Plon, A. L. Beaudet, C. M. Eng, J. R. Lupski, S. R. Lalani, J. Hertecant, R. J. Rodenburg, O. A. Abdul-Rahman, Y. Yang, F. Xia, M. C. Wang, V. R. Sutton.

Friday, October 9

4:30 PM–6:30 PM

Concurrent Platform Session E

57. New Thoughts about Neurodevelopment and Intellectual Disability

Room 309, Level 3, Convention Center

Moderators: Lauren Weiss, UCSF
  Michael Gambello, Emory Univ, Atlanta

283/4:30 Identification of RCBTB1 as novel disease gene for retinal ciliopathy. F. Coppieters, G. Ascari, M. Karlstetter, M. Bauwens, N. De Rocker, A. Boel, K. Vleminckx, M. Van der Eecken, B. P. Leroy, F. Meire, T. Langmann, E. De Baere.

284/4:45 The INVESTICATE project: Identification of New Variation, Establishment of Stem cells, and Tissue Collection Advancing Treatment Efforts. C. Ernst, W. Al-Hertani, N. Mechawar.

285/5:00 The Koolen-de Vries syndrome: A phenotypic comparison of microdeletion and point mutation patients. D. A. Koolen, R. Pfundt, B. P. Coe, J. Gecz, C. Romano, E. E. Eichler, B. B. A. de Vries, DDD Study, KdVS research group.

286/5:15 Exome sequencing suggests Aicardi Syndrome is genetically heterogeneous and not exclusive to females. I. Schrauwen, S. Szelinger, A. L. Siniard, J. J. Corneveaux, A. M. Claasen, R. F. Richholt, M. De Both, B. Hjelm, S. Rangasamy, N. Kulkarni, S. Bernes, J. Buchhalter, M. Russell, A. L. Courtright, K. Ramsey, D. W. Craig, V. Narayanan, M. Huentelman.

287/5:30 Targeted sequencing of 15 genes in a cohort of 169 patients with unexplained lissencephaly detects mutations in 37% of patients. N. Di Donato, AE. Timms, S. Collins, C. Adams, GM. Mirzaa, WB. Dobyns.

288/5:45 Integration of functional “omics” data uncovers mitochondrial deficiency in Smith-Magenis syndrome. J. T. Alaimo, S. V. Mullegama, L. Chen, R. Masand, T. Donti, A. Besse, P. E. Bonnen, B. H. Graham, S. H. Elsea.

289/6:00 Mutations in DDX3X are a common cause of unexplained intellectual disability with gender-specific effects on Wnt signaling. L. Snijders Blok, E. Madsen, J. Juusola, C. Gilissen, D. Baralle, M. R. F. Reijnders, H. Venselaar, C. Helsmoortel, M. T. Cho, A. Hoischen, L. Vissers, T. S. Koemans, W. Wissink-Lindhout, E. E. Eichler, C. Romano, H. Van Esch, C. Stumpel, M. Vreeburg, E. Smeets, K. Oberndorff, B. W. M. van Bon, M. Shaw, J. Gecz, E. Haan, M. Bienek, C. Jensen, B. L. Loeys, A. Van Dijck, A. M. Innes, H. Racher, S. Vermeer.

290/6:15 Mutations in TKT gene are a novel cause of short stature, developmental delay, and congenital heart defects. A. H. Begtrup, L. Boyle, M. M. C. Wamelink, G. S. Salomons, B. Roos, M. T. Cho, A. Dauber, J. Douglas, M. Feingold, S. Saitta, N. Kramer, J. Wynn, W. K. Chung.

Friday, October 9

4:30 PM–6:30 PM

Concurrent Platform Session E

58. Schizophrenia and Brain Development

Room 316, Level 3, Convention Center

Moderators: Loyal Goff, Johns Hopkins Univ, Baltimore
  Karyn Meltz Steinberg, Washington Univ Genome Ctr, St. Louis

291/4:30 Deciphering phenotypic variability of genomic disorders using the 16p11.2 syndromes as a paradigm. K. Männik, A. M. Maillard, K. Popadin, L. Hippolyte, A. Pain, S. Martin-Brevet, A. Alfaiz, E. Migliavacca, J. Kosmicki, S. Lebon, B. Kolk, M. Noukas, A. Metspalu, M. M. van Haelst, M. J. Daly, N. Katsanis, J. S. Beckmann, S. Jacquemont, A. Reymond, 16p11.2 European Consortium, Simons VIP Consortium.

292/4:45 Modeling microcephaly using DNA repair defective induced pluripotent stem cells and cerebral organoids. F. Pirozzi, K. Plona, B. Ward, J. Ngo, T. H. Kim, E. Gilmore, A. Wynshaw-Boris.

293/5:00 3q29 deletion syndrome is associated with feeding problems, reduced birth weight, and a range of neuropsychiatric phenotypes: Results from the 3q29 registry. J. G. Mulle, M. Glassford, J. A. Rosenfeld, A. Freedman, E. McGarry, M. E. Zwick, Unique Rare Chromosome Disorder Support Group.

294/5:15 Schizophrenia risk gene MIR137 modulates neurodevelopment and behavior. Y. Cheng, W. Tan, Z. Teng, B. Bai, L. Lin, Y. Kang, Y. Li, B. Yao, X. Li, N. Xie, J. Peng, D. Chen, P. Jin.

295/5:30 A meta-analysis of >16,000 exomes reveals a dominant, highly penetrant subtype of schizophrenia comorbid with intellectual disability. T. Singh, J. C. Barrett, The UK10K Consortium, The DDD Study.

296/5:45 Schizophrenia associated variation in DPYSL2 perturbs mTOR signaling and produces cellular phenotypes. X. Pham, L. Liu, S. Guang, R. Wang, H. Zhu, A. Pulver, D. Valle, D. Avramopoulos.

297/6:00 Somatic mutations in the MTOR gene cause focal cortical dysplasia type IIb. M. Nakashima, H. Saitsu, N. Takei, J. Tohyama, M. Kato, H. Kitaura, M. Shiina, H. Sirouzu, H. Masuda, K. Watanabe, C. Ohba, Y. Tsurusaki, N. Miyake, Y. Zheng, T. Sato, H. Takebayashi, K. Ogata, S. Kameyama, A. Kakita, N. Matsumoto.

298/6:15 Interrogating the mechanisms of schizophrenia genetic risk in the fully characterized human brain transcriptome. A. E. Jaffe, J. Shin, R. E. Straub, R. Tao, Y. Gao, Y. Jia, L. Collado-Torres, J. T. Leek, T. M. Hyde, J. E. Kleinman, D. R. Weinberger.

Friday, October 9

4:30 PM–6:30 PM

Concurrent Platform Session E

59. Metabolic Traits and Disease: Discovery and Function

Room 318/321, Level 3, Convention Center

Moderators: Karen Mohlke, UNC Chapel Hill
  Damien Croteau-Chonka, Brigham and Women's Hosp, Boston

299/4:30 Large-scale exome chip association analysis identifies novel type 2 diabetes susceptibility loci and highlights candidate effector genes. A. Mahajan, on behalf of the ExT2D Exome Chip Consortium, for PROMIS, CHARGE and T2D-GENES/GoT2D.

300/4:45 Large scale exome array meta-analyses identify numerous novel common, low-frequency, and rare coding variant associations with glycaemia. S. Willems, on behalf of the Meta-Analyses of Glucose and Insulin-related traits Consortium.

301/5:00 Causal mechanisms and balancing selection inferred from genetic associations with polycystic ovary syndrome. F. Day, D. A. Hinds, J. Y. Tung, L. Stolk, U. Styrkarsdottir, R. Saxena, A. Bjonnes, L. Broer, D. B. Dunger, B. V. Halldorsson, D. A. Lawlor, G. Laval, I. Mathieson, W. L. McCardle, Y. Louwers, C. Meun, S. Ring, R. A. Scott, P. Sulem, A. G. Uitterlinden, N. J. Wareham, U. Thorsteinsdottir, C. Welt, K. Stefansson, J. S. E. Laven, K. K. Ong, J. R. B. Perry.

302/5:15 Genetic contributions to long-term severe obesity and leanness defined by electronic medical record phenotyping: A genome-wide association study. C. Schurmann, N. S. Abul-Husn, E. P. Bottinger, R. J. F. Loos.

303/5:30 Integrative personal' omics profiling during periods of disease, weight gain, and loss. M. Snyder, B. Piening, W. Zhou, K. Contrepois, G. Gu, S. Leopold, K. Kukurba, T. Mishra, C. Craig, D. Perleman, E. Sodergren, B. Leopold, T. McLaughlin, G. Weinstock.

304/5:45 Causal FTO obesity variant represses adipocyte browning in humans. M. Kellis.

305/6:00 ExomeChip meta-analysis of 526,508 individuals from five ancestries identifies novel coding variation associated with body mass index. H. M. Highland, V. Turcot, Y. Lu, C. Schurmann, A. E. Justice, K. L. Young, J. Wang, P. Lenzini, M. Graff, A. L. Cupples, T. M. Frayling, J. N. Hirschhorn, G. Lettre, C. M. Lindgren, K. E. North, I. B. Borecki, R. J. F. Loos, for the BBMRI, GoT2D, CHARGE, and GIANT Consortia.

306/6:15 Clustering of exome variants from 6272 individuals with Type 2 diabetes identifies etiological convergence amongst four distinct populations and with other T2D genetic risk factors. C. Sandor, N. Beer, J. Fernandez, F. Honti, J. Steinberg, M. McCarthy, C. Webber, T2D-GENES Consortium, GoT2D Consortium.

Friday, October 9

4:30 PM–6:30 PM

Concurrent Platform Session E

60. The Ins and Outs of Blood Vessel Diseases

Holiday Ballroom 1, 2nd Floor, Hilton Baltimore Hotel

Moderators: Kiran Musunuru, Harvard Univ, Cambridge
  Patricia B. Munroe, Queen Mary Univ, London, UK

307/4:30 Genetic study identifies common variation in PHACTR1 to associate with fibromuscular dysplasia. N. Bouatia-Naji, SR. Kiando, N. Tucker, A. Katz, C. Treard, V. D'Escamard, LJ. Castro-Vega, C. Ye, E. Smith, C. Austin, C. Barlasina, D. Cusi, P. Galan, JP. Empana, X. Jouven, P. Bruneval, JW. Olin, HL. Gornik, PF. Plouin For ARCADIA, IJ. Kullo, DJ. Milan, SK. Ganesh, P. Boutouyrie, J. Kovacic, X. Jeunemaitre.

308/4:45 A rare synonymous variant in GFI1B associated with lower platelet counts reveals a role for alternative GFI1B splice forms in human hematopoiesis. P. Auer, R. Khajuria, J. Huang, U. Schick, J. Johnsen, N. Soranzo, A. Reiner, V. Sankaran.

309/5:00 Meta-analysis of rare and common exome chip variants identifies and replicates S1PR4 and other novel genes influencing blood cell traits. N. Pankratz, on behalf of the CHARGE Hematology Working Group.

310/5:15 Parent of origin genome-wide association studies (GWAS) of cardiovascular disease (CVD) associated phenotypes in the Hutterites. S. V. Mozaffari, J. DeCara, S. Shah, C. Herman, R. Lang, D. Nicolae, C. Ober.

311/5:30 Rare genetic variants inform blood pressure pathophysiology. P. Surendran, F. Drenos, R. Young, H. Warren, J. P. Cook, A. K. Manning, N. Grarup, X. Sim, D. Saleheen, F. W. Asselbergs, C. M. Lindgren, J. Danesh, L. V. Wain, A. S. Butterworth, J. M. M. Howson, P. B. Munroe, CHARGE+, T2D-GENES, GoT2DGenes, ExomeBP, CHD Exome+ Consortium.

312/5:45 Meta-analysis of gene-smoking interactions in blood pressure using 1000 Genomes imputed data from four ethnic groups. Y. Sung, T. Winkler, A. Bentley, M. Brown, T. Bartz, D. Chasman, R. Dorajoo, M. Fornage, N. Franceschini, X. Guo, C. Hayward, S. Kardia, K. Lohman, R. Loos, J. Marten, B. Tayo, C. van Duijn, W. Xu, I. Borecki, L. Cupples, D. Rao, A. Morrison, on behalf of the CHARGE Gene-Lifestyle Interactions Working Group.

313/6:00 Genome-wide study for blood metabolites identifies 62 loci and connects LPA with lipoprotein metabolism from a new perspective. J. Kettunen, on behalf of the MAGNETIC consortium.

314/6:15 Characterisation of the metabolic impact of rare genetic variation within APOC3: Proton NMR based analysis of rare variant gene effects. L. Corbin, F. Drenos, J. Kettunen, P. Wurtz, P. Soininen, A. J. Kangas, A. Hingorani, T. Gaunt, J. P. Casas, M. Ala-Korpela, G. Davey Smith.

Friday, October 9

4:30 PM–6:30 PM

Concurrent Platform Session E

61. From Here to There: Reconstructing Human History

Holiday Ballroom 4, 2nd Floor, Hilton Baltimore Hotel

Moderators: Timothy O'Connor, Univ Maryland and Inst for Genome Sci, Baltimore
  Brenna Henn, Stony Brook Univ

315/4:30 Analysis of more than 800,000 genotypes from individuals born in the United States reveals trends in increasing genetic diversity during the 20th century. A. R. Kermany, M. Barber, J. Byrnes, P. Carbonetto, R. Curtis, J. Granka, E. Han, N. Myres, K. Noto, Y. Wang, C. Ball, K. Chahine.

316/4:45 Reconstructing the population history of New York City. G. M. Belbin, D. Ruderfer, E. A. Stahl, J. Jeff, Y. Lu, R. J. F. Loos, E. P. Bottinger, N. S. Abul-Husn, A. Auton, E. E. Kenny.

317/5:00 Inference of super-exponential human population growth via efficient computation of the site frequency spectrum for generalized models. F. Gao, A. Keinan.

318/5:15 Genome-wide data on 34 ancient Anatolians identifies the founding population of the European Neolithic. I. Lazaridis, D. Fernandes, N. Rohland, S. Mallick, K. Stewardson, S. Alpaslan, N. Patterson, R. Pinhasi*, D. Reich*.

319/5:30 The evolutionary impact of Denisovan ancestry in Australo-Melanesians. S. Sankararaman, S. Mallick, N. Patterson, D. Reich, for The Simons Genome Diversity Project.

320/5:45 IBD sharing in the 1000 Genomes Project Phase 3 data reveals relationships from Neanderthals to present day families. G. Povysil, S. Hochreiter.

321/6:00 Computational reconstruction of a haploid genome from the 18th century. A. Jagadeesan, E. D. Gunnarsdóttir, S. S. Ebenesersdóttir, V. B. Guðmundsdóttir, E. L. þórðardóttir, M. S. Einarsdóttir, J. Dugoujon, C. Fortes-Lima, F. Migot-Nabias, A. Massougbodji, G. Bellis, P. Triska, V. Cerny, L. Pereira, A. Kong, A. Helgason, K. Stefánsson.

322/6:15 Polly: A novel approach for estimating local and global admixture proportion based on rich haplotype models. K. Noto, Y. Wang, M. Barber, J. Byrnes, P. Carbonetto, R. E. Curtis, E. Han, A. Kermany, N. Myres, C. A. Ball, K. Chahine.

Friday, October 9

6:30 PM–6:35 PM

62. C.W. Cotterman Awards Announcement

Ballroom I, Level 4, 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 plaque.


Friday, October 9

6:35 PM–6:40 PM

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

Ballroom I, Level 4, 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 2015 Annual Meeting. This year’s 18 finalists will be acknowledged during the ASHG Policy Forum and Business Meeting.


Friday, October 9

6:40 PM–7:30 PM

64. ASHG Policy Forum and Business Meeting

Ballroom I, Level 4, Convention Center

ASHG Policy Forum: The ASHG Social Issues Committee will review a draft positon statement on the ethical and policy implications of CRISPR-Cas9 technology and genome editing. The committee will solicit feedback and discussion from attendees.

ASHG Membership/Business Meeting: 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 2014 Business Meeting. We encourage discussion from the floor.


Saturday, October 10

8:55 AM–10:15 AM

65. Featured Plenary Abstract Session II

Hall F, Level 1, Convention Center

323/8:55 An integrative model for predicting the regulatory impact of rare non-coding variants on the human transcriptome. Y. Kim, X. Lee, F. Damani, Z. Zappala, J. Davis, E. Tsang, S. B. Montgomery, A. J. Battle, The GTEx Consortium.

324/9:15 Genetic and epigenetic factors affecting regulatory elements underlie lactose intolerance and lactase persistence. R. Jeremian, V. Labrie, O. Buske, E. Oh, C. Ptak, G. Gasiunas, A. Maleckas, R. Petereit, A. Zvirbliene, K. Adamonis, E. Kriukienė, K. Koncevicius, J. Gordevičius, A. Nair, A. Zhang, S. Ebrahimi, G. Oh, V. Siksnys, L. Kupcinskas, M. Brudno, A. Petronis.

325/9:35 Characterizing de novo balanced cytogenetic abnormalities through sequencing in 147 subjects with multiple congenital anomalies. C. Redin, H. Brand, R. L. Collins, V. Pillalamarri, C. Hanscom, T. Kammin, S. Pereira, B. B. Currall, Z. Ordulu, S. Althari, J. Shen, A. Ragavendran, E. C. Liao, E. Mitchell, J. C. Hodge, C. C. Morton, J. F. Gusella, M. E. Talkowski.

326/9:55 Adipose- and maternal- specific regulatory variants at KLF14 influence Type 2 Diabetes risk in women via a female-specific effect on adipocyte physiology and body composition. K. Small, M. Todorcevic, M. Civelek, J. El-Sayed Moustafa, A. Mahajan, M. Horikoshi, A. Hough, C. Glastonbury, G. Thorleifsson, L. Quaye, J. Fernandez, A. Buil, A. Vinuela, M. Yon, M. Simon, S. Sethi, J. Bell, B. Sharifi, U, Thorsteinsdottir, A. L. Gloyn, R. Cox, A. Lusis, F. Karpe, M. McCarthy.

Saturday, October 10

10:30 AM–12:30 PM

Concurrent Platform Session F

66. Computing Functional Variants

Ballroom I, Level 4, Convention Center

Moderators: Xiaoquan Wen, Univ Michigan, Ann Arbor
  Chiara Sabatti, Stanford Univ

327/10:30 Single variant resolution association mapping of inflammatory bowel disease loci. H. Huang, L. Jostins, M. Fang, M. U. Mirkov, M. Georges, J. Barrett, M. J. Daly, the International IBD Genetics Consortium.

328/10:45 Genome sequencing of autism families reveals disruption in non-coding regulatory DNA. T. N. Turner, F. Hormozdiari, M. Duyzend, I. Iossifov, A. Raja, C. Baker, K. Hoekzema, H. A. Stessman, M. C. Zody, B. Nelson, J. Huddleston, R. Sandstrom, J. Smith, D. Hanna, M. Bamshad, J. Stamatoyannopoulos, D. A. Nickerson, R. Darnell, E. E. Eichler.

329/11:00 Fine mapping of psoriasis susceptibility loci: Enrichment of pro-inflammatory genomic marks in lymphocytes and keratinocytes. L. C. Tsoi, S. L. Spain, E. Ellinghaus, P. E. Stuart, T. Esko, T. Pers, X. Wen, F. Capon, J. Knight, T. Tejasvi, H. M. Kang, M. H. Allen, S. Weidinger, J. E. Gudjonsson, S. Koks, K. Kingo, A. Metspalu, G. G. Krueger, J. J. Voorhees, V. Chandran, C. F. Rosen, P. Rahman, D. D. Gladman, A. Reis, R. P. Nair, A. Franke, J.NWN Barker, G. R. Abecasis, R. C. Trembath, J. T. Elder.

330/11:15 Colocalization of eQTLs at WHRadjBMI GWAS loci with multiple association signals highlighted candidate functional genes for body fat distribution. Y. Wu, M. Civelek, C. K. Raulerson, A. He, C. Tilford, C. Fuchsberger, A. E. Locke, H. M. Stringham, A. U. Jackson, N. K. Saleem, N. Narisu, P. S. Chines, P. Gargalovic, T. Kirchgessner, F. S. Collins, M. Boehnke, M. Laakso, A. J. Lusis, K. L. Mohlke.

331/11:30 Fine-mapping GWAS loci containing extensive allelic heterogeneity reveals complex patterns of association. C. N. Spracklen, A. U. Jackson, H. M. Stringham, Y. Wu, M. Civelek, C. Fuchsberger, A. E. Locke, R. Welch, P. S. Chines, N. Narisu, A. J. Lusis, J. K. Kuusisto, F. S. Collins, M. Boehnke, M. Laakso, K. L. Mohlke.

332/11:45 Connecting the regulatory dots at the GWAS discovery phase. A. Madar, D. Chang, F. Gao, A. Sams, Y. Waldman, C. Cunninghame Graham, T. Vyse, A. Clark, A. Keinan.

333/12:00 Identifying critical cell types in complex traits from purified and single-cell expression using a polygenic model. D. Calderon, D. Golan, T. Raj, J. Pritchard.

334/12:15 Integrating genome-wide association and co-expression network data for novel gene discovery. C. R. Farber, L. D. Mesner, J. P. Stains, S. M. Tommasini, M. C. Horowitz, C. J. Rosen.

Saturday, October 10

10:30 AM–12:30 PM

Concurrent Platform Session F

67. Opening Up Big Data

Ballroom III, Level 4, Convention Center

Moderators: Joe Pickrell, New York Genome Ctr,
  Joanna Mountain, 23andMe, Inc, Mountain View

335/10:30 DNA.Land: A community-wide platform to collect millions of genomes-phenomes. Y. Erlich, A. Gordon, N. Pearson, K. Shee, J. Pickrell.

336/10:45 The European Variation Archive: Integrating open-access variation datasets. G. I. Saunders, J. D. Spalding, I. Medina Castello, C. Yenyxe Gonzalez, J. Kandasamy, F. J. Lopez, I. Lappalainen, J. Coll-Moragon, J. M. Mut Lopez, J. Paschall.

337/11:00 The Monarch Initiative: An open science integrated genotype-phenotype platform for disease and model organism discovery. M. A. Haendel, N. L. Washington, N. Vasilevsky, J. Nguyen-Xuan, C. Condit, D. Smedley, M. Brush, S. Köhler, T. Groza, K. Shefchek, H. Hochheiser, S. E. Lewis, P. N. Robinson, C. J. Mungall, The Monarch Initiative.

338/11:15 iCLiKVAL: An open-access tool for adding value to scientific literature one annotation at a time through the power of crowdsourcing. T. D. Taylor, N. Kumar.

339/11:30 A practical guide to drug discovery through phenome-wide association studies. F. Sathirapongsasuti, D. A. Hinds, E. Karrer.

340/11:45 The Human Phenotype Ontology: Semantic unification of common and rare disease. P. Robinson, S. Köhler, D. Moldenhauer, N. Vasilevsky, G. Baynam, T. Zemojtel, L. Schriml, W. Kibbe, P. Schofield, T. Beck, D. Vasant, A. Brookes, A. Zankl, N. Washington, C. Mungall, S. Lewis, M. Haendel, H. Parkinson, T. Groza.

341/12:00 Imputation in the cloud: Lessons learned and future directions. C. Fuchsberger, L. Forer, S. Schönherr, D. Sayantan, F. Kronenberg, G. Abecasis.

342/12:15 LARVA: An integrative framework for Large-scale Analysis of Recurrent Variants in noncoding Annotations. M. Gerstein, L. Lochovsky, J. Zhang, Y. Fu, E. Khurana.

Saturday, October 10

10:30 AM–12:30 PM

Concurrent Platform Session F

68. Statistical Genetics: Analyze Family-wise

Room 307, Level 3, Convention Center

Moderators: Regie Lyn Santos-Cortez, Baylor College of Medicine
  Yun Ju Sung, Washington Univ, St. Louis

343/10:30 Leveraging variant prioritization information in de novo mutation analysis to identify novel autism candidate genes. H. Hu, H. Hu, M. Li, H. Coon, M. Yandell.

344/10:45 SimDenovo: A simulation toolkit to understand the variability in de novo mutation burden in human disease. V. Aggarwala, B. F. Voight.

345/11:00 Relationship inference in big genetic data with >100,000 samples. W.-M. Chen, A. Manichaikul, S. S. Rich.

346/11:15 Mixed model association with family-biased case-control ascertainment. T. Hayeck, N. Zaitlen, P. Loh, A. Gusev, N. Patterson, A. Price.

347/11:30 Dissecting a major linkage signal to identify potential causal variants for serum triglycerides in a founder population. W.-C. Hsueh, A. K. Nair, S. Kobes, L. J. Baier, R. L. Hanson.

348/11:45 Systematic and large-scale investigation of twin and sibling concordance of 1723 traits in a nationally representative health claims cohort. C. M. Lakhani, J. Yang, P. M. Visscher, C. J. Patel.

349/12:00 Heritability estimates for thirty-four traits in a large Ugandan cohort. D. Heckerman, D. Gurdasani, C. Pomilla, R. Nsubuga, C. Kadie, C. Widmer, M. Sandhu.

350/12:15 Leveraging whole genome sequencing in an internal study-specific imputation reference panel for family-based designs. K. Iyer, L. R. Yanek, M. A. Taub, I. Ruczinski, D. Becker, L. Becker, R. A. Mathias.

Saturday, October 10

10:30 AM–12:30 PM

Concurrent Platform Session F

69. The Causes and Consequences of Evolutionary Change

Room 309, Level 3, Convention Center

Moderators: Kirk Lohmueller, UCLA
  Sohini Ramachandran, Brown Univ, Providence

351/10:30 Combined analysis of over 60,000 exomes: Genic constraint, widespread mutational recurrence, and impact on clinical variant interpretation. D. MacArthur, Exome Aggregation Consortium.

352/10:45 Population differentiation analysis of 54,734 European Americans reveals independent evolution of ADH1B gene in Europe and East Asia. K. J. Galinsky, G. Bhatia, P. Loh, S. Georgiev, S. Mukherjee, N. J. Patterson, A. L. Price.

353/11:00 A direct estimate for the human mutation rate from autozygous sequences in thousands of parentally related pedigrees. V. Narasimhan, R. Rahbari, A. Scally, Y. Xue, C. Tyler-Smith, R. Durbin.

354/11:15 Leveraging distant relatedness to quantify human mutation and gene conversion rates. P. Palamara, L. Francioli, G. Genovese, P. Wilton, A. Gusev, H. Finucane, S. Sankararaman, S. Sunyaev, P. DeBakker, J. Wakeley, I. Pe'er, A. Price, The Genome of the Netherlands Consortium.

355/11:30 Genetic diversity on the human X chromosome suggests there is no single pseudoautosomal boundary. M. Wilson Sayres, D. Cotter, S. Brotman.

356/11:45 Comparative epigenomic analysis of regulatory elements in primate stem cells. I. Narvaiza, C. Benner, M. Wang, M. C. Marchetto, M. Ku, T. Swigut, J. Wysocka, F. H. Gage.

357/12:00 Transcriptome diversity associated with ancestry and diet in ethnically diverse East African populations. N. G. Crawford, Y. Ren, R. A. Rawlings-Goss, G. R. Grant, H. Hutton, M. Yeager, S. Chanock, A. Ranciaro, S. Thompson, J. Hirbo, W. Beggs, T. Nyambo, S. Omar, D. Meskel, G. Belay, C. Brown, H. Li, S. A. Tishkoff.

358/12:15 High-coverage RNA sequencing reveals substantial variation associated with geography, environment, and endophenotypic variation. M.J. Fave, A. J. Hodgkinson, J.P. Goulet, J.C. Grenier, H. Gauvin, V. Bruat, T. de Maillard, E. Gbeha, E. Hip-Ki, Y. Idhagdour, P. Awadalla.

Saturday, October 10

10:30 AM–12:30 PM

Concurrent Platform Session F

70. Precision Cancer Sequencing

Room 316, Level 3, Convention Center

Moderators: Dayna Oschwald, New York Genome Ctr, Rockaway Park
  David Wheeler, Baylor Col of Med, Houston

359/10:30 The importance of assaying the matched normal when sequencing cancer genomes. E. Helman, M. Clark, R. Alla, D. Church, S. Boyle, A. Patwardhan, S. Luo, J. Harris, N. Leng, C. Haudenschild, R. Chen, J. West.

360/10:45 Insights into somatic mutation-driven cancer genome evolution: A study of 3,000 cancer genomes across 9 cancer types. Z. Zhao, F. Cheng.

361/11:00 Systematic analysis of mutation distribution in three dimensional protein structures identifies cancer driver genes. A. Fujimoto, Y. Okada, K. Boroevich, T. Tsunoda, H. Taniguchi, H. Nakagawa.

362/11:15 Insights, mechansims, and fundamental significance of copy-neutral loss of heterozygosity detected in oncology samples. S. Schwartz, B. Williford, R. Burnside, I. Gadi, V. Jaswaney, A. Penton, K. Phillips, H. Risheg, J. Schleede, J. Tepperberg, P. Papenhausen.

363/11:30 Genomic analysis reveals novel secondary drivers and progression pathways in skin basal cell carcinoma. X. Bonilla, L. Parmentier, B. King, G. Kaya, H. J. Sharpe, T. McKee, V. Zoete, P. G. Ribaux, F. A. Santoni, K. Popadin, M. Guipponi, M. Garieri, C. Verdan, K. Grosdemange, O. Sumara, M. Eilers, F. J. de Sauvage, I. Aifantis, O. Michielin, S. E. Antonarakis, S. I. Nikolaev.

364/11:45 Recurrent somatic mutation in the MYC associated factor X in brain tumors. H. Nikbakht, M. Montagne, N. Jabado, P. Lavigne, J. Majewski.

365/12:00 The driver landscape of parathyroid carcinoma. C. Pandya, A. V. Uzilov, J. Bellizzi, S. D. Li, W. Yu, M. Stevenson, B. Cavaco, B. T. Teh, R. V. Thakker, H. Morreau, A. Arnold, R. Chen.

366/12:15 Epigenomic profiling of prostate cancer identifies differentially methylated genes in TMPRSS2:ERG fusion positive versus negative tumors. M. S. Geybels, J. J. Alumkal, I. M. Shui, M. Bibikova, B. Klotzle, M. Rinckleb, A. Luedeke, C. Maier, E. A. Ostrander, J. Fan, Z. Feng, J. L. Stanford.

Saturday, October 10

10:30 AM–12:30 PM

Concurrent Platform Session F

71. New Insights in Gene Regulation

Room 318/321, Level 3, Convention Center

Moderators: Michael Talkowski, Harvard Med Sch, Cambridge
  Vivian Cheung, Univ of Michigan, Ann Arbor

367/10:30 Large-scale inference of activating and repressive nucleotides in human cell types using tiling reporter assays. J. Ernst, T. S. Mikkelsen, M. Kellis.

368/10:45 Full-length mRNA sequencing uncovers a widespread coupling between transcription and mRNA processing. P. Hoen, E. de Klerk, M. Vermaat, J. T. den Dunnen, S. W. Turner, P. A. C. 't Hoen.

369/11:00 The role of RNA polymerase II pausing in the mediation of human gene expression. J. Boden, V. G. Cheung.

370/11:15 Reappraising the protein-coding potential of GENCODE using high stringency mass spectrometry. J. M. Mudge, J. Wright, J. Choudhary, J. Harrow.

371/11:30 Post-translational mechanisms buffer protein abundance against transcriptional variation. S. C. Munger, J. M. Chick, P. Simecek, E. L. Huttlin, K. B. Choi, D. M. Gatti, N. Raghupathy, K. L. Svenson, S. P. Gygi, G. A. Churchill.

372/11:45 Convergence of genes and pathways influencing neurodevelopment following suppression of ASD-associated chromatin modifiers and transcriptional regulators in human neural progenitor cells. S. Erdin, A. Sugathan, P. Manavalan, K. M. Hennig, S. D. Sheridan, C. M. Seabra, A. Stortchevoi, A. Ragavendran, M. Biagioli, S. J. Haggarty, J. F. Gusella, M. E. Talkowski.

373/12:00 High-throughput analysis of gene-environment interactions across 250 cellular conditions. F. Luca, G. Moyerbrailean, O. Davis, C. Harvey, A. Alazizi, D. Watza, X. Wen, R. Pique-Regi.

374/12:15 Functional dissection of BCL11A enhancer by Cas9-mediated in situ saturation mutagenesis. M. C. Canver, E. C. Smith, F. Sher, L. Pinello, N. E. Sanjana, O. Shalem, D. D. Chen, P. G. Schupp, D. S. Vinjamur, S. Garcia, S. Luc, Y. Fujiwara, T. Maeda, G. C. Yuan, F. Zhang, S. H. Orkin, G. Lettre, D. E. Bauer.

Saturday, October 10

10:30 AM–12:30 PM

Concurrent Platform Session F

72. Inborn Errors of Metabolism: Novel Disorders, Models, and Observations

Holiday Ballroom 1, 2nd Floor, Hilton Baltimore Hotel

Moderators: Seymour Packman, UCSF
  Kristina Cusmano-Ozog, Children's Nat Med Ctr, Washington, DC

375/10:30 NGLY1 disease causes mitochondrial respiratory chain dysfunction and induction of oxidative stress. J. Kong, M. Peng, E. Nakamaru-Ogiso, M. He, J. Ostrovsky, Y-.J. Kwon, E. McCormick, T. Suzuki, Y. Argon, M. J. Falk.

376/10:45 Mutations in pyruvate dehydrogenase phosphatase regulatory subunit (PDPR) are a novel cause of fatal neonatal cardio-encephalopathy with corneal clouding and lactic acidosis. J. Christodoulou, M. Nafisinia, J. Crawford, R. M. Brown, G. K. Brown, M. H. Menezes, L. G. Riley, W. A. Gold, R. J. Taft, C. Simons.

377/11:00 Signal transducer and activator of transcription 2 (STAT2) deficiency is a novel disorder of mitochondrial fission. R. Shahni, C. M. Cale, G. Anderson, L. D. Osellame, S. Hambleton, T. S. Jacques, Y. Wedatilake, J. W. Taaman, E. Chan, W. Qasim, V. Plagnol, A. Chalasani, M. R. Duchen, K. C. Gilmour, S. Rahman.

378/11:15 Smith-Lemli-Opitz Syndrome iPS cells demonstrate abnormal neuronal differentiation due to 7-dehydrocholesterol impairment of Wnt/β-Catenin signaling. F. D. Porter, A. N. Ton, C. A. Wassif, Y. Xin, P. E. O'Halloran, N. Malik, C. Cluzeau, I. M. Williams, N. S. Trivedi, W. J. Pavan, W. Cho, H. Westphal, K. R. Francis.

379/11:30 A mouse model of cblC deficiency displays reduced survival, growth retardation, and combined methylmalonic acidemia and hyperhomocysteinemia. M. Arnold, J. Sloan, N. Achilly, G. Elliot, J. Fraser, B. Brooks, C. Venditti.

380/11:45 Defects in SLC33A1 impair copper ATPase trafficking and contribute to the clinical and biochemical phenotypes of Huppke-Brendel syndrome. L. Yi, W. H. Tan, P. Huppke, S. G. Kaler.

381/12:00 Inhibition of CTR1 by antisense oligonucleotides in mouse model of Wilson’s disease reduces copper accumulation and improves liver pathology. T. R. Grossman, R. B. Johnson, G. Hung, B. P. Monia, M. McCaleb.

382/12:15 B4GALNT1 deficiency as a cause of hereditary complex movement disorder with Parkinsonism features: A new inborn error of metabolism affecting glycosphingolipid biosynthesis. C. Lourenco, M. Almeida, C. Leprevost, Y. Anikster, W. Marques jr.

Saturday, October 10

10:30 AM–12:30 PM

Concurrent Platform Session F

73. Intellectual Ability and Disability

Holiday Ballroom 4, 2nd Floor, Hilton Baltimore Hotel

Moderators: Alicio Smith, Emory Univ, Atlanta
  Adam Locke, Univ of Michigan, Ann Arbor

383/10:30 74 SNPs associated with education provide insights into brain function and disorders. J. J. Lee, T. Esko, Social Science Genetic Assn Consortium.

384/10:45 Biallelic mutations in human accelerated regions (HARs) are associated with abnormal social and cognitive behavior. R. N. Doan, B. I. Bae, M. Nieto, B. Cubelos, S. Al-Saad, N. M. Mukaddes, C. A. Walsh, The Homozygosity Mapping Consortium for Autism.

385/11:00 B56δ-related protein phosphatase 2A dysfunction identified in patients with intellectual disability. A. Hoischen, D. Haesen, L. E. L. M. Vissers, S. Mehta, M. J. Parker, M. Wright, J. Vogt, S. McKee, N. Cordeiro, T. Kleefstra, M. H. Willemsen, M. R. F. Reijnders, S. Berland, E. Hayman, E. Lahat, E. H. Brilstra, C. L. I. van Gassen, E. Zonneveld-Huijssoon, C. I. de Bie, A. Hoischen, E. E. Eichler, R. Holdhus, V. M. Steen, S. O. Døskeland, D. E. FitzPatrick, M. E. Hurles, V. Janssens, DDD project, Welcome Trust Sanger Inst, Cambridge, UK.

386/11:15 Clinical indexing genes affected by copy number variation in neurodevelopmental disorders. M. Uddin, G. Pellecchia, D. Merico, B. Thiruvahindrapuram, M. Zarrei, T. Nalpathamkalam, K. Tammimies, M. Gazzellone, R.KC. Yuen, S. Walker, A. Chan, L. D’Abate, A. Noor, M. T. Carter, G. Yoon, P. Kannu, C. R. Marshall, M. Speevak, D. J. Stavropoulos, S. W. Scherer.

387/11:30 Functional characterization of novel DEAF1 mutations in clinical whole-exome sequencing of intellectual disability patients and its regulation of the RAI1 gene. L. Chen, P. Jensik, M. Walkiewicz, J. T. Alaimo, S. V. Mullegama, S. H. Elsea.

388/11:45 Investigating the transcriptome wide impact of expanded polyalanine tract mutations in ARX contributing to intellectual disability and seizures. C. Shoubridge, K. Lee, J. Gecz, T. Mattiske.

389/12:00 WD-repeat 47 is essential for the normal brain development through interaction with SCG10 in tubulin-associated processes. B. Yalcin, M. Roos, L. McGillewie, C. Wagner, C. Chevalier, U. K. Sanger Mouse Genetics Project, G. Grenningloh, C. Kinnear, Y. Herault, B. Loos, B. Yalcin.

390/12:15 Single-cell RNA-Seq of human Cajal-Retzius neurons in developing brain. J. Kim, M. Lin, R. Dominguez, T. Souaiaia, C. Walker, A. Camarena, J. Nguyen, J. Herstein, M. Francois, W. Mack, J. Rossen, C. Liu, O. Evagrafov, R. Chow, J. A. Knowles.

Saturday, October 10

1:45 PM–3:45 PM

Concurrent Invited Sessions II

74. Gene Editing/Rewriting the Genome: Moving from Association to Biology and Therapeutics

Ballroom III, Level 4, Convention Center

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

In the current era of personalized medicine, we have identified a large number of genetic variants in patients with various diseases using next-generation sequencing. Recent advances in genetic engineering, genotyping, high-resolution imaging, and biomarker testing have made it easier to deliver the right treatments to the right patients at the right time. These tools are the future of patient care: A personalized medicine approach. Speakers will discuss applications of patient-specific and disease-specific stem cell lines, including gene repair (via tools such as the Cas9 nuclease), disease modeling, drug screening, and regenerative medicine. Panelists will bring experience in clinical genetics, genetic manipulation in stem cells, and disease modeling. The FDA has recently approved phase I/II clinical trials to investigate the safety and efficacy of embryonic stem cell-based retinal cell transplantation, but such therapies require immunosuppression. Patient-specific stem cells may offer an alternative to embryonic stem cells that will skirt the need for immunosuppressive therapy as well as the social and political ramifications of embryonic stem cell research, but their utility extends far beyond such groundbreaking advances and will assist future clinical practice and patient care.


1:45 PM   Treating dominantly inherited brain diseases. B. L. Davidson. Children's Hosp Philadelphia.

2:15 PM   CRISPR-Cas9-mediated mouse model generation with high efficiency and throughput. H. Wang. Jackson Lab, Bar Harbor.

2:45 PM   iPS technology, gene editing, and disease research. R. Jaenisch. Whitehead Inst, Massachusetts Inst Technol, Cambridge.

3:15 PM   The dynamics of pluripotent stem cells define the individual biology of human genomes. R. McKay. Johns Hopkins Univ, Baltimore.

Saturday, October 10

1:45 PM–3:45 PM

Concurrent Invited Sessions II

75. Genetic Control of the Microbiome

Room 307, Level 3, Convention Center

Moderator: George Weinstock, Jackson Lab for Genomic Med, Farmington

The communities of microbes (bacteria, viruses, and eukaryotic microbes) that inhabit various tissues of the body affect and are affected by their host. Yet the microbiome has traditionally been thought of as a collection of innocuous organisms that can be ignored in studies of health and disease. Taking the microbiome into account may be important for accurate phenotype-genotype analysis due to the increasing awareness of the impact the microbes have on different body sites, through the products they produce, their ability to protect against invading organisms, their direct interaction with the cell structures and the extracellular milieu, provoking inflammatory or immune responses, and many other effects. The microbiome thus contributes in many ways to the host phenotype and is itself a phenotypic characteristic to be measured. Variation in microbiome structure due to diet, health status, age, and other factors is being studied extensively, but the effect of host genotype is less well described. However, there are a growing number of examples where the impact of the host genotype on the microbiome has been described, and these serve as precedents for a deeper understanding of the genetic interaction of the host and microbiome. In this session, we will present four examples of the influence of host genotype on the microbiome, and the impact of the microbiome on host phenotype.


1:45 PM   Assessment of effects of microbiome composition on pediatric fatty liver disease. N.H Salzman. Medical College of Wisconsin.

2:15 PM   Host-microbiome interactions through the lens of quantitative genomics. A. Benson. Univ Nebraska, Lincoln.

2:45 PM   Human host genetics and regulation of the gut microbiome. R. Ley. Cornell Univ, Ithaca.

3:15 PM   Personal microbiomes in health and disease. B. Piening. Stanford.

Saturday, October 10

1:45 PM–3:45 PM

Concurrent Invited Sessions II

76. Integrating Genomes and Transcriptomes to Understand Human Disease

Hall F, Level 1, Convention Center

Moderators: Michael J. Clark, Personalis, Menlo Park
  Tuuli Lappalainen, New York Genome Ctr, New York

As sequencing technologies have advanced, DNA and RNA sequencing have become increasingly accessible, facilitating the growth of the human genomics field. Generally research is focused on DNA or RNA rather than both, and rarely are the two analyzed together in an integrated fashion. Often, RNA is thought of as the source of expression data while DNA is the source of mutational information. However, there is an increasing recognition that integrated co-analysis of DNA and RNA allows one to paint a much fuller picture of the molecular genetic state of the cells being studied. Novel DNA variants predicted to be deleterious may not be expressed, which would be missed without RNA analysis. There may be DNA evidence for gene fusions in the form of translocations, but structural variant calling is prone to false positives, so fusion isoforms from RNA are invaluable. DNA variants in putative regulatory elements may not be interpretable without observing the effect on transcription. In this session, we will discuss methods for integrated analysis of DNA and RNA and their application in human genomic research in the areas of cancer genomics, human disease research, and regulation of gene expression.


1:45 PM   Correlative power of DNA to RNA in cancer genomics. E. Mardis. Washington Univ Sch Med, St Louis.

2:15 PM   Identifying rare and causal non-coding variants through transcriptome sequencing. S. Montgomery. Stanford Univ Sch Med, Stanford.

2:45 PM   DNA and RNA integrated analysis in cancer and other disease. D. Hayes. UNC Chapel Hill.

3:15 PM   Integrated analysis of transcriptome and genotype data for understanding non-coding variation. A. Battle. Johns Hopkins Univ, Baltimore.

Saturday, October 10

1:45 PM–3:45 PM

Concurrent Invited Sessions II

77. Life Beyond Additive Variance

Room 316, Level 3, Convention Center

Moderators: Julien F. Ayroles, Princeton
  Andrew G. Clark, Cornell Univ, Ithaca

The current quantitative genetic paradigm is driven by a prevailing view that additive genetic models, focused on the mean effect of alternative alleles, adequately explain variation for most phenotypes. This has led to the identification of a long list of genetic variants contributing to the risk of complex diseases. Unfortunately, a decade after the popularization of GWAS and in spite of much effort, we have fallen short of the goal of explaining most of the heritability for complex traits in terms of allelic effects. This approach is designed to describe the average effect of an allele randomized over a large number of genetic backgrounds and environments. But each individual has faced a unique trajectory of environmental insults, some of which may have quite large genotype-specific effects. Extensive study of agricultural and laboratory model organisms have shown that the genotype-phenotype map is much more complicated than Fisher’s additive model would predict. When measurements can be made with reasonable control of the environment, complex, non-additive interrelationships between loci appear to be the rule and not the exception. Furthermore, these allelic effects are often environmentally sensitive. The paradigm derived from traditional quantitative genetics is at odds with a major goal of medical genetics as we often seek to understand the causal path from genotype to phenotype for individuals and not populations. In this context, the notion of heritability needs to be revisited to be meaningful for medical genetics. When the average allelic effect does not capture a specific allelic effect under certain conditions, whether due to genetic background or environmental effects, current methods will not detect the link between genotype and phenotype. The difficulties faced by the human genetics community to explain the genetic basis of complex traits underscores a fundamental knowledge gap in our understanding of the context dependency of allelic effects.


1:45 PM   Heritability and individual prediction. A. G. Clark. Cornell Univ, Ithaca.

2:15 PM   Obesity, a case for gene by environment interactions. P. Pajukanta. Sch Med at UCLA.

2:45 PM   Exploring the contribution of variance-QTL to phenotypic variation. J. F. Ayroles. Princeton.

3:15 PM   Genetic control of transcription in human immune response. C. Ye. UCSF.

Saturday, October 10

1:45 PM–3:45 PM

Concurrent Invited Sessions II

78. Multiplexed and Multimodal Experimental Dissection of Genetic Variants

Ballroom I, Level 4, Convention Center

Moderators: Jay Shendure, Univ Washington, Seattle
  Melina Claussnitzer, Harvard Med Sch & Broad Inst MIT & Harvard, Cambridge

Genome-wide association studies (GWAS) have yielded thousands of reproducible genotype-phenotype associations. In the past few years, functional genomics, epigenomics, and regulatory genomics datasets have begun to drive the formulation and testing of mechanistic hypotheses that link specific genetic variants within implicated loci to human traits and phenotypes. However, such experimental validations of GWAS associations are overwhelmingly lacking, in large part due to technological limitations on the throughput of the requisite methods. This has resulted in a dearth of experimentally-validated disease models for non-coding variants in particular, despite their central importance in complex trait genetics. As a result, the major mechanisms that underlie the contributions of non-coding variants to the genetic basis of human disease have yet to be clearly established. In this session, we will describe cutting-edge approaches to experimentally validate, in a high-throughput manner, candidate mechanisms underlying observed genotype-phenotype associations. These advances represent the next generation of functional genomic approaches, and raise practical questions for the field regarding the levels of evidence that are required to convincingly establish causality. The session will also highlight the importance of coordinating progress between computational and experimental strategies for determining the genetic underpinnings of disease.


1:45 PM   New experimental approaches to the large-scale functional analysis of observed and potential genetic variation. J. Shendure. Univ Washington, Seattle.

2:15 PM   Network based elucidation and validation of causal genomic variants. A. Califano. Columbia Univ, New York.

2:45 PM   Experimentally validating regulatory mechanisms underlying human disease. T. Reddy. Duke Univ, Durham.

3:15 PM   Mechanistic dissection of metabolic risk variants across multiple phenotypic scales. M. Claussnitzer. Harvard Med Sch & Broad Inst MIT & Harvard, Cambridge.

Saturday, October 10

1:45 PM–3:45 PM

Concurrent Invited Sessions II

79. Optimizing Clinical and Molecular Characterisation and Management in Skeletal Dysplasias: An Exemplary Model for Rare Genetic Diseases.

Room 327, Level 3, Convention Center

Moderators: Melita D. Irving, Guy, London, United Kingdom
  Ravi Savarirayan, Murdoch Childrens Res Inst, Parkville, Melbourne, Australia

The skeletal dysplasias are a group of individually rare but collectively common heritable disorders of skeletal development, growth, and maintenance that present from before birth to adulthood. They serve as a model for many other rare genetic disorders, in terms of the need for accurate clinical and molecular characterization, evidence-based management, and the emerging possibility of pathogenesis-based treatments. Early and accurate diagnosis of these disorders has been greatly facilitated by the widespread clinical application of high-throughput genomic sequencing, leading to increased diagnostic rates in these rare conditions. Resolution of diagnostic uncertainty enables focus to shift towards improving management, including new treatment regimes that have the potential to change natural history and burden of disease. Liaison between clinical and basic sciences can be utilized to achieve this, including maximizing the potential of genomic data to tailor individualized treatments, collecting natural history information to identify disorder-specific management requirements, developing new therapeutic approaches through improved knowledge of molecular pathways and protein network interactions, and testing potential new drugs via well-conducted clinical trials. This session will focus on skeletal dysplasias as a model for rare genetic diseases, highlighting tools for collecting natural history data and healthcare needs data; key diagnostic clinical and molecular features; and management, including novel emerging disease-modifying treatments based on better understanding of molecular pathogenesis. The concepts and advances presented that are unfolding in this group of disorders can be extrapolated to many other rare genetic diseases that might benefit from these “bedside to bench, and back again” approaches.


1:45 PM   Osteogenesis Imperfecta: How an advocacy group initiative established collaborative research for a rare disease, advanced knowledge and care, and fostered an NIH Rare Disease Clinical Research Network to investigate brittle bone diseases. V. Sutton. Baylor Col Med/Texas Children’s Hosp, Houston.

2:15 PM   From emerging new therapies in children to defining and implementing healthcare needs in adults: Cradle to grave management in Achondroplasia. M. D. Irving. Guy, London, United Kingdom.

2:45 PM   The Skeletal Dysplasia Management Consortium (SDMC): An international, multi-disciplinary approach to improve clinical outcome for skeletal dysplasia patients. J. Hoover-Fong. Johns Hopkins Univ, Baltimore.

3:15 PM   Morquio disease and hypophosphatasia: Templates for the journey from disease characterization to life-changing therapeutic management. R. Savarirayan. Murdoch Childrens Res Inst, Parkville, Melbourne, Australia.

Saturday, October 10

1:45 PM–3:45 PM

Concurrent Invited Sessions II

80. Research Partners, Not Subjects: Engaging Indigenous Peoples in Genetics

Holiday Ballroom 4, 2nd Floor, Hilton Baltimore Hotel

Moderators: Rene L. Begay, Univ Colorado, Aurora
  Julian R. Homburger, Stanford Univ

American Indian/Alaska Native (AI/AN) indigenous people consistently suffer worse health outcomes than any minority group in part because they are severely underrepresented in research and, consequently, may be omitted from developments in new genetic technologies and clinical advancements. This disengagement from research participation is a result of past unethical practices by researchers. There is also a concern that a lack of respect for cultural differences persists. This can only serve to exacerbate the health disparities gap as healthcare moves towards precision medicine. Further, disengagement with and from AI/AN communities inhibits our understanding of human diversity. This trainee-led session will provide an overview of the current state of health disparities in genomics research and the research designs/ethical conflicts faced in the past that caused AI/AN communities to become wary of researchers. Suggestions in advocating culturally-sensitive constructs to begin research dialogues with Tribal nations will be discussed. Highlights include examples of community-based participatory research models, an introduction towards Tribally-driven research in American Indian Tribal nations, difficulties studying urban and unrecognized AI/AN communities, and the changing partnership between researchers involving biopolitics over time. All discussions will be framed in the light of reducing healthcare disparities in the context of precision medicine, and topics discussed can be broadened to apply to other underrepresented research communities. Native American geneticists and an ethicist who works with Alaskan Native people will lead this discussion, with balanced moderation by Native and non-Native clinical geneticists. Hence, panelists (all trainees) are intimately cognizant of the biopolitical and social issues at hand.


1:45 PM   The sovereign power of American Indian communities to engage or disengage in genetics research. K. S. Tsosie. Vanderbilt Univ, Nashville.

2:15 PM   IndiGenomics: Indigenizing genomics technologies. K. Fox. Univ Washington, Seattle.

2:45 PM   Staying for tea: An example of community-engaged genetic research. K. M. West. Univ Washington, Seattle.

3:15 PM   Whose risk? A comparison of common and uncommon inheritance, risk, and benefits in genomic research. J. Yracheta. Missouri Breaks Industries, Inc, Eagle Butte.

Saturday, October 10

1:45 PM–3:45 PM

Concurrent Invited Sessions II

81. The Landscape of de novo Point Mutations in the Human Genome: How Many, Where, When and Why?

Room 309, Level 3, Convention Center

Moderators: Alexander Hoischen, Radboud Univ Med Ctr, Nijmegen, Netherlands
  Gil McVean, Univ Oxford, UK

Mutations, the fundamental process by which genomic variation is acquired, fuel evolution and are at the origin of all genetic disease. Hence, defining the mechanisms that control their occurrence is crucial to our basic understanding of genome biology, evolution, and disease mechanisms. Accurate models of mutation rate are also expected to inform disease-gene discovery studies that rely on recurrent de novo mutations. Traditionally, mutation rates have been inferred from evolutionary comparisons or extrapolated from the study of specific loci, but it is now possible to directly assess the mutation rate on a genome-wide basis, using whole-genome sequencing of family trios. These studies concur that 30-100 new point mutations are acquired at each generation, corresponding to a mutation rate of 1.2 x 10-8 per nucleotide. Importantly, this figure only represents a genome-wide average and it is well-recognized that the mutation rate fluctuates across the genome and between individuals. Factors such as local sequence context, replication timing, transcriptional status or paternal age at conception are known to bias the occurrence of spontaneous mutations. Moreover, given that point mutations are acquired through DNA copy-errors (and/or failure of DNA damage repair mechanisms) during replication, preferentially within the paternal germline, a detailed knowledge of these basic biological processes is key to understanding the patterns of nucleotide substitutions. This session will draw on novel insights into the factors driving the occurrence of de novo point mutations in the germline to highlight how variation in mutation rate is predicted to impact genome heterogeneity and mutation functions.


1:45 PM   An evolutionary perspective on human germline mutation. M. Przeworski. Columbia Univ, New York.

2:15 PM   Genome-wide patterns and properties of de novo point mutations. S. Sunyaev. Brigham & Women's Hosp, Boston.

2:45 PM   The selfish effect of paternal age on germline mutations. A. Goriely. Univ Oxford, United Kingdom.

3:15 PM   Ribonucleotides, non-canonical nucleotides embedded in the genome. A. P. Jackson. Univ Edinburgh, United Kingdom.

Saturday, October 10

1:45 PM–3:45 PM

Concurrent Invited Sessions II

82. Translating Genomic Knowledge into Clinical Practice

Holiday Ballroom 1, 2nd Floor, Hilton Baltimore Hotel

Moderator: Marylyn D. Ritchie, Gesinger Hlth Syst; The Pennsylvania State Univ, University Park

Since the dawn of the genomics era, significant progress has been made in the "T1" space - translating scientific discoveries into clinical guidelines - however, challenges remain. We can leverage the expanding resources of electronic health records (EHR) linked to genomic information for progress in this space. Another significant challenge to realizing the goal of meaningful impact on healthcare is bridging the “T2” gap - implementing those translational discoveries in clinical practice ultimately to improve human health. This session will address translating genetic and genomic discoveries into improved human health from the perspectives of genomic data management, operational issues, and ELSI - ethical, legal, and social issues. We will first frame the issue by presenting an example project that illustrated many of the challenges involved. We then delve into the challenges and barriers to implementation, both technical and cultural. We will discuss the heterogeneous skill sets needed to tackle these problems, including expertise across the spectrum of biomedical informatics, epidemiology, and medicine, from molecules to organs and from patients to populations. We will describe how existing technologies and standards support clinical decision support for genomic medicine, and conclude with a specific case study that highlights both the challenges and opportunities inherent in the realization of genomic health.


1:45 PM   Using electronic health record data and biorepositories, from experimental discovery to clinical decision support: Progress and promise. S. A. Pendergrass. Geisinger Hlth Syst, Danville.

2:15 PM   Prospective, multiplexed genotyping to tailor genetic therapy - the Vanderbilt PREDICT program. J. C. Denny. Vanderbilt Univ Sch Med, Nashville.

2:45 PM   Standards to enable genomic clinical decision support: Making knowledge computable. R. R. Freimuth. Mayo Clin, Rochester.

3:15 PM   DTC testing and genomic medicine: A cautionary tale. J. D. Tenenbaum. Duke Univ, Durham.

Saturday, October 10

1:45 PM–3:45 PM

Concurrent Invited Sessions II

83. Understanding Disease Pathogenesis: A Grand Challenge for Model Organisms

Room 318/321, Level 3, Convention Center

Moderators: Philip Hieter, Univ British Columbia, Vancouver
  Jasper Rine, UC Berkeley

The model organisms, yeast, worm, fly, zebrafish, mouse, and others, provide powerful tools for investigating the mechanistic basis of diseases, for identifying and developing potential therapeutic interventions, and for evaluating new treatments. Success in such endeavors will be catalyzed by the establishment of connections, collaboration, and cross-talk between basic and clinician scientists, as novel disease-causing mutations are discovered. Indeed, key aspects of most human disorders can be modeled in experimentally tractable organisms through the analysis of orthologous genes and pathways, using the genetic, biochemical and cell biological toolboxes that have been developed in each model organism. Despite the dramatic increase in the pace of human disease gene discovery, the gap in our understanding of the molecular and cellular bases of the associated diseases continues to grow. Our knowledge of the complete catalogue of highly penetrant, disease-causing mutations is quite limited. This brings a real and immediate need for model organism research platforms to put disease-causing genes into a biological context. This symposium will accent the current relevance of model organism studies for the understanding, diagnosis, and treatment of human disease, and anticipate the future role of model organisms in human disease research. We chose to highlight a diverse set of biological processes and experimental systems to make the point that the principles of cross species analysis of basic gene function extend to the study of all human disorders, and can lead to mechanistic understanding of disease pathogenesis and rationale for the development of new therapies.


1:45 PM   Fruit fly/mouse: A fly approach to personalized cancer therapeutics. R. Cagan. Mount Sinai Hosp, New York.

2:15 PM   Fruit fly/mouse: Molecular genetics of tumor suppressor genes and oncogenes. D. Pan. Johns Hopskins Univ Sch Med, Baltimore.

2:45 PM   Nematode worm: Nutritional regulatory networks. M. Walhout. U Mass Med Sch, Worcester.

3:15 PM   Yeast/zebrafish: Genetic models to determine gene function and a potential therapy for an inherited anemia. C. McMaster. Dalhousie Univ, Halifax, Canada.