Invited Sessions Listing

Tuesday, October 15

1:00 PM–3:00 PM

Concurrent Invited Session I: Non-CME

1. ASHG/ESHG Building Bridges: Potential Policy Implications of Genetic Research into Educational Attainment

TBD, Convention Center

Moderators: Kiran Musunuru, ASHG
  Joris Veltman, ESHG

 

Recent genome-wide association studies (Lee et al., Nature Genetics, 2018) have shown that polygenic scores composed of common variants can explain ~13% of the variance in educational attainment, and this number is set to increase as studies grow. While there has been considerable discussion in policy circles and the media about the ethics of gene editing, the implications of genetic prediction for behavioral and cognitive traits have received less attention. There is an urgent need to consider whether and how the findings from these studies should be applied in public policy. For example, should polygenic scores for educational attainment be used as a component of school admissions processes, or to identify children likely to need particular educational help? What threshold of precision would be necessary for useful deployment? Should we allow antenatal embryo selection based on these scores in IVF clinics? Should insurers be allowed to use polygenic scores in determining policy pricing? What are the potential unintended consequences of such policies, and what does the public think about them? How does knowledge about the heritability of educational attainment affect political notions of equality? How can we stop this debate being hijacked by extremist groups? In this session, genetics and policy experts will present the latest research on these topics and hold a panel discussion.

 

1:00 PM   Introduction. A. I. Young. Univ Oxford, UK.

1:10 PM   Polygenic prediction of education: U.S. attitudes regarding when and how it should be deployed. D. Conley. Princeton Univ.

1:20 PM   Genetics of education and egalitarian policy goals. K. P. Harden. Univ Texas Austin.

1:30 PM   Educational reform, ability, and labor market screening. A. Okbay. Vrije Univ Amsterdam, Netherlands.

1:40 PM   Lost in translation: Bias and methodological challenges in policy applications of polygenic educational scores. M. Mills. Univ Oxford, UK.

1:50 PM   Panel discussion.


Tuesday, October 15

1:00 PM–3:00 PM

Concurrent Invited Session I: Non-CME

2. Deep Learning for Interpretation of Human Genetic Variation

TBD, Convention Center

Moderators: Anshul Kundaje, Stanford Univ
  Alexis Battle, Johns Hopkins Univ, Baltimore

 

A major barrier to the adoption of sequencing in clinical practice is the challenge of interpreting the consequences of genetic variants. Recent advances in deep learning in genomics have led to new classes of models for predicting the molecular and clinical effects of both noncoding and protein-altering variation, which have the potential to complement traditional statistical and bioinformatics methods. This session will showcase the potential for deep neural networks to interpret functional genetic variation and provide new biological insights by learning to extract relevant features directly from sequence. We will also highlight the challenges for this rapidly growing field, particularly around interpretation of models, and the vast quantities of relevant datasets required for successful training of deep neural networks.

 

1:00 PM   Decoding the role of regulatory variation in human disease with deep learning methods. O. Troyanskaya. Princeton Univ.

1:20 PM   Unsupervised deep learning for interpretation of human genetic variation. D. Marks. Harvard Med Sch, Boston.

1:40 PM   Learning the splicing code from primary sequence with deep learning. K. Farh. Illumina Inc, Foster City.

2:00 PM   Sequential regulatory activity prediction across chromosomes enables effective disease association analyses. D. Kelley. Calico Inc, South San Francisco.

2:20 PM   Panel discussion.


Tuesday, October 15

1:00 PM–3:00 PM

Concurrent Invited Session I: Non-CME

3. Genetics on Target: The Role of Genetic Evidence in Drug Discovery and Development, from Vision to Reality

TBD, Convention Center

Moderator: Robert A. Scott, Glaxo Smith Kline, Stevenage, UK

 

The considerable efforts in the human genetics community to identify genomic regions associated with susceptibility to disease has, in large part, been motivated by the potential to identify putative therapeutic targets. However, it remains unclear whether the vast number of associations being identified will translate to a wealth of therapeutic targets. Our panel of speakers have extensive experience in both academia and industry that allows them to reflect on the utility of genetics in drug discovery and development. The session includes six short talks from leading members of the industry and academic communities, followed by a panel discussion. Across the talks, we aim to cover six key themes that complement the overarching aim to provide the community with more insight into what it takes to practically use genetics to guide drug development from target discovery to late-stage validation. These themes are: (1) defining the case for genetics-based drug development; (2) describing how large-scale biobanks can help realise the vision; (3) discussing whether we could extend the idea too far and go wrong by an undue focus on genetics; (4) outlining what is needed to motivate a drug discovery program after finding an association; (5) detailing an ongoing example of a genetically-validated target program from identification to validation; and (6) realizing the vision for genetics-based drug development - what will it really take and how do we get there? We will dedicate the second hour to a panel discussion where the audience and panel will have the chance to respond to each theme and ask questions.

 

1:00 PM   The case for routine integration of genetic evidence into drug development. R. Plenge. Celgene, Cambridge.

1:15 PM   The role for large-scale population studies in enabling genetically-driven drug development. J. Casas. VA Healthcare Boston.

1:30 PM   A good idea gone too far? The appropriate role for genetic evidence in drug discovery. M. Nelson. GSK, Collegeville.

1:45 PM   So, we've found a genetic association: What next? S. John. Biogen, Cambridge.

2:00 PM   Developing a genetically-validated target, through target identification, validation to clinical trial design. J. Hutz. Eisai AiM Inst, Andover.

2:15 PM   Realizing the vision of genetically-driven drug development: What will it take and how do we get there? D. Altshuler. Vertex Pharmaceuticals, Boston.

2:30 PM   Panel discussion.


Wednesday, October 16

10:30 AM–12:30 PM

Concurrent Invited Session II

18. Addressing the Genomics Literacy Gap in Society: A Conversation about the How, What, Why, and Impact of Modern Educational Frameworks

TBD, Convention Center

Moderators: Rivka Glaser, Stevenson Univ, Owings Mills
  Adam Hott, Hudson Alpha Inst Biotech, Huntsville

 

Student: "My grandmother has Alzheimer's, so I have a 50% chance of having it too." Patient: "No one in my family has this, so why should I get tested?" Headline: "Parents May One Day Be Morally Obligated to Edit Their Baby's Genes." How do we know that our energy and time spent in genetics and genomics education are effective? Are we making any difference in the genomic literacy of K-16 students, graduate students, healthcare providers, and the general public? What is standing in the way of the utopian genomically literate populace? As genetics professionals and educators, we recognize the importance of being genomically literate. However, as the pace of genetic and genomic knowledge and technologies increases, gaps in genetic and genomic literacy between genetics professionals and other subsets of the population increases. This session will explore the effectiveness of our genetics and genomics education pipeline. Through both short presentations and a large group panel discussion, this session will foster audience member engagement in a conversation about what is working and what barriers are in the way of a truly genomically literate society.

 

10:30 AM   Introduction.

10:35 AM   Reaching the public to increase community genomic literacy. N. Lamb. HudsonAlpha Inst Biotech, Huntsville.

10:55 AM   Models for teaching and learning about DNA. D. Newman. Rochester Inst Technol.

11:15 AM   Healthcare provider education in genomics. B. Biesecker. Research Triangle Inst, Intl, Washington, D.C.

11:35 AM   Effective undergraduate education for the successful preparation of graduate students. S. McClymont. Johns Hopkins Sch Med, Baltimore.

11:55 AM   Panel discussion.


Wednesday, October 16

10:30 AM–12:30 PM

Concurrent Invited Session II

19. Beyond the Genome Sequence: Integrating Genes, Enhancers, and Pathways in Development and Disease

TBD, Convention Center

Moderators: Sumantra Chatterjee, New York Univ Sch Med
  Tychele N. Turner, Washington Univ Sch Med St Louis

 

Despite progress in cataloging disease-causing genes for various multifactorial disorders, their underlying biology has been difficult to unravel. As large-scale exome and whole-genome sequencing data become available, finding disease-associated variants is becoming easier, but not finding their biological effects. Solving this puzzle will require us to place genes in their correct spatio-temporal context, deciphering their regulatory control and building their gene regulatory networks (GRNs). Building these networks will help us to connect the many coding and non-coding variants by elucidating the highly integrative and interactive properties of the human genome. In this session, we will bring together diverse speakers highlighting the multiple ways of connecting various components of the genome that contribute to a phenotype and disease state. We will discuss work that integrates both computational and experimental approaches to understand how disruption of critical genes and non-coding elements involved in specific processes leads to distinct effects across different cells and tissues. Figuring out these discrete effects will lead to a better understanding of normal developmental processes and the complexities of cellular response in disease. The various talks will demonstrate how comprehension of these networks has an important lesson for systems biology: the whole idea of a system is to provide robustness from variation and mutations, but a well-integrated system can have the opposite effect and lead to disease even when only one primary component is perturbed due to effect amplification through the network.

 

10:30 AM   Transcriptional regulatory networks underpinning Hirschsprung disease. S. Chatterjee. New York Univ Sch Med.

11:00 AM   Highly multiplex genome engineering methods to validate and tie human regulatory elements to their target genes. M. Gasperini. Univ Washington, Seattle.

11:30 AM   Identification of gene regulatory network components in autism. T. N. Turner. Washington Univ Sch Medicine St Louis.

12:00 PM   Systematic approaches to analysis of regulatory variation. M. Maurano. New York Univ Sch Med.


Wednesday, October 16

10:30 AM–12:30 PM

Concurrent Invited Session II

20. DNA in the Public Sphere: How Genomic Information is Used and Protected Outside of Research and Medicine

TBD, Convention Center

Moderators: Cristina Kapustij, NHGRI/NIH, Bethesda
  Sara Katsanis, Duke Univ, Durham

 

Over the years, genetics has grown from a purely academic discipline to one that revolutionized forensics, genealogy, and medicine. Millions of Americans have gained access to their own personal genomic data, with the consumer genomics market value expected to grow to over $300 million in the next four years. As genomics becomes more accessible in the consumer and legal worlds, it has also become entangled in national conversations about race and ethnicity, family reunification, criminal justice, and data privacy. The use of DNA has moved well beyond the clinical and research context and now plays an important role in forensics, disaster response, and border security. This session will bring together experts from diverse fields who will discuss how genomic data are incorporated in their work in various settings, the policies (or lack thereof) that shape this work, and the difficulties in protecting genetic information used in these settings. It will introduce attendees to the importance and limits of genomic information in forensics (especially with the emergence of forensic genealogy), the challenges of sharing DNA data across borders for the identification of missing migrants, and the policy considerations for employing DNA as a biometric for border security. The closing panel will serve as an open forum for discussion on the strengths and weaknesses of relevant policies, as well as opportunities for new policy development around topics such as genomic privacy, security, confidentiality, and transparency.

 

10:30 AM   Introduction. C. Kapustij. NHGRI/NIH, Bethesda.

10:40 AM   Use of genetic information in criminal and civil litigation. S. Mercer. Raquin Mercer LLC, Rockville.

10:55 AM   Solving cold cases using genetic genealogy. C. Moore. Parabon NanoLabs/DNA Detectives, Reston.

11:10 AM   Long-term dead: Identification of missing migrants at the Texas-Mexico border. K. Spradley. Texas State Univ, San Marcos.

11:25 AM   Government and genetics: Balancing national security and humanitarian interests. J. Wagner. Geisinger Hlth Syst, Danville.

11:40 AM   Synthesis and introduction to panel. S. Katsanis. Duke Univ, Durham.

11:50 AM   Panel discussion.


Wednesday, October 16

10:30 AM–12:30 PM

Concurrent Invited Session II

21. Emerging Views of Human Brain Evolution and Development from Comparative Neurogenetics

TBD, Convention Center

Moderators: Armin Raznahan, NIMH, Bethesda
  Jason Stein, Univ North Carolina Chapel Hill

 

The expansion of the human neocortex in anatomically modern humans has, in part, led to our unique cognitive and social abilities. Genome sequencing of our extant relatives, archaic humans, and current human populations has identified loci undergoing selection along the human lineage. However, the specific genetic changes leading to cortical expansion are very poorly understood. Because neuropsychiatric disorders impact cognitive and behavioral domains that are uniquely developed in humans, comparative neurogenetics may also provide fundamental insights into the biology of risk for neuropsychiatric disorders. Functional analyses, described in this session, allow us to annotate the effects of genetic variants under selection on human brain structure, function, and development. Nadav Ahituv will present the functional impact of fixed changes within human accelerated regions of the genome in human and chimpanzee iPSC-derived neural progenitor cells. Amanda Tilot will present a large-scale assessment of how Neanderthal introgression continues to influence a neuroimaging-derived brain-shape phenotype that reflects a uniquely human neurodevelopmental process. Jason Stein will present a series of studies that determine the functional impact of selected alleles on cortical structure using GWAS of cortical structure via MRI. Armin Raznahan will present work that combines in vivo neuroimaging and postmortem transcriptomic maps of the human brain to identify candidate mediators of regional cortical expansion in humans and the role of these expanded systems in neurodevelopmental disorders. Collectively, these presentations will showcase the rapid understanding of genetic variants impacting brain structure and development across human evolution in the burgeoning field of comparative neurogenetics.

 

10:30 AM   Massively parallel dissection of human accelerated regions. N. Ahituv. UCSF.

11:00 AM   Neandertal introgression sheds light on modern human endocranial globularity. A. Tilot. Max Planck Inst Psycholinguistics, Nijmegen, Netherlands.

11:30 AM   Unearthing the evolutionary history of common genetic variants influencing human cortical surface area. J. Stein. Univ North Carolina Chapel Hill.

12:00 PM   Transcriptional decoding of size-dependent brain shape diversity in humans. A. Raznahan. NIMH, Bethesda.


Wednesday, October 16

10:30 AM–12:30 PM

Concurrent Invited Session II

22. Functional Validation of Rare Variants Using Physiologically Relevant Experimental Systems

TBD, Convention Center

Moderators: Daniel C. Koboldt, Nationwide Children's Hosp, Columbus
  Anne O'Donnell-Luria, Boston Children's Hosp

 

Functional validation of genomic variants associated with disease is a vital yet increasingly difficult task in the face of rapidly accelerated genomic discovery. Crucially, it is now far easier and more cost-effective to identify candidate disease-causing variants than it is to determine their biological consequences and mechanisms of pathogenesis. Fortunately, numerous experimental tools and approaches have emerged to investigate the impact of rare variants at a molecular level. Here, we highlight the use of scalable model systems that employ cutting-edge molecular toolkits to interpret human genetic lesions. These include coding and non-coding changes as well as point mutations or copy number variants. Our session features experts in diverse model systems, but the speakers are unified by a common goal of interpreting variation found in humans. Attendees will learn how: (1) CRISPR-enabled enhancer reporter assays have enabled testing thousands of candidate enhancer variants in mice; (2) Zebrafish assays have facilitated gene discovery and copy number variant dissection in rare pediatric syndromes; (3) three-dimensional organoids grown from patient iPS cells make it possible to assess the impact of genomic variants on brain structure and physiology; and (4) Drosophila models offer a tractable means to accelerate both gene discovery and therapeutic development in undiagnosed disorders. In summary, our session will demonstrate how elegant biological approaches can address the major challenges of interpretation and serve as a necessary complement to in silico predictions for the human genetics community.

 

10:30 AM   Linking enhancer variation to human disease in vivo. L. Pennacchio. Lawrence Berkeley Natl Lab.

11:00 AM   Modeling pediatric genetic disease in the developing Zebrafish. E. Davis. Duke Univ Med Ctr, Durham.

11:30 AM   Using brain organoids to investigate rare genomic variants in human neurological disorders. M. Hester. Nationwide Children's Hosp, Columbus.

12:00 PM   Using Drosophila to study new disease associated rare human variants and mechanisms. H. Bellen. Texas Children's Hosp, Houston.


Wednesday, October 16

10:30 AM–12:30 PM

Concurrent Invited Session II

23. Clinical Spotlight: Novel Insights into the Genetics of Reproduction: Precision Medicine and Personalized Assisted Reproductive Technologies

TBD, Convention Center

Moderators: Rima Slim, McGill Univ Hlth Ctr Res Inst, Montreal, Canada
  Lei Wang, Fudan Univ, Shanghai, China

 

Little data is known about the genetic bases of recurrent reproductive loss and infertility mainly due to their genetic heterogeneity. In fact, the genetics of reproductive loss and infertility has a lot of delays relative to other medical disciplines such as neurology, biochemistry, ophthalmology, and pediatrics. The advent of next-generation sequencing (NGS) in the last decade has opened an unprecedented opportunity to tackle genetically heterogeneous conditions and allowed the recent identification of several genes responsible for infertility and reproductive loss in humans. This session will address the genetic bases of female and male reproductive failure and show the impact of NGS on the identification of several of their responsible genes. The first speaker, Aleksandar Rajkovic, will describe his work on gonadal development, germ cell differentiation, and folliculogenesis. He will show how germ cell–specific transcriptional regulators determine the pool of primordial follicles, their activation, reproductive life span, and how their mutations lead to premature ovarian failure. The second speaker, Lei Wang, will talk about the genetic basis of female infertility. He will describe his work on the identification of novel Mendelian phenotypes and genes responsible for abnormalities in oocyte maturation, fertilization, and early embryonic development. The third speaker, Rima Slim, will present her work on a particular form of pregnancy loss, called molar pregnancy. She will describe current knowledge about four causative genes for recurrent moles, their roles in its pathogenesis, and link to recurrent miscarriages and female and male infertility. The fourth speaker, Pierre Ray, will focus on the genetics of male infertility and his identification of several genes responsible for abnormalities in spermatogenesis. The four speakers will end their talks with lists of genes that need to be tested in patients and criteria of patients’ inclusion. The session assembles top experts in their fields, from four different countries, who will bring different academic and medical perspectives since the four countries are under different health care systems and regulations.

 

10:30 AM   Genetic bases of premature ovarian failure. A. Rajkovic. UCSF.

11:00 AM   Missing Mendelian phenotypes in genetic abnormalities of oocyte maturation, fertilization, and embryonic development. L. Wang. Fudan Univ, Shanghai, China.

11:30 AM   Genetic bases and mechanisms of recurrent molar pregnancies. R. Slim. McGill Univ Hlth Ctr Res Inst, Montreal, Canada.

12:00 PM   High-throughput sequencing reveals that a large number of genes is involved in human male infertility. P. Ray. Univ Grenoble Alpes, France.


Wednesday, October 16

10:30 AM–12:30 PM

Concurrent Invited Session II

24. Recent Progress on Identity-by-Descent

TBD, Convention Center

Moderators: Degui Zhi, Univ Texas Hlth Sci Cen Houston
  Xiaoming Liu, Univ South Florida, Tampa

 

Identity-by-Descent (IBD) segments are fundamental genetic concepts and relevant to many aspects of human genetics. While traditionally IBD studies were mostly theoretical studies and on small samples, they have recently become more data-driven thanks to the availability of large cohorts with genotypes and new computational methods. In particular, modern IBD methods have begun to offer new insights into genetic genealogy, recent population history, and disease risks due to rare variants and haplotypes. This session will showcase cutting-edge analytical methods and the new results brought by these methods. A short introduction will be followed by four talks. David Balding will offer insights into theoretical frameworks for IBD and relatedness and applications in association analysis and heritability. Sharon Browning will discuss inference of population history from IBD segments. Ardalan Naseri will review recent efficient methods for identifying IBD segments from very large genotyped samples. Eurie Hong will describe a large collection of genotyped cohorts available at a direct-to-consumer company, their findings, and the implications for society.

 

10:30 AM   Kinship: Theory and practice in genome-wide analyses. D. Balding. Univ Melbourne, Australia.

11:00 AM   Inferring the past thousand years of demographic history using segments of identity by descent. S. Browning. Univ Washington, Seattle.

11:30 AM   Efficient computational methods for identifying IBD segments from biobanks. A. Naseri. Univ Texas Hlth Sci Cent Houston.

12:00 PM   Pedigrees and genealogical records provide a historical portrait of population structure. E. Hong. AncestryDNA LLC, San Francisco.


Wednesday, October 16

10:30 AM–12:30 PM

Concurrent Invited Session II

25. Value Assessment of Genomic Testing from Diverse Stakeholder Perspectives in Health Services

TBD, Convention Center

Moderators: Scott J. Spencer, Univ Washington, Seattle
  Christine Lu, Harvard Univ, Boston

 

We continue to see increased availability of both next-generation sequencing and additional biomedical data. Despite the growth of these resources, we have not seen the sweeping improvements in health that some anticipated. This is due to a variety of challenges related to the translation of genome sciences into clinical care and practice at the patient, provider, health systems, and payer levels for genetic testing. To address several translational challenges, it is critical to (1) understand the evolving marketplace and test quality, (2) understand how genomic information influences how patients and providers pursue healthcare services, (3) apply health economic methods to assess the value utilizing genomic information, and (4) identify strategies and methods for evaluation of genetic tests and tools from various stakeholder perspectives. Considering these challenges, Gillian Hooker will introduce the genetic testing marketplace and discuss attributes associated with test value. Next, Ragan Hart will discuss decision analysis for discerning cost-effectiveness of next-generation sequencing tests, highlight limitations of current value assessment methods, and report on proposed solutions. Additionally, Kurt Christensen will discuss approaches to conducting economic evaluations alongside clinical studies. Finally, Erick Lin will discuss an evidence review process for assessing value associated with diagnostic tests. The presentations will be followed by a panel discussion with all of the speakers. This session intends to offer insights from various experts who are developing and applying solutions as they relate to these questions and how to best utilize genetic data and health data for translational impact in clinical practice.

 

10:30 AM   Clinical genetic testing in the genome era: A view across the U.S. landscape of value, quality, and reimbursement. G. Hooker. Concert Genet, Franklin.

10:50 AM   Decreasing uncertainty within the value assessment process for genomic testing. R. Hart. Stanford Univ.

11:10 AM   Evaluating the economic impact of genomic testing during clinical trials. K. Christensen. Brigham & Women's Hosp, Boston.

11:30 PM   Industry evidence review framework for evaluating diagnostic tests. E. Lin. Blue Cross Blue Shield Assn, Chicago.

11:50 AM   Panel discussion.


Wednesday, October 16

10:30 AM–12:30 PM

Concurrent Invited Session II

26. What about the Phenotype? Integrating Electronic Health Records to Drive Discovery in Precision Health

TBD, Convention Center

Moderators: Anna O. Basile, New York Genome Ctr
  Molly A. Hall, Pennsylvania State Univ, University Park

 

Copious amounts of rich, diverse clinical data have become increasingly available for research through electronic health record (EHR) databanks and clinical repositories. EHRs provide a dense source of longitudinal data that can be integrated for research tasks such as cohort development, outcome ascertainment, and clinical translation. EHR-coupled biorepositories combined with advancements in machine learning approaches and natural language processing provide a unique opportunity for studying the complex architecture of health and disease by using the biomedical products of clinical care. This session will focus on the ways that EHR-extracted data can be leveraged in driving discovery in precision health and genomics. Applications include developing refined phenotype algorithms, elucidating patterns for the purpose of homogeneous patient stratification, using phenome-wide association studies (PheWAS) to find novel relationships among diseases, discovering phenotype-genotype associations, evaluating drug usage, identifying potential drug interactions, and uncovering pleiotropic relationships. This session will also tackle efficient research strategies needed to address challenges and limitations associated with EHR-derived data and analyses including the handling of heterogeneous, multivariate and highly dimensional data, addressing missing attributes, and the computational feasibility of analytic approaches. Overall, the EHR provides an invaluable resource of information that can be leveraged to build accurate predictive models that will aid in uncovering the genetic basis of common diseases as well as potentially advancing diagnosis, treatment, and prevention of disease.

 

10:30 AM   Genotyping to inform phenotyping in electronic health records. D. C. Crawford. Case Western Reserve Univ, Cleveland.

11:00 AM   Human-disease phenotype map derived from an EHR-linked biobank. D. Kim. Univ Pennsylvania, Philadelphia.

11:30 AM   Exploring the phenome and the relationship with the genome using EHR-linked biobanks. M. D. Ritchie. Univ Pennsylvania, Philadelphia.

12:00 PM   Latent phenotype models to improve genetic analyses in incomplete medical records. N. P. Tatonetti. Columbia Univ, New York.


Thursday, October 17

5:30 PM–7:00 PM

67. Presidential Symposium: Genetic Exceptionalism - From Its Beginning to Its End?

TBD, Convention Center

Moderator: Leslie G. Biesecker, ASHG President

 

This symposium will focus on several areas of Genetic Exceptionalism. The speakers will discuss the topic from its origins and history to how it affects everyday practice of genetics. The thesis of this symposium is that exceptionalism is a barrier to the vision of the Society, which is that “People everywhere realize the benefits of human genetics and genomics research.” Exceptionalism creates barriers in academia between geneticists and other scientists. It isolates geneticists from other specialists and providers in hospitals and clinics. This barrier must be broken down to realize these benefits. To address this challenge, we have assembled three distinguished lecturers, who will puncture the exceptionalism balloon. The symposium will close with a moderated panel discussion to discuss how we move forward.

5:30-5:55 pm: How Genetics Got Its Exceptionalism. Robert Resta, MS, CGC, Swedish Hospital, Seattle

5:55-6:20 pm: Behavioral Impact of Predictive Testing: The Unexceptional Contribution of Genetic Information. Dame Theresa Marteau, PhD, DBE, University of Cambridge

6:20-6:45 pm: The Everyday Reality of Genetics in the Clinic: It’s Just Medicine. Kyle Brothers, MD, PhD, University of Louisville

6:45-7:00 pm: Panel Discussion/Q&A

 


Friday, October 18

10:30 AM–12:30 PM

Concurrent Invited Session III

77. Unraveling the Mysteries of Mosaicism: Implications for Biology and Disease

TBD, Convention Center

The human body is composed of approximately 40 trillion cells, derived from a single zygote, yet no two cells are genetically identical. The study of mosaicism has benefited from advances in genomic technology to begin to capture some of this incredible genomic diversity across organs and cell types and to understand the impact on genomic health and disease. This is due not only to dropping sequencing costs, but also to the fact that individual "reads" derive from distinct DNA molecules or cells, enabling both bulk-sequencing and single-cell-sequencing assessment of mosaicism. This session will highlight how post-zygotic mutations, revealed through the study of mosaicism, have advanced our understanding of cell lineage, cell proliferation, responses to drugs, and gene-gene interactions, as well as how they impact human health. The speakers will discuss: (1) how clonal hematopoiesis can influence age-associated disease, (2) how clonal hematopoiesis of indeterminate potential (CHIP) is detected and interpreted in the context of hematological malignancies and response to anti-cancer therapies, (3) how brain somatic mosaicism can be used to understand cellular origins and disease, (4) how somatic pathogenic variants and revertants that rescue germline pathogenic variants influence disease, and (5) how this information impacts both clinical and research geneticists.

 

10:30 AM   Clonal hematopoiesis and its impact on age-associated disease. K. Walsh. Univ Virginia, Charlottesville.

11:00 AM   Impact of oncologic therapy on clonal hematopoiesis and therapy-related myeloid neoplasm in solid tumor patients. K. Bolton. Memorial Sloan Kettering Cancer Ctr, New York.

11:30 AM   One brain, many genomes: Somatic mutation and genomic diversity in human brain. C. A. Walsh. Boston Children's Hospital.

12:00 PM   Implications of somatic pathogenic variants and revertants rescuing germline pathogenic variants for diagnosis and treatment of genetic disorders. K. Choate. Yale Univ, New Haven.


Friday, October 18

10:30 AM–12:30 PM

Concurrent Invited Session III

78. Clinical Spotlight: Basic Research to Clinical Implementation: A Multidisciplinary Overview of the Current State and Future Directions of Clinical Pharmacogenomic Testing

TBD, Convention Center

Moderators: Ulrich Broeckel, Med Col Wisconsin, Milwaukee
  Mary V. Relling, St. Jude Children's Hosp, Memphis

 

This is a multidisciplinary discussion of the current progress and challenges in implementing pharmacogenomic diagnostic testing as part of genomics-guided precision medicine. This session will include updates on the current status and future direction of nomenclature standardization, the role of health professionals in diagnostic implementation, and the translation of basic science from the bench to the clinic. Our session will include talks from a range of scientists and healthcare providers. The interactive panel discussion will allow for audience questions on pharmacogenomic research and clinical implementation. Attendees will be able to ask questions and get insight from a range of healthcare professionals and discuss the need for and different roles in multidisciplinary collaboration for clinical implementation.

 

10:30 AM   From discovery science to clinical implementation: A case study of NUDT15 and thiopurine pharmacogenomics. J. J. Yang. St. Jude Children's Res Hosp, Memphis.

10:55 AM   The Pharmacogene Variation (PharmVar) Consortium: What you need to know. A. Gaedigk. Children's Mercy Kansas City.

11:20 AM   Genetic counselors role and perspective in pharmacogenomics, reimbursement, and provider preferences for result reports. C. A. Campbell. Univ Iowa, Iowa City.

11:45 PM   Pharmacist perspective on pharmacogenomic implementation. D. Gregornik. Children's Hosp Minnesota, Minneapolis.

12:10 PM   Panel discussion.


Friday, October 18

10:30 AM–12:30 PM

Concurrent Invited Session III

79. Cutting-edge Approaches to Interrogating the Genomics of Infectious Disease

TBD, Convention Center

Moderators: Genevieve Wojcik, Stanford Univ Sch Med
  Priya Duggal, Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore

 

Throughout human history, infectious pathogens have exerted enormous selective pressure on our genomes. Infectious disease continues to contribute substantially to global morbidity and mortality, despite remarkable advancements in hygiene and vaccination over the past century. However, infectious disease susceptibility and sequelae are underrepresented in large-scale genomic research even though there is a clear role for genetics. Various studies have shown high heritability of our immune system’s response to antigens, such as the antibody response to measles vaccination at 88.5%. This lack of preeminence is due to several challenges, including the underrepresentation of populations with the highest burden of disease, the difficulty in appropriate comparison groups, the time-sensitive nature of recruitment, and, lastly, the incomplete picture from traditional study designs, where we only assess a small portion of complex host-pathogen genetic interactions. This session will showcase groundbreaking work by four researchers to tackle these challenges and interrogate the dynamic genetic system of host-pathogen interactions. This will include perspectives from real-time recruitment of an infectious disease outbreak, evolutionary analyses examining human and pathogen diversity, community-driven research in Sub-Saharan Africa, and the creation of an atlas of genetic variation for pathogen-driven cellular traits.

 

10:30 AM   What are the challenges and benefits in studying the genetics of infectious diseases? P. Duggal. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore.

11:00 AM   Importance of epidemiological study design in genetic studies of tuberculosis. C. Stein. Case Western Reserve Univ, Cleveland.

11:30 AM   Natural selection contributed to immunological differences between human hunter gatherers and agriculturalists. G. Harrison. Univ Colorado, Anschutz Med Campus, Aurora.

12:00 PM   An atlas of human genetic variation affecting host-pathogen traits. D. Ko. Duke Univ, Durham.


Friday, October 18

10:30 AM–12:30 PM

Concurrent Invited Session III

80. Novel Biomarkers and Emerging Therapeutic Approaches in Mitochondrial Disorders

TBD, Convention Center

Moderators: Fernando Scaglia, Baylor Col Med, Houston
  Amel Karaa, Massachusetts Gen Hosp/Harvard Univ, Cambridge

 

Recent data from disease models highlight whole-organism metabolic remodeling in mitochondrial disorders. Furthermore, these dysfunctional metabolic pathways may be amenable to therapeutic approaches. Although the metabolomics aberrations in mitochondrial disorders have not been completely dissected, some preliminary work has found evidence of disease-specific metabolomics signatures in the blood and tissues of patients with primary mitochondrial disorders. This suggests the potential of metabolomics fingerprints as biomarkers for diagnosis that could be used to follow-up disease progression and monitor potential therapeutic effects in clinical trials. Furthermore, this information could help to shed light into specific pathogenic pathways. Many potential therapeutic approaches for mitochondrial diseases have been proposed and are now at different stages of development. Translating preclinical studies to the bedside remains challenging, and well-controlled trials of high quality are necessary to define the efficacy of potential therapies already in use and to develop novel drugs. Based on the knowledge acquired with previous studies, these future trials may overcome the challenges posed by this heterogeneous group of disorders in the context of multicenter collaborations by selecting numerous subgroups of homogeneous patients and outcome measures that are objective and relevant to patient care and quality of life. The emerging therapies provide exciting promise for clinically meaningful treatments for mitochondrial diseases. This session will highlight the prospects of using an untargeted metabolomics approach to evaluate disease progression and therapeutic interventions in mitochondrial disease and will discuss some of the emergent therapeutic approaches.

 

10:30 AM   Untargeted metabolomic profiling in mitochondrial disease: Emerging biomarkers. S. H. Elsea. Baylor Col Med, Houston.

11:00 AM   Hypoxia as a potential therapeutic approach for mitochondrial disorders. V. K. Mootha. Massachusetts Gen Hosp, Boston.

11:30 AM   Mitochondrial replacement therapy. S. Mitalipov. Oregon Hlth Sci Univ, Portland.

12:00 PM   Nucleoside bypass therapy for mitochondrial disorders. M. Hirano. Columbia Univ Med Ctr, New York.


Friday, October 18

10:30 AM–12:30 PM

Concurrent Invited Session III

81. Poison Exons in Neurodevelopmental Disorders: From Development and Disease to Therapeutic Target

TBD, Convention Center

Moderators: Gemma L. Carvill, Northwestern Univ, Chicago
  Heather C. Mefford, Univ Washington, Seattle

 

This session will focus on the role of poison exons in epilepsy. Poison exons are small exonic regions that, when spliced into an RNA transcript, lead to premature truncation of a protein. Inclusion of poison exons occurs during specific times in neurodevelopment, and splicing occurs in a cell-specific manner. Many of the genes implicated in neurodevelopmental disorders, including epilepsy, autism, and malformations of cortical development, harbor these poison exons. These include ion channels (SCN1A/2A/8A), epigenetic regulators (CHD2, MBD5), and cytoskeletal proteins (FLNA). In this session, Dr. Mefford will open by describing the current genetic landscape of neurodevelopmental disorders and strategies to identify the molecular etiology in undiagnosed cases. Dr. Mefford will also introduce the concept of poison exons and their function. Dr. Zhang will discuss the studies that identified poison exons in neuronal development, the splicing mechanisms that govern their use, and variants detected in patients with malformations of cortical development that disrupt their splicing. Dr. Carvill will discuss the identification of patient-specific variants that lead to aberrant inclusion of poison exons in genes implicated in epilepsy, including SCN1A, and functional studies in patient-derived induced neurons. Dr. Isom will describe an antisense oligonucleotide that targets an SCN1A poison exon, preventing its inclusion and thus restoring full-length protein and preventing SCN1A-related mortality in an animal model of epilepsy.

 

10:30 AM   A role for poison exons in neurodevelopmental disorders. H. C. Mefford. Univ Washington, Seattle.

11:00 AM   Alternative splicing of poison exons during human neuronal development. X. Zhang. Univ Chicago.

11:30 AM   Aberrant inclusion of poison exons leads to premature truncation of ion channels in epilepsy. G. L. Carvill. Northwestern Univ, Chicago.

12:00 PM   Rescuing SCN1A haploinsufficiency using an antisense oligonucleotide (ASO) targeting a poison exon in a genetic model of epilepsy. L. Isom. Univ Michigan, Ann Arbor.


Friday, October 18

10:30 AM–12:30 PM

Concurrent Invited Session III

82. The Intersection of Genetics and the Disability Rights Movement: Beginning a Dialogue about the Impact of Prenatal Genetic Screening and Testing on Historically Stigmatized Populations

TBD, Convention Center

Moderators: Marsha Michie, Case Western Reserve Univ, Cleveland
  Katie Stoll, Genet Support Fndn, Olympia

 

With the expansion of prenatal screening and testing, an increasing number of fetuses are being identified as having genetic variants that can lead to different disabilities. Many of these genetic conditions entail serious health and cognitive issues. However, in a society where people with disabilities have been historically stigmatized through segregation and institutionalization, a genetic diagnosis can also lead to fears and misperceptions based on social biases, particularly when patients are not provided information or support to explain the social context of disability. Traditionally, the medical model of disability has focused on the health issues associated with various genetic conditions; however, research shows that patients also want information about evolving life outcomes and available support and services. Unfortunately, research also shows that many patients are not provided the information and support they need to understand prenatally-diagnosed conditions in a social context. Toward that end, a bioethicist/anthropologist and a public policy expert will moderate a panel of interdisciplinary experts, including a disability studies scholar/clinical psychologist, a geneticist, a clinician, and a patient education expert. The panel will present on the impact of genetic testing on social biases toward people with disabilities, the current implementation of screening and testing, and the current status of the patient support and educational infrastructure. The session will conclude with a robust discussion with the audience about ways geneticists, disability rights scholars, clinicians, and public health policy experts can unite to create deliberate strategies to ensure the equitable representation of the disability rights movement in the genetics field.

 

10:30 AM   Introduction. M. Michie. Case Western Reserve Univ, Cleveland.

10:40 AM   Exploring the roles of implicit bias and attitudes about disability in navigating ethically complex decisions related to prenatal genetic diagnostic testing. K. Ayers. Univ Cincinnati.

10:55 AM   On the intersection of disability identity and advances in IDD science. J. Constantino. Washington Univ Sch Med St Louis.

11:10 AM   An exploration of strategies for merging the social and medical models of disabilities among clinicians and professional societies in an era of expanded prenatal screening and testing. I. Van den Veyver. Baylor Col Med, Houston.

11:25 AM   Addressing the disability rights movement in the practice of genomic medicine through accurate, balanced, and up-to-date patient education strategies. S. Meredith. Univ Kentucky, Lexington.

11:40 AM   Synthesis and introduction to panel. K. Stoll. Genet Support Fndn, Olympia.

11:50 AM   Panel discussion.


Friday, October 18

10:30 AM–12:30 PM

Concurrent Invited Session III

83. The New Frontier of Epigenetics in Cancer: Modifications of Nucleic Acids

TBD, Convention Center

Moderators: Tao P. Wu, Baylor Col Med, Houston
  Yun Huang, Texas A&M, Houston

 

In the last ten years, dramatic advances in sequencing and high-sensitivity analytical technologies have fundamentally changed the field of human molecular genetics research, particularly in cancer diagnosis and treatment. Although human cancer can be driven by the accumulation of genetic mutations, it can also be driven by non-genetic factors such as dysregulation of metabolic pathways or alterations of epigenetic regulatory processes. In this session, we will showcase the extraordinary impact that the abnormal DNA/RNA modifications ("epi-mutations") are making on tumorigenesis. First, Andrew Xiao, will present how a novel DNA methylation (6mA) was discovered in mammals and its function in glioblastoma. Next, Daniel De Carvalho will describe how his novel approach of cfDNA methylation analyses can detect cancer earlier with a blood test. The third speaker, Yun Huang, will present on the role of TET-mediated DNA methylcytosine oxidation in development. Finally, Anjana Rao will show how the novel modifications of cytosine were discovered and present the critical contributions of these modifications to the neoplastic progress. Her research uncovers a new direction for human disease diagnosis and treatment.

 

10:30 AM   Novel DNA methylation N6-mA in mammals. A. Xiao. Yale Univ, New Haven.

11:00 AM   Sensitive tumour detection and classification using plasma cell-free DNA methylomes. D. De Carvalho. Univ Toronto, Canada.

11:30 AM   Role of TET-mediated DNA methylcytosine oxidation in development. Y. Huang. Texas A&M, Houston.

12:00 PM   TET methylcytosine oxidases in cell differentiation, immune responses and cancer. A. Rao. La Jolla Inst for Immunology.


Friday, October 18

10:30 AM–12:30 PM

Concurrent Invited Session III

84. Tribal Colleges and Universities: Teaching Genomics with an Indigenous Perspective

TBD, Convention Center

Moderators: Carla L. Easter, NHGRI, Bethesda
  Francis Onduso, Sitting Bull Col, Fort Yates

 

There are 32 accredited Tribal Colleges and Universities (TCUs) within the United States that serve approximately 30,000 students from more than 250 federally recognized American Indian and Alaska Native tribes. These colleges are chartered by their respective tribal governments, offer degree programs from the humanities to the sciences, and are in service to their respective communities. At the core of tribal colleges is providing quality and supportive higher education opportunities to predominantly American Indian students that are culturally and traditionally based. This session will discuss the importance of teaching genomics at tribal colleges and the various ways that tribal colleges are teaching genetics and genomics with an Indigenous perspective. Specific conversations also will focus on the importance of tribal college faculty and student networks in the field of genomics and the need for increased opportunities for conversations about the ethical, legal, and cultural concerns surrounding genomics for many American Indians and Alaska Natives.

 

10:30 AM   The inclusion of handheld DNA sequencers in classrooms at tribal colleges. R. Arnold. Northwest Indian Col, Bellingham.

11:00 AM   Developing culturally-inclusive genomics education at tribal colleges. K. Tsosie. Turtle Mountain Community Col, Nashville.

11:30 AM   Tribal colleges consortium on genomics training coordinator of the studies in Indigenous Borderlands Program. A. Quijada. Tohono O'odham Community Col, Sells.

12:00 PM   Pursing a career in genomics for tribal college students. T. Vargas. Oglala Lakota Col, Rapid City.