Tuesday, October 10 8:00 AM–9:30 AM
Concurrent Social Issues Sessions I (1–2)
SESSION 1 – Impact of the Current Regulatory Climate on Genetic Studies in Humans
Hall E-3
Moderator: Katherine Neiswanger, Center for Craniofacial and Dental Genetics, University of Pittsburgh, PA
For many human genetics researchers, the current regulatory climate is a source of increasing concern, depending on the specific policies of their local Institutional Review Boards (IRB). In this session, speakers and panelists will address several aspects of this complex topic, such as: Is genetic research inherently different from other research on human beings? What about genetic research on children? How does federal policy become implemented at the local IRB, with specific reference to genetic risk and benefit estimates? Are there consent issues specific to large-scale genomic studies with open-access databases? Do regulatory bodies have a more constricted view of risk than research participants, and is this appropriate? A final question and answer session will explore avenues by which human geneticists can work more effectively with their regulatory counterparts to enable genetic research on human subjects, while protecting them from exploitation or unnecessary risk.8:00 AM Introduction and overview: Local versus federal regulations regarding genetic studies in humans. M. L. Marazita, University of Pittsburgh, PA.
8:15 AM Consent issues for large-scale studies where data access is increasingly open. F. S. Collins, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD.
8:30 AM From subjects to participants: At the crux of benefit and risk. S. F. Terry, The Genetic Alliance, Washington, DC.
8:45 AM Policies and practices of genetics and genomics research. S. B. Haga, Duke University, Durham, NC.
9:00 AM Panel discussion and questions.
Tuesday, October 10 8:00 AM–9:30 AM
Concurrent Social Issues Sessions I (1–2)
SESSION 2 – Delivering the Promise of Personalized Medicine: Challenges for Pharmacogenetics
Hall E-1
Moderator: Wylie Burke, University of Washington School of Medicine, Seattle
Pharmacogenetics, the study of the genetic basis for differences in drug response, promises the tailoring of therapeutic regimes to specific patients’ genomic profiles, an advance widely anticipated to revolutionize both drug evaluation and clinical practice. While the advantages of using genetic information to increase drug efficiency and safety are clear, many important questions remain about the ways in which genetic variation relevant to drug response will be characterized, how such characterizations will direct the stratification of clinical trial participants in an effort to expedite drug development, and whether these choices will promote or impede the broad availability of desired therapeutic interventions. This session will examine the complex nexus of basic science, translational advance, and clinical application relevant to these challenging questions with the aim of identifying the specific social and ethical implications of current practice in this rapidly developing area.8:00 AM Introduction. W. Burke, University of Washington, Seattle.
8:05 AM Pharmacogenetics: Current progress and future prospects. D. B. Goldstein, Duke University, Durham, NC.
8:30 AM The role of pharmacogenomics in drug development: Economic and regulatory considerations. A. M. Issa, University of Houston and The Methodist Hospital, Houston, TX.
8:55 AM Ethical and social implications of genetically targeted therapeutics. S. S.-J. Lee, Stanford University Medical School, Palo Alto, CA.
9:20 AM Discussion.
Tuesday, October 10 8:00 AM–9:30 AM
Concurrent Education Sessions I (3–5)
SESSION 3 – Studying Gene-Environment Interactions to Better Understand the Etiology of Birth Defects
La Nouvelle Ballroom C
Moderator: J. M. Friedman, University of British Columbia, Vancouver British Columbia Canada
Many birth defects appear to be complex, resulting from a combination of risk factors. Even for cases where defects are largely determined by exposures, the genetic background of the infant, mother or both may confer increased susceptibility to environmental effects. Therefore, examining exposures without considering genetic background might obscure the causative role of an exposure. Likewise, studying genetic factors alone might not show associations. Thus, genetic and environmental factors must be considered simultaneously. This session will present techniques, advances and challenges in the identification of gene-environment interactions contributing to birth defects. The session will review the study of gene-environment interactions, discussing accomplishments and limitations using traditional epidemiological study designs and how future studies and alternative designs may address these issues. Specific examples of birth defects studies combining environmental and genetic factors will be presented, as well as methods for identifying novel gene-environment interactions involved in birth defects using animal models.8:00 AM Introduction. J. M. Friedman, University of British Columbia, Children's and Women's Hospital, Vancouver, British Columbia, Canada.
8:10 AM Going beyond nature versus nurture: Advances and challenges in studying genetic and environmental factors together in association studies. M. J. Khoury, Centers for Disease Control and Prevention, Atlanta, GA.
8:30 AM Maternal smoking, genetic variation of glutathione S-transferases, and risk for orofacial clefts. E. J. Lammer, Children's Hospital Research Institute, Oakland, CA.
8:50 AM You are what you eat: The importance of gene-nutrient interactions in the etiology of birth defects. R. H. Finnell, Institute of Biosciences and Technology, Houston, TX.
9:10 AM Of mice and men: Using mouse models to study gene-environment interactions in birth defects. K. Sulik, University of North Carolina , Chapel Hill.
Tuesday, October 10 8:00 AM–9:30 AM
Concurrent Education Sessions I (3–5)
SESSION 4 – Genetic Studies in Special Populations
Room 243-245
Moderator: Jeff Gulcher, deCODE Genetics, Reykjavik, Iceland
Special populations had discrete founders whose descendants experienced genetic isolation as the result of geography, religion, or cultural practice. In turn, these populations accumulated prevalent founder mutations for Mendelian conditions with extended intervals of linkage disequilibrium (LD). The LD has been used for identifying founder mutations for diseases and coalescence times for these mutations. Once identified, these founder mutations have been used for studies of prevalence and penetrance and, in turn, for the creation of genetic programs for prevention or early identification of disease. Among the special populations that have been studied are Icelandics, Sardinians, Amish and Mennonites, and Jews. Over the last 5 to 10 years, several common diseases have been extensively studied in these relatively isolated populations. This approach has come of age and has yielded several genes for common diseases such as schizophrenia, stroke, hyperlipidemia, nephrolithiasis, and myocardial infarction.8:00 AM Introduction. J. Gulcher, deCODE Genetics, Reykjavik, Iceland.
8:10 AM Population genetics in common diseases. K. Stefansson, deCode Genetics, Reykjavik, Iceland.
8:30 AM The Sardinian genetic park of Ogliastra: An ideal isolated population for complex traits. M. Pirastu, National Research Council of Italy and Shardna Lifesciences, Pula, Italy.
8:50 AM Strategies for gene identification, characterization of molecular lesions, and delivery of efficient testing among Amish and Mennonite populations. E. Puffenberger, Clinic for Special Children, Strasburg, PA.
9:10 AM The 4000-year genetic history of Jewish populations. H. Ostrer, New York University School of Medicine, New York.
Tuesday, October 10 8:00 AM–9:30 AM
Concurrent Education Sessions I (3–5)
SESSION 5 – Interpreting Functional Variation in the Human Genome
La Nouvelle Ballroom A/B
Co-Moderators: Emmanouil (Manolis) Dermitzakis, The Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom; and George M. Weinstock, Baylor College of Medicine, Houston, TX
One of the biggest problems in the post-genome era is the interpretation of the nature of variation, nucleotide or large scale, in the human genome. Although we have some idea of how to interpret variation within coding sequences, the majority of functional DNA is non-coding and variation within noncoding sequences is difficult to interpret. In addition, many aspects of coding variation are still unknown (e.g., positive selection). In this session the speakers will present their research efforts in interpreting the function and phenotypic impact of such variation in both coding and noncoding regions and how this relates to the identification of disease variants. These efforts will have a high impact on the understanding of phenotype-genotype associations and the pathophysiology of genetic disorders.8:00 AM The ENCODE project: functional annotation of one percent of the human genome. A. Reymond, Center for Integrative Genomics, Lausanne, Switzerland.
8:20 AM Functional and regulatory variation in the ENCODE regions. E. T. Dermitzakis, The Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
8:40 AM Inference of functional variation in coding and noncoding DNA. A. G. Clark, Cornell University, Ithaca, NY.
9:05 AM Structural variation and disease in the human genome. E. Eichler, University of Washington, Seattle.
Tuesday, October 10 10:00 AM–11:30 AM
Concurrent Social Issues Sessions II (6–7)
SESSION 6 – Behavioral Genetics Beyond the Science: Should Researchers Consider Ethical, Legal, and Social Implications?
Room 243-245
Moderator: Marcus Feldman, Stanford University, Stanford, CA
Behavioral genetics raises a number of issues due to the complexity of human behavior. Understanding what genetic tools can say about such complex and socially-charged traits as intelligence, sexuality, or aggression is an important consideration. Researchers may see the scientific value in and validity of such studies. How these findings are interpreted and used by the public and societal institutions, however, are other important considerations. This session will identify some of the most significant ethical, legal, social, and policy issues raised by anticipated research on behavioral genetics. The role of geneticists in incorporating consideration of these issues into the conduct of research will be discussed. What is the responsibility of researchers who study the genetics of behavior to deal with the potential positive and negative consequences of their work? How, if at all, should ethical, legal, social, and policy considerations affect study design, data analysis, and reporting results?10:00 AM Introduction. M. Feldman, Stanford University, Stanford, CA.
10:10 AM What can genetics say (or not say) about complex traits? D. Goldstein, Duke University, Durham, NC.
10:25 AM How should ethical, legal, and social considerations affect study design, analysis, and reporting? L. Baker, University of Southern California, Los Angeles.
10:40 AM What are the ethical, legal, social, and policy issues to consider? T. Simoncelli, American Civil Liberties Union, New York, NY.
10:55 AM Discussion.
Tuesday, October 10 10:00 AM–11:30 AM
Concurrent Social Issues Sessions II (6–7)
SESSION 7 – Direct to Consumer Genetic Testing: Empowering or Endangering the Public?
Hall E-1
Moderator: Kathy Hudson, The Johns Hopkins University, Washington, DC
Some genetic testing companies are beginning to sell tests directly to consumers, eliminating the need to go to a doctor’s office. Test results usually are made available online, in the privacy of one’s own home. Will at home genetic tests provide useful genetic information in a private, nonthreatening way? Or will these tests pose real risks to health and take advantage of people desperately seeking answers? Panelists will share their diverse perspectives and explore the commercial, legal, medical and ethical issues raised by direct-to-consumer (DTC) marketing of genetic tests. In addition, the panel and audience will consider what position, if any, the ASHG should take regarding DTC genetic testing.10:00 AM Introduction. K. Hudson, Genetics & Public Policy Center, Johns Hopkins University, Washington DC.
10:10 AM Direct-to-consumer DNA testing: The way to the future. H. Coleman, Genelex Corporation, Seattle, WA.
10:25 AM At-home fetal gender DNA testing: Caveat emptor. D. Bianchi, Tufts-New England Medical Center, Boston, MA.
10:40 AM Regulatory landscape for DTC genetic testing. G. Javitt, Johns Hopkins University, Washington, DC.
10:55 AM Panel discussion and questions and answers.
Tuesday, October 10 10:00 AM–11:30 AM
Concurrent Education Sessions II (8–10)
SESSION 8 – Evidence-based Medicine Meets Medical Genetics
La Nouvelle Ballroom C
Co-Moderators: Robert D. Steiner, Oregon Health Sciences University, Portland; and Amy Sturm, The Ohio State University, Columbus
The practice of evidence-based medicine continues to be a challenge in the field of medical genetics. In this session, the speakers will introduce the topic of evidence-based medicine in general, and will also discuss whether or not it currently applies to both rare, pediatric disorders as well as common, chronic diseases of adulthood that have a genetic component. The evaluation of genetic tests and their entry into the clinical arena will also be discussed. Approaches for the systematic collection of evidence to guide the treatment and management of genetic conditions will be presented, including the development of national and international collaborative genetics research networks for testing and evaluating new genetic tests, treatments, and management recommendations for genetic diseases.10:00 AM Evidence-based medicine in rare genetic conditions. R. D. Steiner, Oregon Health Sciences University, Portland.
10:20 AM Evidence-based medicine in common disease genetics. M. T. Scheuner, Rand Corporation, Santa Monica, CA.
10:40 AM Evidence-based evaluation of genetic tests. W. Burke, University of Washington School of Medicine, Seattle.
11:00 AM Efforts for collecting the missing evidence base in medical genetics. M. S. Watson, American College of Medical Genetics, Bethesda, MD.
11:20 AM Questions and answers.
Tuesday, October 10 10:00 AM–11:30 AM
Concurrent Education Sessions II (8–10)
SESSION 9 – Whole Genome Association Studies for Common Diseases
La Nouvelle Ballroom A/B
Moderator: Francis S. Collins, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD
Identifying genetic factors that influence health, disease, and response to treatment is essential to reduce the burden of disease. With the sequencing of the human genome, more efficient genotyping and sequencing technologies, and the International Haplotype Map project, we now have powerful research tools for identifying genetic variants that contribute to common diseases. Researchers can now employ whole genome association studies to uncover regions of the genome and even specific genes contributing to disease susceptibility. We have an historic opportunity to understand key aspects of the complex contributions of genetic variation to health, with major consequences for prevention, diagnosis, and treatment. This session will draw upon recent large, coordinated whole genome association studies to consider the scientific opportunities presented by such studies and the challenges they face, how to mine and analyze the data from such projects, and the opportunities they offer for devising new diagnostics and therapeutics.10:00 AM Introduction. F. S. Collins, National Human Genome Research Institute, National Institutes, of Heath, Bethesda, MD.
10:10 AM Whole genome association studies: The why and how. A. Chakravarti, McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University, Baltimore, MD.
10:30 AM Whole genome association studies: Mining and analyzing data. D. Altshuler, Broad Institute of Harvard and MIT, Cambridge, MA.
10:50 AM Whole genome association studies: Therapeutic opportunities. P. Milos, Pfizer, Inc., Groton, CT.
11:10 AM Questions and answers.
Tuesday, October 10 10:00 AM–11:30 AM
Concurrent Education Sessions II (8–10)
SESSION 10 – Genetics of Type 1 Diabetes
Hall E-3
Moderator: Michael Boehnke, University of Michigan, Ann Arbor
This session will cover the current progress being made in understanding the genetic basis of type 1 diabetes. Four presentations will provide updates on genomewide linkage studies, including an in-depth examination of the MHC, in humans (Type 1 Diabetes Genetics Consortium); results from the first major genomewide association study of type 1 diabetes in humans (Wellcome Trust Case Control Consortium); progress in resolving the genetic basis of type 1 diabetes in mouse; and the search for genes that influence risk of micro- and macrovascular complications of type 1 diabetes. Studies in type 1 diabetes genetics may serve as a model for other complex human diseases, including the coordination of international efforts to collect, characterize, and analyze samples. The use of human (linkage and association) and model system approaches and resources for performing these genetic studies may provide insights for addressing the genetic basis of other "classically complex human traits."10:00 AM Introduction. M. Boehnke, Univ of Michigan, Dept of Biostatistics, Ann Arbor MI.
10:02 AM The Type 1 Diabetes Genetics Consortium: Linkage, fine mapping of the human MHC and beyond. S. S. Rich, Wake Forest University School of Medicine, Winston-Salem, NC.
10:24 AM Whole genome association approaches to the genetic basis of type 1 diabetes: The Wellcome Trust Case Control Consortium. J. Todd, The Wellcome Trust/JDRF Diabetes Inflammation Laboratory, Cambridge, United Kingdom.
10:46 AM Identification and modulation of molecular genetic mechanisms leading to type 1 diabetes in the NOD mouse. L. Wicker, Addenbrooke Hospital, Cambridge, United Kingdom.
11:08 AM Genetic basis of complications of type 1 diabetes. A. Krolewski, Joslin Diabetes Center, Boston, MA.
Tuesday, October 10 1:30 PM–3:30 PM
SESSION 12 – Plenary Abstract Presentations
Hall F
Co-Moderators: Stephen T. Warren, Emory University School of Medicine, Atlanta, GA; and William A, Gahl, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD
1/1:30 Identification of Kalirin gene as a novel coronary artery disease gene through peak-wide association mapping on chromosome 3q13-21. L. Wang, E. R. Hauser, S. H. Shah, C. Haynes, M. Harris, J. Rombaut, D. Crosslin, S. Nelson, A. B. Hale, S. G. Gregory, W. E. Kraus, M. Pericak-Vance, P. J. Goldschmidt-Clermont, J. M. Vance, GENECARD. Investigators.
2/1:50 Mutations in FGF Signaling Pathway Genes Contribute to Cleft Lip and Palate. B. M. Riley, M. A. Mansilla, L. Raffensperger, B. Maher, M. L. Marazita, M. Mohammadi, J. C. Murray.
3/2:10 A functional SNP in proteolipid protein 2 (PLP2) promoter increases ER stress induced apoptosis and confers increased risk of neonatal hypoxic-ischemic brain injury. L. Zhang, T. Wang, D. Valle.
4/2:30 Identification and characterization of a dynactin associated protein (Dynapsin) involved in late-onset Alzheimer disease (AD). J. R. Gilbert, S. Zuchner, C. A. Browning, G. F. Wang, C. R. Lu, P. G. Bronson, C. F. Potocky, S. M. Garvey, C. C. Kroner, J. R. Gibson, J. M. van der Walt, Y. J. Li, P. T. Xu, D. E. Schmechel, W. K. Scott, J. M. Vance, J. L. Haines, E. R. Martin, M. A. Pericak-Vance.
5/2:50 Comprehensive mutation analysis in Costello syndrome, CFC syndrome and Noonan syndrome: clinical and genetic overlap among three disorders. Y. Aoki, T. Niihori, Y. Narumi, H. Kawame, K. Kurosawa, H. Ohashi, M. Filocamo, G. Neri, H. Cavé, A. Verloes, N. Okamoto, R. C. M. Hennekam, G. Gillessen-Kaesbach, D. Wieczorek, M. I. Kavamura, L. Wilson, Y. Suzuki, S. Kure, Y. Matsubara.
6/3:10 In vitro and in vivo effects of farnesyltransferase inhibitors for Hutchinson-Gilford progeria syndrome. B. C. Capell, M. R. Erdos, M. Eriksson, R. Varga, M. Olive, F. Kolodgie, H. Avallone, H. San, X. Qu, L. B. Gordon, R. Virmani, E. G. Nabel, W. A. Gahl, F. S. Collins.
Tuesday, October 10 8:00 PM–10:00 PM
SESSION 14 – Trainee Program: Can I Get There from Here? Different Career Paths for Scientists
Room 243-245
This program is a special session for graduate students and post-doctoral fellows organized by the newly formed Ad Hoc Postdoctoral Committee. ASHG trainees interested in an event designed to broaden their knowledge about rewarding careers ranging from laboratory research to patent law should attend. Members of the biotechnology, patent law, clinical diagnostic, academic research, policy and journalism communities will describe what it takes for PhD recipients to be successful in different scientific careers. Finally, a network session will be open to all participants to discuss these careers and a variety of others including education, public health, and science writing. The event is limited to 250 attendees.8:00 PM Opening Remarks. D. Scholes, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland; Science Policy Fellow, Washington, DC.
8:00 PM Keynote Address: Challenges for Young Scientists. B. Lindstaedt, University of California, San Francisco.
8:00 PM Career Panel. C. C. Morton1, C. Gunter2, N. Katsanis3, P. Frosst4, L. Sung5, 1) Brigham and Women’s Hospital, Boston, Massachusetts; 2) Nature, Washington, DC; 3) The Johns Hopkins University School of Medicine, Baltimore, Maryland; 4) The National Human Genome Research Institute, Bethesda, Maryland; 5) University of Maryland School of Law, Baltimore, Maryland.
9:00 PM Networking reception with representatives from industry, academia, law, education, scientific societies, public health, policy, genetic counseling and other fields.
Wednesday, October 11 8:00 AM–10:30 AM
Concurrent Platform Sessions I (15–21)
SESSION 15 – Molecular Basis of Mendelian Disorders I
Hall F
Co-Moderators: Miriam Meisler, University of Michigan, Ann Arbor; and Daniel H. Cohn, Cedars Sinai Medical Center, Los Angeles, CA
7/8:00 Detection of known and novel human syndromes by high-density oligonucleotide array comparative genomic hybridization (HOaCGH). Y.-S. Fan, D. Barbouth, P. Jayakar, H. Zhu, S. Sacharow, L. J. Elsas.
8/8:15 Slc25a19 is a mouse mitochondrial transporter necessary for viability, neural tube closure, erythropoiesis, and maintenance of mitochondrial thiamine pyrophosphate pools. M. J. Lindhurst, G. Fiermonte, S. Song, E. Struys, F. De Leonardis, A. Chen, A. Castegna, N. Verhoeven, C. K. Mathews, F. Palmieri, L. G. Biesecker.
9/8:30 Mutations in the monogenic diabetes gene HNF4alpha are a novel cause of macrosomia and neonatal hyperinsulinism. A. T. Hattersley, A. Steele, T. Barrett, K. Stals, J. P. Shield, S. Ellard, E. R. Pearson.
10/8:45 HEM Dysplasia and Mouse Ichthyosis are not due to Sterol D14-Reductase Deficiency. C. A. Wassif, K. E. Brownson, W. K. Wilson, M. F. Starost, F. D. Porter.
11/9:00 BBS proteins are necessary for proper function of the regulatory center of the centrosome and spindle pole and for regulation of b-tubulin levels. J. Wei, H. J. Yen, A. Fedler, Q. Qian, C. Searby, M. Andrews, D. Y. Nishimura, S. Patil, V. C. Sheffield.
12/9:15 Demonstration of Genetic Interactions between TRIM32 and other Bardet-Biedl Syndrome Genes. M. K. Tayeh, H.-J. Yen, R. F. Mullins, A. P. Chiang, J. S. Beck, C. C. Searby, T. A. Westfall, H. Griesback, E. M. Stone, D. C. Slusarski, V. C. Sheffield.
13/9:30 The CHD7 protein, mutated in CHARGE syndrome, binds to specific sites on chromatin. P. C. Scacheri, F. Tie, S. R. Lalani, J. W. Belmont, F. S. Collins.
14/9:45 SUMO1 haploinsufficiency can cause cleft lip and palate. I. Saadi, F. S. Alkuraya, J. J. Lund, A. Turbe-Doan, C. C. Morton, R. L. Maas.
15/10:00 Obesity, reduced fertility, and disrupted cicadian rhythm in mice with a targeted mutation in the Prader-Willi syndrome gene MAGEL2. R. Wevrick, S. V. Koslov, J. M. Bischof, A. A. Tennese, J. W. Bogenpohl, R. van Gelder, E. D. Herzog, C. L. Stewart.
16/10:15 LADD syndrome is caused by mutations that reduce the tyrosine kinase activity of FGFR2. E. Rohmann, I. Lax, E. D. Lew, V. P. Eswarakumar, H. G. Brunner, Y. Li, H. Kayserili, J. Schlessinger, B. Wollnik.
Wednesday, October 11 8:00 AM–10:30 AM
Concurrent Platform Sessions I (15–21)
SESSION 16 – Psychiatric Genetics
La Nouvelle Ballroom A/B
Co-Moderators: Allison Ashley-Koch, Duke University, Durham, NC; and Rita Cantor, University of California, Los Angeles
17/8:00 Alcohol dependence is associated with the ZNF699 gene, a human locus related to Drosophila hangover, in the Irish Affected Sib Pair Study of Alcohol Dependence (IASPSAD) sample. B. Riley, G. Kalsi, P.-H. Kuo, V. Vladimirov, D. L. Thiselton, J. Vittum, B. Wormley, M. S. Grotewiel, D. G. Patterson, P. F. Sullivan, E. J. van den Oord, D. Walsh, K. S. Kendler, C. A. Prescott.
18/8:15 A set of putative functional IDE and PLAU variants shows significant, replicable association with Alzheimer's Disease. M. Carrasquillo, S. Younkin, M. Kashino, S. Wilcox, T. Dincman, L. Younkin, L. Ma, F. Zou, N. Taner, M. Allen, R. Petersen, N. Graff-Radford, S. Younkin.
19/8:30 Autosomal dominant early onset Alzheimer disease with cerebral amyloid angiopathy caused by APP duplication: clinical and neuropathological study of five French families. L. Guyant-Maréchal, L. Cabrejo, A. Laquerrière, M. Vercelletto, F. De La Fournière, C. Thomas-Antérion, C. Verny, F. Letournel, F. Pasquier, A. Vital, F. Checler, T. Frebourg, C. Campion, D. Hannequin.
20/8:45 Association study of cerebrospinal fluid amyloid b levels with late-onset Alzheimer disease associated polymorphisms. J. S. K. Kauwe, A. M. Fagan, M. L. Spinner, A. R. Shah, K. Mayo, D. M. Holtzman, A. Grupe, A. Goate.
21/9:00 Genomic convergence in Alzheimer disease. M. Slifer, E. Martin, H. Munger, J. Haines, J. Gilbert, M. Pericak-Vance.
22/9:15 A second MHC susceptibility locus for multiple sclerosis. S. J. Sawcer for the International Multiple Sclerosis Genetics Consortium (IMSGC).
23/9:30 Allelic association of the interleukin 7 receptor gene (IL7R) with multiple sclerosis (MS). S. G. Gregory, S. Schmidt, J. Hart, A. Prokop, J. van der Walt, L. F. Barcellos, C. DeLoa, J. R. Oksenberg, S. L. Hauser, J. L. McCauley, M. A. Pericak-Vance, J. L. Haines.
24/9:45 Compromised mRNA processing and epilepsy in Brunol4 mutant mice. W. Frankel, Y. Yang, C. Mahaffey, T. Maddatu, G. Cox, J. Graber.
25/10:00 A 2p12 locus with two co-regulated genes is associated to dyslexia in Finnish and German populations. H. Anthoni, M. Zucchelli, H. Matsson, J. Schumacher, J. Nopola-Hemmi, H. Lyytinen, G. Schulte-Körne, J. Kere, M. M. Nöthen, M. Peyrard-Janvid.
26/10:15 Reading disability: is the 6p22 locus DCDC2, KIAA0319 or both? Using integromic techniques to resolve the conflict. G. P. Page, A. Patki, K. Zhang, T. Mehta, V. Srinivasasainagendra, H. Main, J. R. Gruen.
Wednesday, October 11 8:00 AM–10:30 AM
Concurrent Platform Sessions I (15–21)
SESSION 17 – Diabetics and Obesity
La Nouvelle Ballroom C
Co-Moderators: Karen Mohlke, University of North Carolina, Chapel Hill; and Hemant Tiwari, University of Alabama, Birmingham
27/8:00 Gene-gene interaction methods for family-based case-control data. D. B. Hancock, E. R. Martin, Y. J. Li, W. K. Scott.
28/8:15 Combining information from multiple common susceptibility polymorphisms increases the predictive power of genetic information: a study of replicated type 2 diabetes variants. M. N. Weedon, M. I. McCarthy, G. Hitman, M. Walker, C. J. Groves, E. Zeggini, N. W. Rayner, B. Shields, K. R. Owen, A. T. Hattersley, T. M. Frayling.
29/8:30 Genome-wide Association Studies of Type 2 Diabetes in Mexican Americans. M. G. Hayes, K. Miyake, C. L. Hanis, G. I. Bell, N. J. Cox.
30/8:45 Type 2 diabetes TCF7L2 risk alleles reduce beta-cell function and increase birth weight. R. M. Freathy, M. N. Weedon, M. I. McCarthy, M. Walker, G. A. Hitman, Y. Ben-Shlomo, G. Davey Smith, S. M. Ring, A. T. Hattersley, T. M. Frayling.
31/9:00 Common SNPs in TCF7L2 are reproducibly associated with type 2 diabetes and reduce the insulin response to glucose in non-diabetic individuals. R. Saxena, L. Gianniny, N. Burtt, V. Lyssenko, C. Giuducci, M. Sjögren, J. Florez, P. Almgren, B. Isomaa, M. Orho-Melander, U. Lindblad, M. Daly, T. Tuomi, J. N. Hirschhorn, K. Ardlie, L. Groop, D. Altshuler.
32/9:15 Genome-wide association analysis of obesity using 304,968 SNPs in 869 Finnish normal glucose tolerant individuals. K. L. Mohlke, A. U. Jackson, L. J. Scott, K. N. Conneely, A. Swift, K. F. Doheny, E. W. Pugh, R. M. Watanabe, G. R. Abecasis, T. T. Valle, J. Tuomilehto, R. N. Bergman, F. S. Collins, M. Boehnke.
33/9:30 Polymorphisms in the SEC8L1 (EXOC4) gene encoding a component of the exocyst complex influence BMI, leptin, and insulin levels in the NHLBI Family Heart Study. J. B. Wilk, J. M. Laramie, S. Williamson, C. Leiendecker-Foster, J. H. Eckfeldt, I. B. Borecki, M. A. Province, R. H. Myers.
34/9:45 Genetic analysis of transcriptional profiles for the identification of genes influencing obesity. J. C. Charlesworth, J. E. Curran, M. P. Johnson, H. H. H. Göring, T. D. Dyer, A. G. Comuzzie, S. A. Cole, M. C. Mahaney, J. B. M. Jowett, J. W. MacCluer, G. R. Collier, E. K. Moses, J. Blangero.
35/10:00 Association testing of candidate genes in the anabolic neuropeptide pathway with obesity among the Samoans of Polynesia. D. T. Smelser, G. Sun, R. Kaushal, P. Pal, S. Viali, J. Tufa, R. Chakraborty, D. E. Weeks, S. T. McGarvey, R. Deka.
36/10:15 Medical Sequencing at the Extremes of Human Body Mass. N. Ahituv, N. Kavaslar, J. Cohen, R. Dent, R. McPherson, L. A. Pennacchio.
Wednesday, October 11 8:00 AM–10:30 AM
Concurrent Platform Sessions I (15–21)
SESSION 18 – Cytogenetics
Hall E-1
Co-Moderators: Brynn Levy, Columbia University, New York, NY; and Marilyn L. Slovak, City of Hope National Medical Center, Duarte, CA
37/8:00 New Insights into Mechanisms and Consequences of Small Marker (Ring) Chromosomes. E. L. Baldwin, L. F. May, C. L. Martin, D. H. Ledbetter.
38/8:15 Detection and characterization of supernumerary marker chromosomes by array CGH. S. A. Horner, S. G. Sulpizio, R. M. Lloyd, B. A. Bejjani, L. G. Shaffer, B. C. Ballif.
39/8:30 Elucidation of the Structure of Inverted Duplications: heterogeneity in the Mechanism of Formation. A. E. Murmann, C. A. Curtis, L. A. Christ, D. F. Conrad, H. Mashek, S. Schwartz.
40/8:45 Molecular analyses of duplications on human chromosome 17p. W. Bi, X. Shi, C. M. B. C. Fonseca, C. Shaw, G. Weissenberger, L. Potocki, J. R. Lupski.
41/9:00 Screening of deletions and duplications in 1500 genomic loci in a single assay. J. Fan, S. J. White, M. Bibikova, L. Zhou, J. Chen, E. Wickham-Garcia, M. E. Kalf, M. Kriek, G. J. B. van Ommen, M. H. Breuning, L. Guo, S.-H. Lu, Q. Zhan, W. Jiang, O. Chan, J. Wang-Rodriguez, D. L. Barker, J. T. den Dunnen.
42/9:15 Elevated rates of sister chromatid exchange at chromosome ends. K. Rudd, C. Friedman, E. Linardopoulou, B. Trask.
43/9:30 The clinical utility of enhanced subtelomere coverage in array CGH. B. C. Ballif, S. G. Sulpizio, R. M. Lloyd, S. Gaskin, S. L. Minier, K. Sundin, M. Lincicum, E. A. Rorem, C. D. Kashork, B. A. Bejjani, L. G. Shaffer.
44/9:45 Summary of clinical implementation of Chromosomal Microarray Analysis (CMA) in 2668 cases. X. Y. Lu, J. Li, A. Patel, M. L. Cooper, W. R. Wells, C. M. Sullivan, T. Sahoo, S. A. Yatsenko, Z. Ou, P. Stankiewicz, J. R. Lupski, C. Chinault, A. L. Beaudet, S. W. Cheung, P. A. Ward.
45/10:00 Validation of SNP Oligonucleotide Microarray Analysis (SOMA) for Clinical Cytogenetic Diagnosis. V. Jobanputra, O. Nahum, K. Anyane-Yeboa, W. Chung, Y. Sun, E. Bottinger, W. Zhang, D. Warburton, B. Levy.
46/10:15 Array CGH is superior to other methodologies at detecting somatic mosaicism. V. R. Sutton, C. Shaw, D. A. Scott, A. Patel, S. Trilochan, A. Pursley, J. Li, P. Stankiewicz, A. C. Chinault, J. R. Lupski, A. L. Beaudet, S. W. Cheung.
Wednesday, October 11 8:00 AM–10:30 AM
Concurrent Platform Sessions I (15–21)
SESSION 19 – Perinatal and Reproductive Genetics
Hall E-3
Co-Moderators: Melissa Fries, Washington Hospital Center, Washington, DC; and Louise Willkins-Haug, Brigham and Women's Hospital, Boston, MA
47/8:00 Association of VEGFR-1, 2, and 3 htSNPs with susceptibility to preeclampsia. S. M. Zeng, J. Yankowitz, J. Murray, D. Merrill.
48/8:15 The genetic susceptibility to retinopathy of prematurity. M. Bizzarro, N. Hussain, B. Jonsson, R. Feng, L. Ment, J. Gruen, H. Zhang, V. Bhandari.
49/8:30 Noninvasive genotyping fetal Kell blood group (KEL1) using cell-free fetal DNA in maternal plasma by MALDI-TOF mass spectrometry. Y. Li, K. Finning, G. Daniels, W. Holzgreve, S. Hahn.
50/8:45 Array-based comparative genomic hybridization (array CGH) for rapid prenatal diagnosis of cytogenetic abnormalities. I. Van den Veyver, T. Sahoo, C. Shaw, S. Kang, D. Del Gaudio, S. Darilek, A. Patel, P. Ward, J. Li, C. Chinault, B. Roa, J. Lupski, A. Beaudet, S. Cheung, C. Eng.
51/9:00 Outcome analysis of pregnancies screening positive for Smith-Lemli-Opitz syndrome. M. Steinraths, A. Mattman, S. Langlois.
52/9:15 Fragile X prenatal analyses show full mutation females at increased risk for mosaic Turner syndrome: Loss of maternal X? C. Dobkin, G. Radu, X. Ding, W. T. Brown, S. L. Nolin.
53/9:30 Polar body vs. blastomere biopsy for PGD: PB or not PB? G. Altarescu, T. Eldar-Geva, B. Brooks, Y. Kaplan, M. Patt, E. J. Margalioth, A. Lahad, E. Levy-Lahad, P. Renbaum.
54/9:45 Germline analysis of the ACVR1B gene as a candidate gene for ovarian failure. H. Dixit, K. L. Rao, J. Nair, V. V. Padmalatha, M. K. Kanakavalli, M. Deenadayal, N. Gupta, B. N. Chakrabarty, L. Singh.
55/10:00 Genetic dissection of male infertility-related molecular pathways by transcriptional profiling of testicular biopsies from patients with non-obstructive azoospermia. A. Tajima, Y. Sakamoto, H. Okada, A. Tanaka, K. Shichiri, K. Tanaka, I. Inoue.
56/10:15 TENR gene mutations in infertile males who display oligospermia or azoospermia. T. D. Brown, L. P. Chorich, L. C. Layman.
Wednesday, October 11 8:00 AM–10:30 AM
Concurrent Platform Sessions I (15–21)
SESSION 20 – Genetic Therapy and Models for Therapy
Room 243-245
Co-Moderators: Ellen Sidransky, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD; and Fernando Scaglia, Baylor College of Medicine, Houston, TX
57/8:00 A Phase 3 study of the efficacy of sapropterin dihydrochloride (tetrahydrobiopterin, 6R-BH4) in reducing phe levels in subjects with phenylketonuria. H. Levy, A. Milanowski, A. Chakrapani, M. Cleary, F. Trefz, C. Whitley, F. Feillet, A. Feigenbaum, J. Bebchuk, H. Christ-Schmidt, A. Dorenbaum.
58/8:15 Clinical Benefit Following Enzyme Replacement Therapy (ERT) with Alglucosidase alpha in Children with Pompe Disease. D. Corzo, C. Spencer, B. Byrne, M. Nicolino, W. L. Hwu, N. Leslie, H. Mandel, E. Wraith, P. Kishnani.
59/8:30 Losartan decreases aortic root dilation in Marfan syndrome. B. S. Brooke, J. P. Habashi, H. C. Dietz.
60/8:45 Angiotensin II Type 1 Receptor Blockade Improves TGFb-induced Failure of Muscle Regeneration in the mdx Mouse Model of Duchenne Muscular Dystrophy. R. D. Cohn, J. P. Habashi, B. L. Loeys, E. C. Klein, M. Gamradt, T. M. Holm, D. P. Judge, H. C. Dietz.
61/9:00 Therapy of PKU by AAV-1 based transfer of PAH and BH4-cofactor genes into skeletal muscle. B. Thony, C. O. Harding, A. Rebuffat, L. Elzazouk, J. A. Wolff, Z. Ding.
62/9:15 N-Acetylmannosamine treatment rescues a mouse model of Hereditary Inclusion Body Myopathy. M. Huizing, E. Klootwijk, B. Galeano, I. Manoli, M.-S. Sun, C. Cicone, D. Darvish, D. Krasnewich, W. A. Gahl.
63/9:30 Coupling of UPR Induction with Aminoglycosides: a Potential Therapeutic Strategy for Genetic Disorders Caused by Nonsense Mutations. N. A. Sharifi, H. C. Dietz.
64/9:45 Wilson Disease: a Pilot Study of Newborn Screening. S. Zafari, C. A. Kroll, J. E. Brown, M. A. Pogatschnik, S. J. Minnich, M. J. Kurke, M. J. Ferber, S. H. Hahn.
65/10:00 Function Follows Form: Differential respiratory capacity of mitochondrial complex I mutants in C. elegans. M. J. Falk, J. Rosenjack, M. A. O'Riordan, M. M. Sedensky, P. G. Morgan.
66/10:15 A zebrafish model of cobalamin C deficiency displays development defects of the central nervous system. J. Sloan, T. Blake, R. J. Chandler, M. S. Tsai, B. P. Brooks, C. P. Venditti.
Wednesday, October 11 8:00 AM–10:30 AM
Concurrent Platform Sessions I (15–21)
SESSION 21 – Mapping, Linkage and Linkage Disequilibrium (Methods)
Room 343-345
Co-Moderators: Michael E. Weale, Duke University, Durham, NC; and David Reich, Harvard University, Boston, MA
67/8:00 A second-generation combined linkage-physical map of the human genome. F. Chen, C. He, X. Kong, W. Chen, M. Hansen, F. L. Hyland, G. C. Kennedy, S. Murray, Y. Turpaz, F. M. De La Vega, J. Ziegle, T. C. Matise.
68/8:15 Patterns of linkage disequilibrium reveal genotyping errors and copy number polymorphisms. P. Scheet, M. Stephens.
69/8:30 Genomewide association study combining incomplete high resolution SNP data with sparse markers from a linkage scan. W.-M. Chen, G. R. Abecasis.
70/8:45 MCMC provides practical linkage analysis on general pedigrees with many STRs or dense SNPs. E. Wijsman, J. Rothstein, E. Thompson.
71/9:00 Hierarchical Modeling in Linkage Disequilibrium Mapping. G. Chen, E. Jorgenson, J. Witte.
72/9:15 The genetics of copy number variation in a founder population. D. Conrad, M. Abney, C. Ober, J. Pritchard.
73/9:30 Development of a densely genotyped Population Reference Sample (POPRES): a resource for population, disease, and pharmacological genetics research. M. R. Nelson, M. Klotsman, A. M. McNeill, Y. Maruyama, C. E. Bowman, D. Morris, M. E. Ehm, E. H. Lai.
74/9:45 Mapping trait loci using inferred Ancestral Recombination Graphs. M. J. Minichiello, R. Durbin.
75/10:00 Capturing Common, Multi-Ethnic Human Variation On A Single Microarray. S. S. Murray, P. C. Ng, K. Kuhn, D. Peiffer, L. Zhou, L. Galver, C. Taylor, K. Gunderson, R. Shen.
76/10:15 A tree based approach to modeling disease associations in the MHC, reveals evidence of class II-independent type 1 diabetes susceptibility loci. J. M. M. Howson, S. Nejentsev, N. M. Walker, S. Field, J. S. Szeszko, H. E. Stevens, D. G. Clayton, J. A. Todd.
Wednesday, October 11 11:00 AM–1:00 PM
Concurrent Invited Sessions I (22–28)
SESSION 22 – Beyond Genome Variation: Epigenetics in Complex Traits
Hall F
Moderator: Andrew Feinberg, The Johns Hopkins University School of Medicine, Baltimore, MD
While it is well established that DNA variation contributes to complex disease, epigenetic variations, i.e., nonsequence changes associated with DNA and heritable during somatic cell division, are emerging as an additional source of diversity contributing to disease risk. In addition to cancer, in which the role of epigenetics is well established, epigenetic variation is associated with aging and environmental perturbation including diet, and it may both mediate and promote genetic alterations in somatic cells. The purpose of this session is to provide an introduction to this new frontier, focusing on examples of cancer as a model of the epigenetics of complex traits, strategies for high throughput epigenome analysis, the challenges of the resulting large quantitative data sets and their incorporation into disease risk modeling, and the epigenome as a target for environmental perturbation and aging.11:00 AM Introduction. A. P. Feinberg, The Johns Hopkins University School of Medicine, Baltimore, MD.
11:05 AM Cancer as a model for understanding complex trait epigenetics. A. P. Feinberg, The Johns Hopkins University School of Medicine, Baltimore, MD.
11:25 AM Incorporating epigenetic hypotheses into genetic epidemiology. M. D. Fallin, The Johns Hopkins University, Baltimore, MD.
11:45 AM Advances in epigenome technology and implications for the study of aging. M. Esteller, Spanish National Cancer Center, Madrid, Spain.
12:05 PM Genomewide approaches to analysis of cytosine methylation. J. Greally, Albert Einstein College of Medicine, Bronx, NY.
12:25 PM Environmental modification of the epigenome. R. Jirtle, Duke University School of Medicine, Durham, NC.
12:45 PM Discussion.
Wednesday, October 11 11:00 AM–1:00 PM
Concurrent Invited Sessions I (22–28)
SESSION 23 – Medical Sequencing in the Genome Era
La Nouvelle Ballroom A/B
Co-Moderators: Elaine R. Mardis, Washington University School of Medicine, St. Louis, MO; and Len A. Pennacchio, Lawrence Berkeley National Laboratory, Berkeley, CA
The triumph of the Human Genome Project requires little embellishment. The availability of the entire euchromatic genomic sequence serves as a routine starting point for a huge multidisciplinary investigator base and has accelerated our understanding of human genome content, organization and evolution. Yet, the greatest fruits of having such an initial blueprint are still to come, as we unravel how genomic changes lead to a plethora of human diseases and to our inter-individual phenotypic diversity. Continued advances in DNA sequencing methodologies and their further cost reductions will significantly increase clinical access to such technology and exponentially increase the availability of medical sequence- based datasets. These resources will undeniably further our understanding of the genetic bases of human disease susceptibility but will also present significant computational challenges to properly interpret their biological relevance.11:00 AM Introduction. E. R. Mardis, Washington University School of Medicine, St. Louis, MO.
11:05 AM Large-scale mutation discovery in ion channels. R. A. Gibbs, Baylor College of Medicine, Houston, TX.
11:28 AM Genetic architecture of plasma lipoprotein levels. H. H. Hobbs, University of Texas Southwestern Medical Center, Dallas.
11:51 AM Gene copy number variation in cancer and other human diseases. M. Wigler, Cold Spring Harbor Laboratories, Cold Spring Harbor, NY.
12:14 PM Genomic characterization of human cancers. R. K. Wilson, Washington University School of Medicine, St. Louis, MO.
12:37 PM Lessons from re-sequencing candidate genes. D. Nickerson, University of Washington School of Medicine, Seattle, WA.
Wednesday, October 11 11:00 AM–1:00 PM
Concurrent Invited Sessions I (22–28)
SESSION 24 – Aneuploidy: Good, Bad and Environmental
La Nouvelle Ballroom C
Moderator: Terry Hassold, Washington State University, Pullman
In the human genetics community, we frequently take a narrow view of aneuploidy, thinking of it as due to meiotic nondisjunction and leading to either miscarriage or birth defects. Clearly, this is an important component of aneuploidy and, as part of this session, we will update recent studies of nondisjunction in humans and mammalian models. However, a variety of studies suggest that we need to expand our thinking of both the causes and consequences of aneuploidy. Accordingly, we will discuss emerging evidence that aneuploidy is an important driver for cancer and will also focus on aneuploid cells in neurons, providing data that we are all mosaics for chromosome abnormalities and that aneuploidy may be necessary for functioning neurons. Finally, we will summarize recent data indicating that exposure to endrocrine disruptors affects meiotic synapsis, recombination and chromosome segregation in mice, suggesting that the environment is an important contributor to aneuploidy.11:00 AM Human meiotic aneuploidy: Where we’ve been, where we’re going. T. Hassold, Washington State University, Pullman.
11:30 AM Aneuploidy and cancer. D. Cleveland, University of California at San Diego, La Jolla.
12:00 NOON Naturally occurring aneuploidy in the brain. J. Chun, The Scripps Research Institute, La Jolla, CA.
12:30 PM Aneuploidy and the environment: are we making things worse? P. Hunt, Washington State University, Pullman.
Wednesday, October 11 11:00 AM–1:00 PM
Concurrent Invited Sessions I (22–28)
SESSION 25 – The DNA Damage Response Pathway, Cancer Susceptibility, and the Public Health
Hall E-1
Co-Moderators: Susanne M. Gollin, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA; and June A. Peters, National Cancer Institute, National Institutes of Health, Rockville, MD
The DNA damage response (DDR) protects us against the harmful effects of DNA and chromosomal breakage. The impact of loss of these defenses extends beyond the rare situations in which loss or altered function of the ataxia telangiectasia gene, ATM and its downstream targets in the DDR (e.g., BRCA, FANC genes) cause familial cancer syndromes and in some cases, chromosomal breakage syndromes. This session will review the DDR pathways and the chromosomal instability syndromes, the impact of DDR gene mutations and polymorphisms on cancer susceptibility in carriers, mouse models for various genes in the DDR and their value in understanding the DDR pathways and cancer susceptibility, interindividual variation in DNA repair capacity and cancer susceptibility, recent research findings on the cellular response to DNA breaks, and pertinent clinical and genetic counseling issues. Genome instability and cancer susceptibility is an important emerging area of cancer genetics and public health genetics.11:00 AM Introduction to DNA damage response genes and their role in preventing human cancer. M. S. Meyn, Hospital for Sick Children, Toronto, Ontario, Canada.
11:25 AM Mouse models of genome instability syndromes. L. Niedernhofer, University of Pittsburgh Cancer Institute, PA.
11:50 AM The role of DNA repair capacity in genetic susceptibility to cancer. X. Wu, M. D. Anderson Cancer Center, University of Texas, Houston.
12:15 PM Visualizing the DNA damage response (DDR): How DDR and telomeric proteins protect against genetic damage. M. S. Meyn, Hospital for Sick Children, Toronto, Ontario, Canada.
12:40 PM Genetic counseling and public health implications of defects in the DNA damage response. J. Peters, National Cancer Institute, National Institutes of Health, Rockville, MD.
Wednesday, October 11 11:00 AM–1:00 PM
Concurrent Invited Sessions I (22–28)
SESSION 26 – RNA-Mediated Toxicity in Neurological Disorders
Hall E-3
Co-Moderators: Laura Ranum, University of Minnesota, Minneapolis; and Peng Jin, Emory University School of Medicine, Atlanta, GA
The most widely accepted view on mechanisms leading to neuronal cell death in neurodegenerative disease is that the main culprits are proteins abnormally modified as the result of mutations, aberrant processing or post-translational modifications. However, over the past few years, new evidence has emerged for the involvement of RNA-mediated mechanisms in a number of degenerative pathologies of the central nervous system. The main objective of this session is to review the most recent advances on the groundbreaking concept of RNA neurotoxicity, and to provide a thought-provoking forum from which working models with a wide implication for human diseases will emerge. This session will particularly focus on DM1, DM2, SCA8, and FXTAS, in which the toxicity of noncoding RNAs has been demonstrated in different animal and cell models.11:00 AM Dynamic mutations and RNA-mediated disease. M. Swanson, University of Florida College of Medicine, Gainesville.
11:30 AM Insights into molecular pathogenesis through comparative studies of DM1, DM2 and SCA8. L. Ranum, University of Minnesota, Minneapolis.
12:00 NOON Molecular pathogenesis of FXTAS. P. J. Hagerman, University of California School of Medicine, Davis.
12:30 PM From fruit fly to bedside: translating lessons from a Drosophila model of FXTAS. P. Jin, Emory University School of Medicine, Atlanta, GA.
Wednesday, October 11 11:00 AM–1:00 PM
Concurrent Invited Sessions I (22–28)
SESSION 27 – Approaches to Identifying Genetic Causes of Congenital Diaphragmatic Hernia
Room 243-245
Co-Moderators: Barbara R. Pober, Massachusetts General Hospital for Children, Boston; and Kate G. Ackerman, Brigham and Women's Hospital, Boston, MA
Congenital diaphragmatic hernia (CDH) is an extremely common birth defect affecting ~1/2500 births and is estimated to constitute up to eight percent of all congenital malformations. The condition remains associated with a high mortality and considerable morbidity among long-term survivors. The etiology is currently unknown in most cases, but new developments from human and model organism investigations indicate a major role for genetic causation of CDH. Four talks will highlight the following: 1) diaphragm and lung embryology; basis of pulmonary hypoplasia; genetic and teratogenic model organisms; 2) prevalence of common cytogenetic abnormalities including microdeletions detected by array based CGH; suggested testing guidelines for both isolated CDH and CDH with anomalies; 3) Fryns syndrome; single gene disorders associated with CDH; differential diagnoses; 4) mutations associated with human CDH; candidate gene sequence analysis and explanation for major pathways currently being sequenced; multiplex families with CDH and linkage analysis.11:00 AM Animal models of developmental diaphragmatic defects: Gateway to candidate gene discovery in humans. K. G. Ackerman, Brigham and Women's Hospital, Boston, MA.
11:30 AM Fryns syndrome and single gene disorders associated with CDH. A. M. Slavotinek, University of California, San Francisco.
12:00 NOON Findings from cytogenetics and array-based comparative genomic hybridization: Methods to identify loci associated with CDH. A. deKlein, Department of clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
12:30 PM Genetic causation of CDH in human populations: Evidence from family studies and candidate gene analyses. B. R. Pober, Massachusetts General Hospital for Children, Boston.
Wednesday, October 11 11:00 AM–1:00 PM
Concurrent Invited Sessions I (22–28)
SESSION 28 – New Thoughts and Alternative Treatments in Phenylketonuria (PKU)
Room 343-345
Moderator: Nenad Blau, University of Zurich, Switzerland
Phenylketonuria (PKU) is a disease of temperate-zone human populations and certain mutations are surprisingly prevalent. How might one explain these features? PKU is the flagship for treatable human genetic disease. Restriction of phenylalanine intake prevents brain damage but disagreement persists on how long the diet should be continued. Adolescents and young adults tend not to comply with dietary treatment and 2/3 of pregnant women (in the USA) do not follow the diet before becoming pregnant. New approaches to treatment are of interest: 1. use of the r- AAV2/8 vector to correct hyperphenylalaninemia in a murine model; 2. treatment of murine PKU with recombinant phenylalanine ammonia lyase; 3. use of tetrahydrobiopterin (6R- BH4) to treat a relatively high proportion of patients with PAH- mutant hyperphenylalaninemia who benefit from the cofactor acting either as a chaperone-like molecule or by overcoming adverse binding kinetics.11:00 AM Introduction. N. Blau, University of Zurich, Switzerland.
11:15 AM Advances in treatment of PKU: An overview. C. R. Scriver, McGill University, Montreal, Quebec, Canada.
11:45 PM Efficiency of tetrahydrobiopterin in cofactor- responsive PKU patients. H. Levy, Children's Hospital Boston, MA.
12:10 PM Mechanisms underlying responsiveness to tetrahydrobiopterin in PKU mutations. A. Martinez, University of Bergen, Norway.
12:35 PM Gene and stem cell therapies for PKU. C. O. Harding, Oregon Health & Science University, Portland.
Wednesday, October 11 2:00 PM–4:30 PM
Concurrent Platform Sessions II (29–35)
SESSION 29 – Clinical Genetics: Genotypes and Phenotypes
Hall F
Co-Moderators: Elizabeth K. Schorry, Cincinnati Children's Hospital, Cincinnati, OH; and Robert A. Saul, Greenwood Genetics Center, Greenwood, SC
77/2:00 UMOD-related familial juvenile hyperuricemic nephropathy: mutation detection rate and mutational spectrum. K. Dahan, L. Labriola, M. L. Lizon, M. Smaers, O. Devuyst, Y. Pirson.
78/2:15 BBS10 mutations in severe antenatal cases with severe cystic kidneys "Meckel-like" type. S. Audollent, L. Baala, R. Khaddour, J. Martinovic, A. Buenerd, G. Leichmeijer, M. Le Merrer, A. Munnich, F. Encha-Razavi, M. C. Gubler, M. Vekemans, T. Attié-Bitach.
79/2:30 Genotype-phenotype correlations at the MKS1 and MKS3 loci in Meckel syndrome and related phenotypes. R. Khaddour, L. Baala, U. M. Smith, C. Ozilou, J. Martinovic, S. Audollent, C. Esculpavit, N. Kadhom, M. Kytalla, A. Munnich, F. Razavi, E. Genin, J. Roume, M. C. Gubler, M. Vekemans, C. A. Johnson, T. Attie-Bitach.
80/2:45 Natural History of Autosomal Recessive Polycystic Kidney Disease/Congenital Hepatic Fibrosis (ARPKD/CHF). M. Gunay-Aygun, E. Font-Montgomery, P. Choyke, L. Guay-Woodford, T. Heller, R. Kleta, P. Mohan, Z. Quezado, W. Gahl.
81/3:00 Mortality in Achondroplasia study: a 40 year follow-up. J. Wynn, M. J. Gambello, T. M. King, A. Scott, K. Waller, J. T. Hecht.
82/3:15 Natural history of 1p36 deletion syndrome: experience with 60 cases. A. Battaglia, J. C. Carey, H. E. Hoyme, ICSG.
83/3:30 Microdeletion encompassing the MAPT gene at chromosome 17q21.3 is associated with developmental delay and learning disability. C. Shaw-Smith, A. Pittman, L. Willatt, H. Martin, L. Rickman, S. Gribble, R. Curley, S. Cumming, C. Dunn, D. Kalaitzopoulos, K. Porter, E. Prigmore, A. Krepischi-Santos, M. Varela, C. Koiffman, A. Lees, C. Rosenberg, H. V. Firth, R. de Silva, N. P. Carter.
84/3:45 CCM2 deletions are a common cause of cerebral cavernous malformations. D. A. Marchuk, C. L. Liquori, M. J. Berg, F. Squitieri, T. P. Leedom, L. Ptacek, E. W. Johnson.
85/4:00 The TBX1 gene in the 22q11.2 deletion and duplication syndromes: a susceptibility factor for mental retardation. D. Heine-Suner, L. Torres-Juan, J. Rosell, M. Morla, F. Garcia-Algas, M. de la Fuente, M. Juan, A. Tubau, M. Bernues, A. Perez-Granero, N. Govea, X. Busquets.
86/4:15 Severe language delay associated with duplication of the Williams-Beuren critical region. J. S. Berg, N. Brunetti-Pierri, B. Nowakowska, E. Obersztyn, C.-T. Fong, A. Summers, A. Patel, A. L. Beaudet, S. W. Cheung.
Wednesday, October 11 2:00 PM–4:30 PM
Concurrent Platform Sessions II (29–35)
SESSION 30 – Genetic Dissection of Complex Traits
La Nouvelle Ballroom A/B
Co-Moderators: Nicholas Wood, University College, London, United Kingdom; and Michael J. Bamshad, University of Washington, Seattle
87/2:00 A genome-wide nonsynonymous SNP panel. L. M. Galver, P. C. Ng, S. Hunt, J. Whitacre, R. Shen, P. Deloukas, S. S. Murray.
88/2:15 Genome-wide association scan for type 2 diabetes in Finns. L. J. Scott, W. L. Duren, L. L. Bonnycastle, H. M. Stringham, A. U. Jackson, M. L. Erdos, P. Chines, N. Narisu, C. J. Willer, K. F. Doheny, E. W. Pugh, N. L. Riebowl, T. T. Valle, J. Tuomilehto, R. N. Bergman, K. L. Mohlke, F. S. Collins, M. Boehnke.
89/2:30 How well do the HapMap SNPs tag functional variants in 217 Drug Metabolizing Enzyme genes? F. C. L. Hyland, K. Lazaruk, K. A. Haque, R. A. Welch, F. M. De La Vega.
90/2:45 Mitochondrial Genetic Regulation of Nuclear Transcription. J. E. Curran, M. P. Johnson, H. H. H. Göring, T. D. Dyer, J. B. M. Jowett, J. W. MacCluer, G. R. Collier, E. K. Moses, J. Blangero.
91/3:00 Analysis of eQTL gene expression data for the identification of complex genetic interactions. K. A. Kim, J. Huang, T. E. Scheetz, R. Swiderski, A. R. Philp, E. M. Stone, V. C. Sheffield.
92/3:15 Gametic Phase Disequilibrium as a Method to Map Deafness Genes. W. Nance, A. Pandya, S. H. Blanton, K. M. Dodson, X. J. Xia, K. O. Welch, K. A. Arnos.
93/3:30 Large scale case-control, family-based and cohort studies of diabetes-susceptibility variants in the TCF7L2 gene. M. I. McCarthy, C. J. Groves, A. Bennett, E. Zeggini, T. M. Frayling, M. N. Weedon, G. A. Hitman, M. Walker, A. T. Hattersley, M.-R. Järvelin.
94/3:45 Efficient multipoint analysis of association studies. B. Servin, P. Scheet, M. Stephens.
95/4:00 Genome -wide Association Studies Incorporating Searching Genetic Interaction Networks. G. Pen, L. Jin, M. Xiong.
96/4:15 Associations of gene expression variation with SNPs and copy number variants (CNVs) in the HapMap samples. B. E. Stranger, M. Forrest, M. Dunning, C. Ingle, C. Beazley, R. Redon, C. Lee, C. Tyler-Smith, A. G. Clark, N. Carter, S. W. Scherer, S. Tavare, P. Deloukas, M. E. Hurles, E. T. Dermitzakis.
Wednesday, October 11 2:00 PM–4:30 PM
Concurrent Platform Sessions II (29–35)
SESSION 31 – Genomics I
La Nouvelle Ballroom C
Co-Moderators: Pui-Yan Kwok, University of California Medical Center, San Francisco; and Xavier Estivill, Pompeu Fabra University, Barcellona, Spain
97/2:00 Genomewide copy-number analysis of parathyroid carcinomas by single nucleotide polymorphism arrays. J. Costa-Guda, N. Kawamata, H. P. Koeffler, A. Arnold.
98/2:15 Global profile of copy number variation in the human genome. C. Lee, H. Aburatani, N. Carter, M. Hurles, K. Jones, S. Scherer, C. Tyler-Smith, Genomic Structural Variation Consortium.
99/2:30 Very-high-resolution mapping of DNA copy-number alterations using high-density tiling oligonucleotide arrays. A. E. Urban, J. O. Korbel, F. Grubert, C. Hart, R. Selzer, T. Richmond, R. Green, B. S. Emanuel, K. Kidd, M. Gerstein, S. M. Weissman, M. Snyder.
100/2:45 Genomic analysis of large tandem arrays in the human genome. C. Lescale, D. Hasson, S. Gmuca, P. E. Warburton.
101/3:00 Experimental identification of regulatory Conserved Non-Coding sequences (CNCs) using the chicken genome. C. Attanasio, F. Chiodini, C. Wyss, J.-M. Matter, S. E. Antonarakis.
102/3:15 A genome-wide portrait of gene copy number variation spanning over 60 million years of human and primate evolution. L. Dumas, Y. Kim, A. Karimpour-Fard, M. Cox, J. Hopkins, J. Pollack, J. Sikela.
103/3:30 Neanderthal Genomics. J. P. Noonan, G. Coop, S. Kudaravalli, D. Smith, J. Krause, J. Alessi, F. Chen, D. Platt, S. Pääbo, J. K. Pritchard, E. M. Rubin.
104/3:45 Population-specific abnormal high density of HapMap QC- SNPs in ENCODE regions: from the 1% towards a high-resolution genome-wide analysis of copy number variants (CNVs) of the human genome. L. Armengol, S. Villatoro, M. Garcia-Aragones, J. R. Gonzalez, X. Estivill, ENCODE Variation Analysis Group.
105/4:00 Discovery of higher-order functional domains within the human genome. R. Thurman, W. S. Noble, J. A. Stamatoyannopoulos.
106/4:15 Long Distance Transcription Networks Characterize ENCODE Regions. S. E. Antonarakis, F. Denoeud, A. Reymond, P. Kapranov, A. Frankish, J. Harrow, R. Guigó, T. R. Gingeras, ENCODE Project Consortium.
Wednesday, October 11 2:00 PM–4:30 PM
Concurrent Platform Sessions II (29–35)
SESSION 32 – Population Genetics and Evolution
Hall E-1
Co-Moderators: Brian C. Verrelli, Arizona State University, Tempe; and Sebastian Zollner, University of Michigan, Ann Arbor
107/2:00 Identifying and comparing sequence determinants of mammalian recombination hotspots. S. R. Myers, A. Kirby, C. Wade, G. A. T. McVean, M. J. Daly, P. J. Donnelly.
108/2:15 Quantifying the distribution of selective effects among newly arising mutations in the human genome. C. D. Bustamante, A. R. Boyko, S. Williamson, K. Lohmueller, R. Hernandez, A. Indap, J. Pillardy, A. Fledel-Alon, R. Nielsen, A. G. Clark.
109/2:30 Accelerated evolution of conserved non-coding sequences in the human genome. S. Prabhakar, J. P. Noonan, S. Paabo, E. M. Rubin.
110/2:45 Demography and selection affection human prtoein coding genes. R. Nielsen, M. Hubisz, C. Bustmante, A. Andres, S. Williamson, A. G. Clark.
111/3:00 Estimating the split time of Human and Neanderthal populations. G. Coop, S. Kudaravalli, J. P. Noonan, D. Smith, J. Krause, J. Alessi, D. Chen, D. Platt, S. Pääbo, J. K. Pritchard, E. M. Rubin.
112/3:15 A worldwide survey of linkage disequilibrium and haplotype variation in the human genome. J. K. Pritchard, D. F. Conrad, G. Coop, M. Jakobsson, X. Wen, J. D. Wall, N. A. Rosenberg.
113/3:30 A new model for South American origins inferred from hierarchical modeling of mtDNA variation. C. Lewis, J. Long.
114/3:45 The Genetic Basis of Lactase Persistence in Africa; evidence for Convergent Adaptation Due to a Shared Cultural Trait in Europeans and Africans. S. A. Tishkoff, F. A. Reed, A. Ranciaro, B. F. Voight, C. C. Babbitt, J. S. Silverman, K. Powell, J. B. Hirbo, H. Mortensen, M. Osman, M. Ibrahim, S. A. Omar, S. Bumpstead, J. K. Pritchard, G. A. Wray, P. Delouckas.
115/4:00 Empirical detection of natural selection at two brain-related genes (FOXP2 and AHI1) but failure to confirm evidence at ASPM. F. Yu, R. S. Hill, A. A. Mignault, R. J. Ferland, C. A. Walsh, D. Reich.
116/4:15 An Ancient Haplotype Pinpoints IGF1's Role In Determining Dog Body Size. N. B. Sutter, M. Gray, K. Chase, P. Quignon, H. G. Parker, S. Davis, E. Karlins, G. Johnson, M. Nordborg, C. D. Bustamante, R. K. Wayne, K. G. Lark, E. A. Ostrander.
Wednesday, October 11 2:00 PM–4:30 PM
Concurrent Platform Sessions II (29–35)
SESSION 33 – Neurogenetics
Hall E-3
Co-Moderators: Joseph D. Buxbaum, Mt. Sinai School of Medicine, New York, NY; and Jeffery M. Vance, Duke University, Durham, NC
117/2:00 Identification of EFHC2 as a quantitative trait locus for fear recognition in Turner Syndrome. L. A. Weiss, S. Purcell, S. Waggoner, K. Lawrence, D. Spektor, M. J. Daly, D. Skuse, P. Sklar.
118/2:15 Why does increasing sample size often dim rather than illuminate? A question of locus heterogeneity. C. W. Bartlett, V. J. Vieland.
119/2:30 Autism Genome Project: Linkage Analyses. B. Devlin.
120/2:45 12q14: a novel linkage region in extended autism families. M. A. Pericak-Vance, D. Q. Ma, D. A. Skaar, A. L. Collins, I. Konidari, J. Crowley, J. Jaworski, R. K. Abramson, H. H. Wright, M. L. Cuccaro, J. R. Gilbert, J. L. Haines.
121/3:00 Genetic testing in autism: how much is enough? G. E. Herman, A. Sommer, B. Enrile, M. Pastore, S. Fitzgerald, J. Atkin, K. L. McBride.
122/3:15 Comprehensive linkage disequilibrium mapping of schizophrenia candidate genes in a large European-ancestry sample. J. Duan, M. Martinez, A. R. Sanders, G. Burrell, C. Hou, D. He, D. Schwartz, N. G. Buccola, B. J. Mowry, R. Freedman, F. Amin, D. W. Black, J. M. Silverman, W. F. Byerley, R. R. Crowe, C. R. Cloninger, D. F. Levinson, P. V. Gejman.
123/3:30 SNP fine mapping in 10q22-23, a region with previous linkage to schizophrenia. P.-L. Chen, V. K. Lasseter, D. Avramopoulos, M. D. Fallin, A. Pulver, D. Valle.
124/3:45 Alleles of reelin gene show association with working memory in Finnish schizophrenia families. J. O. Peltonen, A. Tuulio-Henriksson, A. Loukola, J. Ekelund, T. Paunio, T. Varilo, J. Suvisaari, T. Partonen, J. Lönnqvist, L. Peltonen.
125/4:00 Pharmacogenetic analysis of antipsychotics: comprehensive analysis of pharmacokinetic variants. I. Grossman, Y. Liu, N. Walley, J. Dawson, C. Gumbs, M. Weale, P. Sullivan, D. Goldstein.
126/4:15 Pharmacokinetic gene variants do not influence response or tolerance to citalopram in a STAR*D sample. E. Peters, S. Slager, J. Kraft, G. Jenkins, M. Reinalda, P. McGrath, S. Hamilton.
Wednesday, October 11 2:00 PM–4:30 PM
Concurrent Platform Sessions II (29–35)
SESSION 34 – Genetic Counseling, Testing, and Ethics
Room 243-245
Co-Moderators: Elizabeth A. Balkite, GlaxoSmithKline, Research Triangle Park, NC; and Sylvia A. Metcalfe, MCRI, Royal Children's Hospital, Parkville, VIC, Australia
127/2:00 Provision of Genetic Services in the aftermath of Katrina: the LSU Experience. Y. Lacassie, M. Marble.
128/2:15 Frequency of Fabry disease family histories in a prenatal genetic counseling population. D. Cutillo, H. Travers, E. O'Rourke, E. R. Wassman, D. Ramsey, A. E. Donnenfeld.
129/2:30 Proposition for a multi-step mutation detection in Hemophilia A. N. Lannoy, I. Abinet, C. Verellen, C. Vermylen, C. Hermans, K. Dahan.
130/2:45 Predicting BRCA1 and BRCA2 Mutations in Women with Carcinoma In Situ of the Breast. T. Geva, J. N. Weitzel, A. Dagis, J. A. Longmate, J. O. Culver, M. R. Palomares.
131/3:00 Evaluation of the clinical utility of a Family History Tool. S. M. O'Neill, W. S. Rubinstein, L. S. Acheson, M. T. Ruffin, Family Healthware Evaluation Collaboration.
132/3:15 Providers' knowledge of genetics: a survey of 5,915 individuals and families with genetic conditions. E. K. Harvey, C. E. Fogel, K. D. Christensen, S. F. Terry, J. D. McInerney.
133/3:30 White Americans' Beliefs on Genetic Contributions to Perceived Racial Differences in Athleticism: Impact on Prejudice Toward and Negative Stereotyping of Blacks. E. M. Petty, J. P. Sheldon, T. E. Jayaratne.
134/3:45 Enhanced Oversight of Genetic Testing Laboratories Needed and Supported: Results of a Survey of Laboratory Directors. J. Scott, G. Javitt, J. Murphy, D. Kaufman, S. Katsanis, K. Hudson.
135/4:00 Experience with parental sample submission in abnormal array CGH cases: Is free parental testing helpful? J. Coppinger, B. A. Bejjani, L. G. Shaffer.
136/4:15 Values in conflict: U.S. public attitudes on embryonic stem cell research. K. L. Hudson, D. J. Kaufman, R. Faden, J. Scott.
Wednesday, October 11 2:00 PM–4:30 PM
Concurrent Platform Sessions II (29–35)
SESSION 35 – Development
Room 343-345
Co-Moderators: Roderick R. McInnes, Hospital for Sick Children, Toronto, Ontario, Canada; and Stephanie M. Ware, Cincinnatti Children's Hospital Medical Center, Cincinnatti, OH
137/2:00 Segregation of mtDNA in the female germline. T. Wai, E. A. Shoubridge.
138/2:15 Fmr1 gene family regulates circadian clock in mammals. J. Zhang, Z. Fang, K. Kaasik, C. C. Lee, B. A. Oostra, D. L. Nelson.
139/2:30 Bardet-Biedl syndrome mice have defective hippocampal development associated with mislocalization of neuronal primary cilia receptors. K. Mykytyn, N. F. Berbari, L. M. Bohn, G. A. Bishop.
140/2:45 The Prdm8 transcription factor is essential for the development of rod bipolar cells in the mammalian retina. C. Jung, R. R. McInnes.
141/3:00 Ciliary dysfunction underlies cystic kidney in Oral-Facial-Digital Type I (OFD1) syndrome. A. Zullo, A. Barra, A. Indrieri, A. Cantone, N. Messaddeq, G. Capasso, P. Dollé, P. Igarashi, B. Franco.
142/3:15 A common epigenetic signature distinguishes human embryonic stem cells from differentiated cell populations. M. Bibikova, E. Chudin, B. Wu, L. Zhou, E. Wickham Garcia, Y. Liu, S. Shin, T. W. Plaia, J. M. Auerbach, D. E. Arking, R. Gonzalez, A. Chakravarti, A. Maitra, M. Rao, D. L. Barker, J. F. Loring, J.-B. Fan.
143/3:30 Identification of genes required for normal forebrain development using ENU mutagenesis. D. Beier, A. Tilt, Y. Yun, R. Stottman.
144/3:45 Role of Notch Signaling in Bone Development. F. Engin, G. Zhou, T. Yang, T. Bertin, M. M. Jiang, Y. Chen, Z. Yao, B. Boyce, B. Lee.
145/4:00 Functional and physical interaction between ZIC3 mutants and GLI3 in vitro. L. Zhu, S. Poole, J. W. Belmont.
146/4:15 Neural crest derived osteochondroprogenitor cells predominantly contribute to cranial skeletal repair. P. Leucht, J.-B. Kim, J. A. Helms.
Thursday, October 12 8:00 AM–10:30 AM
Concurrent Platform Sessions III (37–43)
SESSION 37 – Molecular Basis of Mendelian Disorders II
Hall F
Co-Moderators: Jeffrey W. Innis, University of Michigan, Ann Arbor; and Nicholas Katsanis, Johns Hopkins University School of Medicine, Baltimore, MD
147/8:00 Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 cause Aicardi-Goutières syndrome — a Mendelian mimic of congenital viral infection — at the AGS1 locus. Y. J. Crow, A. P. Jackson, P. Lebon, D. E. Barnes, T. Lindahl, The AGS Consortium.
148/8:15 Mutations in each of three Ribonuclease H2 subunits cause Aicardi Goutières Syndrome and mimic congenital viral brain infection. A. P. Jackson, A. Leitch, B. E. Hayward, A. Garner, R. Parmar, E. Griffith, M. Ali, P. Lebon, D. T. Bonthron, C. Ponting, Y. J. Crow, The AGS Consortium.
149/8:30 Familial Thoracic Aortic Aneurysms and Dissection: Rapid Identification of Causative Variants in TGFBR3 through Direct Sequencing of Genes in the TGFb Pathway. N. Avidan, J. Kao, D. Divecha, H. Pannu, D. C. Guo, V. T. Tran-Fadulu, D. H. Kim, S. E. Scherer, R. Gibbs, D. M. Milewicz.
150/8:45 IL-10 and TNF are associated with airflow obstruction in severe Alpha 1-Antitrypsin Deficiency. D. L. DeMeo, E. J. Campbell, A. F. Barker, M. L. Brantly, E. Eden, N. G. McElvaney, R. A. Sandhaus, J. M. Stocks, J. K. Stoller, C. Strange, G. Turino, E. K. Silverman.
151/9:00 Mutations in the SPG8 gene cause hereditary spastic paraplegia. P. N. Valdmanis, I. A. Meijer, A. Reynolds, A. Lei, P. MacLeod, D. Schlesinger, M. Zatz, P. Dion, P. Drapeau, G. A. Rouleau.
152/9:15 Proteomic profiling of hippocampal synaptoneurosomes in the mouse model of fragile X syndrome. M. Nakamoto, D. Cheng, J. Peng, U. Narayanan, R. Alisch, H. Yi, S. T. Warren.
153/9:30 Cornelia de Lange Syndrome and the “Cohesinopathies”. I. Krantz, D. Yaeger, M. Kaur, L. Jackson, M. Deardorff.
154/9:45 An age related homeostasis mechanism is responsible for spontaneous amelioration of hemophilia B Leyden. K. Kurachi, J. S. Huo, A. Ameri, Z. Zhang, E. Kasama, T. Tanaka, J. Hoff, S. Kurachi.
155/10:00 A splice mutation in the small subunit of the AP-1 complex underlie the Erythrokeratodermia variabilis type 3 (EKV3) syndrome. S. Côté, A. Montpetit, E. Brustein, C. Meloche, M. Boudreau, R. Drouin, P. Drapeau, T. J. Hudson, C. A. Drouin, P. Cossette.
156/10:15 The absence of endothelin-2 partially rescues photoreceptor (PR) death in a model of inherited photoreceptor degeneration (IPD). A. Bramall, M. J. Szego, L. Pacione, P. D'Orléans-Juste, M. Yanagisawa, R. R. McInnes.
Thursday, October 12 8:00 AM–10:30 AM
Concurrent Platform Sessions III (37–43)
SESSION 38 – Molecular Basis of Disorders with Complex Inheritance
La Nouvelle Ballroom A/B
Co-Moderators: Lisa Barcellos, University of California, Berkley; and Lindsey A. Criswell, University of California, San Francisco
157/8:00 Telomere length in the Amish: heritability and association with age and sex-specific parental effects. O. T. Njajou, R. M. Cawthon, C. M. Damcott, S.-H. Wu, S. Ott, E. H. Blackburn, A. R. Shuldiner, B. D. Mitchell, W.-C. Hsueh.
158/8:15 A Common Ancestral Haplotype Located at 4q13.2 Confers Susceptibility to ADHD. M. Arcos-Burgos, M. Jain, S. Domene, S. Shively, D. Wallis, H. Stanescu, J. D. Karkera, M. T. Acosta, K. Berg, R. Kleta, E. Roessler, A. Vortmeyer, D. Pineda, J. D. Palacio, F. Lopera, J. Meyer, K. P. Lesch, J. E. Bailey-Wilson, F. X. Castellanos, M. Muenke.
159/8:30 Genetic association between interferon regulatory factor 5 (IRF5) and systemic lupus erythematosus in three ethnic groups. J. A. Kelly, K. M. Kaufman, A. J. Adler, B. J. Herring, S. G. Frank, J. Kilpatrick, J. T. Merrill, J. A. James, G. R. Bruner, J. B. Harley.
160/8:45 NALP1, a key regulator of the innate immune system, is a novel major gene for multiple autoimmune/autoinflammatory disease. Y. Jin, C. Mailloux, D. Bennett, C. Dinarello, P. Fain, R. Spritz.
161/9:00 Prevalent filaggrin mutations are a major genetic factor for atopy, atopic dermatitis and eczema-associated asthma. W. H. I. McLean, A. Sandilands, A. Terron-Kwiatkowski, S. P. Lee, Y. Zhao, H. Liao, G. O'Regan, A. D. Irvine, C. N. A. Palmer, F. J. D. Smith.
162/9:15 Psoriasis-associated alleles from the haplotype block harboring PSORS1 within the HLA class I interval have differential enhancer activity compared to wild type alleles. L. Cao, Y. Liu, C. Helms, M. Fernandez, A. Bowcock.
163/9:30 A genomewide association study of putative functional SNPs leads to the identification of two psoriasis loci — IL12B and IL23R — in 3 independent white North American sample sets. A. B. Begovich, S. J. Schrodi, M. Leppert, G. Krueger, M. Cargill.
164/9:45 A systematic genomewide association study of 19,779 coding SNPs with putative function identifies a novel susceptibility gene for Crohn disease. A. Franke, J. Hampe, P. Rosenstiel, A. Till, K. Huse, M. Albrecht, G. Mayr, F. M. De La Vega, J. Briggs, M. Wenz, S. Guenther, D. A. Gilbert, N. Prescott, T. Lengauer, C. Matthew, M. Krawczak, S. Schreiber.
165/10:00 Linkage and association of the CHD7 gene with susceptibility to adolescent idiopathic scoliosis. C. Wise, X. Gao, D. Gordon, J. Gillum, R. Browne, C. Helms, D. Zhang, S. Shoemaker, M. Lovett, A. Bowcock, J. Herring.
166/10:15 Candidate gene analyses for nonsyndromic cleft lip (CL) with or without cleft palate (CP) in families from six countries. M. L. Marazita, B. S. Maher, J. C. Murray, A. Lidral, L. L. Field, T. Goldstein McHenry, M. E. Cooper, S. Daak-Hirsch, A. Jugessur, B. Riley, L. Moreno, P. Chines.
Thursday, October 12 8:00 AM–10:30 AM
Concurrent Platform Sessions III (37–43)
SESSION 39 – Genomics II
La Nouvelle Ballroom C
Co-Moderators: Richard A. Gibbs, Baylor College of Medicine, Houston, TX; and Penelope E. Bonnen, Rockefeller University, New York, NY
167/8:00 A voxelation map of gene expression in a mouse brain section. M. H. Chin, A. Geng, A. Khan, W. J. Qian, S. Levy, R. D. Smith, R. M. Leahy, D. J. Smith.
168/8:15 Brain Imaging As A Strategy for Genome-Wide Scan Data Reduction for Neuropsychiatric Illness. S. G. Potkin, F. Macciardi, L. Friedman, J. Turner, J. H. Fallon, W. Bunney, D. Keator, D. Goldstein, N. Schork.
169/8:30 Towards delineating cell types in the mouse central nervous system: a genome-scale high resolution expression map of the adult mouse brain. S. Sunkin, C. Dang, M. Hawrylycz, J. Hohmann, E. Lein, P. Wohnoutka, A. Jones.
170/8:45 Genomic Approaches for Pathway Identification in Regenerating Sensory Epithelia of the Inner Ear. D. Alvarado, K. Powder, D. Hawkins, S. Bashiardes, V. Bhonagiri, R. Veile, J. Speck, M. Warchol, M. Lovett.
171/9:00 Large-scale genetic investigation of genomewide transcriptional profiles. H. H. H. Göring, J. E. Curran, M. P. Johnson, T. D. Dyer, J. B. M. Jowett, M. C. Mahaney, J. W. MacCluer, G. R. Collier, E. K. Moses, J. Blangero.
172/9:15 Large-scale In Vivo Enhancer Analysis of Extremely Conserved Human Non-coding Sequence. L. A. Pennacchio, A. Visel, N. Ahituv, S. Prabhakar, I. Dubchak, E. M. Rubin.
173/9:30 Genomewide strategies to identify DNaseI hypersensitive sites. G. E. Crawford, S. Davis, P. C. Scacheri, G. Ranaud, P. S. Meltzer, T. G. Wolfsberg, F. S. Collins.
174/9:45 ChIP on CHIP analysis of neocentromere inner kinetochore chromatin domain structure. A. L. Alonso, F. Cheung, D. Hasson, B. Fritz, A. Ladurner, P. E. Warburton.
175/10:00 A Practical View of Genome-Wide Association Studies. M. Li, W. Guan, R. S. Spielman, C. Li.
176/10:15 Exon resequencing - the search for sequence variation in the human genome. J. Rogers, J. Allen, H. Arbery, G. Bethel, R. Bennett, S. Bhaskar, A. Dunham, M. Bush, J. Burton, J. Durham, T. Eades, M. Earthrowl, S. Hunt, S. Leonard, K. McLay, D. Niblett, R. Norris, A. Sanderson, Y. Umrania, A. Coffey.
Thursday, October 12 8:00 AM–10:30 AM
Concurrent Platform Sessions III (37–43)
SESSION 40 – Genetic Epidemiology
Hall E-1
Co-Moderators: Chris Lange, Harvard University, Boston, MA; and Eden R. Martin, Duke University, Durham, NC
177/8:00 Intra- and inter-population genotype reconstruction from tagging SNPs. P. Paschou, M. W. Mahoney, A. Javed, J. R. Kidd, A. J. Pakstis, S. Gu, K. K. Kidd, P. Drineas.
178/8:15 The Optimal Minor Allele Frequency (OMAF) for a SNP-Disease Association Studies. I. P. Gorlov, O. Y. Gorlova, S. Sunyaev, M. R. Spitz, C. I. Amos.
179/8:30 Quantifying the effects of allele frequency differences and allelic phase on LD captured by tag SNPs derived from incompletely ascertained data: theoretical basis, models and impact on LD mapping. R. Lazarus, B. Raby, W. Qiu, E. K. Silverman, S. T. Weiss.
180/8:45 Comparisons of genome coverage can be misleading as indicators of the power of SNP sets or chips for association studies. J. Marchini, C. Spencer, Z. Su, P. Donnelly.
181/9:00 Designing optimal two-stage genome-wide association studies. A. D. Skol, L. J. Scott, G. R. Abecasis, M. Boehnke.
182/9:15 Initial Discovery and Replication in Whole Genome Association Scans: a Sequential Analysis Approach. B. S. Maher, R. J. Weyant, T. McHenry, M. L. Marazita.
183/9:30 Prioritized subset analysis in genome-wide association studies. C. Li, M. Li, E. M. Lange, R. M. Watanabe.
184/9:45 Improving Power in Genome-Wide Association Studies: Weights Tip the Scale. K. Roeder, L. Wasserman, B. Devlin.
185/10:00 Distinguishing single from multiple association signals within a gene. K. L. Lunetta, J. Dupuis.
186/10:15 Increased power to detect disease genes in genetic linkage and whole genomewide association studies by employing a functional human gene network. L. Franke, B. P. C. Koeleman, F. Dudbridge, M. Egmon
