ASHG: 2006 Annual Meeting - Daily Session Listing

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.

Sponsored by Illumina, Inc.

Tuesday, October 10 1:00 PM–1:30 PM

SESSION 11 – Presidential Address: Our Society and the Scientist-Citizen

Hall F

Stephen T. Warren
ASHG President
Emory University School of Medicine, Atlanta, GA

As investigators and practitioners of our wonderful field of human genetics, it is easy to become so engrossed in our daily work that we occasionally risk losing sight of all the external influences that affect our professional lives. Social, governmental, and educational policies are evolving, and the dynamics are often driven by the most influential but not necessarily the most well informed. Governmental actions can affect how we practice our craft, indeed they can legislatively ban aspects of our work, and limit the scope of our efforts. Often the actions taken mirror social opinions that influence what should or should not be taught in our schools. As human geneticists I believe we have a special responsibility to be aware of and participate in the dialog surrounding these issues.

As a prominent biomedical society we must be more active to educate and influence our legislative bodies at the federal and state levels. Toward this end, at the spring ASHG Board of Directors meeting in Washington DC, we set aside a day to meet with members of Congress and their staff regarding genetic nondiscrimination legislation and NIH funding. I encourage you all to get involved in these advocacy efforts. Meet with your representative, either at their home office or when you visit the DC area. Invite your elected officials to your laboratory to see first hand that NIH funding goes well beyond Bethesda (a common misconception on the hill is that the NIH appropriation is for the Bethesda campus). When you receive an email from ASHG (or any other professional societies) regarding an upcoming congressional vote, please be sure to make your opinion known to your representative or senator.

In addition to active participation in science policy, education is the other cornerstone to enhanced biomedical research. The Society is expanding its efforts in public education. Consider participating by joining the ASHG mentor network; become a human genetics advocate and invest in the future of our field. People fear the unknown, and I believe some of the mistrust of “genetics research” by the public is due a lack of understanding and journalistic sensationalism. If you read a newspaper article that does not give a balanced view of what we do, write a letter to the editor. We do good work that benefits society and we must continually make that point clear.

Finally, not all efforts should be external to the ASHG. We need more involvement in our Society by its members. Participation is essential to the growth, vibrancy and success of the organization. Play a role in the direction that ASHG takes and let your voice be heard regarding how our Society can better serve members. For example, seek nomination to one of the ASHG committees. This year we set up a postdoctoral fellow committee to develop meeting content specifically for those in training and to let the board know the ideas and concerns of that demography of our membership. Similarly, we are developing a program to involve our early career members, for example, assistant professors and those in comparable positions, to learn more about the Society and how to play an active role in it as well as to provide networking opportunities. Please attend this year’s business meeting to hear updates on the exciting activities of ASHG. Only through engagement of the membership can we really be a strong and positive force influencing the many aspects of the future of human genetics.

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 3:30 PM–4:30 PM

SESSION 13 – Peter Gruber Foundation Prize in Genetics

Hall F

A gold medal and a $250,000 prize will be presented to Dr. Elizabeth H. Blackburn, Morris Herzstein Professor of Biology and Physiology in the Department of Biochemistry and Biophysics at the University of California, San Francisco. This prize is awarded annually to a leading scientist or group of scientists working in genetics, in recognition of groundbreaking contributions and fundamental insights in the field of genetics research. These may include original discoveries in genomic organization, function, regulation variation, and transmission. The Peter Gruber Prize recognizes her achievements in research and science advocacy.

By discovering the unique structure and mechanism of replication of telomeres, the ends of chromosomes, Dr. Blackburn demonstrated that these genetic elements play a fundamental role in normal development, and in carcinogenesis.

She has characterized telomerase, the enzyme responsible for making telomeres, in normally aging cells, in cancer cells, and in stem cells, enabling the development of new drugs based on these biological roles.

Her accuracy and honesty in debates on therapeutic cloning and stem cell research have raised public awareness of the importance of this work, and she is a model for the role of the scientist as citizen.

The Peter Gruber Foundation gives international prizes in genetics, neuroscience, justice, women’s rights, and cosmology. Its goal is to recognize, honor, and encourage individuals who have transformed their field, and by shining a spotlight on them, to encourage others to follow in their footsteps.

Past winners are:

   Robert H. Waterston
   Mary-Claire King
   H. Robert Horvitz
   Rudolf Jaenisch
   David Botstein
   Eric Knudsen
   Seymour Benzer

Elizabeth Blackburn was selected to win the 2006 Prize by a distinguished advisory panel that included:

   David Botstein
   Uta Francke
   Robert H. Waterston
   Mary-Claire King
   H. Robert Horvitz
   Rudolf Jaenisch

For further information about the Peter Gruber Foundation’s prizes, please visit http://www.petergruberfoundation.org

Reponses of Cells and Organisms to Altered Telomere Maintenance
Telomeres are the structures that protect and stabilize the ends of chromosomes, ensuring genomic stability. Telomeres consist of simple DNA sequences, which bind protein factors and make a “cap”. Without telomeric DNA and its special way of replicating, chromosome ends dwindle away, eventually causing cells to stop dividing, a process called cellular senescence. The enzyme telomerase replenishes the DNA at telomeres, partly counteracting the progressive shortening of telomeres throughout the human life span. Although telomerase activity is normally kept in check in adult human cells, throughout life a certain level of telomerase is still required for replenishment of tissues, such as the immune system. Recent findings have highlighted the importance of telomerase and telomere length maintenance. For example, low telomerase in white blood cells in young to middle aged humans was found to be associated with six of the known major risk factors for cardiovascular disease.

In contrast to many normal cells in human adults, late-stage cancer cells characteristically have very high telomerase levels. A major known function of telomerase in cancer is to replenish telomeric DNA and maintain cell immortality. However, knocking down the high telomerase in cancer cells also inhibited their growth surprisingly rapidly, even without telomere shortening. Rapid and distinct cellular and transcriptional responses were elicited by reducing the level of telomerase RNA component. The distinctive alterations in the gene-expression profiles were predicted to be associated with diminished cancer progression. These and other recent results indicate that telomerase likely plays roles in other aspects of cancer known to be central to cancer progression.

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.

By advance registration only

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.

Sponsored by BioMarin Pharmaceutical, Inc.

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.

Wednesday, October 11 6:30 PM–8:00 PM

SESSION 36 – ASHG Publications Workshop/Boxed Supper: Demystifying the Road to Publication

Room 353-354

Moderator: Robin E. Williamson, Deputy Editor, The American Journal of Human Genetics, Boston, MA

Publishing experimental results is a goal of most researchers, but the process is often filled with frustration and disappointment. For many authors, organizing and discussing data in a clear and concise fashion is a cumbersome task. Additionally, it is difficult to know which journal is the most appropriate for a manuscript. At the journal office, editors often receive papers that lack a few fundamental pieces that would have allowed an extra level of consideration. Also, peer-review is an essential part of the publication system, but it is only as effective as the comments that are generated and the response of the authors to the reviews. At this session, the editors from three prominent genetics journals will offer some guidelines to follow during the publication and review process. Following the speakers' presentations, there will be a 20-minute question and answer session with a panel of editors from a variety of journals.

6:30 PM Before submission. C. C. Morton, The American Journal of Human Genetics.

6:50 PM At the Journal. R. A. King, University of Minnesota, Minneapolis.

7:10 PM The peer-review process. J. C. Carey, American Journal of Human Genetics.

7:30 PM Questions and answers.

Admittance only by advance ticket purchase

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. Egmont-Petersen, C. Wijmenga.

Thursday, October 12 8:00 AM–10:30 AM

Concurrent Platform Sessions III (37–43)

SESSION 41 – Cancer Genetics

Hall E-3

Co-Moderators: Wendy S. Rubenstein, Evanston Northwestern Healthcare, Evanston, IL; and M. Stephen Meyn, Hospital for Sick Children, Toronto, Ontario, Canada

187/8:00 Systematic analysis of tumor genetic alterations on Cancer Genome WorkBench (CGWB). J. Zhang, R. Finney, W. Rowe, M. Edmonson, T. Dracheva, J. Jen, J. Struewing, K. Buetow.

188/8:15 Gene expression profiling of archival specimens distinguishes BRCA1-mutated from sporadic breast cancers. W. S. Rubinstein, X. Ge, K. L. Kaul, H. T. Lynch.

189/8:30 Common coding variants in CASP8 and TGFB1 increase breast cancer risk. A. Cox, A. Dunning, P. Pharoah, M. Garcia-Closas, D. Easton, The Breast Cancer Association Consortium.

190/8:45 A genomewide association study in breast cancer. D. Easton, P. D. P. Pharoah, A. M. Dunning, K. Pooley, D. R. Cox, D. Ballinger, D. Thompson, D. G. R. Evans, D. Eccles, N. Rahman, M. R. Stratton, J. Peto, O. Fletcher, B. A. J. Ponder.

191/9:00 NAT2 and NER genetic variants and susceptibility to sporadic prostate cancer in African Americans. S. E. Hooker, C. Bonilla, C. A. Ahaghotu, R. A. Kittles.

192/9:15 Strong Evidence for a Prostate Cancer Susceptibility Gene at Chromosome 17q22. E. Lange, C. Robbins, E. Gillanders, S. Zheng, J. Xu, Y. Wang, K. White, B. Chang, L. Ho, J. Trent, J. Carpten, W. Isaacs, K. Cooney.

193/9:30 IGF1 and IGFBP3 gene polymorphisms are associated with plasma levels and prostate cancer risk in African Americans. R. A. Kittles, C. Grenade, C. Bonilla, E. R. Santos, W. Hernandez, C. Ahaghotu.

194/9:45 Gender-Related Clinical Features in a Large Cohort of Cowden Syndrome (CS) and Bannayan-Riley-Ruvalcaba Syndrome (BRRS) Patients with PTEN Mutations. R. Pilarski, J. Stephens, H. Hampel, X. P. Zhou, C. Eng.

195/10:00 Mutation Positive and Mutation Negative Cowden and Bannayan-Riley-Ruvalcaba Syndrome Patients and Normal Controls Defined by Distinct 10q-Haplotypes. M. G. Pezzolesi, Y. Li, X. P. Zhou, R. Pilarski, L. Shen, C. Eng.

196/10:15 Cleft Families Have a Higher Risk of Developing Several Types of Cancer. R. Menezes, M. E. Cooper, K. M. Bardi, C. A. Brandon, A. R. Vieira, M. L. Marazita.

Thursday, October 12 8:00 AM–10:30 AM

Concurrent Platform Sessions III (37–43)

SESSION 42 – Clinical and Genetic Heterogeneity: How to Sort It Out

Room 243-245

Co-Moderators: Pamela S. Trapane, Medical College of Wisconsin, Milwaukee; and Scott D. McLean, San Antonio Military Pediatric Center, Lackland Air Force Base, TX

197/8:00 Variable functional impairment of RMRP mutations explain genotype - phenotype correlation in Cartilage hair hypoplasia and Anauxetic dysplasia. C. T. Thiel, G. Mortier, I. Kaitila, A. Rauch.

198/8:15 All is heterogeneous: Surveying clinical, genetic, and allelic heterogeneity in autosomal recessive congenital ichthyosis. K. M. Eckl, J. Kurtenbach, M. Nätebus, W. Küster, H. Traupe, A. Önal Akan, H. C. Hennies.

199/8:30 Genetic heterogeneity in Stüve-Wiedemann Syndrome. N. Dagoneau, L. I. Al Gazali, A. David, E. Flori, A. Green, B. C. J. Hamel, M. Le Merrer, F. Prieur, A. Raas-Rothschild, J. Vigneron, A. Munnich, V. Cormier-Daire.

200/8:45 Mutation screening and phenotype analysis is 48 patients with a clinical diagnosis of CFC or Costello syndromes and no mutation in PTPN11 and HRAS. A. Verloes, C. Nava, M. Gérard-Blanluet, C. Baumann, T. Niihori, Y. Narumi, Y. Aoki, Y. Matsubara, B. Arveiler, D. Lacombe, H. Cavé.

201/9:00 KRAS, BRAF, MAP2K1/2 and MAPK1/3 mutation analysis in cardio-facio-cutaneous (CFC) syndrome: genotype and phenotype correlation. Y. Narumi, Y. Aoki, T. Niihori, G. Neri, H. Cavé, A. Verloes, C. Nava, M. I. Kavamura, N. Okamoto, K. Kurosawa, H. Ohashi, R. C. M. Hennekam, L. Wilson, G. Gillessen-Kaesbach, D. Wieczorek, P. Lapunzina, S. Kure, Y. Matsubara.

202/9:15 Molecular studies and phenotype correlation in Costello syndrome. K. W. Gripp, L. Nicholson, K. M. B. Vinette, A. E. Lin, J. D. Hoffman, D. L. Stabley, K. Sol-Church.

203/9:30 Molecular dissection of NF1-related disease features in segmental NF1 patients. O. Maertens, S. De Schepper, J. Vandesompele, S. Janssens, F. Speleman, E. Legius, L. Messiaen.

204/9:45 Eight genes associated with nonsyndromic X-linked mental retardation: the whole is the sum of its parts. H. Gao, K. Gonzalez, J. Filiano, J. Zheng, L. Chen, L. Moore, V. Kimonis, S. Sommer.

205/10:00 A Novel Missense Mutation, p.R808W, in the HOPA Gene is Present in 10% of a Cohort of FG Syndrome Families. H. Risheg, M. J. Friez, J. M. Graham, Jr., J. B. Moeschler, R. C. Rogers, J. M. Opitz, R. E. Stevenson, C. E. Schwartz.

206/10:15 Germline and somatic mosaicism at the PHOX2B locus in Late-Onset Central Hypoventilation syndrome. J. Amiel, D. Trochet, L. de Pontual, A. Munnich, S. Lyonnet.

Thursday, October 12 8:00 AM–10:30 AM

Concurrent Platform Sessions III (37–43)

SESSION 43 – Metabolic Disorders

Room 343-345

Co-Moderators: David Kronn, Staatsburg, NY; and K. Michael Gibson, Children's Hospital, Pittsburg, PA

207/8:00 Lysosomal N-acetyltransferase deficient in mucopolysaccharidosis type IIIC is encoded by the TMEM76 gene on human chromosome 8. A. Pshezhetsky, V. Seyrantepe, S. Durand, N. M. Roslin, A. Verner, C. E. Beesley, I. Maire, B. Poorthuis, J. van de Kamp, O. van Diggelen, T. J. Hudson, T. M. Fujiwara, K. Morgan.

208/8:15 Mutations in TMEM76 are associated with N-acetyltransferase deficiency in mucopolysaccharidosis type III C patients. M. Hrebicek, L. Mrazova, J. Majewski, L. Noskova, H. Hartmannova, R. Ivanek, A. Cizkova, H. Poupetova, J. Sikora, J. Urinovska, V. Stranecky, J. Zeman, S. Kmoch.

209/8:30 Life without sulfatases: a mouse model lacking all sulfatase activities. C. Settembre, I. Annunziata, C. Spampanato, G. Cobellis, E. Nusco, M. Sardiello, E. Zito, M. P. Cosma, A. Ballabio.

210/8:45 Combined saposin C and D mutations in mice affect processing of prosaposin and lead to a severe neurological phenotype with predominant glucosylceramide and hydroxy ceramide accumulation. Y. Sun, M. Zamzow, H. Ran, B. Quinn, W. P. Witte, G. A. Grabowski.

211/9:00 Chediak Higashi syndrome: a genotype-phenotype correlation. W. Westbroek, D. Adams, A. Koshoffer, H. Dorward, A. Helip-Wooley, M. Huizing, J. Parkes, R. Kleta, R. Boissy, W. A. Gahl.

212/9:15 The function of BLOC-2 in lysosome-related organelle biogenesis. A. Helip Wooley, W. Westbroek, H. Dorward, P. Held, M. Ayub, R. Boissy, M. Huizing, W. A. Gahl.

213/9:30 Megamitochondria formation in a murine model of Mut class methylmalonic acidemia. R. J. Chandler, M. S. Tsai, J. Sloan, P. M. Zerfas, V. Hoffmann, C. P. Venditti.

214/9:45 Metabolic disturbances in mice heterozygous for mevalonate kinase deficiency. K. M. Gibson, A. S. Pappu, R. D. Steiner, G. F. Hoffmann, E. J. Hager.

215/10:00 Identification of a novel role of excess copper in enhancing apoptotic potential of Arg72 variant of p53: New insights into molecular pathophysiology of Indian Childhood Cirrhosis. R. Prasad, N. Sharma, B. R. Thapa, G. Kaur.

216/10:15 Congenital Erythropoietic Porphyria: High Affinity Purification, NMR Resonance Assignments, and Localization of the Active Site of Human Uroporphyrinogen III Synthase. L. Cunha, M. Kuti, D. F. Bishop, M. Mezei, L. Zeng, M.-M. Zhou, R. J. Desnick.

Thursday, October 12 1:30 PM–2:15 PM

SESSION 44 – William Allan Award Presentation and Lecture

Hall F

This award, which includes $10,000 and an engraved medal, is presented for substantial scientific contributions to human and medical genetics carried out over a lifetime of scientific inquiry.

Introduced by:
Professor Patricia A. Jacobs
Co-director of Research
Wessex Regional Genetics Laboratory
Salisbury District Hospital
Salisbury, Wiltshire, United Kingdom

Recipient:
Dorothy Warburton
Professor of Clinical Genetics and Development
Columbia University, New York, NY

Having It All

“Having it all” is a phrase usually applied to the attempt, implicitly by a woman, to combine career and family life without short-changing either. While happily the traditional meaning is valid in my case, the phrase also describes my life in human genetics in several other ways. First, cytogenetics has allowed me to combine two seemingly disparate passions: a love of playing with numbers and a fascination with new laboratory techniques. Thus my work has involved epidemiological and population studies of spontaneous abortions, chromosome abnormalities and ovarian aging. It has also involved the development and application of cytogenetic techniques, starting with autoradioagraphy, chromosome banding, in situ hybridization and somatic cell hybridization, and moving into the molecular era of FISH, CGH and genomic microarray analysis. Secondly, I have derived great personal satisfaction from being able to combine both clinical and research activities during almost forty years of directing a clinical cytogenetics lab in an academic setting. Cytogenetic analysis has revealed a vast array of chromosome aberrations associated with congenital malformations and/or mental retardation, and defined many new syndromes. Studying these aberrations has also impacted on our basic knowledge of chromosome structure and function, epigenetics and cancer. I have seen human genetics change from a discipline where patients contemplating pregnancy could be counseled only about Mendelian or empirical risks to one that now offers prenatal diagnosis for a large number of conditions and treatment for a few.

Lastly, “having it all” can also be used as a metaphor for the human genome project, which I have seen come to fruition since attending the first human gene mapping conference in 1973. The new tools available have revealed that small-scale copy number variation is widespread in the genome, and may be associated with pathology or phenotypic variation. Cytogenetics has entered an exciting era of “ultra high-resolution” chromosome analysis via microarray, which is likely to have as big an impact on human genetics as conventional cytogenetics did in the past. At the same time, it is still true that complete trisomy, no matter how diagnosed, remains the most common cause of mortality and morbidity among human conceptions. The molecular and evolutionary explanation of why our species is so prone to meiotic error, and the extraordinary phenomenon of its association with maternal aging, remain among the most significant and intriguing unsolved problems in biology. We do not really have it all: there is much to come.

Thursday, October 12 2:15 PM–2:30 PM

Leadership Award Presentation

Hall F

This award is presented to an individual whose professional achievements have fostered and enriched the development of various human genetics disciplines. Potential recipients should exemplify the enduring leadership and vision required to ensure that the field of human genetics will flourish and successfully assimilate into the broader context of science, medicine, and health. They also may have made major contributions to awareness or understanding of human genetics by policy makers or by the general public. A plaque and $2500 will be presented to the awardee at the annual meeting.

Presenter:
Michael M. Kaback, Professor
Department of Pediatrics and Reproductive Medicine,
University of California, San Diego

Recipient:
David L. Rimoin, Professor of Pediatrics, Medicine and Human Genetics
University of California, Los Angeles, School of Medicine/Cedars-Sinai Hospital, Los Angeles, CA

The Society’s newest award will be presented for the first time to Dr. David Rimoin, Professor of Pediatrics, Medicine and Human Genetics, David Geffen School of Medicine at UCLA and Steven Spielberg Chair and Director of the Medical Genetics Institute, Cedars-Sinai Medical Center. In addition to his many well-recognized research and educational achievements, particularly in the area of skeletal dysplasias, he served as the founding president of the American Board of Medical Genetics (ABMG), which established the educational standards for certification of medical geneticists and the accreditation of training programs throughout the nation. He was also the founding president of the American College of Medical Genetics (ACMG) and then president of its Foundation, whose primary goal is to foster education in medical genetics to the practitioner, as well as the public. He was responsible for establishing the American College of Medical Genetics annual meetings in conjunction with the March of Dimes to provide an educational forum for clinical geneticists and other individuals providing genetic services.

Thursday, October 12 2:30 PM–3:30 PM

SESSION 45 – ASHG Membership/Business Meeting

Hall F

Presiding: Stephen T. Warren, ASHG President

Reports highlighting current Society business are presented to inform the members and anyone else attending the meeting. The minutes of the previous meeting are presented for approval. Committee chairpersons report on their activities for the year and discuss plans for the upcoming year. Retiring board members are thanked for their years of service.

The meeting offers an opportunity for members to discuss items of new business. All members are encouraged to attend.

Thursday, October 12 4:00 PM–6:00 PM

Concurrent Invited Sessions II (46–52)

SESSION 46 – Is the "Blockbuster" Model of Drug Discovery Dead? The Utility of Pharmacogenetics

Hall F

Moderator: Patrick F. Sullivan, University of North Carolina, Chapel Hill

Traditional models of drug discovery, particularly the "blockbuster" model, are widely believed to be in crisis. For some diseases, few new medicines are in the pipeline and there are persistent safety concerns. The genetic personalization of treatment may help, but the current research base allows few firm conclusions. Recent developments suggest that this situation may be changing. In the wake of advances from large-scale genomic initiatives, the capacity for the pharmacogenetic prediction of treatment response and adverse side-effects may be improving due to a new generation of studies. Indeed, the genetics of drug response/adverse drug reactions may be more tractable phenotypes than the genetics of disease predisposition. The purpose of this invited session is to describe these developments. We provide examples of where genotype-clinical phenotype correlations are compelling and appear to be ready for clinical translation (warfarin and gefitinib) and examples that have not worked out as consistently along with the regulatory perspective of the United States FDA.

4:00 PM Introduction. P. F. Sullivan, University of North Carolina, Chapel Hill.

4:05 PM Pharmacogenetics: Lessons learned and the "Blockbuster" model. D. Goldstein, Duke University, Durham, NC.

4:30 PM A comprehensive pharmacogenetic analysis of antipsychotic use in the CATIE schizophrenia trial. P. F. Sullivan, University of North Carolina, Chapel Hill.

4:45 PM The pharmacogenetics of warfarin response. M. Rieder, University of Washington, Seattle.

5:05 PM Gefitinib: The genetics of treatment response and resistance. D. Bell, Center for Cancer Research, Massachusetts General Hospital, Charlestown.

5:25 PM A regulatory perspective on pharmacogenetics in drug development and clinical practice. L. Lesko, Food and Drug Administration, Silver Spring, MD.

5:45 PM Questions and answers.

Thursday, October 12 4:00 PM–6:00 PM

Concurrent Invited Sessions II (46–52)

SESSION 47 – The Clinical Implications of Epigenetic Reprogramming in Early Mammalian Development

La Nouvelle Ballroom A/B

Co-Moderators: Carolyn Brown, University of British Columbia, Vancouver, Canada; and Wendy Robinson, University of British Columbia, Vancouver, Canada

While it is well-established that structural and numerical chromosome abnormalities arise frequently during meiosis and early embryo development, abnormalities in chromatin structure (i.e., epigenetic alterations) may also be important in human disorders, ranging from classical imprinting syndromes to intrauterine growth restriction, obesity and diabetes. But what do we really know about how epigenetic programming can be altered in gametogenesis and early placental and embryo development? And how can we test for such abnormalities in clinical samples? This workshop is meant to "set the stage" in terms of our knowledge of normal and abnormal epigenetic programming in mammalian development and lead to a discussion of the possible medical implications of epigenetic change. The emphasis of this session will be on the types of epigenetic alterations that may occur in early development and factors influencing epigenetic change.

4:00 PM Introduction. W. Robinson, University of British Columbia, Vancouver, Canada.

4:10 PM Epigenetic marking during gametogenesis. L. Lefebvre, University of British Columbia, Vancouver, Canada.

4:35 PM Epigenetic reprogramming and instability in preimplantation embryos. T. Haaf, Johannes Gutenberg University, Mainz, Germany.

5:05 PM Clinical implications of epigenetic change. R. Weksberg, Hospital for Sick Children, Toronto, Ontario, Canada.

5:30 PM Chromosome and genomewide epigenetic change: lessons from the X. C. Brown, University of British Columbia, Vancouver, Canada.

Thursday, October 12 4:00 PM–6:00 PM

Concurrent Invited Sessions II (46–52)

SESSION 48 – Preterm Birth as a Common Complex Disorder: The Implications of Applied Genomic Research

La Nouvelle Ballroom C

Moderator: Cynthia A. Moore, Centers for Disease Control and Prevention, Atlanta, GA

Preterm birth is the number one obstetrical problem today, exacting a huge toll upon individuals, families, and society. In addition to being the leading cause of neonatal mortality, prematurity contributes to lifelong morbidity for many children. The incremental rise in preterm birth in the United States continued in 2004, reaching 12.5% (almost 500,000 births), the highest rate ever reported. But, despite the lifelong impact of prematurity on health, there are few effective strategies to predict preterm birth and fewer clinical interventions to prevent preterm birth. Prematurity is increasingly appreciated to result from the interaction of environmental influences on varying genetic backgrounds, and thus it can be approached as a common complex disorder, using the tools of genetic epidemiology and applied genomic research. This session will outline applied genomic research approaches to preterm birth and propose broad implications for clinical care and public health.

4:00 PM Introduction. C. A. Moore, Centers for Disease Control and Prevention, Atlanta, GA.

4:05 PM Heritability in prematurity: New insights into the genetics of preterm birth. K. Ward, Kapi'olani Hospital, Honolulu, HI.

4:30 PM Genetics to genomics: A framework for approaching preterm birth as a common complex disorder. S. Dolan, March of Dimes, and Albert Einstein College of Medicine, White Plains, NY.

4:55 PM Meta-analysis and knowledge integration: Implications for research on complex disease. J. P. Ioannidis, University of Ioannina School of Medicine, Ioannina, Greece.

5:20 PM Implications of applied genomic research for public health: What will it take to bring down the rate of preterm birth? M. Khoury, Centers for Disease Control and Prevention, Atlanta, GA.

5:40 PM Questions and answers.

Thursday, October 12 4:00 PM–6:00 PM

Concurrent Invited Sessions II (46–52)

SESSION 49 – Infectious Diseases as Agents of Natural Selection on the Human Genome

Hall E-1

Moderator: Jeremy Martinson, University of Pittsburgh, PA

Human genetic variation affects the severity of infectious disease progression for many pathogens. Individual polymorphisms, and epistatic interactions between them, substantially influence the host response to infection. Immune- response genes and non-immune genes are involved, but the innate immune response is emerging as a system in which these effects are most pronounced. Quantitative immune variation, arising from promoter mutations or from Copy-Number Polymorphisms (CNPs), influences the host response to pathogens, especially the early stages of infection, and has recently been demonstrated in the defensin and cytokine systems. Advances in genome analysis now enable these phenomena to be quantified, and candidate-gene approaches are completed by techniques that can detect patterns of disease-resistance polymorphism in whole-genome SNP datasets. This session will present examples of recent work that has utilized these approaches to detect many new loci affecting resistance to pathogens such as malaria, tuberculosis, and viral diseases such as HIV and hepatitis.

4:00 PM Malaria pressure on the human genome: A paradigm for genomic epidemiology of common disease. D. Kwiatkowski, Oxford University, Wellcome Trust Centre for Human Genetics, United Kingdom.

4:25 PM Natural selection on genes influencing susceptibility to infectious disease. M. J. Bamshad, University of Washington, Seattle.

4:50 PM Convergent evolution and population structure in Africa: Implications for disease intervention. S. Tishkoff, University of Maryland, College Park.

5:15 PM Innate immunity genes and susceptibility to pulmonary tuberculosis. W. Scott, Duke University Medical Center, Durham, NC.

5:40 PM Adaptive evolution of immune and inflammatory related genes: Insights from genomewide scans of positive selection. J. Akey, University of Washington, Seattle.

Thursday, October 12 4:00 PM–6:00 PM

Concurrent Invited Sessions II (46–52)

SESSION 50 – Genetic Disorders of Intracellular Protein Routing

Hall E-3

Moderator: Marjan Huizing, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland

Genetic mutations that result in human disease provide insights into the complex mechanisms of protein routing within the cell. In this session, distinct cellular compartments, their protein routing, and the associated genetic disorders will be addressed. Topics include protein folding and quality control in the endoplasmic reticulum, protein glycosylation and sorting in the Golgi complex, and endosomal and caveolar protein trafficking to and from distinct organelles and the plasma membrane. Each speaker will address groups of human genetic disorders associated with each compartment and the insights that specific disorders provide into the underlying cellular mechanisms. These cellular insights are ultimately essential for a rational approach to therapies.

4:00 PM Traffic jams: a compendium of human diseases that affect intracellular transport processes. M. Huizing, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD.

4:30 PM Disorders of protein routing through the Golgi complex. H. H. Freeze, Burnham Institute for Medical Research, La Jolla, CA.

5:00 PM RAB GTPases and endocytic trafficking in health and disease. A. Wandinger-Ness, University of New Mexico Health Sciences Center, Albuquerque.

5:30 PM Caveolins, caveolae and lipid rafts in cellular transport: From cell biology to medicine. M. P. Lisanti, Albert Einstein College of Medicine, Bronx, NY.

Thursday, October 12 4:00 PM–6:00 PM

Concurrent Invited Sessions II (46–52)

SESSION 51 – Inherited Telomerase Deficiencies and Human Disease

Room 243-245

Moderator: Peter Lansdorp, British Columbia Cancer Agency, Vancouver, British Columbia, Canada

In order to distinguish a normal telomere from a double strand break, a minimum number of telomere repeats must “cap” each chromosome end. The length of each repeat array will reflect a unique history of addition and losses. Telomere losses are known to occur sporadically as well as with every replication cycle. Losses of telomeric DNA are countered by the telomerase enzyme containing telomerase RNA (encoded by the TERC gene) and a reverse transcriptase protein (encoded by TERT gene) as minimal components. Telomerase activity is limiting in most somatic (stem) cells and the average length of telomere repeats in most somatic cells shows a highly significant decline with age. In this session basic aspects of telomere and telomerase biology will be reviewed together with recent observations indicating that haplo-insufficiency for either the TERC or TERT gene can give rise to disease including autosomal dominant dyskeratosis congenita (DKC) and aplastic anemia.

4:00 PM Molecular principles of human telomerase function and dysfunction in disease. K. Collins, University of California, Berkeley.

4:30 PM Dyskeratosis congenita: a disease of defective telomere maintenance. I. Dokal, Imperial College London, United Kingdom.

5:00 PM Mechanisms of telomere loss. P. M. Lansdorp, BC Cancer Agency, Vancouver, British Columbia, Canada.

5:30 PM Pathophysiology and treatment of bone marrow failure resulting from mutations in telomerase genes. N. Young, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.

Thursday, October 12 4:00 PM–6:00 PM

Concurrent Invited Sessions II (46–52)

SESSION 52 – Clinical, Molecular and Genetic Update on Endocrine Tumors

Room 343-345

Moderator: Stephen J. Marx, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD

New genetic and molecular information clarifies thyroid and parathyroid tumors, chromaffin tumors, multiple endocrine neoplasia types 1 and 2, and Carney Complex. There are important implications in counseling, in normal signal transduction pathways, and in tumorigenesis. An endocrine neoplasia syndrome can express striking metabolic features from hormone excess. Traditionally, these features have defined carriers and have given tools to monitor tumor burden. Other morbid features are from benign and malignant neoplasia of endocrine and sometimes non-endocrine tissues. Focus on the phenotypes from hormone excess in these syndromes has sped discoveries about genetics and tumorigenesis. Not only does mutation testing in the germline benefit rare families, but mutation testing in somatic tissues benefits management of cases with similar common variety tumors. Some of the disturbed molecular pathways are already promising for interventions against neoplasia in vitro, and some are already under exploration in clinical trials.

4:00 PM Introduction. S. J. Marx, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, MD.

4:02 PM Parathyroid tumor genetics. A. J. Arnold, University of Connecticut Health Center, Farmington.

4:22 PM Genomic medicine practice: Lessons learned from pheochromocytoma. C. Eng, Genomic Medicine Institute, The Cleveland Clinic Lerner Research Institute, Cleveland, OH.

4:42 PM MEN1 Gene function and molecular diagnosis. A. E. Bale, Yale University, School of Medicine, New Haven, CT.

5:02 PM c-AMP and protein kinase A signaling in endocrine and other tumors. C. A. Stratakis, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.

5:22 PM How thyroid cancers start: Non-overlapping mutations of multiple MAPK genes. J. A. Fagin, University of Cincinatti, OH.

5:42 PM Questions and answers.

Thursday, October 12 8:00 PM–9:30 PM

Special Plenary Session

SESSION 53 – Defining and Celebrating Human Variation

Hall F

Moderator: Stephen T. Warren, Emory University School of Medicine, Atlanta, GA

The Genographic Project, directed by Explorer-in-Residence, Dr. Spencer Wells, is a five-year effort to map humanity’s genetic journey through the ages. Research labs across the globe have scientists visiting remote regions in a comprehensive effort to map migration and assess the world’s remaining indigenous and ethnic population isolates. An overview of the genetic findings will help explain the diversity and source of variation in human populations.

In an effort to bring context to the variation we represent, Rick Guidotti, an energetic and talented photographer, will share his passion and vision of the importance of celebrating human differences.

This symposium will engage the audience and enlighten the scientific perspective of our daily laboratory and patient activities.

Deep ancestry: inside the Genographic Project. S. Wells, National Geographic Society, Washington, DC.

The spirit of difference. R. Guidotti, Positive Exposure, New York, NY.

Friday, October 13 8:00 AM–10:30 AM

Concurrent Platform Sessions IV (54–60)

SESSION 54 – Modifiers and Interactors

Hall F

Co-Moderators: Neena L. Champaigne, University of Texas Medical Branch, Galveston; and V. Reid Sutton, Baylor College of Medicine, Houston, TX

217/8:00 Could Glucocerebrosidase mutations affect alpha-synuclein aggregation by toxic gain-of-function? O. Goker-Alpan, D. Urban, B. Stubblefield, M. Cookson, B. Giasson, E. Sidransky.

218/8:15 A prospective study of two major age-related macular degeneration susceptibility alleles and interactions with modifiable risk factors. D. A. Schaumberg, S. E. Hankinson, Q. Guo, E. Rimm, D. J. Hunter.

219/8:30 Complement Factor H Polymorphism Tyr402His and Cuticular Drusen. M. A. Grassi, J. C. Folk, T. E. Scheetz, C. M. Taylor, V. C. Sheffield, E. M. Stone.

220/8:45 Glaucoma-causing myocilin mutations require association with the Peroxisomal Targeting Signal-1 Receptor (PTS1R) to elevate intraocular pressure. V. C. Sheffield, A. R. Shepard, N. Jacobson, J. C. Miller, I.-H. Pang, H. T. Steely, C. Searby, E. M. Stone, A. F. Clark.

221/9:00 TRMU related to tRNA modification is a nuclear modifier gene for the phenotypic expression of the deafness-associated mitochondrial 12S rRNA mutation. M. Guan, Q. Yan, X. Li, Y. Bykhovskaya, I. del Castillo, P. Hajek, T. Suzuki, M. Shohat, X. Estivill, J. Lu, N. Fischel-Ghodsian.

222/9:15 Co-chaperones of the glucocorticoid receptor and depression during pregnancy. E. R. Katz, T. C. Deveau, D. J. Newport, Z. N. Stowe, J. F. Cubells, E. B. Binder.

223/9:30 Epistatic Effect Between 11q22 and 17p11 for Attention-Deficit/Hyperactivity Disorder in the Paisa Genetic Isolate. M. Jain, F. X. Castellanos, D. Pineda, F. Lopera, J. Palacio, K. Berg, J. Bailey-Wilson, M. Muenke, M. Arcos-Burgos.

224/9:45 Assessing the effect of missense variants in oligogenic disease. N. A. Zaghloul, C. C. Leitch, N. Katsanis.

225/10:00 RET-dependent and RET-independent Hirschsprung diseases. L. de Pontual, A. Pelet, D. Trochet, S. Antonorakis, R. Tourraine, A. Munnich, F. Jaubert, M. Goossens, J. Feingold, S. Lyonnet, J. Amiel.

226/10:15 Penetrance of craniofacial anomalies in mouse models of Smith-Magenis syndrome is modified in trans by genomic sequence surrounding Rai1. J. Yan, W. Bi, J. R. Lupski.

Friday, October 13 8:00 AM–10:30 AM

Concurrent Platform Sessions IV (54–60)

SESSION 55 – Cardiovascular Genetics

La Nouvelle Ballroom A/B

Co-Moderators: Ulrich Broeckel, Medical College of Wisconsin, Milwaukee; and Evadnie Rampersaud, University of Maryland, Baltimore

227/8:00 Identification and replication of GATA2 polymorphisms associated with familial early onset coronary artery disease. J. J. Connelly, C. Haynes, L. Wang, S. H. Shah, J. E. Cox, D. Crosslin, A. B. Hale, T. Wang, S. Nelson, D. C. Crossman, C. B. Granger, J. L. Haines, C. J. H. Jones, J. M. Vance, P. J. Goldschmidt-Clermont, W. E. Kraus, E. R. Hauser, S. G. Gregory.

228/8:15 The First Genome-wide Scan to search for Genes predisposing to Coronary Artery Disease using 500,000 Single Nucleotide Polymorphism (SNP) marker set. A. Stewart, R. McPherson, L. Vo, Y. Wang, J. Rutberg, G. Ewart, G. Wells, K. Williams, N. Kavaslar, H. Doelle, S. Hebert, T. Naing, R. Roberts.

229/8:30 USF1 and coronary heart disease; allelic imbalance of a transcription factor results in differential regulation of lipid metabolism- and immune genes. J. Naukkarinen, V. Lyssenko, L. Groop, M.-R. Taskinen, L. Peltonen.

230/8:45 Genome-wide association scans identify SNPs associated with Metabolic Syndrome risk factors. K. A. Frazer, J. S. Kooner, C. A. Aguilar-Salinas, D. A. Hinds, C. L. Hyde, J. C. Chambers, G. R. Warens, J. Scott, D. S. Lee, P. M. Milos, D. R. Cox, J. F. Thompson.

231/9:00 Genomewide association with eleven intermediate phenotypes for CVD in women. D. I. Chasman, D. T. Miller, P. Kozlowski, J. Suk Danik, R. Lazarus, R. Y. L. Zee, N. R. Cook, D. J. Kwiatkowski, P. M. Ridker.

232/9:15 VLDLR common genetic variation is associated with very low-density lipoprotein (VLDL), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) particle density. D. C. Crawford, A. S. Nord, M. D. Badzioch, J. Ranchalis, M. Ahearn, C. Bertucci, E. M. Wijsman, M. J. Rieder, D. A. Nickerson, G. P. Jarvik.

233/9:30 Four Genes in the Hypertension Pathway are confirmed to be Genetic Markers for Insulin Resistance. X. Guo, K. D. Taylor, S. Cheng, B. Fang, J. Cui, A. H. Xiang, M. J. Quiñones, J. C. Ramirez, W. A. Hsueh, T. A. Buchanan, L. J. Raffel, J. I. Rotter.

234/9:45 Genes of the extracellular matrix contribute to the development of intracranial aneurysms. Y. M. Ruigrok, G. J. E. Rinkel, R. van 't Slot, M. Wolfs, S. Tang, C. Wijmenga.

235/10:00 Prospective study of warfarin dosage requirements based on CYP2C9 and VKORC1 genotypes. M. Lee, M. H. Weng, L. S. Lu, H. P. Juang, T. H. Lee, F. M. Sun, J. Y. Wu, Y. T. Chen.

236/10:15 Discovery and association of gamma-glutyml carboxylase (GGCX) polymorphism with warfarin dosing. M. J. Rieder.

Friday, October 13 8:00 AM–10:30 AM

Concurrent Platform Sessions IV (54–60)

SESSION 56 – Cancer Genetics and Cytogenetics

La Nouvelle Ballroom C

Co-Moderators: Susanne M. Gollin, University of Pittsburgh, PA; and Barbara K. Goodman, Duke University Medical Center, Durham, NC

237/8:00 An interphase fluorescence in situ hybridization (FISH) assay for the detection of 3q26.2/EVI1 rearrangements in myeloid malignancies. D. Bobadilla, E. Enriquez, G. Alvarez, P. Gaytan, D. Smith, M. L. Slovak.

238/8:15 Common leukemia-associated genetic alterations are present in healthy individuals: silent micro-mosaicism or latent predisposition? D. Mercer, M. M. Li.

239/8:30 Silencing of the oncosuppressor gene FHIT in normal cells leads to dysregulation of mitosis related pathways. L. Roz, F. Andriani, G. Sozzi.

240/8:45 TMEM16A is amplified and overexpressed in head and neck cancer. U. Duvvuri, B. J. Henson, X. Huang, J. S. White, R. A. Parikh, R. Seethala, A. El-Naggar, J. R. Grandis, S. M. Gollin.

241/9:00 MOM-PAP-A detects ultrarare deletions and demonstrates that normal lung contains the EGFR microdeletions commonly found in lung cancers. Z. Chen, J. Feng, S. Sommer.

242/9:15 A role for the developmental gene NOTCH2 in hepatoblastoma. R. A. Schultz, G. E. Tomlinson, D. Rakheja, T. Chen, N. R. Schneider, K. Wilson, C. Echebiri, B. A. Hirschman, A. R. Brothman, P. Eis, T. A. Richmond, R. R. Selzer, J. H. Feusner, M. Malogolowkin, R. L. Stallings, Children's Oncology Group.

243/9:30 Genomic analysis of sentinel lymph nodes: in search of predictive markers of breast cancer metastasis. B. R. Haddad, S. L. Santos, E. M. Ribeiro, J. D. Rone, C. A. Urban, R. S. Lima, I. J. Cavalli, L. R. Cavalli.

244/9:45 Adrenocortical hyperplasia or adenomas are associated with inhibition of phosphodiesterase 11A in carriers of PDE11A gene sequence variants and in pde11a^+/- mice. A. Horvath, C. Giatzakis, S. Boikos, K. Griffin, E. Stein, J. Surapisitchat, A. Robinson-White, I. Bossis, V. Kamvissi, P. Soni, J. A. Carney, J. Bertherat, P. Gregersen, E. Remmers, J. Beavo, C. Stratakis.

245/10:00 Mutator genes permissive for genomic rearrangements at Alu repeats. K. M. Chisholm, P. L. Welcsh, M.-C. King.

246/10:15 Study of the Involvement of the Fanconi Anemia Proteins in ALT Telomere Maintenance. H. Root, M. S. Meyn.

Friday, October 13 8:00 AM–10:30 AM

Concurrent Platform Sessions IV (54–60)

SESSION 57 – Admixture and Population Flow

Hall E-1

Co-Moderators: Michael Seldin, University of California, Davis; and Jonathan Pritchard, University of Chicago, IL

247/8:00 The Genetic Structure of Human Populations in Africa. F. A. Reed, A. Froment, M. W. Smith, S. M. Williams, S. A. Omar, M. J. Kotze, G. S. Pretorius, M. Ibrahim, O. Doumbo, M. Thera, C. Wambebe, S. E. Dobrin, J. L. Weber, S. A. Tishkoff.

248/8:15 Construction and analysis of a novel database of human neutral polymorphisms. M. F. Hammer, M. P. Cox, D. W. Garrigan, A. Woerner, T. Severson, J. D. Wall.

249/8:30 Patterns of gene flow between human populations. D. Garrigan, Z. Mobasher, S. B. Kingan, M. M. Pilkington, M. F. Hammer.

250/8:45 Patterns of admixture in Latino populations. A. Ruiz-Linares, S. Wang, G. Bedoya, C. Bortolini, H. Nicolini, W. Klitz, J. Molina, N. Freimer, R. Barrantes, G. Mazzotti, C. Gallo, J. Dipierri, E. Alfaro, N. Bianchi, G. Bailliet, F. Rothhammer, F. Salzano, M. Feldman, N. Rosenberg.

251/9:00 Genomic diversity and population structure of Native Americans. S. Wang, M. Jakobsson, S. Ramachandran, G. Bedoya, W. Rojas, M. Parra, J. Molina, G. Mazzotti, C. Gallo, D. Labuda, W. Klitz, R. Barrantes, C. Bortolini, F. Salzano, F. Rothhammer, M. Feldman, N. Rosenberg, A. Ruiz-Linares.

252/9:15 Practical solution for population stratification in genome-wide association scans and targeted studies. A. L. Price, N. J. Patterson, R. M. Plenge, M. E. Weinblatt, N. A. Shadick, J. Butler, C. D. Campbell, A. Ramos, A. Ruiz-Linares, J. N. Hirschhorn, D. Reich.

253/9:30 Definition and Application of European Substructure Information. M. F. Seldin, R. Shigeta, P. Villoslada, C. Selmi, L. Klareskog, P. K. Gregersen.

254/9:45 Whole Genome Association Studies in Admixed Populations. N. Risch, H. Tang.

255/10:00 Admixture mapping for acute inflammatory markers in African Americans: results from the Health and Body Composition Study. E. Ziv, N. Patterson, G. J. McDonald, A. Tandon, D. Hu, L. Pawlikowska, P. Y. Kwok, Y. Liu, A. Reiner, W. C. Hsueh, J. Zmuda, R. Ferrell, R. Liu, T. Harris, S. Cummings, D. Reich.

256/10:15 Admixture mapping identifies 8q24 as a locus explaining >39% of prostate cancer cases in younger African American men. D. Reich, M. L. Freedman, C. A. Haiman, N. Patterson, G. J. McDonald, A. Tandon, A. Waliszewska, K. Penney, C. Montague, K. Ardlie, E. M. John, I. Oakley-Girvan, A. S. Whittemore, K. A. Cooney, S. A. Ingles, D. Altshuler, B. E. Henderson.

Friday, October 13 8:00 AM–10:30 AM

Concurrent Platform Sessions IV (54–60)

SESSION 58 – Genomic Rearrangements

Hall E-3

Co-Moderators: Simon G. Gregory, Duke University, Durham, NC; and Stuart Schwartz, University of Chicago, IL

257/8:00 Delineation of breakpoints in chromosomal rearrangements: continued examination of the mechanism and complexity of rearrangements. H. Ho, C. Astbury, L. Christ, M. Falk, C. Fitzpatrick, M. Graf, H. Mashek, S. Schwartz.

258/8:15 Chromosome Rings/Markers as a Model to Determine Rearrangement Mechanisms. C. Fitzpatrick, L. Christ, C. Crowe, M. Graf, S. Schwartz.

259/8:30 Comparative analysis on deletion polymorphisms using gene expression data. S. Gopalakrishnan, Z. S. Qin.

260/8:45 Discovery of novel recurrent genomic disorders from the duplication architecture of the human genome. A. J. Sharp, S. Hansen, R. R. Selzer, Z. Cheng, R. Regan, J. A. Hurst, C. A. Fitzpatrick, T. A. Richmond, D. Pinkel, P. S. Eis, S. Schwartz, S. L. Knight, E. E. Eichler.

261/9:00 A new mechanism for genomic rearrangements causing genomic disorders. J. A. Lee, J. R. Lupski.

262/9:15 Molecular cytogenetic analysis of 149 breakpoints in 76 cases with apparently balanced chromosome rearrangements. D. R. FitzPatrick, J. A. Fantes, E. Borland, J. Ramsay, D. Donnai, J. Clayton-Smith, V. van Heyningen, G. Black.

263/9:30 Novel contiguous gene deletions and duplications in patients with developmental delay, mental retardation, and dysmorphology. S. Aradhya, M. Manning, A. M. Cherry.

264/9:45 Segmental duplications on 10q are linked to complex genomic rearrangements associated with neurobehavioral abnormalities. J. Balciuniene, N.-P. Feng, B. Hirsch, L. Charnas, D. Avramopoulos, D. Valle, L. Schimmenti, S. Selleck.

265/10:00 Array-based comparative genomic hybridization identifies high frequency of cryptic chromosomal rearrangements in patients with syndromic autism spectrum disorders. M. L. Jacquemont, S. Leclerq, D. Sanlaville, R. Redon, V. Malan, O. Raoul, V. Cormier-Daire, S. Lyonnet, J. Amiel, M. Le Merrer, D. Héron, M. C. de Blois, M. Prieur, M. Vekemans, N. P. Carter, A. Munnich, L. Colleaux, A. Philippe.

266/10:15 Holoprosencephaly: clinical and genetic study about 350 patients (1996-2006). S. Odent, L. Pasquier, C. Dubourg, C. Bendavid, C. Henry, S. Jaillard, M. R. Durou, I. Gicquel, V. David.

Friday, October 13 8:00 AM–10:30 AM

Concurrent Platform Sessions IV (54–60)

SESSION 59 – Effects of Non-coding RNAs

Room 243-245

Co-Moderators: Stylianos E. Antonarakis, University of Geneva, Switzerland; and Albert R. La Spada, University of Washington, Seattle

267/8:00 Mapping of small RNAs in the human ENCODE regions. C. Borel, M. Gagnebin, C. Gehrig, E. Kriventseva, E. Zdobnov, S. E. Antonarakis.

268/8:15 CTCF regulates ataxin-7 gene expression through promotion of an antisense non-coding RNA: a novel system of transcriptional control linking CTCF with non-coding RNA's. V. V. Pineda, R. T. Libby, G. Dunn, S. Baccam, A. C. Smith, S. J. Tapscott, G. N. Filippova, B. L. Sopher, A. R. La Spada.

269/8:30 Bidirectional expression of the SCA8 mutation: evidence for polyglutamine inclusions and CUG RNA gain-of-function effects. R. S. Daughters, Y. Ikeda, D. L. Tuttle, T. Zu, M. L. Moseley, J. W. Day, M. S. Swanson, L. P. W. Ranum.

270/8:45 XIST-dependent silencing following expression of an inducible human XIST transgene in human somatic cells. C. J. Brown, J. C. Chow, S. Sidhu.

271/9:00 Overexpression of CUGBP suppresses the Fragile X CGG premutation repeat induced neurodegeneration in D. melanogaster. O. Sofola, R. Duan, P. Jing, D. Nelson, J. Botas.

272/9:15 Evidence for paternal allele-specific chromatin extension and looping of the SNRPN to UBE3A locus in mature neurons by FISH. K. N. Thatcher, R. O. Vallero, J. M. LaSalle.

273/9:30 Identification of mouse miRNAs expressed exclusively or preferentially in retina. P. Witmer, S. Xu, J. Mendell, D. Valle.

274/9:45 MicroRNA expression profiling of lung cancer cell lines. A. Pertsemlidis, Irnov, L. Du, J. Schageman, S. Goodson, J. M. Thompson, S. Hammond, L. Girard, M. Sato, J. Shay, A. F. Gazdar, J. D. Minna.

275/10:00 Specific microRNA deregulation in follicular thyroid cancer and clinical implications. F. Weber, R. E. Teresi, C. Eng.

276/10:15 RNA interference-mediated allele-specific silencing rescues sialic acid levels in the dominant disorder sialuria. E. Klootwijk, P. J. Savelkoul, C. Ciccone, D. Krasnewich, W. A. Gahl, M. Huizing.

Friday, October 13 8:00 AM–10:30 AM

Concurrent Platform Sessions IV (54–60)

SESSION 60 – Bone and Connective Tissue Disorders

Room 343-345

Co-Moderators: Jacqueline T. Hecht, University of Texas, Houston; and Joan C. Marini, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD

277/8:00 Nosology and Classification of Genetic Skeletal Disorders. A. Superti-Furga, S. Unger, and the ISDS Nosology Group.

278/8:15 COL11A1-gene is Both Linked to and Associated with Human Stature. J. Kettunen, E. Costiander, S. Sammalisto, L. Peltonen, M. Perola.

279/8:30 Deficiency of Prolyl 3-Hydroxylase (Leprecan) Causes a Novel Recessive Metabolic Disorder of Bone Resembling Lethal/Severe Osteogenesis Imperfecta. W. A. Cabral, W. Chang, A. M. Barnes, D. R. Eyre, M. A. Weis, S. Leikin, E. Makareeva, N. V. Kuznetsova, K. N. Rosenbaum, C. Kozma, C. J. Tifft, P. Smith, J. C. Marini.

280/8:45 Recessive Lethal Form of Osteogenesis Imperfecta Caused by Null Mutations in CRTAP. A. M. Barnes, W. Chang, R. Morello, W. A. Cabral, E. Makareeva, N. Kouznetsova, S. Leikin, M. A. Weis, D. R. Eyre, T. E. Uveges, J. J. Mulvihill, U. T. Sundaram, B. Lee, J. C. Marini.

281/9:00 CRTAP is required for collagen 3-prolyl hydroxylation and loss of its function causes recessive osteogenesis imperfecta. R. Morello, T. K. Bertin, P. Castagnola, H. P. Bachinger, F. H. Glorieux, P. H. Byers, D. R. Eyre, B. F. Boyce, B. Lee.

282/9:15 A loss of function mutation in the fibulin-4 gene causes a severe form of recessive cutis laxa. V. Hucthagowder, N. Sausgruber, K. H. Kim, B. Angle, L. Y. Marmorstein, Z. Urban.

283/9:30 Pseudoxanthoma Elasticum-like disorder with generalized cutis laxa and clotting deficiency represents a novel genetic entity. O. M. Vanakker, L. Martin, D. Gheduzzi, B. P. Leroy, V. Guerci, P. Coucke, I. Pasquali-Ronchetti, A. De Paepe.

284/9:45 A cohort of patients with generalized Fibromuscular Dysplasia and features of Ehlers-Danlos Syndrome: a new phenotype. N. B. McDonnell, J. Yang, W. Chen, B. Griswold, C. A. Francomano.

285/10:00 The Spine and the Craniocervical Junction in Ehlers-Danlos Syndrome. C. A. Francomano, R. Razza, B. Griswold, P. Bolognese, T. Milhorat, N. B. McDonnell.

286/10:15 Distal arthrogryposis type 5 is caused by defects of myosin. R. Toydemir, L. B. Jorde, M. Bamshad.

Friday, October 13 11:00 AM–1:00 PM

Special Session

SESSION 61 – Stem Cells: Science, Art and Applications

Hall F

The pluripotent nature of stem cells offers promise for regeneration of a variety of cell types and tissues. That promise, in turn, provides hope for victims of numerous diseases previously considered incurable. For this symposium, Dr. Weiss begins with a description of the isolation and characterization of forebrain neural stem cells and their potential use in repairing the injured brain. Dr. Daley then provides a discussion of his methodology for preparing customized stem cells, with productive results. Dr. Orkin provides details on how stem cells are controlled at the molecular level. Finally, Dr. Grompe expounds on the surprising ability of the liver to repopulate via hepatic stem cells. Each expert employs a model system to demonstrate the dynamic underpinnings of tissue homeostasis, i.e., the action of stem cells. Each presentation addresses the feasibility of using stem cells for the renewal of impaired organs and tissues, whether damaged by genetic, environmental, or traumatic causes. Stem cell therapy stands at our doorstep, about to enter the future of medicine.

11:00 AM Forebrain neural stem cells: from basic biology to brain repair. S. Weiss, University of Calgary, Alberta, Canada.

11:30 AM Customized stem cells. G. Daley, Children's Hospital, Boston, MA.

12:00 NOON Molecular control of stem cells. S. Orkin, Dana Farber Cancer Institute, Boston, MA.

12:30 PM Liver stem cells and liver repopulation. M. Grompe, Oregon Health and Sciences University, Portland.

Friday, October 13 2:30 PM–2:45 PM

SESSION 62 – ASHG Trainee Award Presentations

Hall F

Moderator: David Valle, The Johns Hopkins University, Institute of Genetic Medicine, Howard Hughes Medical Institute, Baltimore, MD

The Society will present $500 to each awardee for outstanding research presented by a trainee in each of the following areas: predoctoral clinical, postdoctoral clinical, predoctoral basic, postdoctoral basic, predoctoral translational, and postdoctoral translational. Finalists have been selected from nominees who submitted abstracts in the competition. Their names are listed in the section of this book entitled “Trainee Awards Program.”

Friday, October 13 2:45 PM–2:50 PM

SESSION 63 – C. W. Cotterman Award

Hall F

Monetary awards of $500 each and commemorative plaques will be presented to the first authors of the best papers published in The American Journal of Human Genetics during the previous year on which the first author is either a pre- or postdoctoral trainee and an ASHG member. Each September, the editorial board of the Journal selects the articles that best represent outstanding contributions to the field of genetics. Two awards are presented annually.

Presenter:
Cynthia C. Morton, editor
The American Journal of Human Genetics
Brigham & Women's Hospital, Boston, Massachusetts

Friday, October 13 2:50 PM–3:15 PM

SESSION 64 – Curt Stern Award

Hall F

The Curt Stern Award is granted yearly to a scientist or scientists for major scientific achievement in human genetics that has occurred in the last 10 years. The work could be a single discovery or a series of contributions on a similar or related topic. The Award honors the memory of Curt Stern (1902-1981) as an outstanding pioneer in human genetics and ASHG president in 1956. An engraved crystal award and $2500 will be presented to the awardee at the annual meeting.

Presenter: Victor A. McKusick, University Professor of Medical Genetics
The Johns Hopkins University School of Medicine, Baltimore, MD

Recipient: Harry C. Dietz
Victor McKusick Professor of Medicine and Genetics; Investigator, Howard Hughes Medical Institute; Professor of Pediatrics, Institute of Genetic Medicine
The Johns Hopkins University School of Medicine, Baltimore, Maryland

Reflections on the Value of “Sticking with” Marfan Syndrome
I am commonly asked why I stick with Marfan research given that the work after gene discovery is often more difficult and tedious than simply moving on to the next gene and disease. A growing trend in medical genetics is to emphasize common and complex traits, perhaps at the expense of dwindling excitement and resources devoted to relatively rare Mendelian disorders. Here, my thoughts are flavored by my life’s experiences as a clinician who also happens to do research. If I had been asked 10 years ago about the prospects of developing a productive medical therapy for a systemic disorder of connective tissue such as Marfan syndrome, I would have placed the chances just slightly ahead of curing a chromosomal disorder. My continuing dedication to Marfan syndrome was more a reflection of obligation to my patients, as opposed to perceived opportunity. At that time we thought that the pathogenesis of Marfan syndrome simply reflected loss of physical integrity of the tissues due to a deficiency of the structural protein fibrillin-1. It was a clinical encounter (including unbiased and astute questioning by a patient) that first challenged this paradigm. Why should weakness of the tissues lead to overgrowth of the bones? Why, for that matter, should it lead to the craniofacial features of Marfan syndrome, valve thickening, or low muscle mass and tone? We turned to mouse models of Marfan syndrome to address these issues, and learned that fibrillin-1 normally regulates the activation of and signaling by the TGFbeta family of cytokines. Furthermore, antagonism of TGFbeta using either neutralizing antibodies or the FDA-approved drug losartan could prevent the multisystem manifestation of Marfan syndrome including lung emphysema, aortic aneurysm and failed muscle regeneration in the mouse model. Having established this foundation for Marfan syndrome, we learned that excess TGFbeta signaling contributes to overlapping disease phenotypes including other forms of syndromic aortic aneurysm and emphysema and failed muscle regeneration in the mdx mouse model of Duchenne muscular dystrophy. A clinical trial of losartan for Marfan syndrome will begin soon, and this strategy has proven equally powerful in ameliorating muscle disease in mdx mice. Sticking with Marfan syndrome (or, more generally, rare Mendelian disorders) remains an obligation based upon the contributions (through personal commitment) such patients have made to the maturation of genetic technologies and human genetics as a discipline. This and other examples also underscore the privilege and opportunity that continues to be granted by these individually rare but collectively indispensable partners in research.

Friday, October 13 3:15 PM–3:30 PM

SESSION 65 – ASHG Award for Excellence in Human Genetics Education

Hall F

Nominees for this award have made a contribution that is recognized nationally or internationally as being of exceptional quality and great importance to human genetics education. An award of $2500 and a plaque will be presented to the awardee at the annual meeting.

Introduced by: Robert Nussbaum
Chief of the Division of Medical Genetics and Holly Smith Professor of Medicine, Department of Medicine
University of California, San Francisco.

Recipient:
Roberta “Bonnie” Pagon
Professor of Pediatrics
University of Washington, Seattle

This award is being presented to Dr. Pagon for her tireless work in the development of the GeneTests database that includes GeneReviews. These resources are indispensable educational tools for geneticists and counselors wishing to learn abut the practical aspects of caring for patients with genetic diseases. The information is freely available on the web and is playing a major role in the education of our genetic fellows, counseling students and clinicians.

Friday, October 13 3:30 PM–5:30 PM

SESSION 66 – Distinguished Speakers' Symposium: Understanding and Treating Genetic Diseases

Hall F

Moderator: William A. Gahl, National Human Genome Research Institute, Bethesda, MD

Despite remarkable conservation of many DNA sequences throughout evolution, cataclysmic alterations in the genes of certain pathways signal the generation of a new species. Dr. Ajit Varki illustrates this phenomenon by detailing profound differences in the glycosylation systems of apes and human. Those differences are primarily manifest by changes in the metabolic handling of sialic acid, the terminal, charged carbohydrate on N-linked and O-linked oligosaccharides that provide untold diversity to proteins and lipids alike. Nobelist Peter Agre follows with an exposition of aquaporin water channels responsible for the movement of water across membranes. The elegant discovery of these elemental systems provides new understanding of trans-cellular water fluxes and serves as a basis for therapeutic interventions. Finally, Dr. Alain Fischer explains the genetics of immune deficiency and the current state of the art regarding the application of gene therapy, complete with a rationale for the pitfalls and promise of this treatment modality in severe combined immune deficiency.

3:30 PM Genetic differences between humans and great apes: finding a bundle of needles in the haystack. A. Varki, University of California, San Diego.

4:10 PM Aquaporin water channels: from atomic structure to clinical medicine. P. Agre, The Johns Hopkins University School of Medicine, Baltimore, MD.

4:40 PM Inherited deficiencies of the immune system: from pathophysiology to therapy. A. Fischer, Hopital Necker-Enfants Malades, Paris, France.

POSTER PRESENTATION LISTINGS