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Conference Program
 
Human Single Nucleotide Polymorphisms & Disease
Understanding the Genetic Origin of Human Diseases and Natural Differences
August 3-8, 2014
Stonehill College
Easton, MA
Chair:
Emil Alexov

Vice Chair:
Anna R. Panchenko

In biology, we are now at the point where the latest advances of experimental and computational methods have opened a new perspective - quick and non-expensive DNA sequencing. Next-generation sequence technologies, among them exome sequencing, have brought the dream of individual genome identification close to reality. However, new advances in genome sequencing are necessary but not sufficient for understanding the allelic variation in human genes and identifying functionally important variants. Specific human phenotype is largely determined by stability, activity, and interactions between numerous biomolecules which work together to provide specific cellular functions. Although the majority of genetic variations are likely to be neutral, a substantial fraction of them might explain the origins of Mendelian and complex diseases. For example, somatic mutations may contribute significantly to tumorigenesis, and driver mutations may alter key signaling pathways which allow cancer cells to sustain proliferative signaling. However, finding functionally important mutations and distinguishing positively-selected from passenger mutations remains an unsolved problem.

Many computational and experimental methods have been developed to estimate the effects of mutations on proteins. Computational approaches are available to estimate the folding or binding free energy change of mutants using detailed atomic models, empirical or statistical potentials. Large-scale mutagenesis, alanine scanning, biochemical, and structural studies assess the experimental effects of mutations and amino acid substitutions on conformation, activity, and function of proteins. Discussion of new developments and new approaches in this field will be one of the main topics of this Gordon Conference. In parallel, significant efforts were invested to catalog naturally occurring genetic differences, those found in the general population (dbSNP, HGVbase, the Human Gene Mutation Database, the TopoSNP database and many others); and those known to be disease-associated (a few examples include the Online Mendelian Inheritance in Man database (OMIM) and the COSMIC database). The rapid growth of these databases and the current status of collection and categorization of genomic variation data will be another important topic of the conference. Database developers and researchers will have the opportunity to get together and bridge their research.

Another aspect of the conference is to bring together researchers working in the field of biological networks and pathways. Indeed, a defect in a single gene may sometimes be pathological, while in other cases a series of mutations in different genes are responsible for a disease. How can the understanding of biomolecular interaction networks contribute to predictions of the effects of mutations on cellular function? The conference participants will be able to share ideas about how to reveal the interplay between molecular characteristics of individual elements within a network and the network’s topological properties.

The conference will bring together people that work on diverse experimental and computational aspects related to inferring and analyzing the effect of human mutations on protein function and their role in causing cancer and rare diseases. The topic of this conference, which has not been addressed in previous Gordon meetings, will attract researchers for essential discussions and exchanging ideas. It will help to advance the field by merging genomics and proteomics approaches, and by bringing together scientists who work on the same problems from different perspectives. We especially hope that it will provide a stimulating environment where students, postdocs and junior investigators can present and discuss their research with the best minds in the field. We hope the meeting will have significant impact on the research and development in the field of genetic variations and rare mutations. We have designed a meeting agenda to include researchers from the US, Europe, and Asia, representing both basic and applied research in the field.


Contributors

SUNDAY
2:00 pm - 9:00 pmArrival and Check-in
6:00 pmDinner
7:30 pm - 7:40 pmWelcome / Introductory Comments by GRC Site Staff
7:40 pm - 9:30 pmGenomic Variability and Disease
7:40 pm - 7:50 pm Discussion Leaders: Emil Alexov (Clemson University, USA) and Anna Panchenko (National Center for Biotechnology Information, NIH, USA)
"Introduction"
7:50 pm - 8:30 pm James Lupski (Baylor College of Medicine, Houston, USA)
"Clinical Genomics: Merging Human Genetics and Genomics"
8:30 pm - 8:40 pm Discussion
8:40 pm - 9:20 pm Debora Marks (Harvard Medical School, USA)
"In Silico Deep Mutational Scanning Using Evolutionary Co-Variation"
9:20 pm - 9:30 pm Discussion
MONDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmDisease-Causing, Harmless Mutations and the Role of Natural Selection
9:00 am - 9:10 am Discussion Leader: Mauno Vihinen (Lund University, Sweden)
"Introduction"
9:10 am - 9:50 am Ludmila Prokunina-Olsson (National Cancer Institute, NIH, USA)
"Pseudogenization of a Novel Human Interferon, IFN-λ4, Through a Derived Common Genetic Variant: The Role in Disease and Natural Selection"
9:50 am - 10:00 am Discussion
10:00 am - 10:30 am Coffee Break
10:30 am - 11:10 am Shamil Sunyaev (Harvard Medical School, Boston, USA)
"Widespread Suppression of Human Disease Mutations Detected by Comparative Genomics"
11:10 am - 11:20 am Discussion
11:20 am - 12:00 pm Sean Mooney (Buck Institute for Research on Aging, Novato, USA)
"Putting It All Together: Probabilistic Identification of Impactful and Disease Associated Variants in and Around Genes"
12:00 pm - 12:10 pm Discussion
12:10 pm - 12:25 pm Howard Edenberg (Indiana University School of Medicine, USA)
"Genetics of Alcoholism"
12:25 pm - 12:30 pm Discussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session
6:00 pmDinner
7:30 pm - 9:30 pmCharacterizing the Common Patterns of Human Genetic Variation
7:30 pm - 7:40 pm Discussion Leader: Gerhard (Gerry) Coetzee (USC/Norris Cancer Center, USA)
"Introduction"
7:40 pm - 8:20 pm Ben Busby (National Center for Biotechnology Information, NIH, USA)
"Accessing Human Genetic Variation in the Rising Era of Individual Genome Sequence"
8:20 pm - 8:35 pm Discussion
8:35 pm - 9:15 pm Daniel MacArthur (Massachusetts General Hospital, Boston, USA)
"Functional Annotation of Protein-Coding Variants from Over 90,000 Humans"
9:15 pm - 9:30 pm Discussion
TUESDAY
7:30 am - 8:30 amBreakfast
8:30 amGroup Photo
9:00 am - 12:30 pmAssessing the Effect of Missense Mutations on Protein Biophysical Characteristics
9:30 am - 9:40 am Discussion Leader: Ruth Nussinov (National Cancer Institute, NIH, USA)
"Introduction"
9:10 am - 9:50 am Ozlem Keskin (Koc University, Istanbul, Turkey)
"Three Dimensional Structures in Signaling Pathways Reveal Mechanisms of Oncogenic Mutations and SNPs in Diseases"
9:50 am - 10:00 am Discussion
10:00 am - 10:30 am Coffee Break
10:30 am - 11:10 am Roland Dunbrack (Institute of Cancer Research, Philadelphia, USA)
"The Structures of Biological Assemblies and Predicting the Phenotypes of Missense Mutations"
11:10 am - 11:20 am Discussion
11:20 am - 12:00 pm Rita Casadio (University of Bologna, Italy)
"The Effect of Disease-Related Variations on Protein Stability: A Large-Scale Investigation"
12:00 pm - 12:10 pm Discussion
12:10 pm - 12:25 pm Hans-Werner Mewes (German Research Center for Environmental Health)
"Psychiatric Diseases: A Most Complex Problem for Genetics"
12:25 pm - 12:30 pm Discussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session
6:00 pmDinner
7:30 pm - 9:30 pmRegulatory SNPs, Phenotype Prediction and Disease
7:30 pm - 7:40 pm Discussion Leader: Laura Elnitski (National Human Genome Research Institute, NIH, USA)
"Introduction"
7:40 pm - 8:20 pm Nadav Ahituv (University of California at San Francisco, San Francisco, USA)
"Functional Characterization of Gene Regulatory Elements"
8:20 pm - 8:35 pm Discussion
8:35 pm - 8:50 pm Zoya Ignatova (University of Potsdam, Germany)
"tRNA-Mediated Rescue of Defective CFTR Function Caused by a Common Silent Polymorphism"
8:50 pm - 8:55 pm Discussion
8:55 pm - 9:10 pm Lipika Ray (IBBR, UMD, USA)
"CAGI: Critical Assessment of Genome Interpretation"
9:10 pm - 9:15 pm Discussion
9:15 pm - 9:25 pm Daniel Helbling (Medical College of Wisconsin, USA)
"Living Patient with De Novo Novel Missense Sequence Variant of DNM1L Mitochondrial Fission/Fusion Gene"
9:25 pm - 9:30 pm Discussion
WEDNESDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmMissense Mutations and Protein-Protein Networks
9:00 am - 9:10 am Discussion Leader: Martin Schiller (University of Nevada)
"Introduction"
9:10 am - 9:50 am Haiyuan Yu (Cornell University)
9:50 am - 10:00 am Discussion
10:00 am - 10:30 am Coffee Break
10:30 am - 11:10 am Tanja Kortemme (University of California at San Francisco, San Francisco, USA)
"Functional Consequences of Modulating Interaction Specificity in Protein Networks"
11:10 am - 11:20 am Discussion
11:20 am - 12:00 pm Roded Sharan (Tel-Aviv University, Tel-Aviv, Israel)
"Protein Networks: From Topology to Logic"
12:00 pm - 12:10 pm Discussion
12:10 pm - 12:25 pm Alessandro Didonna (University of California San Francisco, USA)
"Discovering the Effects of a Multiple Sclerosis-AAssociated SNP on the EVI5 Interactome"
12:25 pm - 12:30 pm Discussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session
6:00 pmDinner
7:00 pm - 7:30 pmBusiness Meeting
Nominations for the Next Vice Chair; Fill in Conference Evaluation Forms; Discuss Future Site and Scheduling Preferences; Election of the Next Vice Chair
7:30 pm - 9:30 pmIdentification of Core Pathways and Driver Genes in Cancer
7:30 pm - 7:40 pm Discussion Leader: Teresa Przytycka (National Center for Biotechnology Information, NIH, USA)
"Introduction"
7:40 pm - 8:20 pm Gábor Balázsi (University of Texas, Houston, USA)
"Synthetic Regulatory Networks for Reprogramming Metastatic Cancer"
8:20 pm - 8:35 pm Discussion
8:35 pm - 9:15 pm Stan Lipkowitz (National Cancer Institute, NIH, USA)
"Oncogenic Mutations in Cbl Proteins"
9:15 pm - 9:30 pm Discussion
THURSDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmPrediction of Disease Related Genes and Mutations
9:00 am - 9:10 am Discussion Leader: Maricel Kann (University of Maryland, Baltimore, USA)
"Introduction"
9:10 am - 9:50 am Natarajan Kannan (University of Georgia, Athens, USA)
"Identifying Pathogenic Mutations in the Kinome Using an Evolutionary Systems Approach"
9:50 am - 10:00 am Discussion
10:00 am - 10:30 am Coffee Break
10:30 am - 11:10 am Mark Gerstein (Yale University, New Haven, USA)
"Human Genome Annotation and Predicting Disease Drivers"
11:10 am - 11:20 am Discussion
11:20 am - 12:00 pm Philip Jager (Brigham and Women's Hospital, Boston, USA)
"Construction, Validation, and Deployment of Predictive Models for Common Neurodegenerative Diseases"
12:00 pm - 12:10 pm Discussion
12:10 pm - 12:25 pm Cristina Marino-Buslje (Fundación Instituto Leloir, Argentina)
"Activating Mutations Cluster in the 'Molecular Brake' Regions of Protein Kinases. Implications for Driver Mutation Prediction"
12:25 pm - 12:30 pm Discussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session
6:00 pmDinner
7:30 pm - 9:30 pmPersonalized Medicine and Rare Diseases
7:30 pm - 7:40 pm Discussion Leader: Yana Bromberg (Rutgers University, New Brunswick, USA)
"Introduction"
7:40 pm - 8:20 pm Rachel Karchin (Johns Hopkins University, USA)
"A Probabilistic Framework to Predict Clinical Phenotypic Traits from Genome Sequencing"
8:20 pm - 8:35 pm Discussion
8:35 pm - 9:15 pm Charles Sanders (Vanderbilt University, Nashville, USA)
"Peripheral Myelin Protein 22 and Charcot-Marie-Tooth Disease"
9:15 pm - 9:30 pm Discussion
FRIDAY
7:30 am - 8:30 amBreakfast
9:00 amDeparture

 
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