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KEYNOTE SPEAKER

Computational methods for sequencing studies in Mendelian and complex traits genetics

Shamil Sunyaev
Brigham & Women’s Hospital

Rapid development of technology propels applications of DNA sequencing in genetics of both Mendelian and complex trait phenotypes. In Mendelian genetics, sequencing of a single parent-child trio frequently provides promising candidate mutations. Known population genetics parameters and experience with real cases suggest that only a few variants usually fit the inheritance pattern under the assumption of complete penetrance. These variants are further prioritized at the gene level based on available genetic data, functional data, data on expression and interactions. At the variant level, we are developing computational methods for predicting functionally significant mutations. Statistical models informed by population genetics provide estimates of the background probability to observe variants fitting the inheritance pattern by chance. Sequencing studies of individual human patients with Mendelian disorders lead to discoveries of new biology. The success of finding causal variants in small samples in Mendelian genetics does not translate to complex trait genetics. The promise of sequencing studies in complex trait genetics is grounded in population genetics and in success of candidate gene sequencing studies. Sequencing studies require a toolkit of statistical methods different from studies of common variants. These methods can be assisted by functional considerations and take into account allele frequency distribution. However, power of sequencing studies focusing on rare variants is low and many current studies are underpowered. A study of Early Onset Myocardial Infarction provides an example of exome-wide significant signals detected in a sequencing study.

Brief bio

Shamil Sunyaev received his PhD from Moscow Insitute of Physics and Technology (MIPT) and completed postdoctoral training at European Molecular Biology Laboratory (EMBL). He is now an Associate Professor at Genetics Division, Brigham & Women's Hospital, Harvard Medical School. He is also a member of Harvard-M.I.T. Health Sciences and Technology Division. His interests include computational analysis of human genetic variation, comparative genomics and computational proteomics.

 

 

Last Modified on: 16 Aug 2013

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