February 24 2016

2:00 pm 1100 Terasaki LSB

This seminar is sponsored by Dept. of Human Genetics, MIMG, and Institute for Quantitative and Computational Biosciences

Melissa Gymerk
Harvard-MIT Health Sciences and Technology

Dissecting the contribution of repetitive genetic variation to human traits


Recent studies have made substantial progress in identifying genetic variants associated with disease and molecular phenotypes in humans. However, these studies have primarily focused on single nucleotide polymorphisms \(SNPs\), ignoring more complex variants that have been shown to play important functional roles. Here, I focus on short tandem repeats \(STRs\), one of the most polymorphic and abundant classes of genetic variation. I will first present lobSTR, a novel algorithm for genotyping STRs from whole-genome sequencing datasets. Next, I will describe insights into population-wide trends of STR variation revealed by applying lobSTR to thousands of sequencing datasets to generate the largest and highest quality STR catalog to date. I will then show how we used this catalog to conduct a genome-wide analysis of the contribution of STRs to gene expression in humans. This survey revealed that STRs explain 10-15% of the heritability of expression mediated by all common cis variants and potentially play an important role in clinically relevant conditions. Finally, I will discuss preliminary analyses incorporating functional genomics data with high quality complex variant genotypes to predict and validate the function of non-coding variants driving common human diseases. Altogether, these results highlight the putative phenotypic contribution of complex variants and the opportunity for a wealth of genetic discoveries to be gained by expanding analyses to less understood regions of the genome.











































































































































































































































































































































































































































































































































































































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