Aug 13, Kelley Harris: Signatures of demographic history and error-prone polymerase activity in large genomic datasets

Speaker_photo

Kelley Harris, UC Berkeley

I am an applied math Ph.D. student at U.C Berkeley studying population genetics and evolutionary genomics. I work with Rasmus Nielsen and Yun Song on developing methods for DNA sequence analysis that are derived mainly from coalescent theory. I began this work as an M.Phil. student with Richard Durbin at the Wellcome Trust Sanger Institute.

Title: Signatures of demographic history and error-prone polymerase activity in large genomic datasets

When two individuals are closely related to each other, their genomes contain long regions of DNA that are inherited from recent common ancestors. In these regions, genetic mutations distinguishing one individual from the other will be very far apart, and one can find long tracts of identity by state (IBS) where the two genomes are completely identical. Aligning the two genomes and measuring the distances between all sites where they differ, we can obtain a length distribution of IBS tracts that is highly informative about past population size changes and gene flow events. Using coalescent theory, we can derive the expected length distribution of IBS tracts under a variety of demographic models and demonstrate the use of this framework to date key events in the population histories of humans and polar bears. We make these inferences by obtaining models that predict observed IBS tract length distributions to a high degree of accuracy, but we also observe that real genomic data contains an excess of very short IBS tracts that cannot be explained by any demographic processes. We argue that these short IBS tracts are created by multinucleotide mutations (MNMs) that give rise to multiple SNPs in a single generation. We infer the prevalence and distribution of MNMs in a large dataset of 1,092 human genomes by quantifying deviations from patterns that we expect to observe if all SNPs arise independently. In doing so, we uncover a mutation pattern characteristic of the error-prone DNA polymerase Pol zeta, suggesting that some MNMs result from the action of this enzyme in the human germline. 

Seminar details

Date: August 13, 2014

Time: Lunch will be served at 1:00pm & Lecture will follow at 1:15pm

Location: Clark S361

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