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CCB Seminar: Why are most human phenotypes so extremely polygenic?

April 20 @ 3:00 pm - 4:00 pm

Talk by Dr. Jonathan Pritchard (Professor of Genetics and of Biology, Stanford University)

Zoom link: https://berkeley.zoom.us/j/99751830878

Abstract:
One of the central challenges in genetics is to understand the mapping from genetic variation to phenotypic variation. During the past 15 years, genome-wide association studies (GWAS) have been used to study the genetic basis of a wide variety of complex diseases and other traits. One surprising result from GWAS has been that for a wide range of complex traits, including traits as diverse as height, cholesterol levels, or schizophrenia, even the most important loci contribute just a small fraction of the phenotypic variance. Instead, most of the genetic variance comes from tiny contributions from ~104—105 variants spread across most of the genome. Our group has argued that these observations do not fit neatly into classical conceptual models of genetics.

In this talk I will describe work that we have done to make sense of these observations. We can understand this at two levels. At a mechanistic level, we propose that this is due to the impact of small genetic perturbations that flow through highly-connected cellular regulatory networks (the “omnigenic model”); at a population genetics level, we argue that there is an important additional role of so-called selective “flattening” that reduces the contributions of the most important genes. This talk will weave together results from GWAS analysis, theory, and experimental measurement of regulatory networks in T cells.

 

Bio: Jonathan Pritchard is a Professor of Biology and Genetics at Stanford University.  He grew up mainly in England, and studied at Penn State, Stanford and Oxford before joining the faculty of the University of Chicago in 2001. He returned to Stanford to take his current position in 2013. His lab has done wide-ranging research on using genetics to study human population structure, history, and adaptation, as well as on understanding the mechanisms that link genetic variation to variation in gene regulation and complex traits. His current work focuses on the genetic basis of complex traits in humans, and on genetic approaches to studying human population history and adaptation.

Details

Date:
April 20
Time:
3:00 pm - 4:00 pm