The Impact of Genetic Variation on Gene Regulation from RNA to Protein in Humans

  • Zia Khan of UMCP
  • A Genomics@JHU Seminar
  • When: October 17, 2016, 13:30
  • Where: The Barber Conference Room at Charles Commons
    10 E 33rd Street
    Baltimore, MD 21218
  • Light refreshments served at 1:00 PM


zia-khanUnderstanding how genotype and environment interact to impact phenotypic variation is a central goal of genetics. Studies of important phenotypes in humans such as disease risk and drug toxicity have identified genomic regions and variants of interest. Yet, in many cases, the mechanisms by which these variants act are less clear. Gaining a better understanding of how genetic variation impacts gene regulation might ultimately bridge this gap. While substantial progress has been made in identifying genetic variants that impact mRNA expression, the downstream effects of these variants on translation and protein abundance remain poorly understood. We collected high-throughput quantitative mass spectrometry data along with ribosomal profiling data from 62 densely genotyped lymphoblastoid cell lines from the YRI population from the 1000 Genomes Project, for which RNA-seq data was also available. From our analysis, we find substantial sharing of genetic effects on gene regulation from mRNA to protein, presumably through effects on transcriptional regulation. However, a large fraction of these variants have attenuated effects on protein abundance, suggesting that their downstream effects might be buffered. We find scarce evidence of variants that effect ribosome occupancy. Our data indicate variants that effect protein abundance, independent of mRNA expression, are likely due to changes in post-translational regulation as opposed to regulation of protein translation. Overall, our study highlights the importance of studying multiple gene regulatory layers to better understand the effects of genetic variation on gene regulation and ultimately, important phenotypic traits. I will end the talk with some recent collaborative work to better understand chronological age associated effects on gene expression in immune cells. This large-scale study aims to better understand the interaction between genotype, gene regulation, and healthy human aging.


Zia Khan: “zia at”
Center for Bioinformatics and Computational Biology, University of Maryland College Park

Genomics @ JHU Seminar Series

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