Identifying genetic variation with diet and sex-dependent effects in diversity outbred mice.

Douglas Perkins

Document Type

Article

Publication Date

Summer 2017

JAX Location

In: Student Reports, Summer 2017, Jackson Laboratory

Abstract

Linkage analysis and genome-wide association studies have discovered a vast number of associations between genetic variants and phenotypes such as transcript and protein expression, but the influence of diet and sex in regulating these associations is not well characterized. Diet is known to playa role in disease development, however there is considerable variation among the human population in susceptibility to disease in response to diet. This suggests that the effect of diet on disease likely stems from alterations in transcript and protein expression only in the presence of certain genetic variants. Sex differences in disease are also documented, and may in part act through a similar mechanism. Using high performance computing and R statistical programming, we observed distant genetic effects on transcript and protein abundance for many genes that were mediated by diet and/or sex. Hotspots of distant genetic effects were also observed. local genetic effects were rare, but we identified a number of local eQTls that were sex-specific. For one locus that affected the expression of many transcripts in a distant, sex-dependent manner, we integrated additional data to predict a member of the Serpin protein family as the underlying causal regulator.

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