May 17, 2013

Variation and genetic control of protein abundance in humans

Nature
Linfeng WuMichael P Snyder

Abstract

Gene expression differs among individuals and populations and is thought to be a major determinant of phenotypic variation. Although variation and genetic loci responsible for RNA expression levels have been analysed extensively in human populations, our knowledge is limited regarding the differences in human protein abundance and the genetic basis for this difference. Variation in messenger RNA expression is not a perfect surrogate for protein expression because the latter is influenced by an array of post-transcriptional regulatory mechanisms, and, empirically, the correlation between protein and mRNA levels is generally modest. Here we used isobaric tag-based quantitative mass spectrometry to determine relative protein levels of 5,953 genes in lymphoblastoid cell lines from 95 diverse individuals genotyped in the HapMap Project. We found that protein levels are heritable molecular phenotypes that exhibit considerable variation between individuals, populations and sexes. Levels of specific sets of proteins involved in the same biological process covary among individuals, indicating that these processes are tightly regulated at the protein level. We identified cis-pQTLs (protein quantitative trait loci), including variants not...Continue Reading

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  • Citations101

Mentioned in this Paper

Quantitative Trait Loci
HapMap
Transcription, Genetic
Protein Biosynthesis
Gene Expression
Mass Spectrometry
Proteomics
Proteome
NR4A2 protein, human
Poly(A) Tail

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