Variation and genetic control of protein abundance in humans.
Nature
; 499(7456): 79-82, 2013 Jul 04.
Article
em En
| MEDLINE
| ID: mdl-23676674
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 detected by previous transcriptome studies. This study demonstrates the feasibility of high-throughput human proteome quantification that, when integrated with DNA variation and transcriptome information, adds a new dimension to the characterization of gene expression regulation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article