Comprehensive Cis-Regulation Analysis of Genetic Variants in Human Lymphoblastoid Cell Lines.

Abstract:

:Genetic variants can influence the expression of mRNA and protein. Genetic regulatory loci such as expression quantitative trait loci (eQTLs) and protein quantitative trait loci (pQTLs) exist in several species. However, it remains unclear how human genetic variants regulate mRNA and protein expression. Here, we characterized six mechanistic models for the genetic regulatory patterns of single-nucleotide polymorphisms (SNPs) and their actions on post-transcriptional expression. Data from Yoruba HapMap lymphoblastoid cell lines were analyzed to identify human cis-eQTLs and pQTLs, as well as protein-specific QTLs (psQTLs). Our results indicated that genetic regulatory loci primarily affected mRNA and protein abundance in patterns where the two were well-correlated. While this finding was observed in both humans and mice (57.5% and 70.3%, respectively), the genetic regulatory patterns differed between species, implying evolutionary differences. Mouse SNPs generally targeted changes in transcript expression (51%), whereas in humans, they largely regulated protein abundance, independent of transcription levels (55.9%). The latter independent function can be explained by psQTLs. Our analysis suggests that local functional genetic variants in the human genome mainly modulate protein abundance independent of mRNA levels through post-transcriptional mechanisms. These findings clarify the impact of genetic variation on phenotype, which is of particular relevance to disease risk and treatment response.

journal_name

Front Genet

journal_title

Frontiers in genetics

authors

Wang Y,He B,Zhao Y,Reiter JL,Chen SX,Simpson E,Feng W,Liu Y

doi

10.3389/fgene.2019.00806

subject

Has Abstract

pub_date

2019-09-10 00:00:00

pages

806

issn

1664-8021

journal_volume

10

pub_type

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