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Hum Mol Genet. 2010 Dec 15;19(24):4939-47. doi: 10.1093/hmg/ddq418. Epub 2010 Sep 27.

Genetic determinants of HSP70 gene expression following heat shock.

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1
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.

Abstract

The regulation of heat shock protein expression is of significant physiological and pathophysiological significance. Here we show that genetic diversity is an important determinant of heat shock protein 70 expression involving local, likely cis-acting, polymorphisms. We define DNA sequence variation for the highly homologous HSPA1A and HSPA1B genes in the major histocompatibility complex on chromosome 6p21 and establish quantitative and specific assays for determining transcript abundance. We show for lymphoblastoid cell lines established from individuals of African ancestry that following heat shock, expression of HSPA1B is associated with rs400547 (P 3.88 × 10(-8)) and linked single nucleotide polymorphisms (SNPs) located 62-93 kb telomeric to HSPA1B. This association was found to explain 31 and 29% of the variance in HSPA1B expression following heat shock or in resting cells, respectively. The associated SNPs show marked variation in minor allele frequency among populations, being more common in individuals of African ancestry, and are located in a region showing population-specific haplotypic block structure. The work illustrates how analysis of a heritable induced expression phenotype can be highly informative in defining functionally important genetic variation.

PMID:
20876613
PMCID:
PMC2989893
DOI:
10.1093/hmg/ddq418
[Indexed for MEDLINE]
Free PMC Article
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