Causes and Consequences of Chromatin Variation Between Inbred Mice

Overview

Journal PLoS Genet

Specialty Genetics

Date 2013 Jun 21

PMID 23785304

Citations 15

Authors

Mona Hosseini

Leo Goodstadt

Jim R Hughes

Monika S Kowalczyk

Marco De Gobbi

Georg W Otto

Richard R Copley

Richard Mott

Douglas R Higgs

Jonathan Flint

Affiliations

Soon will be listed here.

Abstract

Variation at regulatory elements, identified through hypersensitivity to digestion by DNase I, is believed to contribute to variation in complex traits, but the extent and consequences of this variation are poorly characterized. Analysis of terminally differentiated erythroblasts in eight inbred strains of mice identified reproducible variation at approximately 6% of DNase I hypersensitive sites (DHS). Only 30% of such variable DHS contain a sequence variant predictive of site variation. Nevertheless, sequence variants within variable DHS are more likely to be associated with complex traits than those in non-variant DHS, and variants associated with complex traits preferentially occur in variable DHS. Changes at a small proportion (less than 10%) of variable DHS are associated with changes in nearby transcriptional activity. Our results show that whilst DNA sequence variation is not the major determinant of variation in open chromatin, where such variants exist they are likely to be causal for complex traits.

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