Causes and consequences of chromatin variation between inbred mice

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 str...

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Main Authors: Hosseini, M, Goodstadt, L, Hughes, J, Kowalczyk, MS, De Gobbi, M, Otto, G, Copley, R, Mott, R, Higgs, D, Flint, J
Format: Journal article
Language:English
Published: Public Library of Science 2013
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author Hosseini, M
Goodstadt, L
Hughes, J
Kowalczyk, MS
De Gobbi, M
Otto, G
Copley, R
Mott, R
Higgs, D
Flint, J
author_facet Hosseini, M
Goodstadt, L
Hughes, J
Kowalczyk, MS
De Gobbi, M
Otto, G
Copley, R
Mott, R
Higgs, D
Flint, J
author_sort Hosseini, M
collection OXFORD
description 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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spelling oxford-uuid:d33591b4-cdb8-452c-98f0-066565987dd42022-03-27T08:09:44ZCauses and consequences of chromatin variation between inbred miceJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d33591b4-cdb8-452c-98f0-066565987dd4EnglishSymplectic Elements at OxfordPublic Library of Science2013Hosseini, MGoodstadt, LHughes, JKowalczyk, MSDe Gobbi, MOtto, GCopley, RMott, RHiggs, DFlint, JVariation 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.
spellingShingle Hosseini, M
Goodstadt, L
Hughes, J
Kowalczyk, MS
De Gobbi, M
Otto, G
Copley, R
Mott, R
Higgs, D
Flint, J
Causes and consequences of chromatin variation between inbred mice
title Causes and consequences of chromatin variation between inbred mice
title_full Causes and consequences of chromatin variation between inbred mice
title_fullStr Causes and consequences of chromatin variation between inbred mice
title_full_unstemmed Causes and consequences of chromatin variation between inbred mice
title_short Causes and consequences of chromatin variation between inbred mice
title_sort causes and consequences of chromatin variation between inbred mice
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