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: 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
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-06-01
Series:PLoS Genetics
Online Access:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1003570&type=printable
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author 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
author_facet 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
author_sort Mona Hosseini
collection DOAJ
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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institution OA Journals
issn 1553-7390
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language English
publishDate 2013-06-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS Genetics
spelling doaj-art-15b7bbf556e64a6e8f69b4f366fa1d442025-08-20T02:05:36ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042013-06-0196e100357010.1371/journal.pgen.1003570Causes and consequences of chromatin variation between inbred mice.Mona HosseiniLeo GoodstadtJim R HughesMonika S KowalczykMarco de GobbiGeorg W OttoRichard R CopleyRichard MottDouglas R HiggsJonathan FlintVariation 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.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1003570&type=printable
spellingShingle 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
Causes and consequences of chromatin variation between inbred mice.
PLoS Genetics
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
url https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1003570&type=printable
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