Open AccessCauses and Consequences of Chromatin Variation between Inbred Mice
Author(s) -
Mona Hosseini,
Leo Goodstadt,
Jim R. Hughes,
Monika S. Kowalczyk,
Marco De Gobbi,
G. Otto,
Richard R. Copley,
Richard Mott,
Douglas R. Higgs,
Jonathan Flint
Publication year - 2013
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.1003570
Subject(s) - biology , chromatin , genetics , genetic variation , variation (astronomy) , inbred strain , phenotype , evolutionary biology , dna , gene , physics , astrophysics
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.