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PMID: 19270704 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

The impact of copy number variation on local gene expression in mouse hematopoietic stem and progenitor cells.

Nature genetics ·Vol. 41 ·No. 4 ·2009-04-00 ·Pages 430-7

Cahan P, Li Y, Izumi M, Graubert TA

Abstract

The extent to which differences in germline DNA copy number contribute to natural phenotypic variation is unknown. We analyzed the copy number content of the mouse genome to sub-10-kb resolution. We identified over 1,300 copy number variant regions (CNVRs), most of which are <10 kb in length, are found in more than one strain, and, in total, span 3.2% (85 Mb) of the genome. To assess the potential functional impact of copy number variation, we mapped expression profiles of purified hematopoietic stem and progenitor cells, adipose tissue and hypothalamus to CNVRs in cis. Of the more than 600 significant associations between CNVRs and expression profiles, most map to CNVRs outside of the transcribed regions of genes. In hematopoietic stem and progenitor cells, up to 28% of strain-dependent expression variation is associated with copy number variation, supporting the role of germline CNVs as key contributors to natural phenotypic variation in the laboratory mouse.

MeSH Terms
Animals Chromosome Mapping Gene Duplication Gene Expression Regulation Genes, X-Linked Genetic Variation Genome Hematopoietic Stem Cells/cytology,physiology Mice Mice, Inbred C57BL/genetics Recombination, Genetic Species Specificity Stem Cells/cytology,physiology X Chromosome
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Cahan Patrick
Department of Internal Medicine, Division of Oncology, Stem Cell Biology Section, Washington University, St Louis, MO, USA.
Li Yedda
Izumi Masayo
Graubert Timothy A
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
DOI
10.1038/ng.350
Published
2009-04-00
Epub
2009-00-08
Pages
430-7
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC2728431
Subset
IM
Grants
NHLBI NIH HHS · R01 HL082973 · United States
NHGRI NIH HHS · T32 HG000045 · United States
NCI NIH HHS · CA101937 · United States
NCI NIH HHS · P30 CA091842 · United States
NCI NIH HHS · P01 CA101937-010006 · United States
NHLBI NIH HHS · R01 HL082973-01 · United States
NCI NIH HHS · P30 CA91842 · United States
NCI NIH HHS · P01 CA101937 · United States
NCRR NIH HHS · S10 RR015867-01 · United States
Databases
GEO
GSE10656, GSE2031
External Links
PubMed source DOI: 10.1038/ng.350 PMC Full Text View journal details
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