TY - JOUR
T1 - The impact of copy number variation on local gene expression in mouse hematopoietic stem and progenitor cells
AU - Cahan, Patrick
AU - Li, Yedda
AU - Izumi, Masayo
AU - Graubert, Timothy A.
N1 - Funding Information:
This work was supported in part by a grant from the US National Institutes of Health/National Cancer Institute (CA101937). P.C. was supported in part by the National Human Genome Research Institute (T32 HG000045) and a Kauffman Fellowship. Mice were provided through a collaboration with the Mouse Phenome Project (The Jackson Laboratory, Bar Harbor, Maine). Additional mice were provided by M. You (Washington University). We thank T. Ley, D. Link and M. Walter for helpful discussions. Cell sorting was done by the High Speed Cell Sorter Core in the Alvin J. Siteman Cancer Center at Washington University School of Medicine. The Siteman Cancer Center is supported in part by an NCI Cancer Center Support Grant (P30 CA91842).
PY - 2009/4
Y1 - 2009/4
N2 - 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.
AB - 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.
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U2 - 10.1038/ng.350
DO - 10.1038/ng.350
M3 - Article
C2 - 19270704
AN - SCOPUS:63449086972
VL - 41
SP - 430
EP - 437
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 4
ER -