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

Nat Genet. 2009 Apr;41(4):430-7. doi: 10.1038/ng.350. Epub 2009 Mar 8.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromosome Mapping
  • Gene Duplication
  • Gene Expression Regulation*
  • Genes, X-Linked
  • Genetic Variation*
  • Genome
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / physiology*
  • Mice
  • Mice, Inbred C57BL / genetics
  • Recombination, Genetic
  • Species Specificity
  • Stem Cells / cytology
  • Stem Cells / physiology*
  • X Chromosome

Associated data

  • GEO/GSE10656
  • GEO/GSE2031