Nature Genetics32, 432 - 437 (2002)
Published online: 15 October 2002; | doi:10.1038/ng992
Detection of regulatory variation in mouse genes
Christopher R. Cowles1, Joel N. Hirschhorn1, 2, 3, David Altshuler1, 2, 4
& Eric S. Lander1, 5
1
Whitehead Institute and MIT Center for Genome Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA.
2
Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
3
Divisions of Genetics and Endocrinology, Children's Hospital, Boston, Massachusetts, USA.
4
Department of Molecular Biology and Diabetes Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.
5
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Correspondence should be addressed to Eric S. Lander lander@wi.mit.edu
Functional polymorphism in genes can be classified as coding variation, altering the amino-acid sequence of the encoded protein, or regulatory variation, affecting the level or pattern of expression of the gene. Coding variation can be recognized directly from DNA sequence, and consequently its frequency and characteristics have been extensively described. By contrast, virtually nothing is known about the extent to which gene regulation varies in populations. Yet it is likely that regulatory variants are important in modulating gene function: alterations in gene regulation have been proposed to influence disease susceptibility and to have been the primary substrate for the evolution of species1. Here, we report a systematic study to assess the extent of cis-acting regulatory variation in 69 genes across four inbred mouse strains. We find that at least four of these genes show allelic differences in expression level of 1.5-fold or greater, and that some of these differences are tissue specific. The results show that the impact of regulatory variants can be detected at a significant frequency in a genomic survey and suggest that such variation may have important consequences for organismal phenotype and evolution. The results indicate that larger-scale surveys in both mouse and human could identify a substantial number of genes with common regulatory variation.
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