Letter
Nature 448, 1050-1053 (30 August 2007) | doi:10.1038/nature06067; Received 14 April 2007; Accepted 5 July 2007; Published online 29 July 2007
A sequence-based variation map of 8.27 million SNPs in inbred mouse strains
Kelly A. Frazer1, Eleazar Eskin2, Hyun Min Kang3, Molly A. Bogue4, David A. Hinds1, Erica J. Beilharz1, Robert V. Gupta1, Julie Montgomery1, Matt M. Morenzoni1, Geoffrey B. Nilsen1, Charit L. Pethiyagoda1, Laura L. Stuve1, Frank M. Johnson5, Mark J. Daly6,7, Claire M. Wade6,7 & David R. Cox1
- Perlegen Sciences, 2021 Stierlin Court, Mountain View, California 94043, USA
- Department of Computer Science and Department of Human Genetics, University of California, Los Angeles, Los Angeles, California 90095, USA
- Department of Computer Science and Engineering, University of California, San Diego, La Jolla, California 92093, USA
- The Jackson Laboratory, Bar Harbor, Maine 04609, USA
- Toxicology Operations Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
- Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
- Center for Human Genetic Research, Massachussets General Hospital, 185 Cambridge St, Boston, Massachusetts 02114, USA
Correspondence to: Kelly A. Frazer1 Correspondence and requests for materials should be addressed to K.A.F. (Email: frazer.kelly@scrippshealth.org).
A dense map of genetic variation in the laboratory mouse genome will provide insights into the evolutionary history of the species1 and lead to an improved understanding of the relationship between inter-strain genotypic and phenotypic differences. Here we resequence the genomes of four wild-derived and eleven classical strains. We identify 8.27 million high-quality single nucleotide polymorphisms (SNPs) densely distributed across the genome, and determine the locations of the high (divergent subspecies ancestry) and low (common subspecies ancestry) SNP-rate intervals2, 3, 4, 5, 6 for every pairwise combination of classical strains. Using these data, we generate a genome-wide haplotype map containing 40,898 segments, each with an average of three distinct ancestral haplotypes. For the haplotypes in the classical strains that are unequivocally assigned ancestry, the genetic contributions of the Mus musculus subspecies—M. m. domesticus, M. m. musculus, M. m. castaneus and the hybrid M. m. molossinus—are 68%, 6%, 3% and 10%, respectively; the remaining 13% of haplotypes are of unknown ancestral origin. The considerable regional redundancy of the SNP data will facilitate imputation of the majority of these genotypes in less-densely typed classical inbred strains to provide a complete view of variation in additional strains.
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