The mosaic structure of variation in the laboratory mouse genome

Most inbred laboratory mouse strains are known to have originated from a mixed but limited founder population in a few laboratories. However, the effect of this breeding history on patterns of genetic variation among these strains and the implications for their use are not well understood. Here we p...

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Bibliographic Details
Published in:Nature (London) 2002-12, Vol.420 (6915), p.574-578
Main Authors: Daly, Mark J, Wade, Claire M, Kulbokas, Edward J, Kirby, Andrew W, Zody, Michael C, Mullikin, James C, Lander, Eric S, Lindblad-Toh, Kerstin
Format: Article
Language:English
Subjects:
Albinism - genetics
Animals
Base Sequence
Cloning
Genetic diversity
Genetic Variation - genetics
Genome
Genomics
Haplotypes - genetics
Humanities and Social Sciences
Laboratory animals
letters-to-nature
Mice
Mice, Inbred C57BL
Mice, Inbred Strains - genetics
Monophenol Monooxygenase - genetics
multidisciplinary
Mutation - genetics
Phenotype
Polymorphism, Single Nucleotide - genetics
Recombination, Genetic - genetics
Rodents
Science
Science (multidisciplinary)
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Summary:Most inbred laboratory mouse strains are known to have originated from a mixed but limited founder population in a few laboratories. However, the effect of this breeding history on patterns of genetic variation among these strains and the implications for their use are not well understood. Here we present an analysis of the fine structure of variation in the mouse genome, using single nucleotide polymorphisms (SNPs). When the recently assembled genome sequence from the C57BL/6J strain is aligned with sample sequence from other strains, we observe long segments of either extremely high (∼40 SNPs per 10 kb) or extremely low (∼0.5 SNPs per 10 kb) polymorphism rates. In all strain-to-strain comparisons examined, only one-third of the genome falls into long regions (averaging >1 Mb) of a high SNP rate, consistent with estimated divergence rates between Mus musculus domesticus and either M. m. musculus or M. m. castaneus. These data suggest that the genomes of these inbred strains are mosaics with the vast majority of segments derived from domesticus and musculus sources. These observations have important implications for the design and interpretation of positional cloning experiments.
ISSN:0028-0836
1476-4687
DOI:10.1038/nature01252