Sequence divergence of <it>Mus spretus </it>and <it>Mus musculus </it>across a skin cancer susceptibility locus

• Main Authors: Balmain Allan, Mao Jian-Hua, Cho Hee-Yeon, Gladman Nicholas, Dworkin Amy M, Fleming Jessica L, Mahler Kimberly L, Toland Amanda
• Format: Article
• Language: English
• Published: BMC 2008-12-01
• Series: BMC Genomics
• Online Access: http://www.biomedcentral.com/1471-2164/9/626

<p>Abstract</p> <p>Background</p> <p><it>Mus spretus </it>diverged from <it>Mus musculus </it>over one million years ago. These mice are genetically and phenotypically divergent. Despite the value of utilizing <it>M. musculus </it>and <it>M. spretus </it>for quantitative trait locus (QTL) mapping, relatively little genomic information on <it>M. spretus </it>exists, and most of the available sequence and polymorphic data is for one strain of <it>M. spretus</it>, Spret/Ei. In previous work, we mapped fifteen loci for skin cancer susceptibility using four different <it>M. spretus </it>by <it>M. musculus </it>F1 backcrosses. One locus, <it>skin tumor susceptibility 5 </it>(<it>Skts5</it>) on chromosome 12, shows strong linkage in one cross.</p> <p>Results</p> <p>To identify potential candidate genes for <it>Skts5</it>, we sequenced 65 named and unnamed genes and coding elements mapping to the peak linkage area in outbred <it>spretus</it>, Spret/EiJ, FVB/NJ, and NIH/Ola. We identified polymorphisms in 62 of 65 genes including 122 amino acid substitutions. To look for polymorphisms consistent with the linkage data, we sequenced exons with amino acid polymorphisms in two additional <it>M. spretus </it>strains and one additional <it>M. musculus </it>strain generating 40.1 kb of sequence data. Eight candidate variants were identified that fit with the linkage data. To determine the degree of variation across <it>M. spretus</it>, we conducted phylogenetic analyses. The relatedness of the <it>M. spretus </it>strains at this locus is consistent with the proximity of region of ascertainment of the ancestral mice.</p> <p>Conclusion</p> <p>Our analyses suggest that, if <it>Skts5 </it>on chromosome 12 is representative of other regions in the genome, then published genomic data for Spret/EiJ are likely to be of high utility for genomic studies in other <it>M. spretus </it>strains.</p>