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Letter

Contribution of Asian mouse subspecies Mus musculus molossinus to genomic constitution of strain C57BL/6J, as defined by BAC-end sequence–SNP analysis

¹ Technology and Development Team for Mammalian Cellular Dynamics, BioResource Center, RIKEN Tsukuba Institute, Tsukuba, Ibaraki 305-0074, Japan ² Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-0006, Japan ³ Sequence Technology Team, Genome Core Technology Facility, RIKEN Genomic Sciences Center, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan ⁴ Department of Developmental Genetics, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 862-0976, Japan ⁵ Human Genome Research Group, Genomic Sciences Center, RIKEN Yokohama Institute, Tsurumi-ku, Yokohama 230-0045, Japan ⁶ Division of Population Genetics, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan ⁷ Kitasato Institute for Life Science, Kitasato University, Sagamihara, Kanagawa 228-8555 Japan ⁸ Mammalian Genetics Laboratory, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan ⁹ Mouse Functional Genomics Research Groups, Genomic Sciences Center, RIKEN Yokohama Institute, Yokohama, Kanagawa 244-0804, Japan

MSM/Ms is an inbred strain derived from the Japanese wild mouse, Mus musculus molossinus. It is believed that subspecies molossinus has contributed substantially to the genome constitution of common laboratory strains of mice, although the majority of their genome is derived from the west European M. m. domesticus. Information on the molossinus genome is thus essential not only for genetic studies involving molossinus but also for characterization of common laboratory strains. Here, we report the construction of an arrayed bacterial artificial chromosome (BAC) library from male MSM/Ms genomic DNA, covering 1x genome equivalent. Both ends of 176,256 BAC clone inserts were sequenced, and 62,988 BAC-end sequence (BES) pairs were mapped onto the C57BL/6J genome (NCBI mouse Build 30), covering 2,228,164 kbp or 89% of the total genome. Taking advantage of the BES map data, we established a computer-based clone screening system. Comparison of the MSM/Ms and C57BL/6J sequences revealed 489,200 candidate single nucleotide polymorphisms (SNPs) in 51,137,941 bp sequenced. The overall nucleotide substitution rate was as high as 0.0096. The distribution of SNPs along the C57BL/6J genome was not uniform: The majority of the genome showed a high SNP rate, and only 5.2% of the genome showed an extremely low SNP rate (percentage identity = 0.9997); these sequences are likely derived from the molossinus genome.

¹⁰ Corresponding authors.
E-mail: abe{at}rtc.riken.jp; fax 81 29-836-9199.
E-mail: hide{at}gsc.riken.go.jp; fax 81 45-503-9170.
E-mail: tshirois{at}lab.nig.ac.jp; fax 81 55-981-6817.

[Supplemental material is available online at www.genome.org, and the MSM BAC database is available at http://stt.gsc.riken.jp/msm/ or http://analysis1.lab.nig.ac.jp/Mus_musculus/.]

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