Frazer Kelly A, Eskin Eleazar, Kang Hyun Min, Bogue Molly A, Hinds David A, Beilharz Erica J, Gupta Robert V, Montgomery Julie, Morenzoni Matt M, Nilsen Geoffrey B, Pethiyagoda Charit L, Stuve Laura L, Johnson Frank M, Daly Mark J, Wade Claire M, Cox David R
Perlegen Sciences, 2021 Stierlin Court, Mountain View, California 94043, USA.
Nature. 2007 Aug 30;448(7157):1050-3. doi: 10.1038/nature06067. Epub 2007 Jul 29.
A dense map of genetic variation in the laboratory mouse genome will provide insights into the evolutionary history of the species 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 intervals 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.
实验室小鼠基因组中的高密度遗传变异图谱将有助于深入了解该物种的进化历史,并增进对品系间基因型与表型差异关系的理解。在此,我们对4个野生来源品系和11个经典品系的基因组进行了重测序。我们识别出827万个高质量单核苷酸多态性(SNP),它们在基因组中密集分布,并确定了经典品系每对组合的高(不同亚种祖先)和低(共同亚种祖先)SNP率区间的位置。利用这些数据,我们生成了一个全基因组单倍型图谱,包含40,898个片段,每个片段平均有三种不同的祖先单倍型。对于明确确定祖先的经典品系中的单倍型,小家鼠亚种——小家鼠、小鼠、栗色小鼠和杂种小家鼠的遗传贡献分别为68%、6%、3%和10%;其余13%的单倍型祖先来源未知。SNP数据中相当程度的区域冗余将有助于在分型密度较低的经典近交系中推算出这些基因型中的大多数,从而全面了解其他品系中的变异情况。
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