Wade Claire M, Kulbokas Edward J, Kirby Andrew W, Zody Michael C, Mullikin James C, Lander Eric S, Lindblad-Toh Kerstin, Daly Mark J
Whitehead Institute for Biomedical Research and Whitehead/MIT Center for Genome Research, 9 Cambridge Center, Cambridge, Massachusetts 02139, USA.
Nature. 2002 Dec 5;420(6915):574-8. doi: 10.1038/nature01252.
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 (approximately 40 SNPs per 10 kb) or extremely low (approximately 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.
大多数近交系实验小鼠品系已知起源于少数实验室中混合但有限的奠基群体。然而，这种繁育历史对这些品系间遗传变异模式的影响及其使用的意义尚未得到充分理解。在此，我们利用单核苷酸多态性（SNP）对小鼠基因组变异的精细结构进行了分析。当将最近组装的C57BL/6J品系基因组序列与其他品系的样本序列进行比对时，我们观察到多态性率极高（每10 kb约40个SNP）或极低（每10 kb约0.5个SNP）的长片段。在所有检测的品系间比较中，只有三分之一的基因组落入高SNP率的长区域（平均>1 Mb），这与小家鼠与小家鼠或小家鼠栗色亚种之间的估计分化率一致。这些数据表明，这些近交系的基因组是镶嵌体，绝大多数片段源自小家鼠和小家鼠的来源。这些观察结果对定位克隆实验的设计和解释具有重要意义。
