Large-scale discovery and genotyping of single-nucleotide polymorphisms in the mouse
Large-scale discovery and genotyping of single-nucleotide polymorphisms in the mouse
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DOI：
10.1038/74215
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发表时间：
2000-04-01
期刊：
影响因子：
30.8
通讯作者：
Lander, ES
中科院分区：
文献类型：
--
作者：
Lindblad-Toh, K;Winchester, E;Lander, ES
单核苷酸多态性（SNPs）在人类遗传学中备受关注，因为它们极其丰富且非常适合自动化的大规模基因分型。然而，人类的SNPs不如其他类型的遗传标记（如简单序列长度多态性或微卫星）信息量大，因此绘制性状图谱需要更多的基因座。SNPs为实验性遗传生物（如小鼠）提供了类似的优势，而且不会损失信息量，因为双等位基因标记在分析近交系之间的杂交时是完全有信息的。在此我们报道了对小鼠基因组中SNPs的大规模分析。我们测定了8个小鼠品系的核苷酸多态性比率，并使用高密度寡核苷酸阵列在1755个序列标签位点（STSs）中鉴定出了2848个SNPs。这些SNPs中有四分之三已被定位在小鼠基因组上，提供了小鼠的第一代SNP图谱。我们还开发了一种多重基因分型方法，通过该方法，对每只动物仅需进行6次基因分型反应就可进行基因组扫描。
Single-nucleotide polymorphisms (SNPs) have been the focus of much attention in human genetics because they are extremely abundant and well-suited for automated large-scale genotyping, Human SNPs, however, are less informative than other types of genetic markers (such as simple-sequence length polymorphisms or microsatellites) and thus more loci are required for mapping traits. SNPs offer similar advantages for experimental genetic organisms such as the mouse, but they entail no loss of informativeness because bi-allelic markers are fully informative in analysing crosses between inbred strains. Here we report a large-scale analysis of SNPs in the mouse genome. We characterized the rate of nucleotide polymorphism in eight mouse strains and identified a collection of 2,848 SNPs located in 1,755 sequence-tagged sites (STSs) using high-density oligonucleotide arrays. Three-quarters of these SNPs have been mapped on the mouse genome, providing a first-generation SNP map of the mouse. We have also developed a multiplex genotyping procedure by which a genome scan can be performed with only six genotyping reactions per animal.