An SNP map of the human genome generated by reduced representation shotgun sequencing
An SNP map of the human genome generated by reduced representation shotgun sequencing
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DOI：
10.1038/35035083
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发表时间：
2000-09-28
期刊：
影响因子：
64.8
通讯作者：
Lander, ES
中科院分区：
文献类型：
--
作者：
Altshuler, D;Pollara, VJ;Lander, ES
大多数基因组变异可归因于单核苷酸多态(SNPs)，因此它为追踪疾病基因和种群历史提供了最高的分辨率(1-3)。有人提出，30,000-500,000个SNPs的密集图谱可以用来扫描人类基因组，寻找与常见疾病相关的单倍型(4-6)。在这里，我们描述了一种简单但强大的方法，称为简化表示鸟枪(RRS)测序，用于创建SNP图谱。RRS从几个个体中重新采样特定的基因组子集，并使用高精度的SNP检测算法比较得到的序列。该方法可以通过与现有基因组序列的比对来扩展，增加SNPs的产量并提供MAP位置。SNP联盟是一个由学术中心、制药公司和一个私人基金会组成的国际合作组织，它正在使用这些方法来发现和释放至少30万个人类SNP。我们通过RRS发现了47,172个人类SNPs，该联盟总共识别了148,459个SNPs。更广泛地说，RRS有助于在生物医学和农业上重要的物种中快速、廉价地构建SNP图谱。RRS发现的SNPs也为大规模基因分型提供了独特的优势。
Most genomic variation is attributable to single nucleotide polymorphisms (SNPs), which therefore offer the highest resolution for tracking disease genes and population history(1-3). It has been proposed that a dense map of 30,000-500,000 SNPs can be used to scan the human genome for haplotypes associated with common diseases(4-6). Here we describe a simple but powerful method, called reduced representation shotgun (RRS) sequencing, for creating SNP maps. RRS re-samples specific subsets of the genome from several individuals, and compares the resulting sequences using a highly accurate SNP detection algorithm. The method can be extended by alignment to available genome sequence, increasing the yield of SNPs and providing map positions. These methods are being used by The SNP Consortium, an international collaboration of academic centres, pharmaceutical companies and a private foundation, to discover and release at least 300,000 human SNPs. We have discovered 47,172 human SNPs by RRS, and in total the Consortium has identified 148,459 SNPs. More broadly, RRS facilitates the rapid, inexpensive construction of SNP maps in biomedically and agriculturally important species. SNPs discovered by RRS also offer unique advantages for large-scale genotyping.