Altshuler D, Pollara V J, Cowles C R, Van Etten W J, Baldwin J, Linton L, Lander E S
Whitehead Institute/MIT Center for Genome Research, Cambridge, Massachusetts 02142, USA.
Nature. 2000 Sep 28;407(6803):513-6. doi: 10.1038/35035083.
Most genomic variation is attributable to single nucleotide polymorphisms (SNPs), which therefore offer the highest resolution for tracking disease genes and population history. 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. 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.
大多数基因组变异可归因于单核苷酸多态性（SNP），因此SNP为追踪疾病基因和种群历史提供了最高分辨率。有人提出，一张包含3万至50万个SNP的密集图谱可用于扫描人类基因组，以寻找与常见疾病相关的单倍型。在此，我们描述一种简单但强大的方法，称为简化基因组枪击测序（RRS），用于创建SNP图谱。RRS对来自多个个体的基因组特定子集进行重新采样，并使用高度精确的SNP检测算法比较所得序列。该方法可通过与现有基因组序列比对进行扩展，增加SNP的产量并提供图谱位置。这些方法正被SNP联盟（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）用于发现和发布至少30万个人类SNP。我们通过RRS发现了47172个人类SNP，该联盟总共已鉴定出148459个SNP。更广泛地说，RRS有助于在生物医学和农业重要物种中快速、廉价地构建SNP图谱。通过RRS发现的SNP在大规模基因分型方面也具有独特优势。
