Mullikin J C, Hunt S E, Cole C G, Mortimore B J, Rice C M, Burton J, Matthews L H, Pavitt R, Plumb R W, Sims S K, Ainscough R M, Attwood J, Bailey J M, Barlow K, Bruskiewich R M, Butcher P N, Carter N P, Chen Y, Clee C M, Coggill P C, Davies J, Davies R M, Dawson E, Francis M D, Joy A A, Lamble R G, Langford C F, Macarthy J, Mall V, Moreland A, Overton-Larty E K, Ross M T, Smith L C, Steward C A, Sulston J E, Tinsley E J, Turney K J, Willey D L, Wilson G D, McMurray A A, Dunham I, Rogers J, Bentley D R
The Sanger Centre, Hinxton, Cambridge, UK.
Nature. 2000 Sep 28;407(6803):516-20. doi: 10.1038/35035089.
The human genome sequence will provide a reference for measuring DNA sequence variation in human populations. Sequence variants are responsible for the genetic component of individuality, including complex characteristics such as disease susceptibility and drug response. Most sequence variants are single nucleotide polymorphisms (SNPs), where two alternate bases occur at one position. Comparison of any two genomes reveals around 1 SNP per kilobase. A sufficiently dense map of SNPs would allow the detection of sequence variants responsible for particular characteristics on the basis that they are associated with a specific SNP allele. Here we have evaluated large-scale sequencing approaches to obtaining SNPs, and have constructed a map of 2,730 SNPs on human chromosome 22. Most of the SNPs are within 25 kilobases of a transcribed exon, and are valuable for association studies. We have scaled up the process, detecting over 65,000 SNPs in the genome as part of The SNP Consortium programme, which is on target to build a map of 1 SNP every 5 kilobases that is integrated with the human genome sequence and that is freely available in the public domain.
人类基因组序列将为测量人类群体中的DNA序列变异提供一个参考。序列变异决定了个体的遗传组成部分，包括诸如疾病易感性和药物反应等复杂特征。大多数序列变异是单核苷酸多态性（SNP），即在一个位置上出现两个交替的碱基。比较任何两个基因组会发现每千碱基大约有1个SNP。一个足够密集的SNP图谱将能够检测出导致特定特征的序列变异，前提是它们与特定的SNP等位基因相关联。在这里，我们评估了获取SNP的大规模测序方法，并构建了人类22号染色体上2730个SNP的图谱。大多数SNP位于转录外显子的25千碱基范围内，对关联研究很有价值。我们已经扩大了这一过程，作为SNP联盟计划的一部分，在基因组中检测到了超过65000个SNP，该计划的目标是构建一个每5千碱基有1个SNP的图谱，该图谱与人类基因组序列整合且可在公共领域免费获取。
