Matise Tara C, Sachidanandam Ravi, Clark Andrew G, Kruglyak Leonid, Wijsman Ellen, Kakol Jerzy, Buyske Steven, Chui Buena, Cohen Patrick, de Toma Claudia, Ehm Margaret, Glanowski Stephen, He Chunsheng, Heil Jeremy, Markianos Kyriacos, McMullen Ivy, Pericak-Vance Margaret A, Silbergleit Arkadiy, Stein Lincoln, Wagner Michael, Wilson Alexander F, Winick Jeffrey D, Winn-Deen Emily S, Yamashiro Carl T, Cann Howard M, Lai Eric, Holden Arthur L
Department of Genetics, Rutgers University, Piscataway, NJ, 08840, USA.
Am J Hum Genet. 2003 Aug;73(2):271-84. doi: 10.1086/377137. Epub 2003 Jul 3.
Recent advances in technologies for high-throughout single-nucleotide polymorphism (SNP)-based genotyping have improved efficiency and cost so that it is now becoming reasonable to consider the use of SNPs for genomewide linkage analysis. However, a suitable screening set of SNPs and a corresponding linkage map have yet to be described. The SNP maps described here fill this void and provide a resource for fast genome scanning for disease genes. We have evaluated 6,297 SNPs in a diversity panel composed of European Americans, African Americans, and Asians. The markers were assessed for assay robustness, suitable allele frequencies, and informativeness of multi-SNP clusters. Individuals from 56 Centre d'Etude du Polymorphisme Humain pedigrees, with >770 potentially informative meioses altogether, were genotyped with a subset of 2,988 SNPs, for map construction. Extensive genotyping-error analysis was performed, and the resulting SNP linkage map has an average map resolution of 3.9 cM, with map positions containing either a single SNP or several tightly linked SNPs. The order of markers on this map compares favorably with several other linkage and physical maps. We compared map distances between the SNP linkage map and the interpolated SNP linkage map constructed by the deCode Genetics group. We also evaluated cM/Mb distance ratios in females and males, along each chromosome, showing broadly defined regions of increased and decreased rates of recombination. Evaluations indicate that this SNP screening set is more informative than the Marshfield Clinic's commonly used microsatellite-based screening set.
基于单核苷酸多态性（SNP）的高通量基因分型技术的最新进展提高了效率并降低了成本，因此现在考虑将SNP用于全基因组连锁分析变得合理。然而，尚未描述合适的SNP筛选集和相应的连锁图谱。本文描述的SNP图谱填补了这一空白，并为疾病基因的快速基因组扫描提供了资源。我们在一个由欧裔美国人、非裔美国人和亚洲人组成的多样化样本中评估了6297个SNP。对这些标记进行了检测稳健性、合适的等位基因频率以及多SNP簇信息性的评估。来自56个人类多态性研究中心家系的个体，总共具有超过770个潜在信息性减数分裂，用2988个SNP的子集进行基因分型以构建图谱。进行了广泛的基因分型错误分析，所得的SNP连锁图谱平均图谱分辨率为3.9 cM，图谱位置包含单个SNP或几个紧密连锁的SNP。该图谱上标记的顺序与其他几个连锁图谱和物理图谱相比具有优势。我们比较了SNP连锁图谱与deCode Genetics小组构建的内插SNP连锁图谱之间的图谱距离。我们还评估了雌性和雄性沿每条染色体的cM/Mb距离比，显示出重组率升高和降低的大致区域。评估表明，这个SNP筛选集比马什菲尔德诊所常用的基于微卫星的筛选集信息更丰富。
