A 3.9-centimorgan-resolution human single-nucleotide polymorphism linkage map and screening set
A 3.9-centimorgan-resolution human single-nucleotide polymorphism linkage map and screening set
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DOI：
10.1086/377137
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发表时间：
2003-08-01
影响因子：
9.8
通讯作者：
Holden, AL
中科院分区：
文献类型：
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作者：
Matise, TC;Sachidanandam, R;Holden, AL
基于单核苷酸多态(SNP)的高通量基因分型技术的最新进展提高了效率和成本，因此现在考虑使用SNP进行全基因组连锁分析是合理的。然而，一个合适的SNPs筛选集和相应的连锁图谱尚未被描述。这里描述的SNP图谱填补了这一空白，并为快速扫描疾病基因提供了资源。我们在一个由欧洲裔美国人、非洲裔美国人和亚洲人组成的多样性小组中评估了6297个SNPs。对这些标记的检测稳定性、合适的等位基因频率和多SNP簇的信息量进行了评估。来自56个人类多态中心的个体，总共有1770个潜在的信息减数分裂，用2988个SNPs的子集进行了基因分型，用于构建图谱。进行了广泛的基因分型误差分析，得到的SNP连锁图谱的平均图谱分辨率为3.9 cM，图谱位置包含单个SNP或几个紧密连锁的SNP。这张地图上的标记顺序与其他几个链接和物理地图相比是有利的。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。我们还评估了沿着每条染色体的雌性和雄性的厘米/Mb距离比率，显示了重组率增加和减少的大致区域。评估表明，该SNP筛查集比马什菲尔德诊所常用的基于微卫星的筛查集更具信息量。
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 1770 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.