Large-scale validation of single nucleotide polymorphisms in gene regions
Large-scale validation of single nucleotide polymorphisms in gene regions
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DOI：
10.1101/gr.2421604
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发表时间：
2004-08-01
期刊：
影响因子：
7
通讯作者：
Braun, A
中科院分区：
文献类型：
--
作者：
Nelson, MR;Marnellos, G;Braun, A
使用大量双等位基因单核苷酸多态性 (SNP) 的全基因组关联研究已被提议作为识别常见疾病相关基因的潜在强大方法。为了组装适合大规模关联的 SNP 集合，我们设计了针对主要位于已知和预测基因区域内的 226,099 个公开可用的 SNP 的检测。使用基于芯片的 MALDI-TOF 质谱法和混合 DNA 估算了 92 名 CEPH 白种人样本中的等位基因频率。在 204,200 个设计的功能性检测中，125,799 个 SNP 被确定为多态性（次要等位基因频率 >0.02），其中 101,729 个唯一映射到人类基因组。许多常用的 RefSNP 注释可以预测多态性状态，并可用于改进从公共领域选择 SNP 进行遗传研究。这组独特的多态性 SNP 位于 LocusLink 中注释的 66% 已知和预测基因的 10 kb 范围内，这可能对大规模疾病关联研究有用。
Genome-wide association studies using large numbers of bi-allelic single nucleotide polymorphisms (SNPs) have been proposed as a potentially powerful method for identifying genes involved in common diseases. To assemble a SNP collection appropriate for large-scale association, we designed assays for 226,099 publicly available SNPs located primarily within known and predicted gene regions. Allele frequencies were estimated in a sample of 92 CEPH Caucasians using chip-based MALDI-TOF mass spectrometry with pooled DNA. Of the 204,200 designed assays that were functional, 125,799 SNPs were determined to be polymorphic (minor allele frequency >0.02), of which 101,729 map uniquely to the human genome. Many of the commonly available RefSNP annotations were predictive of polymorphic status and could be used to improve the selection of SNPs from the public domain for genetic research. The set of uniquely mapping, polymorphic SNPs is located within 10 kb of 66% of known and predicted genes annotated in LocusLink, which could prove useful for large-scale disease association Studies.