高效发现人类基因编码区的单核苷酸多态性

Efficient discovery of single-nucleotide polymorphisms in coding regions of human genes.

作者信息

Hu G, Modrek B, Riise Stensland H M F, Saarela J, Pajukanta P, Kustanovich V, Peltonen L, Nelson S F, Lee C

机构信息

Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, USA.

出版信息

Pharmacogenomics J. 2002;2(4):236-42. doi: 10.1038/sj.tpj.6500109.

DOI:10.1038/sj.tpj.6500109

PMID:12196912

Abstract

Single nucleotide polymorphisms in protein coding regions (cSNPs) are of great interest for their effects on phenotype and potential for mapping disease genes. We have identified 5,400 novel exonic SNPs from alignments of public EST data to the draft human genome sequence, and approximately 12,000 more novel exonic SNPs from EST cluster alignments. We found 82% of the genomic-aligned SNPs and 63% of the EST-only SNPs to be detectably polymorphic in 20 Finnish DNA samples. 37% of the SNPs mapped to known protein coding regions, yielding 6,500 distinct, novel cSNPs from the two datasets. These data reveal selection against mutations that alter protein structure, and distinct classes of genes under strongly positive vs. negative pressure from natural selection for amino acid replacement (detected by K(A)/K(S)ratio). We have searched these cSNPs for compatibility with the amino acid profile at each site and structural impact on protein core stability.

摘要

蛋白质编码区域的单核苷酸多态性（cSNP）因其对表型的影响以及在疾病基因定位方面的潜力而备受关注。我们通过将公共EST数据与人类基因组草图序列进行比对，鉴定出了5400个新的外显子SNP，并且通过EST簇比对又发现了约12000个新的外显子SNP。我们发现，在20份芬兰DNA样本中，82%的基因组比对SNP和63%的仅EST来源的SNP具有可检测到的多态性。37%的SNP映射到已知的蛋白质编码区域，从这两个数据集中产生了6500个不同的新cSNP。这些数据揭示了对改变蛋白质结构的突变的选择，以及在氨基酸替换的自然选择的强正压与负压下不同类别的基因（通过K(A)/K(S)比率检测）。我们已经在这些cSNP中搜索了与每个位点的氨基酸谱的兼容性以及对蛋白质核心稳定性的结构影响。