Determination of ancestral alleles for human single-nucleotide polymorphisms using high-density oligonucleotide arrays
Determination of ancestral alleles for human single-nucleotide polymorphisms using high-density oligonucleotide arrays
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DOI：
10.1038/9674
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发表时间：
1999-06-01
期刊：
影响因子：
30.8
通讯作者：
Collins, FS
中科院分区：
文献类型：
--
作者：
Hacia, JG;Fan, JB;Collins, FS
在这里，我们报告了基于高密度寡核苷酸阵列(DNA芯片)的分析的应用，以确定当前人类群体中单核苷酸多态(SNPs)的遥远历史。我们分析了来自23只普通黑猩猩、19只侏儒黑猩猩和11只大猩猩基因组DNA样本的397个人类SNP位点的同源序列(见CEPH：来自阿米什、委内瑞拉和犹他州的家系(1))。根据这些数据，我们确定了214个提出的祖先等位基因(在人类和黑猩猩的最后一个共同祖先中发现的序列)。在一个不同的人类群体中，我们发现频率较高的SNP等位基因比频率较低的等位基因更有可能是祖先，但也有例外。我们还发现了三个共同的人类/侏儒黑猩猩多态，都涉及CpG二核苷酸，以及两个共同的人类/大猩猩多态，其中一个涉及CpG二核苷酸。我们证明，基于微阵列的分析方法可以对物种内和物种间的遗传变异进行快速比较序列分析。
Here we report the application of high-density oligonucleotide array (DNA chip)-based analysis to determine the distant history of single nucleotide polymorphisms (SNPs) in current human populations. We analysed orthologues for 397 human SNP sites (identified in CEPH:pedigrees from Amish, Venezuelan and Utah populations(1)) from 23 common chimpanzee, 19 pygmy chimpanzee and 11 gorilla genomic DNA samples. From this data we determined 214 proposed ancestral alleles (the sequence found in the last common ancestor of humans and chimpanzees). In a diverse human population set, we found that SNP alleles with higher frequencies were more likely to be ancestral than less frequently occurring alleles, There were, however, exceptions. We also found three shared human/pygmy chimpanzee polymorphisms, all involving CpG dinucleotides, and two shared human/gorilla polymorphisms, one involving a CpG dinucleotide. We demonstrate that mi;microarray-based assays allow rapid comparative sequence analysis of intra- and interspecies genetic variation.