Bhangale Tushar R, Rieder Mark J, Livingston Robert J, Nickerson Deborah A
Department of Bioengineering, University of Washington, Seattle, WA 98195-7730, USA.
Hum Mol Genet. 2005 Jan 1;14(1):59-69. doi: 10.1093/hmg/ddi006. Epub 2004 Nov 3.
Despite being the second most frequent type of polymorphism in the genome, diallelic insertion-deletion polymorphisms (indels) have received far less attention in the study of sequence variation. In this report, we describe an approach that can detect indels in the heterozygous state and can comprehensively identify indels in the target sequence. Using this approach, we identified 2393 indels in a set of 330 candidate genes, i.e. an average of seven indels per gene with about two indels per gene being common (minor allele frequency >or=0.1). We compared the population genetic characteristics of indels with substitutions in this data. Our data supported the findings that deletions occur more frequently in the human genome. 5'-UTR and coding regions of the genes showed a significantly lower diversity for indels compared with other regions, suggesting differences in effects of selection on indels and substitutions. Sequence diversity and pairwise linkage disequilibrium (LD) findings of the different populations were similar to earlier results and included a greater skew towards low-frequency variants and a faster rate of LD decay in the African-descent population compared with the non-African populations. Within populations, the allele frequency spectra and LD-decay profiles for indels were similar to substitutions. Overall, the findings suggest that, although the mechanisms giving rise to indels may be different from those causing substitutions, the evolutionary histories of indels and substitutions are similar, and that indels can play a valuable role in association studies and marker selection strategies.
尽管双等位基因插入缺失多态性（indels）是基因组中第二常见的多态性类型，但在序列变异研究中受到的关注却少得多。在本报告中，我们描述了一种能够检测杂合状态下的indels并能全面识别目标序列中indels的方法。使用这种方法，我们在一组330个候选基因中鉴定出2393个indels，即平均每个基因有7个indels，其中约每个基因有2个常见indels（次要等位基因频率≥0.1）。我们在该数据中比较了indels与替换的群体遗传特征。我们的数据支持了人类基因组中缺失发生更频繁这一发现。与其他区域相比，基因的5'-UTR和编码区域的indels多样性显著更低，这表明选择对indels和替换的影响存在差异。不同群体的序列多样性和成对连锁不平衡（LD）结果与早期结果相似，包括与非非洲人群相比，非洲裔人群中低频变异的偏向性更大以及LD衰减速率更快。在群体内部，indels的等位基因频率谱和LD衰减曲线与替换相似。总体而言，这些发现表明，尽管产生indels的机制可能与导致替换的机制不同，但indels和替换的进化历史相似，并且indels在关联研究和标记选择策略中可以发挥重要作用。
