An Unusual Haplotype Structure on Human Chromosome 8p23 Derived From the Inversion Polymorphism
An Unusual Haplotype Structure on Human Chromosome 8p23 Derived From the Inversion Polymorphism
复制标题
DOI：
10.1002/humu.20775
复制
发表时间：
2008-10-01
期刊：
影响因子：
3.9
通讯作者：
Zeng, Changqing
中科院分区：
文献类型：
--
作者：
Deng, Libin;Zhang, Yuezheng;Zeng, Changqing
染色体倒位是一种重要的基因组变异类型，与进化和疾病发病机制有关。在这里，我们描述了染色体8 p23的3.8 Mb倒位多态性的精细遗传结构。使用来自209个不相关样本的1,073个SNP的HapMap数据，这些样本来自CEPH-犹他州居民，其祖先来自北方和西欧（CEU）;尼日利亚伊巴丹的约鲁巴人（YRI）;以及亚洲人（Asian）样本，包括来自中国北京的汉族人（CHB）和来自日本东京的日本人（JPT）-我们成功地推导出了所有418个单倍型的倒位方向。特别地，基于主成分分析（PCA）鉴定不同的单倍型亚组。这样的遗传亚结构是一致的聚类模式的基础上相邻连接树重建，这揭示了在所有样品中共有四个单倍型分支。中期荧光原位杂交（FISH）在一个子集的10个HapMap样本验证了他们的倒位方向预测的PCA或系统发育树重建。外群单倍型在YRI进化枝之一内的定位表明人类NCBI Build 36-倒置顺序最可能是祖先取向。此外，在该区域的群体分化测试和相对扩展单倍型纯合性（REHH）分析发现了多个选择信号，也在一个群体特异性的方式。在XKR 6处检测到阳性选择信号。这些结果揭示了倒位多态性与群体特异性遗传结构的相关性，以及在进化过程中维持8 p23区域大的染色体重排的各种选择模式的可能机制。此外，我们的研究还表明，基于单体型的聚类方法，如主成分分析，可以应用于在基因组，大规模的隐性倒位多态性的扫描。《Mutat》29（10），1209-1216，2008年。(c)2008 Wiley-Liss，Inc.
Chromosomal inversion is an important type of genomic variations involved in both evolution and disease pathogenesis. Here, we describe the refined genetic structure of a 3.8-Mb inversion polymorphism at chromosome 8p23. Using HapMap data of 1,073 SNPs generated from 209 unrelated samples from CEPH-Utah residents with ancestry from northern and western Europe (CEU); Yoruba in Ibadan, Nigeria (YRI); and Asian (ASN) samples, which were comprised of Han Chinese from Beijing, China (CHB) and Japanese from Tokyo, Japan (JPT)-we successfully deduced the inversion orientations of all their 418 haplotypes. In particular, distinct haplotype, subgroups were identified based on principal component analysis (PCA). Such genetic substructures were consistent with clustering patterns based on neighbor-joining tree reconstruction, which revealed a total of four haplotype clades across all samples. Metaphase fluorescence in situ hybridization (FISH) in a subset of 10 HapMap samples verified their inversion orientations predicted by PCA or phylogenetic tree reconstruction. Positioning of the outgroup haplotype within one of YRI clades suggested that Human NCBI Build 36-inverted order is most likely the ancestral orientation. Furthermore, the population differentiation test and the relative extended haplotype homozygosity (REHH) analysis in this region discovered multiple selection signals, also in a population-specific manner. A positive selection signal was detected at XKR6 in the ASN population. These results revealed the correlation of inversion polymorphisms to population-specific genetic structures, and various selection patterns as possible mechanisms for the maintenance of a large chromosomal rearrangement at 8p23 region during evolution. In addition, Our study also showed that haplotype-based clustering methods, such as PCA, can be applied in scanning for cryptic inversion polymorphisms at a genome,wide scale. Hum Mutat 29(10), 1209-1216, 2008. (c) 2008 Wiley-Liss, Inc.