The chromosome 17q21.31 inversion is a 900-kb common structural polymorphism found primarily in European population. Although the genetic flux within inversion region was assumed to be considerable suppressed, it is still unclear about the details of genetic exchange between the H1 (non-inverted sequence) and H2 (inverted sequence) haplotypes of this inversion. Here we describe a refmed map of genetic exchanges between pairs of gene arrangements within the 17q21.31 region. Using HapMap phase II data of 1,546 single nucleotide polymorphisms, we successfully deduced 96 H1 and 24 H2 haplotypes in European samples by neighbor-joining tree reconstruction. Furthermore, we identified 15 and 26 candidate tracts with reciprocal and non-reciprocal genetic exchanges, respectively. In all 15 regions harboring reciprocal exchange, haplotypes reconstructed by clone sequencing did not support these exchange events, suggesting that such signals of exchange between two sister chromosomes in certain heterozygous individual were caused by phasing error regions. On the other hand, the finished clone sequencing across 4 of 26 tracts with non-reciprocal genetic flux confirmed that this kind of genetic exchange was caused by gene conversion. In summary, as crossover between pairs of gene arrangements had been considerably suppressed, gene conversion might be the most important mechanism for genetic exchange at 17q21.31.
人类基因组国际单体型图计划(The International Haplotype Map Project,HapMap)旨在构建全基因组范围的常见遗传变异数据库,为复杂性疾病、人类进化和其它遗传学研究提供基础数据。此研究基于HapMap计划第Ⅰ期数据,通过群体基因组学策略对亚、欧、非人群中的正选择信号进行扫描。在基因组范围建立了一个包含多层次信息(基因、窗口、大型区域)的正选择图谱。研究表明:人类基因组中存在一定程度的正选择,正选择的"候选窗口"占总筛查窗口的~5%;基因组中的正选择信号集中于某些特定的染色体区域;确定了62个可能受到强正选择的大型区域,以及区域内相应的88个受到强正选择的"候选基因"。研究还发现人群特异的选择在人群的分化过程中发挥了重要的作用。此研究将为后续的人类进化和自然选择研究提供新的线索。
Objective: To investigate the distributions of human leukocyte antigen (HLA)-A and-B alleles and HLA-A-B haplotypes in the Yi ethnic minority of the Yunnan Province, situated in southwestern China. Methods: DNA typing for HLA-A and-B loci was performed using the polymerase chain reaction-sequence-based typing (PCR-SBT) method on 114 randomly selected healthy individuals of the Yi population. The allelic frequencies of HLA-A and-B loci were calculated by direct counting and HLA-A-B haplotypes were estimated using the expectation maximization algorithm. Results: A total of 17 HLA-A and 38 HLA-B alleles were found in the Yi population. The most frequent alleles were A2402 (32.46%), A1101 (26.32%), and A0203 (10.09%) at the HLA-A locus and B4601 (12.28%), B1525 (10.09%), B4001 (8.77%), and B3802 (7.89%) at the HLA-B locus. The predominant HLA-A-B haplotypes were A2402-B1525 (7.86%) and A0203-B3802 (5.64%), followed by A1101-B4001 (4.69%). Phylogenetic analysis indicates that the Yi population in the Honghe, Yunnan Province of China basically belongs to groups of southeastern Asian origin, but shares some characteristics with northeastern Asian groups. Conclusion: The present study may add to the understanding of HLA polymorphism in the Yi ethnic group that was poorly defined previously, and provide useful information for bone marrow transplantation, anthropological research, and forensic sciences as well as for disease-association studies.
Population genomic approaches, which take advantages of high-throughput genotyping, are powerful yet costly methods to scan for selective sweeps. DNA-pooling strategies have been widely used for association studies because it is a cost-effective alternative to large-scale individual genotyping. Here, we performed an SNP-MaP (single nucleotide polymorphism microarrays and pooling) analysis using samples from Eurasia to evaluate the efficiency of pooling strategy in genome-wide scans for selection. By conducting simulations of allelotype data, we first demonstrated that the boxplot with average heterozygosity (HET) is a promising method to detect strong selective sweeps with a moderate level of pooling error. Based on this, we used a sliding window analysis of HET to detect the large contiguous regions (LCRs) putatively under selective sweeps from Eurasia datasets. This survey identified 63 LCRs in a European population. These signals were further supported by the integrated haplotype score (iHS) test using HapMap II data. We also confirmed the European-specific signatures of positive selection from several previously identified genes (KEL, TRPV5, TRPV6, EPHB6). In summary, our results not only revealed the high credibility of SNP-MaP strategy in scanning for selective sweeps, but also provided an insight into the population differentiation.