title: An unusual haplotype structure on human chromosome 8p23 derived from the inversion polymorphism.
abstract: 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.
authors.affiliation: Beijing Institute of Genomics, Chinese Academy of Sciences, P.R. China.
authors.forename: Libin
authors.initials: L
authors.lastname: Deng
authors.forename: Yuezheng
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Kang
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Hongbin
authors.initials: H
authors.lastname: Zhao
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.forename: Chaohua
authors.initials: C
authors.lastname: Li
authors.forename: Hao
authors.initials: H
authors.lastname: Pan
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Tang
authors.forename: Dunmei
authors.initials: D
authors.lastname: Wang
authors.forename: Tianhua
authors.initials: T
authors.lastname: Niu
authors.forename: Huanming
authors.initials: H
authors.lastname: Yang
authors.forename: Changqing
authors.initials: C
authors.lastname: Zeng
mesh_terms: D007446:Chromosome Inversion / Q000235:genetics*; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D014644:Genetic Variation; D005828:Genetics, Population; D015894:Genome, Human; D006239:Haplotypes; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide