Genetic variation and hitchhiking between structurally polymorphic Alu insertions and HLA-A, -B, and -C alleles and other retroelements within the MHC class I region

Authors

  • J. K. Kulski,

    Corresponding author
    1. Centre for Forensic Science, The University of Western Australia, Nedlands, WA 6008, Australia
    2. Division of Molecular Life Science, Department of Genetic Information, School of Medicine, Tokai University, Isehara, Kanagawa, Japan
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  • A. Shigenari,

    1. Division of Molecular Life Science, Department of Genetic Information, School of Medicine, Tokai University, Isehara, Kanagawa, Japan
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  • H. Inoko

    1. Division of Molecular Life Science, Department of Genetic Information, School of Medicine, Tokai University, Isehara, Kanagawa, Japan
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Jerzy K. Kulski, PhD
Centre for Forensic Science
The University of Western Australia
Mailbag M420
35 Stirling Highway
Crawley
Nedlands
WA 6009
Australia
Tel: +61 8 6488 7286
Fax: +61 8 6488 7285
e-mail: kulski@me.com

Abstract

We investigated structurally polymorphic Alu insertions (POALINs) at five loci in the major histocompatibility complex (MHC) class I genomic region to determine their allele and haplotype frequencies and associations with the human leukocyte antigen (HLA)-A, -B, and -C genes in three populations, the Australian Caucasians, Japanese, and African Americans. The POALINs varied in allelic frequency between 0% and 42.3% with significant differences between populations at three of the five loci. The linkage disequilibrium (LD) between Alu insertions and the HLA-A, -B, or -C alleles and previously published polymorphic retroelements (four SVA and human endogenous retrovirus type 9 (HERVK9) loci) within the class I region of the MHC were calculated in pairwise analyses of haplotypes to show strong allelic associations and possible crossing-over events between some loci. Each POALIN was in significant LD with a variety of HLA-A, -B, or -C two-digit alleles probably as a result of hitchhiking. The POALINs helped to further stratify the HLA-A:B:C haplotypes into different POALIN:HLA-A:B:C haplotype frequencies. Of the multilocus haplotype analyses, the seven- and eight-locus haplotypes showed the largest number of differences between the populations, and fewer matched haplotypes between populations that ranged, for example, from 49% for HLA-B:HLA-A haplotypes to 7% for AluMICB:HLA-B:HLA-C:AluTF:AluHJ:HLA-A:AluHG:AluTF haplotypes in the Japanese. This comparative study of multilocus POALINs in the HLA class I region of three ethnic populations shows that POALINs alone or together with the HLA class I alleles and other retroelements are informative ancestral markers for assessing the interrelationship of HLA class I haplotype lineages, LD, and genetic diversity within the same and/or different populations.

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