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Polymorphic SVA retrotransposons at four loci and their association with classical HLA class I alleles in Japanese, Caucasians and African Americans

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An Erratum to this article was published on 28 May 2010

Abstract

Polymorphic insertion frequencies of the retrotransposons known as the “SVA” elements were investigated at four loci in the MHC class I genomic region to determine their allele and haplotype frequencies and associations with the HLA-A, -B or -C genes for 100 Japanese, 100 African Americans, 174 Australian Caucasians and 66 reference cell lines obtained from different ethnic groups. The SVA insertions representing different subfamily members varied in frequency between none for SVA-HF in Japanese and 65% for SVA-HB in Caucasians or African Americans with significant differences in frequencies between the three populations at least at three loci. The SVA loci were in Hardy–Weinberg equilibrium except for the SVA-HA locus which deviated significantly in African Americans and Caucasians possibly because of a genomic deletion of this locus in individuals with the HLA-A*24 allele. Strong linkage disequilibria and high percentage associations between the human leucocyte antigen (HLA) class I gene alleles and some of the SVA insertions were detected in all three populations in spite of significant frequency differences for the SVA and HLA class I alleles between the three populations. The highest percentage associations (>86%) were between SVA-HB and HLA-B*08, -B*27, -B*37 to -B*41, -B*52 and -B*53; SVA-HC and HLA-B*07; SVA-HA and HLA-A*03, -A*11 and -A*30; and SVA-HF and HLA-A*03 and HLA-B*47. From pairwise associations in the three populations and the homozygous cell line results, it was possible to deduce the SVA and HLA class I allelic combinations (haplotypes), population differences and the identity by descent of several common HLA-A allelic lineages.

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Acknowledgements

We thank Paula M Moolhuijzen for her help with the initial bioinformatics genomic analysis for some of the PCR primer sets, Professor M Ota for the Japanese HLA-typed DNA samples, Dr. Campbell Witt for the Australian Caucasian HLA-typed DNA samples and Dr. Takashi Shiina for helpful discussions.

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Authors and Affiliations

  1. Centre for Forensic Science, The University of Western Australia, Nedlands, Western Australia, 6008, Australia

    Jerzy K. Kulski

  2. Division of Molecular Life Science, Department of Genetic Information, School of Medicine, Tokai University, Isehara, Kanagawa, Japan

    Jerzy K. Kulski, Atsuko Shigenari & Hidetoshi Inoko

  3. Centre for Forensic Science, The University of Western Australia, Mailbag M420. 35 Stirling Highway, Crawley, Western Australia, 6009, Australia

    Jerzy K. Kulski

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  1. Jerzy K. Kulski
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Correspondence to Jerzy K. Kulski.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s00251-010-0453-0

Electronic supplementary materials

Below is the link to the electronic supplementary material.

Supplementary Table S1

Percentage frequency of diplotypes at four SVA loci in African Americans (AA), Australian Caucasians (AC) and Japanese (J) (PDF 24.9 kb)

Supplementary Table S2

Maximum-likelihood haplotype frequencies and population differences at four polymorphic SVA insertions loci, SVA-HF, SVA-HA, SVA-HC and SVA-HB, in African Americans (A), Australian Caucasians (C) and Japanese (J). The analysis was performed using the conventional EM algorithm in the ARLEQUIN software package.**** (PDF 29.6 kb)

Supplementary Table S3

Percentage association and LD as a D′ or r 2 measure between SVA insertions and HLA-A and HLA-B alleles at paired loci in African Americans (PDF 39.4 kb)

Supplementary Table S4

Percentage association and LD as a D′ or r 2 measure between SVA insertions and HLA-A, HLA-B and HLA-C alleles at paired loci in Caucasians (PDF 35.6 kb)

Supplementary Table S5

Percentage association and LD as a D prime or r-squared measure between SVA insertions and HLA-A, HLA-B and HLA-C alleles at paired loci in japanese (PDF 28.8 kb)

Supplementary Fig. S1

Nucleotide sequence of the SVA PCR products including the PCR primer sequences (red letters), the SVA flanking sequences (black letters), the SVA sequence (green letters) and the flanking target site duplication (TSD) sequences (underlined blue letters). The names of the primer sequences (Table 2) are shown in parenthesis (PDF 72.9 kb)

Supplementary Fig. S2

Theoretical scheme for evolution of SVA/HLA class I haplotypes. HLA-Xn is a HLA class I gene (X) and allele (n) which mutated to an allele Xm or exchanged with gene alleles HLA-Xc1, -Xc2 or -Xc3 by crossing over or gene conversion. The original SVAi insertion and its linkage with HLA-Xn in this model is assumed to have occurred in a population with a high frequency of the HLA-Xn allele 3 Mya and then evolved over 1.2 × 105 generations to the present time (PDF 55.2 kb)

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Kulski, J.K., Shigenari, A. & Inoko, H. Polymorphic SVA retrotransposons at four loci and their association with classical HLA class I alleles in Japanese, Caucasians and African Americans. Immunogenetics 62, 211–230 (2010). https://doi.org/10.1007/s00251-010-0427-2

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