The distribution of polymorphic Alu insertions within the MHC class I HLA-B7 and HLA-B57 haplotypes

Abstract

There are five polymorphic Alu insertion (POALIN) loci within the major histocompatibility complex (MHC) class I region that have been strongly associated with HLA class I alleles, such as HLA-A1, HLA-A2 and HLA-B57. In order to assess the variability and frequency of POALIN distribution within two common HLA-B haplotypes, we detected the presence of the MHC class I POALIN by PCR in a panel of 15 individuals with HLA-B57 and 47 homozygous individuals with 7.1 AH (HLA-B7, -Cw7, -A3) obtained from the Australian Bone Marrow Donor Registry, and also from four families (25 individuals) containing the HLA-B57 allele. Only two of the 47 HLA-B7 genotypes had a detectable POALIN, whereas all of the HLA-B57 genotypes had at least one or more POALINs present, confirming that certain MHC class I haplotypes are relatively POALIN-free and others are POALIN-enriched. Six distinct HLA-B57 haplotypes, based on differences at the HLA-A locus and three of five POALIN loci, were identified that appear to have evolved by different mechanisms, including either by shuffling different combinations of conserved alpha and beta blocks or by recombination events involving two or more previously generated HLA-B57 haplotypes.

MHC class I polymorphic Alu insertion (POALIN) allele and haplotype frequencies in the Arabs of the United Arab Emirates and other world populations

“…An interesting overall trend with the UAE Alu haplotype frequencies in Table is that the null haplotype (0.295) and the single Alu insertion haplotype (0.438) account for 0.7331 of the total frequency, and when added together with the two Alu insertion haplotypes (0.195), they account for 0.928 of the total frequency. Similar trends are evident for other world populations (Supporting Information Table ), which suggests that the haplotypes with more than two Alu insertions are most likely to be the result of recombination or haplotype shuffling (Dunn et al, ; Dunn, Tait, et al, ). The recombination or haplotype shuffling of MHC POALIN haplotypes in combination with HLA genotyping warrants investigation in more detail to better characterize the HLA allelic associations with infectious, autoimmune and chronic diseases.…”

“…The AluMICB insertion is strongly associated with a greater number of different alleles at its neighbouring HLA locus than the other POALIN. It was associated strongly with HLA‐B*13 , HLA‐B*44 , HLA‐B*48 , HLA‐B*55 , HLA‐B*57 and HLA‐B*73 (Dunn et al, ; Dunn, Romphruk, et al, ; Dunn, Tait, et al, ; Kulski et al, ), whereas the AluHJ insertion is associated mostly with HLA‐A*01 and HLA‐A*24 , and the AluHG insertion is limited mainly to HLA‐A*02 and to a lesser degree with HLA‐A*11 and HLA‐A*32 (Kulski & Dunn, ). This suggests that the AluMICB insertion within intron 1 of the MICB gene is older than the other POALIN in the class I region and that the different HLA‐B alleles associated with AluMICB share the same lineage, and/or the associations have arisen by recombination events between the MICB and HLA‐B genes.…”

“…This suggests that the AluMICB insertion within intron 1 of the MICB gene is older than the other POALIN in the class I region and that the different HLA‐B alleles associated with AluMICB share the same lineage, and/or the associations have arisen by recombination events between the MICB and HLA‐B genes. The AluMICB*02 may have first appeared in a subpopulation carrying MICB*01021 (or the HLA‐B*13~MICB*01021 haplotype) before co‐evolving with MICB*0105 (or the HLA‐B*57~MICB*0105 haplotype) (Dunn, Tait, et al, ).…”

“…The remaining three POALINs, AluHJ , AluHG and AluHF , are located within the alpha block, close to the HLA‐J pseudogene, and the HLA‐G and HLA‐F nonclassical genes, respectively. These five MHC POALINs were used previously in an anthropological analysis of human populations (Dunn, Choy, Phipps, & Kulski, ; Dunn, Romphruk, Leelayuwat, Bellgard, & Kulski, ) and for evaluating their linkage relationship as inferred haplotypes with the HLA class I genes in African, European, American and Asian populations (Dunn et al, ; Dunn, Naruse, Inoko, & Kulski, ; Dunn, Ota, Inoko, & Kulski, ; Dunn, Romphruk, et al, ; Dunn, Tait, & Kulski, ; García‐Obregón et al, ; Kulski & Dunn, ; Tian, Wang, Cai, & Li, ; Yao, Shi, Shi, Lin, Tao, et al, ; Yao, Shi, Shi, Lin, Yu, et al, ). A number of recent studies used these MHC POALINs to detect the effects of isolation and for genetic drift in shaping the human genetic variation and differentiating human groups according to ethnic ancestry (García‐Obregón et al, ; Gómez‐Pérez et al, ; Yao et al, ).…”

The distribution of major histocompatibility complex class I polymorphic Alu insertions and their associations with HLA alleles in a Chinese population from Malaysia

“…The low occurrence of multiple POALINs in the same haplotype is not surprising because the generation of a new Alu insertion site is known to be a rare event (4), the MHC class I region is a relatively small (2 Mb) target region for insertions in comparison with the overall haploid genome size of 3.2 Gb and there are many different HLA haplotypes that might be associated with the occasional Alu insertion and drift towards a substantial frequency. Nevertheless, there are HLA haplotypes with multiple POALIN sites, such as those associated with the HLA‐B57 alleles that were deduced to have been generated by recombination or DNA segmental shuffling between haplotypes carrying single and different polymorphic Alu elements rather than by independent insertions of two or more elements within the same haplotype (32).…”