Polymorphic major histocompatibility complex class IIAluinsertions at five loci and their association withHLA-DRB1and -DQB1in Japanese and Caucasians

Abstract

We investigated polymorphic Alu insertion (POALIN) frequencies at five loci in the major histocompatibility complex (MHC) class II genomic region to determine their allele and haplotype frequencies and associations with the human leukocyte antigen (HLA)-DRB1 and -DQB1 genes for 100 Japanese, 174 Australian Caucasians and 67 HLA reference cell lines obtained from different ethnic groups. The POALINs varied in frequency between 11% and 57% with significant differences between the Japanese and Caucasians at three loci. One POALIN locus deviated significantly from Hardy-Weinberg equilibrium (HWE) and four POALIN loci were in significant linkage disequilibrium and had a high percentage association with a variety of HLA-DRB1 or -DQB1 two-digit alleles. Inferred haplotype analysis among two-locus, five-locus and seven-locus haplotype structures showed maximum differences between the Japanese and Caucasians with the seven-locus haplotypes. The most common multilocus haplotype in Caucasians was DRB1*1501/DQB1*0602/AluDQ1/AluDRB1/AluORF10/AluDPB2 (6.7%), whereas the second most common allele HLA-DRB1*15 (17.5%) in Japanese was associated with three or four Alu insertions. The HLA class II POALINs also differentiated within and between HLA-DRB1 super-haplotypes DR1, DR8, DR51, DR52 and DR53. This is the first comparative population study of multilocus POALINs in the HLA class II region, which shows that POALINs whether investigated alone or together with the HLA class II alleles are informative genetic markers for the identification of allele and haplotype lineages and variations within the same and/or different populations.

The MHC, disease and selection

“…The class I region appears to have undergone repeated duplication and loss, some of which is associated with retroviral sequences [77,78]. Two other regions exhibit CNV.…”

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

“…It appears from the MDS plot and the phylogenic trees that the use of five Alu MHC class I insertions may not be enough to enable reliable differentiation between closely related populations, such as the Spanish, British and Australian Europeans. Additional POALINs such as those within the MHC class II region (Kulski, Shigenari, Shiina, & Inoko, ), together with HLA alleles (Kulski & Dunn, ; Kulski et al, ), could give a more definitive result in a comprehensive comparative analysis of lineage. In this regard, there are at least six POALIN in the class II region of the HLA supra‐locus that were investigated in the Japanese and Australian Europeans (Kulski, Shigenari, Shiina, et al, ) and Chinese Han (Shi et al, ), but not in other world populations.…”

“…Additional POALINs such as those within the MHC class II region (Kulski, Shigenari, Shiina, & Inoko, ), together with HLA alleles (Kulski & Dunn, ; Kulski et al, ), could give a more definitive result in a comprehensive comparative analysis of lineage. In this regard, there are at least six POALIN in the class II region of the HLA supra‐locus that were investigated in the Japanese and Australian Europeans (Kulski, Shigenari, Shiina, et al, ) and Chinese Han (Shi et al, ), but not in other world populations. There is also an AluOR POALIN in the olfactory receptor (OR) gene region 325.8 kb telomeric of the HLA‐F locus that was shown to significantly differentiate between the Japanese, Australian European and African American populations (Kulski, Shigenari, & Inoko, ).…”

Young Alu insertions within the MHC class I region in native American populations: Insights into the origin of the MHC‐Alu repeats

“…These include selective neutrality of the Alu markers, the existence of a single common mutation for all chromosomes with the same Alu repeat (identity by descent not just by state), the possibility of knowing the ancestral state (absence of the insertion), and the nonexistence of a known mechanism for the specific removal of an Alu element (Batzer and Deininger, ; Terreros et al, ; among others). Likewise, haplotype combinations of Alu loci from autosomal chromosomes are considered to be useful lineage markers, as they have proved to be efficient for detecting heterogeneity among human groups with different genetic ancestry (Dunn et al, ; Kulski and Dunn, ; Kulski et al, ; Tian et al, ; Yao et al, ).…”