The frequency and association of polymorphic Alu insertions (POALINs) with human leucocyte antigen (HLA) class I genes within the class I genomic region of the major histocompatibility complex (MHC) have been reported previously for three populations: the Australian Caucasian, Japanese and north-eastern Thai populations. Here, we report on the individual insertion frequency of the five POALINs within the MHC class I region, their HLA-A and HLA-B associations, the POALIN haplotype frequencies and the HLA-A/POALIN four-loci haplotype frequencies in the Malaysian Chinese population. The phylogenetic relationship of the four populations based on the five POALIN allele frequencies was also examined. In the Malaysian Chinese population, the POALIN AluyHG was present at the highest frequency (0.560), followed by AluyHJ (0.300), AluyMICB (0.170), AluyTF (0.040) and AluyHF (0.030). The most frequent five-loci POALIN haplotype of the 16 inferred haplotypes was the AluyHG single insertion haplotype at a frequency of 0.489. Strong associations were present between AluyHJ and HLA-A24, HLA-A33 and HLA-A11 and between AluyHG and HLA-A2, HLA-A24 and HLA-A11, and these were reflected by the inferred haplotype frequencies constructed from the combination of the HLA-A locus and the AluyHG, AluyHJ and AluyHF loci. The strongest association of AluyMICB was with the HLA-B54 allele (five of five), whereas the associations with the other 17 HLA-B alleles were weak, moderate or undetermined. Phylogenetic analysis of the five POALIN allele frequencies places the Malaysian Chinese closest to the Japanese and north-eastern Thai populations in the same cluster and separate to the Australian Caucasian population. The MHC POALINs are confirmed in this study to be informative genetic markers in lineage (haplotype) analysis, population genetics and evolutionary relationships, especially in studying the MHC genomic region.
A fundamental endeavor of the International Histocompatibility and Immunogenetics Workshop (IHIW) was assembling a collection of DNA samples homozygous through the MHC genomic region. This collection proved invaluable for assay development in the histocompatibility and immunogenetics field, for generating the human reference genome, and furthered our understanding of MHC diversity. Defined by their HLA-A, -B, -C and -DRB1 alleles, the combined frequency of the haplotypes from these individuals is ~20% in Europe. Thus, a significant proportion of MHC haplotypes, both common and rare throughout the world, and including many associated with disease, are not yet represented. In this workshop component, we are collecting the next generation of MHC-homozygous samples, to expand, diversify and modernize this critical community resource that has been foundational to the field. We asked laboratories worldwide to identify samples homozygous through all HLA class I and/or HLA class II genes, or through whole-genome SNP genotyping or sequencing, to have extensive homozygosity tracts within the MHC region. The focus is non-Europeans or those having HLA haplotypes less common in Europeans. Through this effort, we have obtained samples from 537 individuals representing 294 distinct haplotypes, as determined by their HLA class I and II alleles, and an additional 50 haplotypes distinct in HLA class I or II alleles. Although we have expanded the diversity, many populations remain underrepresented, particularly from Africa, and we encourage further participation. The data will serve as a resource for investigators seeking to characterize variation across the MHC genomic region for disease and population studies.