Allele frequencies of human platelet antigens in Banjar, Bugis, Champa, Jawa and Kelantan Malays in Peninsular Malaysia.

OBJECTIVES: The major aims of this study are to characterise and compile allelic data of human platelet antigen (HPA)-1 to -6 and -15 systems in five Malay sub-ethnic groups in Peninsular Malaysia. BACKGROUND: HPAs are polymorphic glycoproteins expressed on the surface of platelet membranes and are genetically differentiated across ethnogeographically unrelated populations. METHODS: Blood samples were obtained with informed consent from 192 volunteers: Banjar (n = 30), Bugis (n = 37), Champa (n = 51), Jawa (n = 39) and Kelantan (n = 35). Genotyping was done using polymerase chain reaction-sequence specific primer method. RESULTS: In general, frequencies of HPAs in the Malay sub-ethnic groups are more similar to those in Asian populations compared with other more distinct populations such as Indians, Australian Aborigines and Europeans. CONCLUSIONS: This study provides the first HPA datasets for the selected Malay sub-ethnic groups. Subsequent analyses including previously reported HPA data of Malays, Chinese and Indians revealed details of the genetic relationships and ancestry of various sub-populations in Peninsular Malaysia. Furthermore, the comprehensive HPA allele frequency information from Peninsular Malaysia provided in this report has potential applications for future study of diseases, estimating risks associated with HPA alloimmunization and for developing an efficient HPA-typed donor recruitment strategy.

Distribution of cytokine gene polymorphisms in five Malay subethnic groups in Peninsular Malaysia.

In this survey, we have successfully genotyped 22 single nucleotide polymorphisms in the 13 cytokine genes for five Malay subethnic groups (Kelantan, Acheh, Mandailing, Minangkabau and Patani Malays) using polymerase chain reaction-sequence-specific primer cytokine genotyping kit (Invitrogen, Carlsbad, CA, USA). Most of the cytokine genes showed similar pattern of allelic spectra with wild-type alleles (e.g. ILIa-889/C, ILIB+3962/C and IL6 nt565/G) that represent more than 80% in the studied Malay subethnic groups. These newly observed cytokine alleles and subsequent analyses clearly indicate genetic contribution from Asia in the studied Malay subethnic groups with evidence of admixture from neighbouring populations in Patani Malays. The cytokine data sets for the five Malay subethnic groups deposited in this report can also be used as reference standard for searching suitable donor for allograft transplant and diseases association study. This is particularly relevance as our analyses showed differences between the Malay subethnic groups and other populations screened for cytokine genes.

Killer immunoglobulin-like receptor diversity in Malay subethnic groups of Peninsular Malaysia.

The KIR system shows variation at both gene content and allelic level across individual genome and populations. This variation reflects its role in immunity and has become a significant tool for population comparisons. In this study, we investigate KIR gene content in 120 unrelated individuals from the four Malay subethnic groups (Kelantan, Jawa, Banjar and Pattani Malays). Genotyping using commercial polymerase chain reaction-sequence-specific primer (PCR-SSP) kits revealed a total of 34 different KIR genotypes; 17 for Kelantan, 15 for Banjar, 14 for Jawa and 13 for Pattani Malays. Two new variants observed in Banjar Malays have not previously been reported. Genotype AA and haplotype A were the most common in Jawa (0.47 and 0.65, respectively), Banjar (0.37 and 0.52, respectively) and Pattani (0.40 and 0.60, respectively) Malays. In contrast, Kelantan Malays were observed to have slightly higher frequency (0.43) of genotype BB as compared with the others. Based on the KIR genes distribution, Jawa, Pattani and Banjar subethnic groups showed greater similarity and are discrete from Kelantan Malays. A principal component plot carried out using KIR gene carrier frequency shows that the four Malay subethnic groups are clustered together with other South-East Asian populations. Overall, our observation on prevalence of KIR gene content demonstrates genetic affinities between the four Malay subethnic groups and supports the common origins of the Austronesian-speaking people.

Molecular approaches to transfusion medicine in Polynesians and Maori in New Zealand.

In recent years, with the application of genotyping technology, there has been a substantial increase in the number of reported blood group alleles. This survey was designed to evaluate new molecular blood group genotyping methods and compile reference blood group data sets for Polynesian and Maori subjects. Subsequent analyses of these results were used to calculate probability of random match, to trace Polynesian ancestry and migration patterns and to reveal past and present episodes of genetic admixture. Genomic DNA samples from Maori and Polynesian subjects were drawn from the Victoria University of Wellington DNA Bank and genotyped using combination of commercial PCR-SSP kits, hybridization SNP assay services or sequence-based typing. This survey also involves compilation of serological ABO and Rhesus blood group data from RakaiPaaka Iwi tribal members for comparison with those generated during our molecular blood group study. We observed perfect consistency between results obtained from all molecular methods for blood group genotyping. The A, O, DCcEe, DCCee, MNs, K-k+, Jk(a+b-), Jk(a+b+), Fy(a+b-), Fy(a+b+), Di(a+b-), Co(a+b-) and Do(a-b+) were predominant blood group phenotypes in both Polynesians and Maori. Overall, our survey data show only small differences in distributions of blood group phenotypes between Polynesian and Maori groups and their subgroups. These differences might be associated with selection, population history and gene flow from Europeans. In each case, we estimate that patients with certain blood groups have a very low probability of an exact phenotypic match, even if the patients were randomly transfused with blood from donors of their own ethnicity. The best way to avoid haemolytic transfusion reaction in such cases is to perform a pretransfusion cross-match and recruit increased numbers of donors with rare phenotype profiles. The conclusion of this study is that application of molecular method covering as many known variants as possible may help to improve the accuracy blood group genotyping and potentially conserve the routine requirements of transfusion centres.

Human platelet antigens frequencies in Maori and Polynesian populations.

BACKGROUND: Allele frequencies of human platelet antigens (HPA) reflect population history and possibility of platelet-specific alloimmunization. Here, we report on screening of variants at HPA loci for Polynesian and Maori subjects. OBJECTIVES: Our aims are to evaluate new HPA genotyping methods, compile and analyse new HPA datasets for these subjects, use HPA data for tracing ancestry, migration patterns, genetic admixture and its potential influence on health. MATERIALS AND METHODS: A total of 75 Maori and 25 Polynesian DNA samples were genotyped using commercial BAGene HPA-TYPE DNA-SSP kits, BLOODchip hybridization SNP assays and DNA sequence based typing. RESULTS: Genotyping was successful and cross validation of PCR-SSP and BLOODchip gave 100% agreement. Among the HPA loci tested, only six are dimorphic (HPA-1 to -3, -5, -6 and -15) and all others are monomorphic. The Polynesians and Maori have the 'a' allele form as the most common for all loci except HPA-15. CONCLUSIONS: The newly observed HPA data as well as principal coordinate analysis clearly indicate genetic contributions from both, Asia and Australasia in Maori and Polynesian populations together with recent admixture with Europeans. In addition, different prevalences of HPA alleles among Polynesian, Maori and European populations contribute towards different risk profiles for platelet-specific alloimmunization. This is the first report for these populations and our findings are of direct practical relevance for blood transfusion centres, the management of pregnancies, assessment of neonatal alloimmune thrombocytopenia and management of multi-transfused patients.

HLA and MICA polymorphism in Polynesians and New Zealand Maori: implications for ancestry and health.

Data from HLA typing studies have made significant contributions to genetic theories about the Austronesian diaspora and the health of descendant populations. To help further unravel pattern and process elements, we have typed HLA and MICA loci at high resolution in DNA samples from well defined groups of Maori and Polynesian individuals. Our results show a restricted set of HLA class I alleles compared with other well characterised populations. In contrast, the class II HLA-DRB1 locus seems to be diverse in Maori and Polynesians and both groups show high frequencies of HLA-DRB1(∗)04:03, -DRB1(∗)08:03, -DRB1(∗)09:01 and -DRB1(∗)12:01. Our survey also provides the first ever MICA datasets for Polynesians and reveal unusual distributions and associations with the HLA-B locus. Overall, our data provide further support for a hybrid origin for Maori and Polynesians. One novel feature of our study is the finding that the gene sequence of the HLA-B(∗)40:10 allele in Polynesians is a recombinant of HLA-B(∗)55:02 and -B(∗)40:01. HLA-B(∗)40:10 is in close association with HLA-C(∗)04:03, an allele identified as a hybrid of HLA-C(∗)04 and -C(∗)02. In this respect, our data resemble those reports on Amerindian tribes where inter-allele recombination has been a common means of generating diversity. However, we emphasize that Amerindian gene content per se is only a very minor element of the overall Polynesian genepool. The wider significance of HLA and MICA allele frequencies across the Pacific for modern day health is also discussed in terms of the frequency relative to reference populations of disease known to be associated with specific HLA and MICA markers. Thus, Polynesians and Maori are largely unaffected by "European autoimmune diseases" such as ankylosing spondylitis, uveitis and coeliacs disease, yet there are several Maori- and Polynesian-specific autoimmune diseases where the HLA and MICA associations are still to be determined.

16(th) IHIW: analysis of HLA population data, with updated results for 1996 to 2012 workshop data (AHPD project report).

We present here the results of the Analysis of HLA Population Data (AHPD) project of the 16th International HLA and Immunogenetics Workshop (16IHIW) held in Liverpool in May-June 2012. Thanks to the collaboration of 25 laboratories from 18 different countries, HLA genotypic data for 59 new population samples (either well-defined populations or donor registry samples) were gathered and 55 were analysed statistically following HLA-NET recommendations. The new data included, among others, large sets of well-defined populations from north-east Europe and West Asia, as well as many donor registry data from European countries. The Gene[rate] computer tools were combined to create a Gene[rate] computer pipeline to automatically (i) estimate allele frequencies by an expectation-maximization algorithm accommodating ambiguities, (ii) estimate heterozygosity, (iii) test for Hardy-Weinberg equilibrium (HWE), (iv) test for selective neutrality, (v) generate frequency graphs and summary statistics for each sample at each locus and (vi) plot multidimensional scaling (MDS) analyses comparing the new samples with previous IHIW data. Intrapopulation analyses show that HWE is rarely rejected, while neutrality tests often indicate a significant excess of heterozygotes compared with neutral expectations. The comparison of the 16IHIW AHPD data with data collected during previous workshops (12th-15th) shows that geography is an excellent predictor of HLA genetic differentiations for HLA-A, -B and -DRB1 loci but not for HLA-DQ, whose patterns are probably more influenced by natural selection. In Europe, HLA genetic variation clearly follows a north to south-east axis despite a low level of differentiation between European, North African and West Asian populations. Pacific populations are genetically close to Austronesian-speaking South-East Asian and Taiwanese populations, in agreement with current theories on the peopling of Oceania. Thanks to this project, HLA genetic variation is more clearly defined worldwide and better interpreted in relation to human peopling history and HLA molecular evolution.

Using HLA loci to inform ancestry and health in Polynesian and Maori populations.

Human leukocyte antigens (HLA) are important genetic markers of tissue identity and accurately reflect ancestral history. The work reported in this paper provides a detailed description of HLA polymorphism in Polynesian and Maori individuals in relation to other populations. Our study concerns HLA classes I and II antigens in Polynesian (N = 36) and Maori (N = 114) subjects genotyped at two digit resolution by New Zealand Blood Service Laboratory in Auckland using polymerase chain reaction-sequence specific oligonucleotide and PCR-SSP technologies. We have also compared our data with those from other Austronesian-speaking Mongoloid and Papuan-speaking Australoid populations in order to test previously published account of the origin of Proto-Polynesians via gender-biassed gene flow between these two ancestral populations. We use principal coordinate analysis for this purpose, arguing this approach to be superior to tree-based methods, because of factors associated with population history and admixture. Our data are in general agreement with earlier work and reflect received wisdom on the dual origin of Proto-Polynesians. They also show the way in which the genetic make-up of Polynesian and Maori subjects is changing due to intermarriage with Europeans.