Molecular approaches to tissue transplantation and transfusion medicine in Maori and Polynesians in New Zealand

Abstract

<p>My thesis is focused on using new and existing molecular technologies to survey immune system (i.e. HLA, KIR and MICA), blood group and HPA genes in Polynesian and Maori subjects. I have compiled large datasets for these individuals including first ever molecular typing blood group, HPA and MICA. I have also compared my data with those from previous genetic studies of KIR and HLA for the four Polynesian sub-populations and HLA for Maori. Combined with previous information in a small scale meta-analysis, the results presented here were interpreted for the first time in the light of new theories about the hybrid origin of Proto-Polynesians via gender-biased gene flow between Austronesian-speaking Mongoloids and Papuan-speaking Australoids. Phylogenetic and principal component/coordinate analyses show that Polynesian sub-populations are closer to each other and are end populations of the great Austronesian Diaspora. Estimation based on HLA class I and II allele frequencies show a wide range (55:45 to 90:10) of ASM:P-SA ancestral fractions in Maori and other Polynesians. The same phenomenon was observed for blood group, HPA and KIR data. Thus, findings from the present study generally support the account deduced from Y-chromosome, mtDNA and genome wide SNP data, and are in accord with the emergent picture from linguistics and archaeology studies. The data collected bear more or less directly on questions of health including tissue matching for transfusion and transplant surgery, disease resistance and the relative incidence of autoimmune disease in these ethnic groups. Tissue matching of HLA, MICA, KIR, blood group and HPA is a fundamental element in transfusion and transplant surgery and it is vital that these technologies take accurate account of the ethnic origins of both donors and recipients. This is important due to significant differences between Polynesians and people of European origin, who form the majority segment of the modern day multi-ethnic country of New Zealand. The prevalence of HLA, MICA, KIR, blood group and HPA and their potential influence on the health of modern day Maori and Polynesians were also discussed. This study was intentionally designed to validate new molecular blood group and HPA typing methods in Polynesian and Maori populations. Scores for the other loci are based on the application of pre-existing technologies. Validation using three different blood group and HPA genotyping methods (i.e. PCR-SSP, SBT and SNP assay) gave 100% concordance and thus reflects the accuracy of the new DNA-based methods. Overall, molecular genotyping does seem to offer the opportunity to improve the efficiency of high quality transfusion services, but should include all known variants that are associated with serological expression. In conclusion, the present molecular genetics study has successfully compiled new HLA, MICA, blood groups, HPA and KIR datasets for Polynesians and Maori, used the datasets for dual analyses of ancestry and health, and demonstrated the reliability of current genotyping platforms that would suit well the needs of transfusion and transplantation centres. In general, this thesis has strongly endorsed the indigenous biomedicine approach, and particularly will be valuable to Asia-Pacific populations of Austronesian peoples.</p>