Molecular Approaches to Tissue Transplantation and Transfusion Medicine in Maori and Polynesians in New Zealand

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Molecular Approaches to Tissue Transplantation and Transfusion Medicine in Maori and Polynesians in New Zealand MOLECULAR APPROACHES TO TISSUE TRANSPLANTATION AND TRANSFUSION MEDICINE IN MAORI AND POLYNESIANS IN NEW ZEALAND BY EDINUR HISHAM ATAN A thesis submitted to the Victoria University of Wellington in fulfilment of the requirements for the degree of Doctor of Philosophy in Cell and Molecular Bioscience Victoria University of Wellington 2013 Abstract My thesis is focussed 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 i 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. ii Acknowledgements I wish to take this opportunity to express my deep appreciation to my supervisor Dr Geoffrey Keith Chambers. He has helped me to plan a very good research framework for my PhD, continues to monitor my research progress closely and gives prompt answers to any questions forwarded to him. I am very grateful by the support, consideration, advice and suggestions given by my other supervisors and collaborators, Dr Paul Dunn (New Zealand Blood Service), Dr Rod Lea (Griffith University, Australia), Dr Paul Norman (Stanford University), Dr Peter Parham (Stanford University), Dr Zlatibor Velickovic (University of Sydney, Australia) and Dr Medhat Askar (Cleveland Clinic, Ohio). My PhD has been supported by a wide range of New Zealand, Malaysian and United States of America agencies. I acknowledge with thanks the support given by the School of Biological Sciences, Victoria University of Wellington, Universiti Sains Malaysia, Ministry of Higher Education, Malaysia, The Tissue Typing Laboratory of the New Zealand Blood Service, Auckland, The Department of Structural Biology, Stanford University of Medicine and Allogen Laboratories and the Transplant Center, Cleveland Clinic, Ohio. I would like to thank all the participants, local Maori and Polynesian communities including Te Iwi o RakaiPaaka tribal members, New Zealand Central Region Ethics Committee and Victoria University Human Ethics committe for their involvement and approval. I extend my particular thanks for administrative services provided by Paul Marsden (Victoria University), Patricia Stein (Victoria University) and Mary Murray (Victoria University) and technical assistance from Maximiliano Crosetti (Progenika Biopharma S.A and Grifols International), William Perry (Grifols Australia), Martina Prager (BAG Health Care GmbH, Lich, iii Germany), Gabi Henschel (BAG Health Care GmbH, Lich, Germany), Dr Jordi Bozzo (Progenika Biopharma S.A and Grifols International) and Dr Abeer Madbouly (United States National Marrow Donor Program). Special thanks are expressed to Dr Josep Azar, Phil Servid, Kosala Sirisena, Amy Hoo, Shalen, Sebastian, Miles, Olivia, Heather Constable, Aashi, Pop, Cong Zong, Maheshini, Leighton Thomas, Zurin, Wan Joe, Mamat, MWPGS and all others that have kept me happy, healthy and rational. To my wife, Tengku Puteri Nadiah Tengku Baharuddin Shah, my parents, Atan Mohamed and Zawiah Mohamad, my beloved kids, Puteri Elena Aisya and Putera Eiman Shah…thank you for your love and all I have is yours. iv List of abbreviations A adenine A-SM Austronesian-speaking Mongoloid bp base pair C cytosine DMSO dimethyl sulfoxide DNA deoxyribonucleic Acid dNTP deoxynucleotide triphosphate EDTA ethylene diamine tetra acetic G guanine H2O water GVHD graft versus host disease HLA human leukocye antigen HPA human platelet antigen HWE Hardy-Weinberg equilibrium kb kilo base KIR killer cell immunoglobulin-like receptor LD linkage disequilibrium M molar MgCl2 magnesium chloride MHC major histocompatibility complex MICA major histocompatibility complex class I chain-related gene A mM millimolar mtDNA mitochondrial DNA v ng nanogram NJ neigbor-joining PCA principle component PCO principle coordinate PCR polymerase chain reaction P-SA Papuan-speaking Australoid psi pound force per square inch RFLP restriction fragment length polymorphism RNA ribonucleic acid rpm revolution per minutes T thymine Taq Thermus aquatic SBT sequence based typing SNP single nucleotide polymorphism SSOP sequence specific oligonucleotide probe SSP sequence specific primer TBE tris-borate-ethylene diamine tetra acetic acid U unit μg microgram μl microliter UV ultra violet V volt Y-STRs Y-chromosome short tandem repeats vi List of related publications and presentations A. Journals 1. Chambers, G.K. & Edinur, H.A. (2013) Genetic relationships between Malays and Maori. In: The changing values of Malays, Maori and Pacific Islanders (eds. Rahman W.R.A. & Higgins T.R.), 6-37. Chair of Malay Studies & Victoria University Foundation, Wellington, New Zealand. ISBN: 9780475124005. 2. Edinur, H.A., Dunn, P.P. J., Hammond, L., Selwyn, C., Velickovic, Z.M, Lea, R.A. & Chambers, G.K (2012) Using HLA loci to inform ancestry and health in Polynesian and Maori populations. Tissue Antigens, 80, 509-522. 3. Riccio, M.E., Buhler, S., Nunes, J.M., Vangenot, C., Cuenod, M., Currat, M., Di, D., Andreani, M., Boldyreva, M., Chambers, G., Chernova, M., Chiaroni, J., Darke, C., Di Cristofaro, J., Dubois V., Dunn, P., Edinur, H.A., Elamin, N., Eliaou, J.-F., Grubic, Z., Jaatinen, T., Kanga, U., Kervaire, B., Kolesar, L., Kunachiwa, W., Lokki, M.L., Mehra, N., Nicoloso, G., Paakkanen, R., Voniatis D.P., Papasteriades, C., Poli, F., Richard, L., Alonso I.R., Slavcev, A., Sulcebe, G., Suslova, T., Testi, M., Tiercy J.-M., Varnavidou, A., Vidan-Jeras, B., Wennerstrom, A. & Sanchez-Mazas, A. (2013) 16th IHIW: Analysis of HLA Population Data, with updated results for 1996 to 2012 workshop data (AHPD project report). International Journal of Immunogenetics, 40, 21-30. 4. Edinur, H.A., Dunn, P.P.J., Lea, R.A. & Chambers, G.K. (2013) Human platelet antigens frequencies in Maori and Polynesian populations. Transfusion Medicine, 23, 330-337. vii 5. Edinur, H.A., Dunn, P.P.J., Hammond, L., Selwyn, C., Askar, M., Velickovic, Z.M., Lea, R.A. & Chambers, G.K. (2013) HLA and MICA polymorphism in Polynesians and New Zealand Maori: Implications for ancestry and health. Human Immunology, 74, 1119-1129. 6. Edinur, H.A., Dunn, P.P.J., Lea, R.A. & Chambers, G.K. (2013) Molecular approaches to transfusion medicine in Polynesians and Maori in New Zealand. International Journal of Immunogenetics. In press. B. Oral and poster presentations 1. Atan, E.H., Lea, R.A., Dunn, P. & Chambers, G.K. (2010) HLA class I antigens in Polynesia, Wellington Health and Biomedical Research Society, 79th Scientific Meeting, Great Hall, Museum Building, Massey University,
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