GENETIC CHARACTERIZATION OF NUCLEOTIDE ANALOGUE TRANSPORTERS ABCC4 AND ABCC5 GENE LOCI GWEE PAI CHUNG (B.Sc.(Pharm.)(Hons.), NUS) A THESIS SUBMITTED FOR THE DEGREE OF DOCTOR OF PHILOSOPHY DEPARTMENT OF BIOCHEMISTRY FACULTY OF MEDICINE NATIONAL UNIVERSITY OF SINGAPORE 2005 ACKNOWLEDGEMENTS I acknowledge with gratitude the colleagues and friends that have in one way or another contributed to the completion of this thesis. I am especially indebted to Dr Caroline Lee, my supervisor for taking me under her wing as a graduate student. She was instrumental in providing expert advice, reviewing publications, as well as editing of this thesis. The strategies adopted here in this thesis were part of her vision to study polymorphisms in the drug transporters. I would also like to thank Professor Samuel Chong for his input especially in recommending the use of minisequencing method for multiple SNP genotyping. Human genomic DNA samples were obtained from the Department of Paediatrics through his help. Many of the statistical analyses especially for the long-range haplotype test were initially written and modified by Tang Kun, with assistance from Wang Zihua and Wang Jingbo. Thanks must also go to Ngoi Soo Mun who was involved in the DNA extraction of blood samples and Sew Pui Hoon who assisted in the genotyping of ABCC5. Wang Baoshuang and Ren Jianwei gave generously of their time to guide me and I benefited from their expertise in cloning. I must express my gratitude to my family who provided unwavering support throughout these years and gave me the freedom to pursue the choices I made. Last but not least, my friends have enriched my life and helped me keep my sense of humour. “So Long, and Thanks for all the Fish.” . GENETIC CHARACTERIZATION OF NUCLEOTIDE ANALOGUE TRANSPORTERS ABCC4 AND ABCC5 GENE LOCI GWEE PAI CHUNG (B.Sc.(Pharm.)(Hons.),. DEGREE OF DOCTOR OF PHILOSOPHY DEPARTMENT OF BIOCHEMISTRY FACULTY OF MEDICINE NATIONAL UNIVERSITY OF SINGAPORE 2005 ACKNOWLEDGEMENTS I acknowledge with gratitude the colleagues and. samples and Sew Pui Hoon who assisted in the genotyping of ABCC5. Wang Baoshuang and Ren Jianwei gave generously of their time to guide me and I benefited from their expertise in cloning. I must