The ABCC5 transporter is a ubiquitously expressed ATP-dependent efflux pump that exports nucleotide analogues, including thiopurine anticancer drugs and antiviral drugs. Polymorphisms within this gene may be associated with differences in response to these drugs between different individuals. Haplotype mapping may facilitate the identification of causal genetic variations in association studies. Here, we report the characterization of the haplotype and linkage disequilibrium (LD) profiles across the entire 100 kb of the ABCC5 gene in five ethnically unique populations. Of 24 single nucleotide polymorphisms (SNPs) examined, 16 were observed to occur at high frequency in all five populations and were used for further haplotype and LD analyses. The ABCC5 gene was found to be in strong LD in all populations with half-length LD (LD0.5) estimated to be between 106 and 293 kb long and useful LD extending beyond 100 kb. Low haplotype diversity was observed in the four non-African populations, where the total number of observed haplotypes constituted less than 22% of the predicted number of haplotypes in a simulated population that has undergone maximum recombination. Four and six tagging SNPs, which could account for approximately 90% of observed haplotypes, were identified in the non-African and African-American populations, respectively.
Departments of aBiochemistry
dDivision of Medical Sciences, National Cancer Center, Singapore
cPediatrics and Obstetrics and Gynecology, National University of Singapore, Singapore
eDepartments of Pediatrics and Gynecology and Obstetrics, and McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Sponsorship: This study was supported by a grant from the BioMedical Research Council (BMRC) (01/1/21/17/054), Singapore to C.G.L. Lee and E.J.D. Lee.
Correspondence and requests for reprints to Caroline G. Lee, Division of Medical Sciences, National Cancer Center, Level 6, Laboratory 5, 11 Hospital Drive, Singapore 169610, Singapore
Tel: +65 643 68353; fax: +65 62241778;
Received 7 June 2004 Accepted 26 September 2004