title: Linkage disequilibrium and haplotype architecture for two ABC transporter genes (ABCC1 and ABCG2) in Chinese population: implications for pharmacogenomic association studies.
abstract: Information about linkage disequilibrium (LD) patterns and haplotype structures for candidate genes is instructive for the design and analysis of genetic association studies for complex diseases and drug response. ABCC1 and ABCG2 are genes coding for two multidrug resistance (MDR) associated transporters; they are also related to some pathophysiological traits. To pinpoint the LD profiles of these MDR genes in Chinese, we systemically screened 27 unrelated individuals for single nucleotide polymorphisms (SNPs) in the coding and regulatory regions of these genes, and thereby characterized their haplotype structures. Despite marked variations in haplotype diversity, LD pattern and intragenic recombination intensity between the two genes, both loci could be partitioned into several LD blocks, in which a modest number of haplotypes accounted for a high fraction of the sampled chromosomes. We concluded that each locus has its own genomic LD profile, but that they still share a common segmental LD architecture with low haplotype diversity. Our data will benefit genetic association studies of complex traits and drug response possibly related to these genes.
authors.affiliation: Laboratory of Systems Biology, Beijing Institute of Radiation Medicine, Beijing 100850 PR China.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: B
authors.initials: B
authors.lastname: Hao
authors.forename: K
authors.initials: K
authors.lastname: Zhou
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.forename: S
authors.initials: S
authors.lastname: Wu
authors.forename: G
authors.initials: G
authors.lastname: Zhou
authors.forename: Y
authors.initials: Y
authors.lastname: Zhu
authors.forename: F
authors.initials: F
authors.lastname: He
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D002681:China; D018432:Drug Resistance, Multiple / Q000235:genetics; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008957:Models, Genetic; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D011995:Recombination, Genetic
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; C116614:ABCG2 protein, human; C421109:multidrug resistance-associated protein 1