(A) Position of the seven SNPs along the
VKORC1
gene.
VKORC1 is a 4.1 kb gene (GenBank accession number AY587020) located at 16p11.2. The three exons of the gene are represented as boxes, with 5′UTR and 3′UTR regions colored in grey and coding regions in black. Flanking and intronic regions are represented as thin and thick lines, respectively. The seven studied SNPs are shown in their sequential order along the VKORC1 gene. The functional polymorphism rs9923231 located in the promoter, is highlighted in red and the SNP already present in the Illumina 650K chip in blue. Physical position along chromosome 16 is indicated in kb below. (B) Distribution of
VKORC1
haplotypes at the global and regional level. For each haplotype, SNPs are listed in the same sequential order than in Figure 1A. Ancestral and derived alleles are shown in blue and orange, respectively. Haplotype labels H1 to H7 were given according to the global haplotype frequency. AF, sub-Saharan Africa; ME, Middle East; EUR, Europe; CSA, Central South Asia; EA, East Asia; OCE, Oceania; AM, America. (C) Median-joining network of the inferred
VKORC1
haplotypes at the global level. Circles areas are proportional to the global haplotype frequency and branch lengths to the number of mutations separating haplotypes. Labels of haplotypes are indicated in corresponding circles, and labels of mutations on the network branches. The haplotype carrying the -1639A allele conferring the AVK sensitivity phenotype (H1) is shown in red and the ancestral haplotype (H6) in black.