Population genetics and comparative genetics of CLDN1, a gene involved in hepatitis C virus entry.

The claudin-1 gene (CLDN1) is a member of a family of genes that encodes proteins found in tight junctions and it has recently been implicated as one of several receptors for late stage binding of hepatitis C virus (HCV). Exploration of the population genetics of this gene could be informative, especially in the investigation of a possible genetic contribution to HCV infection. Comparison to a highly similar gene, claudin-7 (CLDN7) could provide insight into the recent molecular evolution of CLDN1. Mean interspecies conservation score was 0.11 (SD 0.28) for CLDN1 and 0.31 (SD 0.43) for CLDN7. Re-sequence analysis was performed across all exons and evolutionarily conserved regions in CLDN1 (13 kb in total) and CLDN7 (2 kb in total) in 204 chromosomes drawn from the SNP500Cancer resource of four self-described ethnic groups in the US. For CLDN1, 133 SNPs were identified as well as 8 indels and an AC repeat length polymorphism. For CLDN7, 5 SNPs were identified. Assessment of nucleotide diversity (including F(st), theta and pi statistics) did not show evidence for recent positive or negative selection in either gene. The pattern of linkage disequilibrium was determined for each group and there is substantial difference for common SNPS (>5%) between populations as well as genes, further supporting the absence of signatures of recent selection.