Identification of 142 single nucleotide polymorphisms in 41 candidate genes for rheumatoid arthritis in the Japanese population

Single-nucleotide polymorphisms (SNPs) can make an important contribution t o our understanding of genetic backgrounds that may influence medical condi tions and ethnic diversity. We undertook a systematic survey of genomic DNA for SNPs located not only in coding sequences but also in non-coding regio ns (e.g., introns and 5' flanking regions) of selected genes. Using DNA sam ples from 48 Japanese patients with rheumatoid arthritis (RA) as templates, we surveyed 41 genes that represent candidates for RA, screening a total o f 104 kb of DNA (30 kb of coding sequences and 74 kb of non-coding DNA). Wi thin this 104 kb of genomic sequences we identified 163 polymorphisms (1 pe r 638 bases on average), of which 142 were single-nucleotide substitutions and the remainder, insertions or deletions. Of the coding SNPs, 52% were no n-synonymous substitutions, and non-conservative amino acid changes were ob served in a quarter of those. Sixty-nine polymorphisms showed high frequenc ies for minor alleles (more than 15%) and 20 revealed low frequencies (<5%) . Our results indicated a greater average distance between SNPs than others have reported, but this disparity may reflect the type of genes surveyed a nd/or the relative ethnic homogeneity of our test population.