Sequence-based Analysis of the CYP2D6*36-CYP2D6*10 Tandem-type Arrangement, a Major CYP2D6*10 Haplotype in the Japanese Population

Summary: The frequency of the CYP2D6*10 allele (100C > T) in the Japanese is relatively high (0.3–0.4), and the two *10 -related genes, Ch1 (currently *10B ) and Ch2 ( *36 ), and their tandem arrangement Ch 2 -Ch 1 ( *36-*10B ) have been reported. Although the tandem form of *36-*10 is assumed to be a major form, no detailed information has been reported for its intervening and flanking regions. Thus in this study, the tandem-type *36-*10B and the single-type *10 were analyzed by long-range PCR and sequencing of the subsequent nested PCR products. The sequence of the entire *36-*10 region confirmed the recombination of CYP2D6*10 with CYP2D7P . Also, we found that most of the *10B -harbor-ing haplotypes have the upstream *36 gene and that the majority of the remaining haplotypes are the single-type *10B . Haplotype frequencies of the single-type *10 and *36 - *10B were 0.06 and 0.30, respectively, in the subjects analyzed. Additionally, several novel single nucleotide polymorphisms (SNPs) were found in the *36 region and several *36 haplotypes were identified. This sequence information is an important addition to the CYP2D6 sequence data that was obtained by the human genome project.