Genetic linkage mapping of the human steroid 5 alpha-reductase type 2 gene (SRD5A2) close to D2S352 on chromosome region 2p23-->p22.

Two steroid 5 alpha-reductase isoenzymes catalyze the conversion of testosterone into dihydrotestosterone, the more bioactive androgen, which is essential for male phenotypic sexual differentiation and for androgen-mediated growth of such tissues and organs as the prostate. Inherited mutations in SRD5A2 cause male pseudohermaphroditism. The SRD5A1 and SRD5A2 genes encoding the steroid 5 alpha-reductase type 1 and type 2 isoenzymes have been previously assigned by in situ hybridization to 5p15 and 2p23, respectively. To map the SRD5A2 gene by linkage analysis, a novel RsaI RFLP detected in exon I and a TA repeat polymorphism found in exon V were genotyped in eight CEPH reference families. A two-point linkage analysis was performed between these polymorphisms and the chromosome 2 microsatellite markers of Généthon and NIH/CEPH. The closest linkage was observed with D2S352 (Zmax = 24.06; thetamax = 0.001) in the region 2p23-->p22. To further define the localization of SRD5A2, a framework map, including nine Généthon markers flanking the polymorphic SRD5A2 locus, was built by multipoint linkage analysis. This led to a high-resolution genetic map of the region flanking the polymorphic SRD5A2 gene, including the nine Généthon markers and three NIH/CEPH markers, yielded the following order: tel-D2S48-D2S149-D2S320-D2S171-D2S165- [D2S352/SRD5A2]-D2S367-[D2S19/D2S177]-[ D2S391/CALM]-D2S378-cen.