Morissette J, Durocher F, Leblanc J F, Normand T, Labrie F, Simard J
MRC Group in Molecular Endocrinology, CHUL Research Center, Québec, Canada.
Cytogenet Cell Genet. 1996;73(4):304-7. doi: 10.1159/000134362.
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.
两种甾体5α-还原酶同工酶催化睾酮转化为生物活性更强的雄激素双氢睾酮，双氢睾酮对于男性表型性分化以及前列腺等组织和器官的雄激素介导生长至关重要。SRD5A2基因的遗传性突变会导致男性假两性畸形。先前通过原位杂交分别将编码1型和2型甾体5α-还原酶同工酶的SRD5A1和SRD5A2基因定位到5p15和2p23。为了通过连锁分析定位SRD5A2基因，在8个CEPH参考家系中对在第I外显子中检测到的一种新的RsaI RFLP和在第V外显子中发现的TA重复多态性进行了基因分型。对这些多态性与Généthon和NIH/CEPH的2号染色体微卫星标记进行了两点连锁分析。在2p23→p22区域观察到与D2S352的最紧密连锁（Zmax = 24.06；thetamax = 0.001）。为了进一步确定SRD5A2的定位，通过多点连锁分析构建了一个框架图，其中包括位于多态性SRD5A2基因座两侧的9个Généthon标记。这产生了一个多态性SRD5A2基因侧翼区域的高分辨率遗传图谱，包括9个Généthon标记和3个NIH/CEPH标记，顺序如下：端粒-D2S48-D2S149-D2S320-D2S171-D2S165- [D2S352/SRD5A2]-D2S367-[D2S19/D2S177]-[ D2S391/CALM]-D2S378-着丝粒。
