Genetic linkage mapping of HSD3B1 and HSD3B2 encoding human types I and II 3β-hydroxysteroid dehydrogenase/Δsup5/sup-Δsup4/sup-isomerase close to D1S514 and the centromeric D1Z5 locus

摘要

The enzyme 3β-hydroxysteroid dehydrogenase/Δ5-Δ4-isomerase (3β-HSD) catalyses an essential step in the biosynthesis of all steroid hormones. Consequently, classical 3β-HSD deficiency is responsible for a severe form of congenital adrenal hyperplasia. The HSD3B1 and HSD3B2 genes encoding the types I and II 3β-HSD isoenzymes, respectively, have been previously assigned by in situ hybridization to the chromosome 1p13.1 region. To determine the physical distance between these two genes, NotI and SacIIdigests of genomic DNA were resolved by pulse-field gel electrophoresis and hybridized with type I and type II 3β-HSD cDNAs used as probes. The detection of a single band under low stringency conditions indicates that HSD3B1 and HSD3B2 are located within an approximately 0.29 megabase SacII DNA fragment. We constructed a high resolution genetic map of the region flanking the polymorphic HSD3B1 and HSD3B2 genes including ten Généthon markers and the two NIH/CEPH markers AMY2B and D1Z5. The HSD3B1A and HSD3B2A markers were mapped relative to other reference markers through eight CEPH reference families. The order of polymorphic genes and markers is: pter-[AMY2B-DlS239]-DlS457-DlS502-D1S250-D1S252-[HSD3B1A-HSD3B2A-D1S514]-[D1Z5-D1S442]-D1S305-D1S303-D1S484-qter. The D1S514 marker was thus closely linked to HSD3B1A (θ < 0.001; lod =14.13) and HSD3B2 (θ = 0.008; lod = 35.36). The HSD3B loci are located 1–2 cM of the centromeric m