Cloning, expression, and physical mapping of the 3 beta-hydroxysteroid dehydrogenase gene cluster (HSD3BP1-HSD3BP5) in human

Seven members of the human 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) gene family (HGMW-approved symbols HSD3BP1-HSD3BP5) have been cloned and p hysically mapped. HSD3B1 and 2 express 3 beta-HSD enzymes; HSD3B psi 1-5 ar e unprocessed pseudogenes that are closely related to HSD3B1 and 2 but cont ain no corresponding open reading frames. mRNA is expressed from psi 4 and psi 5 in several tissues, but with altered splice sites that disrupt readin g frames. A 0.5-Mb contig of 3 yeast artificial chromosome and 32 bacterial artificial chromosome genomic clones contained no additional members of th e gene family. The seven genes and pseudogenes mapped within 230 kb in the order HSD3B psi 5-psi 4-psi 3-HSD3B1-psi 1-psi 2-HSD3B2 HSD3B1 and 2 are in direct repeat, 100 kb apart. Six HSD3B2 mutations involve substitutions th at are present in several of the pseudogenes, In four cases, mutations aros e in CpG sites that are conserved within the gene cluster. The tendency for CpG sites to mutate by transition provides an adequate explanation for the se HSD3B2 mutations, which are unlikely to be due to recombination or conve rsion within the gene family. (C) 1999 Academic Press.