The human 3β-hydroxysteroid dehydrogenase (3β-HSD) gene cluster on chromosome 1p13 contains a presumptive pseudogene; 3β-HSD and CYP17 do not segregate with dominantly inherited hirsutism
| Autor: | R G Sutcliffe, K Vass, K Frank-Raue, Norma Morrison, Martin W. McBride, A J Russell, Elizabeth Boyd, Claude Szpirer, N J Craig |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Genetic Markers
Male Hirsutism endocrine system 3-Hydroxysteroid Dehydrogenases Pseudogene Molecular Sequence Data Biology Polymerase Chain Reaction Exon Endocrinology Reference Values Gene cluster Humans Point Mutation Genomic library Molecular Biology Gene In Situ Hybridization Fluorescence DNA Primers Genes Dominant Genetics Genomic Library Polymorphism Genetic Base Sequence Chromosome Mapping Steroid 17-alpha-Hydroxylase Chromosome Exons Molecular biology Stop codon Pedigree Chromosomes Human Pair 1 Genetic marker Multigene Family Female Steroids |
| Zdroj: | Journal of Molecular Endocrinology. 15:167-176 |
| ISSN: | 1479-6813 0952-5041 |
| DOI: | 10.1677/jme.0.0150167 |
| Popis: | Four hirsute females from a family exhibiting idiopathic dominant hirsutism were examined. Basal blood levels of Δ5 and Δ4 steroids were within the normal range, but ACTH stimulation led to increases in 17-hydroxypregnenolone and dehydroepiandrosterone that were significantly above control levels. Using polymorphic genetic markers, the genes for cytochrome P450c17 encoded by CYP17, and the type I and II forms of 3β-hydroxysteroid dehydrogenase (3β-HSD) were found not to segregate with hirsutism in this family, though a base substitution was detected in the 3′ end of exon 1 of the gene for 3β-HSD type I in three of the four patients investigated. Analysis of PCR amplification products by denaturing gradient gel electrophoresis (DGGE) and sequencing revealed a novel homologue of exon 3 of 3β-HSD. DNA of one of the affected patients was used to create a genomic library in λ gem11 and clones containing the novel homologue were obtained and partially sequenced. The equivalent clone was obtained from a genomic library of an unrelated normal individual. The sequences of the clones from patient and control were identical and homologous to exons 2–4 of human 3β-HSD types I and II. No difference was found in the PCR primer sites that flanked the exon 3 homologue which led to its detection on DGGE gels. In both clones, stop codons and deletions were identified in the exon 4 homologue, leading to the deduction that the sequence comes from a pseudogene, which we call 3β-HSD Ψ1. The pseudogene mapped to chromosome 1p13. It was concluded that dominantly inherited idiopathic hirsutism in this rare kindred was not due to deficiencies in 3β-HSD types I, II, or Ψ, or of CYP17. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|