title: Genetic linkage mapping of the CYP11A1 gene encoding the cholesterol side-chain cleavage P450scc close to the CYP1A1 gene and D15S204 in the chromosome 15q22.33-q23 region.
abstract: The first rate-limiting step in the biosynthesis of all mammalian steroid hormones is the conversion of cholesterol to pregnenolone by the cholesterol side-chain cleavage enzyme, P450scc. The human CYP11A1 gene, encoding the mitochondrial P450scc, has been previously assigned by in situ hybridization to 15q23-q24 region. To map the CYP11A1 gene with linkage analysis, a novel TAAAA repeat polymorphism, found in its promoter region, was genotyped in the eight largest CEPH reference families, which included 91 children, 16 parents and 26 grandparents. Two-point linkage analysis was performed between this tetra-allelic polymorphism and the chromosome 15 microsatellite markers of Généthon as well as the tetranucleotide polymorphism of the CYP19 gene and a MspI RFLP of the CYP1A1 gene. A close linkage was observed with D15S204 (Z max = 27.33; theta max = 0.009) and CYP1A1 gene (Z max = 6.62; theta max = 0.001), but not with the CYP19 gene (Z max = 4.06; theta max = 0.26). The CYP19 gene that encodes the P450arom was rather closely linked with D15S123 (Z max = 31.04; theta max = 0.001). A framework map, including Généthon markers flanking the polymorphic CYP11A1 and CYP19 genes, was built by multipoint linkage analysis. Thereafter, a high-resolution genetic map of the 15q15-q25.3 region was constructed, yielding to the following order: cen-D15S214-[D15S123; CYP19]-D15S117-D15S159-D15S153-D15S983-[++ +D15S204; CYP11A1; CYP1A1]-D15S211-D15S152-D15S199-tel. Thus, the CYP11A1 gene is closely linked with the CYP1A1 gene, whereas it is located approximately 27.4 cM telomeric to the CYP19 gene.
authors.affiliation: Laboratory of Hereditary Cancers, CHUL Research Centre, Canada.
authors.forename: F
authors.initials: F
authors.lastname: Durocher
authors.forename: J
authors.initials: J
authors.lastname: Morissette
authors.forename: J
authors.initials: J
authors.lastname: Simard
mesh_terms: D000483:Alleles; D001483:Base Sequence; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics*; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D017931:DNA Primers; D019363:Cytochrome P-450 CYP1A1; D002786:Cholesterol Side-Chain Cleavage Enzyme