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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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.

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.[1]


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