Genetic linkage mapping of the dehydroepiandrosterone sulfotransferase (STD) gene on the chromosome 19q13.3 region
- Laval Univ. Quebec (Canada)
In the human liver and adrenal, there is a single hydroxysteroid sulfotransferase, which catalyzes the transformation of dehydroepiandrosterone to dehydroepiandrosterone sulfate, the most abundantly circulating steroid in humans, and also catalyzes the sulfation of a series of other 3{beta}-hydroxysteroids as well as cholesterol. Dehydroepiandrosterone sulfate serves as precursor for the formation of active androgens and estrogens in several peripheral tissues, indicating that hydroxysteroid sulfotransferase plays a pivotal role in controlling the hormonal action of sex steroids by regulating their bioavailability. We recently elucidated the structure of the gene encoding hydroxysteroid sulfotransferase (STD), also designated dehydroepiandrosterone sulfotransferase, which spans 17 kb and contains six exons. The STD gene was preliminarily assigned to chromosome 19 by polymerase chain reaction (PCR) amplification of DNA from a panel of human/rodent somatic cell hybrids. To locate the STD gene, the novel biallelic polymorphism found in intron 2 was genotyped in eight CEPH reference families by direct sequencing of PCR products. Two-point linkage analysis was first performed between the latter polymorphism and chromosome 19 markers from Genethon and NIH/CEPH. The closest linkage was observed with D19S412 (Z{sub max} = 9.23; {theta}{sub max} 0.038) and HRC (Z{sub max} =5.95; {theta}{sub max}0.036), located on the 19q13.3 region. A framework map including six Genethon markers flanking the polymorphic STD gene was created by multipoint linkage analysis. Thereafter, a high-resolution genetic map of the region was constructed, yielding to the following order: qter-D19S414-D19S224-D19S420-D19S217-(APOC2-D19S412)-(STD-HRC)-KLK-D19S22-D19S180-PRKCG-D19S418-tel. 24 refs., 2 figs.
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 443882
- Journal Information:
- Genomics, Journal Name: Genomics Journal Issue: 3 Vol. 29; ISSN GNMCEP; ISSN 0888-7543
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BASIC STUDIES
BIOLOGICAL MARKERS
DNA SEQUENCING
GENE MUTATIONS
GENETIC MAPPING
GENOTYPE
HUMAN CHROMOSOME 19
HYBRIDIZATION
HYDROXYANDROSTENONE
POLYMERASE CHAIN REACTION
RESOLUTION
SOMATIC CELLS
STATISTICS
STEROID HORMONES
STRUCTURE-ACTIVITY RELATIONSHIPS
SULFATION
TRANSFERASES