Two genes encoding steroid 21-hydroxylase [21-OHase; steroid 21-monooxygenase; steroid, hydrogen-donor:oxygen oxidoreductase (21-hydroxylating); Ec 188.8.131.52], a cytochrome P-450 enzyme, have been located within the HLA major histocompatibility complex. Congenital adrenal hyperplasia due to 21-OHase deficiency is a common inherited disorder of cortisol biosynthesis which is in genetic linkage disequilibrium with certain extended HLA haplotypes. These haplotypes include characteristic serum complement allotypes. A series of cosmid clones was isolated from a human genomic library by using a probe encoding part of the fourth component of complement, C4. These clones also hybridized with a probe encoding most of human 21-OHase. Restriction mapping and hybridization analysis showed that there are two 21-OHase genes, each located near the 3' end of one of the two C4 genes. Hybridization with probes specific for the 5' and 3' ends of the 21-OHase gene showed that the 21-OHase and C4 genes all have the same orientation. The 21-OHase genes 3' to C4A and C4B carry Taq I fragments of 3.2 and 3.7 kilobases (kb), respectively. Both of these fragments are found in genomic DNA of most individuals. In DNA from an individual with the severe, 'salt-wasting' form of 21-OHase deficiency who was homozygous for HLA-A3;Bw47;C4A*1;C4B*Q0(null); DR7, the 3.7-kb Taq I fragment is absent, whereas hormonally normal individuals homozygous for HLA-A1;B8;C4A*Q0; C4B*1;DR3 do not carry the 3.2-kb Taq I fragment. These data suggest that the 21-OHase 'B' gene (3.7-kb Taq I fragment) is functional but the 21-OHase 'A' gene (3.2-kb Taq I fragment) is not.
|Original language||English (US)|
|Number of pages||5|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - 1985|
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