Two genes encoding steroid 21-hydroxylase are located near the genes encoding the fourth component of complement in man.
Two genes encoding steroid 21-hydroxylase [21-OHase; steroid 21-monooxygenase; steroid, hydrogen-donor: oxygen oxidoreductase (21-hydroxylating); EC 1.14.99.10], 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 T aq 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.
White
P C
PC
Grossberger
D
D
Onufer
B J
BJ
Chaplin
D D
DD
New
M I
MI
Dupont
B
B
Strominger
J L
JL
D002872:Chromosome Deletion; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D003181:Complement C4 / Q000235:genetics*; D004262:DNA Restriction Enzymes; D005784:Gene Amplification; D005796:Genes; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D009693:Nucleic Acid Hybridization; D013255:Steroid 21-Hydroxylase / Q000235:genetics*; D013250:Steroid Hydroxylases / Q000235:genetics*
D003181:Complement C4; D006680:HLA Antigens; D013250:Steroid Hydroxylases; D013255:Steroid 21-Hydroxylase; D004262:DNA Restriction Enzymes