Mapping of steroid 21-hydroxylase genes adjacent to complement component C4 genes in HLA, the major histocompatibility complex in man.

TLDR

Complement component genes in the human HLA region have been mapped, and hybridization with adrenal mRNA suggests an adjacent adrenal‑expressed gene near the C4A and C4B loci. Sequencing a 430‑bp fragment and comparing it to cytochrome P‑450 21‑hydroxylase sequences from bovine, porcine, and rat identified the gene as human steroid 21‑hydroxylase, with mapping aided by a bovine‑based synthetic oligonucleotide. The 2.4‑kb mRNA fragment hybridizes to a 4.5‑kb duplicated genomic region located approximately 1.5‑kb downstream of both C4A and C4B.

Abstract

The genes for four components (C) of complement in the human major histocompatibility complex (HLA) have been aligned previously in a series of overlapping cosmid cloned inserts. Those inserts, which contained the two C4 genes C4A and C4B, hybridized with human adrenal mRNA, indicating that they contain a gene expressed in the adrenal. The mRNA fraction of 2.4 kilobases (kb) hybridizes with genomic DNA of 4.5 kb, which is duplicated and lies about 1.5 kb 3' of both the C4A and the C4B complement genes. Sequencing of a 430-base section and comparison with the published cDNA sequence of bovine cytochrome P-450 21-hydroxylase, peptide sequences of porcine 21-hydroxylase, and a cDNA sequence of a rat liver cytochrome P-450 identified the gene as coding for human steroid 21-hydroxylase [steroid,hydrogen-donor:oxygen oxidoreductase (21-hydroxylating), EC 1.14.99.10]. Mapping of the gene was helped by use of a synthetic oligonucleotide based on the bovine cDNA sequence.