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Two 21-hydroxylase [P-450(C21)] genes have been isolated from a human genomic library using a bovine P-450(C21) cDNA. The insert DNAs containing the P-450(C21) genes were also hybridized with the sequences of the 5' or 3' end regions of human C4 cDNA, indicating a close linkage of the P-450(C21) gene to the C4 gene. Sequence analysis has revealed that the two P-450(C21) genes are both approximately equal to 3.4 kilobases long and split into 10 exons. Comparing the two sequences, we found that the two genes are highly homologous including their introns and flanking sequences, but that three mutations render one of the two P-450(C21) genes nonfunctional--1 base insertion, an 8-base deletion, and a transition mutation--all of which may cause premature termination of the translation. Tandem arrangement of the highly homologous pseudo- and genuine genes in close proximity could account for the high incidence of P-450(C21) gene deficiency by homologous gene recombination.

Complete nucleotide sequence of two steroid 21-hydroxylase genes tandemly arranged in human chromosome: a pseudogene and a genuine gene.