Two distinct areas of unequal crossingover within the steroid 21-hydroxylase genes produce absence of CYP21B
We mapped crossover sites in chimeric, recombinant CYP21 genes from six patients with salt-losing congenital adrenal hyperplasia (CAH). Nucleotide sequences unique to the CYP21A pseudogene or to the active CYP21B gene were mapped using gene-specific restriction sites and oligonucleotide hybridizatio...
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Veröffentlicht in: | Genomics (San Diego, Calif.) Calif.), 1989-10, Vol.5 (3), p.397-406 |
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Zusammenfassung: | We mapped crossover sites in chimeric, recombinant
CYP21 genes from six patients with salt-losing congenital adrenal hyperplasia (CAH). Nucleotide sequences unique to the
CYP21A pseudogene or to the active
CYP21B gene were mapped using gene-specific restriction sites and oligonucleotide hybridizations. Each chimeric
CYP21 gene in the
CYP21-deletion linked haplotypes contained sequences near the 5′ end that were characteristic of
CYP21A and only a single transition from sequences of
CYP21A to those of
CYP21B at the 3′ end. The transitions all occurred within either of two discrete regions (+470 to +999 and +1375 to +1993). All eight chimeric
CYP21 genes coupled with HLA-Bw47 in five unrelated patients had the
CYP21A-CYP21B sequence transition within the same gene region (+1375 to +1993). One of the three other “
CYP21B deletion” haplotypes (HLA-B7) had a sequence transition within this same region, while in the other two haplotypes (HLA-B61 and HLA-B18) the transition occurred between base pairs +470 and +999. By contrast, both
CYP21 genes in a haplotype containing a gene conversion of
CYP21B to
CYP21A contained apparent transitions between sequences of
CYP21A and
CYP21B. We conclude that a single, unequal crossingover between the
CYP21A and the
CYP21B genes yields deletion of the active
CYP21 gene and salt-losing CAH and that these crossingovers do not occur randomly within the
CYP21 genes of our patients. |
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ISSN: | 0888-7543 1089-8646 |
DOI: | 10.1016/0888-7543(89)90002-5 |