Skip to main content
NCBI home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1988 Jan;42(1):17–25.

Evidence for frequent gene conversion in the steroid 21-hydroxylase P-450(C21) gene: implications for steroid 21-hydroxylase deficiency.

Y Higashi 1, A Tanae 1, H Inoue 1, Y Fujii-Kuriyama 1
PMCID: PMC1715324  PMID: 2827462

Abstract

Oligonucleotide probes specific for the deleterious mutations harbored in the P-450(C21)A pseudogene and oligonucleotide probes specific for the corresponding sequences in the B gene were prepared to examine the molecular lesions in the P-450(C21) gene of P-450(C21)-deficient patients. Using these gene-specific probes, we performed Southern blot analyses of genomic DNAs from 11 patients and eight normal individuals. At least one allele of the B gene (the 3.7-kb TaqI fragment) in a patient was inactivated by mutations caused by recombination with the A gene. The A genes in normal individuals and patients seemed to be replaced frequently (i.e., 10/19 individuals) in their 3' portions by B gene sequences. All of these alterations occurred without changing the characteristic length (3.2 kb) of the TaqI fragment of the A gene, a result strongly suggesting that frequent gene conversions and/or intragenic recombinations have happened in the P-450(C21) genes. Densitometric analysis of the autoradiograms from hybridization experiments revealed extensive variation (from one to five copies) in the copy number of the A gene (the 3.2-kb TaqI fragment) whereas that of the B gene (the 3.7-kb TaqI fragment) was relatively constant at two or three copies.

Full text

PDF
17

Images in this article

20Figure 1
on p.20
24Figure 4
on p.24

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amos D. B., Bashir H., Boyle W., MacQueen M., Tiilikainen A. A simple micro cytotoxicity test. Transplantation. 1969 Mar;7(3):220–223. doi: 10.1097/00007890-196903000-00023. [DOI] [PubMed] [Google Scholar]
  2. Carroll M. C., Campbell R. D., Porter R. R. Mapping of steroid 21-hydroxylase genes adjacent to complement component C4 genes in HLA, the major histocompatibility complex in man. Proc Natl Acad Sci U S A. 1985 Jan;82(2):521–525. doi: 10.1073/pnas.82.2.521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Donohoue P. A., van Dop C., McLean R. H., White P. C., Jospe N., Migeon C. J. Gene conversion in salt-losing congenital adrenal hyperplasia with absent complement C4B protein. J Clin Endocrinol Metab. 1986 May;62(5):995–1002. doi: 10.1210/jcem-62-5-995. [DOI] [PubMed] [Google Scholar]
  4. Dupont B., Oberfield S. E., Smithwick E. M., Lee T. D., Levine L. S. Close genetic linkage between HLA and congenital adrenal hyperplasia (21-hydroxylase deficiency). Lancet. 1977 Dec 24;2(8052-8053):1309–1312. doi: 10.1016/s0140-6736(77)90362-2. [DOI] [PubMed] [Google Scholar]
  5. Gutai J. P., Kowarski A. A., Migeon C. J. The detection of the heterozygous carrier for congenital virilizing adrenal hyperplasia. J Pediatr. 1977 Jun;90(6):924–929. doi: 10.1016/s0022-3476(77)80560-x. [DOI] [PubMed] [Google Scholar]
  6. Higashi Y., Yoshioka H., Yamane M., Gotoh O., Fujii-Kuriyama Y. Complete nucleotide sequence of two steroid 21-hydroxylase genes tandemly arranged in human chromosome: a pseudogene and a genuine gene. Proc Natl Acad Sci U S A. 1986 May;83(9):2841–2845. doi: 10.1073/pnas.83.9.2841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Miyada C. G., Klofelt C., Reyes A. A., McLaughlin-Taylor E., Wallace R. B. Evidence that polymorphism in the murine major histocompatibility complex may be generated by the assortment of subgene sequences. Proc Natl Acad Sci U S A. 1985 May;82(9):2890–2894. doi: 10.1073/pnas.82.9.2890. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. New M. I., Levine L. S. Recent advances in 21-hydroxylase deficiency. Annu Rev Med. 1984;35:649–663. doi: 10.1146/annurev.me.35.020184.003245. [DOI] [PubMed] [Google Scholar]
  9. Shiroishi T., Sagai T., Natsuume-Sakai S., Moriwaki K. Lethal deletion of the complement component C4 and steroid 21-hydroxylase genes in the mouse H-2 class III region, caused by meiotic recombination. Proc Natl Acad Sci U S A. 1987 May;84(9):2819–2823. doi: 10.1073/pnas.84.9.2819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  11. Speiser P. W., Dupont B., Rubinstein P., Piazza A., Kastelan A., New M. I. High frequency of nonclassical steroid 21-hydroxylase deficiency. Am J Hum Genet. 1985 Jul;37(4):650–667. [PMC free article] [PubMed] [Google Scholar]
  12. Werkmeister J. W., New M. I., Dupont B., White P. C. Frequent deletion and duplication of the steroid 21-hydroxylase genes. Am J Hum Genet. 1986 Oct;39(4):461–469. [PMC free article] [PubMed] [Google Scholar]
  13. White P. C., Grossberger D., Onufer B. J., Chaplin D. D., New M. I., Dupont B., Strominger J. L. Two genes encoding steroid 21-hydroxylase are located near the genes encoding the fourth component of complement in man. Proc Natl Acad Sci U S A. 1985 Feb;82(4):1089–1093. doi: 10.1073/pnas.82.4.1089. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. White P. C., New M. I., Dupont B. HLA-linked congenital adrenal hyperplasia results from a defective gene encoding a cytochrome P-450 specific for steroid 21-hydroxylation. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7505–7509. doi: 10.1073/pnas.81.23.7505. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES