Skip to main content
PMC home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1988 Dec;43(6):922–928.

Gyrate atrophy of the choroid and retina: assignment of the ornithine aminotransferase structural gene to human chromosome 10 and mouse chromosome 7.

J J O'Donnell 1, K Vannas-Sulonen 1, T B Shows 1, D R Cox 1
PMCID: PMC1715611  PMID: 3195589

Abstract

Gyrate atrophy of the choroid and retina is an autosomal recessive, blinding human disease caused by a deficiency of the mitochondrial matrix enzyme ornithine aminotransferase (OAT). Since human OAT cDNA hybridizes to DNA sequences on both human chromosomes 10 and X, a locus coding for OAT enzyme activity may be present on one or both of these human chromosomes. We have used a series of mouse-human somatic cell hybrids, in combination with starch gel electrophoresis and a histochemical stain for OAT enzyme activity, to assign the structural gene for OAT to human chromosome 10. Our results suggest that the human X chromosome does not contain a locus coding for OAT enzyme activity. In addition, we have used a panel of Chinese hamster-mouse hybrids to assign the murine Oat structural gene to mouse chromosome 7. Our findings, combined with recent molecular studies, indicate that human OAT probes specific for chromosome 10 will be useful for the diagnosis and genetic counseling of individuals at risk for gyrate atrophy.

Full text

PDF

Images in this article

924Figure 1
on p.924

Selected References

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

  1. Barrett D. J., Bateman J. B., Sparkes R. S., Mohandas T., Klisak I., Inana G. Chromosomal localization of human ornithine aminotransferase gene sequences to 10q26 and Xp11.2. Invest Ophthalmol Vis Sci. 1987 Jul;28(7):1037–1042. [PubMed] [Google Scholar]
  2. Cox D. R., Epstein C. J. Comparative gene mapping of human chromosome 21 and mouse chromosome 16. Ann N Y Acad Sci. 1985;450:169–177. doi: 10.1111/j.1749-6632.1985.tb21491.x. [DOI] [PubMed] [Google Scholar]
  3. Cox D. R., Epstein L. B., Epstein C. J. Genes coding for sensitivity to interferon (IfRec) and soluble superoxide dismutase (SOD-1) are linked in mouse and man and map to mouse chromosome 16. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2168–2172. doi: 10.1073/pnas.77.4.2168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cox D. R., Sawicki J. A., Yee D., Appella E., Epstein C. J. Assignment of the gene for beta 2-microglobulin (B2m) to mouse chromosome 2. Proc Natl Acad Sci U S A. 1982 Mar;79(6):1930–1934. doi: 10.1073/pnas.79.6.1930. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hooper M., Hardy K., Handyside A., Hunter S., Monk M. HPRT-deficient (Lesch-Nyhan) mouse embryos derived from germline colonization by cultured cells. Nature. 1987 Mar 19;326(6110):292–295. doi: 10.1038/326292a0. [DOI] [PubMed] [Google Scholar]
  6. Inana G., Totsuka S., Redmond M., Dougherty T., Nagle J., Shiono T., Ohura T., Kominami E., Katunuma N. Molecular cloning of human ornithine aminotransferase mRNA. Proc Natl Acad Sci U S A. 1986 Mar;83(5):1203–1207. doi: 10.1073/pnas.83.5.1203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kennaway N. G., Weleber R. G., Buist N. R. Gyrate atrophy of choroid and retina: deficient activity of ornithine ketoacid aminotransferase in cultured skin fibroblasts. N Engl J Med. 1977 Nov 24;297(21):1180–1180. doi: 10.1056/nejm197711242972116. [DOI] [PubMed] [Google Scholar]
  8. Kuehn M. R., Bradley A., Robertson E. J., Evans M. J. A potential animal model for Lesch-Nyhan syndrome through introduction of HPRT mutations into mice. Nature. 1987 Mar 19;326(6110):295–298. doi: 10.1038/326295a0. [DOI] [PubMed] [Google Scholar]
  9. McCulloch J. C., Arshinoff S. A., Marliss E. B., Parker J. A. Hyperornithinemia and gyrate atrophy of the choroid and retina. Ophthalmology. 1978 Sep;85(9):918–928. doi: 10.1016/s0161-6420(78)35598-6. [DOI] [PubMed] [Google Scholar]
  10. Mitchell G. A., Brody L. C., Looney J., Steel G., Suchanek M., Dowling C., Der Kaloustian V., Kaiser-Kupfer M., Valle D. An initiator codon mutation in ornithine-delta-aminotransferase causing gyrate atrophy of the choroid and retina. J Clin Invest. 1988 Feb;81(2):630–633. doi: 10.1172/JCI113365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. O'Donnell J. J., Sandman R. P., Martin S. R. Deficient L-ornithine: 2-oxoacid aminotransferase activity in cultured fibroblasts from a patient with gyrate atrophy of the retina. Biochem Biophys Res Commun. 1977 Nov 21;79(2):396–399. doi: 10.1016/0006-291x(77)90170-x. [DOI] [PubMed] [Google Scholar]
  12. Ramesh V., Benoit L. A., Crawford P., Harvey P. T., Shows T. B., Shih V. E., Gusella J. F. The ornithine aminotransferase (OAT) locus: analysis of RFLPs in gyrate atrophy. Am J Hum Genet. 1988 Feb;42(2):365–372. [PMC free article] [PubMed] [Google Scholar]
  13. Ramesh V., Eddy R., Bruns G. A., Shih V. E., Shows T. B., Gusella J. F. Localization of the ornithine aminotransferase gene and related sequences on two human chromosomes. Hum Genet. 1987 Jun;76(2):121–126. doi: 10.1007/BF00284906. [DOI] [PubMed] [Google Scholar]
  14. Ramesh V., Shaffer M. M., Allaire J. M., Shih V. E., Gusella J. F. Investigation of gyrate atrophy using a cDNA clone for human ornithine aminotransferase. DNA. 1986 Dec;5(6):493–501. doi: 10.1089/dna.1.1986.5.493. [DOI] [PubMed] [Google Scholar]
  15. Ruddle F. H., Nichols E. A. Starch gel electrophoretic phenotypes of mouse times human somatic cell hybrids and mouse isozyme polymorphisms. In Vitro. 1971 Nov-Dec;7(3):120–131. doi: 10.1007/BF02617955. [DOI] [PubMed] [Google Scholar]
  16. Shih V. E., Berson E. L., Mandell R., Schmidt S. Y. Ornithine ketoacid transaminase deficiency in gyrate atrophy of the choroid and retina. Am J Hum Genet. 1978 Mar;30(2):174–179. [PMC free article] [PubMed] [Google Scholar]
  17. Shows T. B., Brown J. A., Haley L. L., Byers M. G., Eddy R. L., Cooper E. S., Goggin A. P. Assignment of the beta-glucuronidase structural gene to the pter leads to q22 region of chromosome 7 in man. Cytogenet Cell Genet. 1978;21(1-2):99–104. doi: 10.1159/000130882. [DOI] [PubMed] [Google Scholar]
  18. Shows T., Eddy R., Haley L., Byers M., Henry M., Fujita T., Matsui H., Taniguchi T. Interleukin 2 (IL2) is assigned to human chromosome 4. Somat Cell Mol Genet. 1984 May;10(3):315–318. doi: 10.1007/BF01535253. [DOI] [PubMed] [Google Scholar]
  19. Simell O., Takki K. Raised plasma-ornithine and gyrate atrophy of the choroid and retina. Lancet. 1973 May 12;1(7811):1031–1033. doi: 10.1016/s0140-6736(73)90667-3. [DOI] [PubMed] [Google Scholar]
  20. Takki K. K., Milton R. C. The natural history of gyrate atrophy of the choroid and retina. Ophthalmology. 1981 Apr;88(4):292–301. doi: 10.1016/s0161-6420(81)35031-3. [DOI] [PubMed] [Google Scholar]
  21. Thomas K. R., Capecchi M. R. Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell. 1987 Nov 6;51(3):503–512. doi: 10.1016/0092-8674(87)90646-5. [DOI] [PubMed] [Google Scholar]
  22. Trijbels J. M., Sengers R. C., Bakkeren J. A., De Kort A. F., Deutman A. F. L-Ornithine-ketoacid-transaminase deficiency in cultured fibroblasts of a patient with hyperornithinaemia and gyrate atrophy of the choroid and retina. Clin Chim Acta. 1977 Sep 1;79(2):371–377. doi: 10.1016/0009-8981(77)90431-4. [DOI] [PubMed] [Google Scholar]
  23. Valle D., Kaiser-Kupfer M. I., Del Valle L. A. Gyrate atrophy of the choroid and retina: deficiency of ornithine aminotransferase in transformed lymphocytes. Proc Natl Acad Sci U S A. 1977 Nov;74(11):5159–5161. doi: 10.1073/pnas.74.11.5159. [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