Skip to main content
NCBI home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1987 Nov;41(5):925–932.

Exclusion of catalytic and regulatory subunits of cAMP-dependent protein kinase as candidate genes for the defect causing cystic fibrosis.

P Scambler 1, O Oyen 1, B Wainwright 1, M Farrall 1, H Y Law 1, X Estivill 1, M Sandberg 1, R Williamson 1, T Jahnsen 1
PMCID: PMC1684338  PMID: 3479018

Abstract

Cystic fibrosis (CF) is a common autosomal recessive disease with significant morbidity and mortality. Defects in cAMP control mechanisms are implicated in the pathophysiology of the disease. The mutation causing CF has been localized to chromosome 7q22-7q31.1. We have used (1) somatic-cell hybrids containing this region of the human genome in a mouse background and (2) segregation analysis in families to exclude both the genes coding for a catalytic subunit and three distinct regulatory subunits of cAMP-dependent protein kinase as candidates for the gene defect in CF. Two of these genes--those for the human homologue of the mouse type I regulatory subunit and the human homologue of the rat type II regulatory subunit--map to human chromosome 7.

Full text

PDF
925

Images in this article

928Fig. 1
on p.928
929Fig. 2
on p.929
929Fig. 3
on p.929

Selected References

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

  1. Beaudet A., Bowcock A., Buchwald M., Cavalli-Sforza L., Farrall M., King M. C., Klinger K., Lalouel J. M., Lathrop G., Naylor S. Linkage of cystic fibrosis to two tightly linked DNA markers: joint report from a collaborative study. Am J Hum Genet. 1986 Dec;39(6):681–693. [PMC free article] [PubMed] [Google Scholar]
  2. Croce C. M., Koprowski H. Somatic cell hybrids between mouse peritoneal macrophages and SV40-transformed human cells. I. Positive control of the transformed phenotype by the human chromosome 7 carrying the SV40 genome. J Exp Med. 1974 Nov 1;140(5):1221–1229. doi: 10.1084/jem.140.5.1221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Davies K. E., Gilliam T. C., Williamson R. Cystic fibrosis is not caused by a defect in the gene coding for human complement C3. Mol Biol Med. 1983 Sep;1(2):185–190. [PubMed] [Google Scholar]
  4. Davis P. B., Kaliner M. Autonomic nervous system abnormalities in cystic fibrosis. J Chronic Dis. 1983;36(3):269–278. doi: 10.1016/0021-9681(83)90062-0. [DOI] [PubMed] [Google Scholar]
  5. Eiberg H., Mohr J., Schmiegelow K., Nielsen L. S., Williamson R. Linkage relationships of paraoxonase (PON) with other markers: indication of PON-cystic fibrosis synteny. Clin Genet. 1985 Oct;28(4):265–271. doi: 10.1111/j.1399-0004.1985.tb00400.x. [DOI] [PubMed] [Google Scholar]
  6. Estivill X., Schmidtke J., Williamson R., Wainwright B. Chromosome assignment and restriction fragment length polymorphism analysis of the anonymous DNA probe B79a at 7q22 (HMG8 assignment D7S13). Hum Genet. 1986 Nov;74(3):320–322. doi: 10.1007/BF00282558. [DOI] [PubMed] [Google Scholar]
  7. Farrall M., Watson E., Bates G., Bell G., Bell J., Davies K. A., Estivill X., Kruyer H., Law H. Y., Lench N. Further data supporting linkage between cystic fibrosis and the met oncogene and haplotype analysis with met and pJ3.11. Am J Hum Genet. 1986 Dec;39(6):713–719. [PMC free article] [PubMed] [Google Scholar]
  8. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  9. Frizzell R. A., Rechkemmer G., Shoemaker R. L. Altered regulation of airway epithelial cell chloride channels in cystic fibrosis. Science. 1986 Aug 1;233(4763):558–560. doi: 10.1126/science.2425436. [DOI] [PubMed] [Google Scholar]
  10. Jahnsen T., Hedin L., Kidd V. J., Beattie W. G., Lohmann S. M., Walter U., Durica J., Schulz T. Z., Schiltz E., Browner M. Molecular cloning, cDNA structure, and regulation of the regulatory subunit of type II cAMP-dependent protein kinase from rat ovarian granulosa cells. J Biol Chem. 1986 Sep 15;261(26):12352–12361. [PubMed] [Google Scholar]
  11. Knowles B. B., Solter D., Trinchieri G., Maloney K. M., Ford S. R., Aden D. P. Complement-mediated antiserum cytotoxic reactions to human chromosome 7 coded antigen(s): immunoselection of rearranged human chromosome 7 in human-mouse somatic cell hybrids. J Exp Med. 1977 Feb 1;145(2):314–326. doi: 10.1084/jem.145.2.314. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Knowles M., Gatzy J., Boucher R. Relative ion permeability of normal and cystic fibrosis nasal epithelium. J Clin Invest. 1983 May;71(5):1410–1417. doi: 10.1172/JCI110894. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lathrop G. M., Lalouel J. M., Julier C., Ott J. Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3443–3446. doi: 10.1073/pnas.81.11.3443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lee D. C., Carmichael D. F., Krebs E. G., McKnight G. S. Isolation of a cDNA clone for the type I regulatory subunit of bovine cAMP-dependent protein kinase. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3608–3612. doi: 10.1073/pnas.80.12.3608. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. McPherson M. A., Dormer R. L., Bradbury N. A., Dodge J. A., Goodchild M. C. Defective beta-adrenergic secretory responses in submandibular acinar cells from cystic fibrosis patients. Lancet. 1986 Nov 1;2(8514):1007–1008. doi: 10.1016/s0140-6736(86)92616-4. [DOI] [PubMed] [Google Scholar]
  16. Park M., Dean M., Cooper C. S., Schmidt M., O'Brien S. J., Blair D. G., Vande Woude G. F. Mechanism of met oncogene activation. Cell. 1986 Jun 20;45(6):895–904. doi: 10.1016/0092-8674(86)90564-7. [DOI] [PubMed] [Google Scholar]
  17. Quinton P. M., Bijman J. Higher bioelectric potentials due to decreased chloride absorption in the sweat glands of patients with cystic fibrosis. N Engl J Med. 1983 May 19;308(20):1185–1189. doi: 10.1056/NEJM198305193082002. [DOI] [PubMed] [Google Scholar]
  18. Sato K., Sato F. Defective beta adrenergic response of cystic fibrosis sweat glands in vivo and in vitro. J Clin Invest. 1984 Jun;73(6):1763–1771. doi: 10.1172/JCI111385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Scambler P. J., Estivill X., Bell G., Farrall M., McLean C., Newman R., Little P. F., Frederick P., Hawley K., Wainwright B. J. Physical and genetic analysis of cosmids from the vicinity of the cystic fibrosis locus. Nucleic Acids Res. 1987 May 11;15(9):3639–3652. doi: 10.1093/nar/15.9.3639. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Scambler P. J., Law H. Y., Williamson R., Cooper C. S. Chromosome mediated gene transfer of six DNA markers linked to the cystic fibrosis locus on human chromosome seven. Nucleic Acids Res. 1986 Sep 25;14(18):7159–7174. doi: 10.1093/nar/14.18.7159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Scambler P. J., McPherson M. A., Bates G., Bradbury N. A., Dormer R. L., Williamson R. Biochemical and genetic exclusion of calmodulin as the site of the basic defect in cystic fibrosis. Hum Genet. 1987 Jul;76(3):278–282. doi: 10.1007/BF00283623. [DOI] [PubMed] [Google Scholar]
  22. Scambler P. J., Wainwright B. J., Farrall M., Bell J., Stanier P., Lench N. J., Bell G., Kruyer H., Ramirez F., Williamson R. Linkage of COL1A2 collagen gene to cystic fibrosis, and its clinical implications. Lancet. 1985 Nov 30;2(8466):1241–1242. doi: 10.1016/s0140-6736(85)90765-2. [DOI] [PubMed] [Google Scholar]
  23. Scambler P. J., Wainwright B. J., Watson E., Bates G., Bell G., Williamson R., Farrall M. Isolation of a further anonymous informative DNA sequence from chromosome seven closely linked to cystic fibrosis. Nucleic Acids Res. 1986 Mar 11;14(5):1951–1956. doi: 10.1093/nar/14.5.1951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Tsui L. C., Buchwald M., Barker D., Braman J. C., Knowlton R., Schumm J. W., Eiberg H., Mohr J., Kennedy D., Plavsic N. Cystic fibrosis locus defined by a genetically linked polymorphic DNA marker. Science. 1985 Nov 29;230(4729):1054–1057. doi: 10.1126/science.2997931. [DOI] [PubMed] [Google Scholar]
  25. Uhler M. D., Carmichael D. F., Lee D. C., Chrivia J. C., Krebs E. G., McKnight G. S. Isolation of cDNA clones coding for the catalytic subunit of mouse cAMP-dependent protein kinase. Proc Natl Acad Sci U S A. 1986 Mar;83(5):1300–1304. doi: 10.1073/pnas.83.5.1300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Wainwright B. J., Scambler P. J., Schmidtke J., Watson E. A., Law H. Y., Farrall M., Cooke H. J., Eiberg H., Williamson R. Localization of cystic fibrosis locus to human chromosome 7cen-q22. 1985 Nov 28-Dec 4Nature. 318(6044):384–385. doi: 10.1038/318384a0. [DOI] [PubMed] [Google Scholar]
  27. Wainwright B. J., Scambler P. J., Williamson R. Regional localization of three probes closely linked to the cystic fibrosis locus by deletion analysis. Cytogenet Cell Genet. 1987;44(2-3):101–102. doi: 10.1159/000132352. [DOI] [PubMed] [Google Scholar]
  28. Welsh M. J., Liedtke C. M. Chloride and potassium channels in cystic fibrosis airway epithelia. 1986 Jul 31-Aug 6Nature. 322(6078):467–470. doi: 10.1038/322467a0. [DOI] [PubMed] [Google Scholar]
  29. White R., Woodward S., Leppert M., O'Connell P., Hoff M., Herbst J., Lalouel J. M., Dean M., Vande Woude G. A closely linked genetic marker for cystic fibrosis. 1985 Nov 28-Dec 4Nature. 318(6044):382–384. doi: 10.1038/318382a0. [DOI] [PubMed] [Google Scholar]
  30. Widdicombe J. H., Welsh M. J., Finkbeiner W. E. Cystic fibrosis decreases the apical membrane chloride permeability of monolayers cultured from cells of tracheal epithelium. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6167–6171. doi: 10.1073/pnas.82.18.6167. [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