Skip to main content
PMC home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1992 Oct;51(4):736–740.

Mutation analysis of the cystic fibrosis transmembrane regulator gene in native American populations of the southwest

Theresa A Grebe, Winifred W Doane, Sarah F Richter, Carol Clericuzio, R A Norman, William K Seltzer, Susan N Rhodes, Bruce E Goldberg, Lucy S Hernried, Melody McClure, Gail Kaplan
PMCID: PMC1682804  PMID: 1384321

Abstract

We report DNA and clinical analyses of cystic fibrosis (CF) in two previously unstudied, genetically isolated populations: Pueblo and Navajo Native Americans. Direct mutation analysis of six mutations of the CFTR gene–namely, ΔF508, G542X, G551D, R553X, N1303K, and W1282X–was performed on PCR-amplified genomic DNA extracted from blood samples. Haplotype analyses with marker/enzyme pairs XV2c/TaqI and KM19/PstI were performed as well. Of the 12 affected individuals studied, no ΔF508 mutation was detected; only one G542X mutation was found. None of the other mutations was detected. All affected individuals have either an AA, AC, or CC haplotype, except for the one carrying the G542X mutation, who has the haplotype AB. Clinically, six of the affected individuals examined exhibit growth deficiency, and five (all from the Zuni Pueblo) have a severe CF phenotype. Four of the six Zunis with CF are also micro-cephalic, a finding not previously noted in CF patients. Our DNA data have serious implications for risk assessment of CF carrier status for these people.

Full text

PDF
737

Selected References

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

  1. Beaudet A. L., Feldman G. L., Fernbach S. D., Buffone G. J., O'Brien W. E. Linkage disequilibrium, cystic fibrosis, and genetic counseling. Am J Hum Genet. 1989 Mar;44(3):319–326. [PMC free article] [PubMed] [Google Scholar]
  2. Cutting G. R., Kasch L. M., Rosenstein B. J., Zielenski J., Tsui L. C., Antonarakis S. E., Kazazian H. H., Jr A cluster of cystic fibrosis mutations in the first nucleotide-binding fold of the cystic fibrosis conductance regulator protein. Nature. 1990 Jul 26;346(6282):366–369. doi: 10.1038/346366a0. [DOI] [PubMed] [Google Scholar]
  3. Estivill X., Chillon M., Casals T., Bosch A., Morral N., Nunes V., Gasparini P., Seia A., Pignatti P. F., Novelli G. Delta F508 gene deletion in cystic fibrosis in southern Europe. Lancet. 1989 Dec 9;2(8676):1404–1404. doi: 10.1016/s0140-6736(89)92024-2. [DOI] [PubMed] [Google Scholar]
  4. Gasparini P., Nunes V., Savoia A., Dognini M., Morral N., Gaona A., Bonizzato A., Chillon M., Sangiuolo F., Novelli G. The search for south European cystic fibrosis mutations: identification of two new mutations, four variants, and intronic sequences. Genomics. 1991 May;10(1):193–200. doi: 10.1016/0888-7543(91)90500-e. [DOI] [PubMed] [Google Scholar]
  5. Kerem B. S., Zielenski J., Markiewicz D., Bozon D., Gazit E., Yahav J., Kennedy D., Riordan J. R., Collins F. S., Rommens J. M. Identification of mutations in regions corresponding to the two putative nucleotide (ATP)-binding folds of the cystic fibrosis gene. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8447–8451. doi: 10.1073/pnas.87.21.8447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kerem B., Rommens J. M., Buchanan J. A., Markiewicz D., Cox T. K., Chakravarti A., Buchwald M., Tsui L. C. Identification of the cystic fibrosis gene: genetic analysis. Science. 1989 Sep 8;245(4922):1073–1080. doi: 10.1126/science.2570460. [DOI] [PubMed] [Google Scholar]
  7. Lemna W. K., Feldman G. L., Kerem B., Fernbach S. D., Zevkovich E. P., O'Brien W. E., Riordan J. R., Collins F. S., Tsui L. C., Beaudet A. L. Mutation analysis for heterozygote detection and the prenatal diagnosis of cystic fibrosis. N Engl J Med. 1990 Feb 1;322(5):291–296. doi: 10.1056/NEJM199002013220503. [DOI] [PubMed] [Google Scholar]
  8. Miller S. A., Dykes D. D., Polesky H. F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988 Feb 11;16(3):1215–1215. doi: 10.1093/nar/16.3.1215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Osborne L., Knight R., Santis G., Hodson M. A mutation in the second nucleotide binding fold of the cystic fibrosis gene. Am J Hum Genet. 1991 Mar;48(3):608–612. [PMC free article] [PubMed] [Google Scholar]
  10. Riordan J. R., Rommens J. M., Kerem B., Alon N., Rozmahel R., Grzelczak Z., Zielenski J., Lok S., Plavsic N., Chou J. L. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science. 1989 Sep 8;245(4922):1066–1073. doi: 10.1126/science.2475911. [DOI] [PubMed] [Google Scholar]
  11. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  12. Vidaud M., Fanen P., Martin J., Ghanem N., Nicolas S., Goossens M. Three point mutations in the CFTR gene in French cystic fibrosis patients: identification by denaturing gradient gel electrophoresis. Hum Genet. 1990 Sep;85(4):446–449. doi: 10.1007/BF02428305. [DOI] [PubMed] [Google Scholar]

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

RESOURCES