Skip to main content
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1985 Jan;37(1):42–51.

Discrimination among the human beta A, beta S, and beta C-globin genes using allele-specific oligonucleotide hybridization probes.

A B Studencki, B J Conner, C C Impraim, R L Teplitz, R B Wallace
PMCID: PMC1684544  PMID: 2983543

Abstract

Synthetic nonadecanucleotides complementary to the human beta A-, beta S-, or beta C-globin sequences were used as hybridization probes to screen human genomic DNA samples for these genes. The oligonucleotides were 32P-labeled and used as probes to genotype restriction endonuclease digests of human genomic DNA. The data obtained show that hybridization with oligonucleotide probes, unlike restriction fragment length polymorphism (RFLP) analysis or direct restriction enzyme digestion, can be used to directly distinguish among the three alleles of beta-globin, beta A, beta S, and beta C, when present either in one (heterozygous) or two copies.

Full text

PDF
42

Images in this article

Selected References

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

  1. Antonarakis S. E., Boehm C. D., Giardina P. J., Kazazian H. H., Jr Nonrandom association of polymorphic restriction sites in the beta-globin gene cluster. Proc Natl Acad Sci U S A. 1982 Jan;79(1):137–141. doi: 10.1073/pnas.79.1.137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baird M., Driscoll C., Schreiner H., Sciarratta G. V., Sansone G., Niazi G., Ramirez F., Bank A. A nucleotide change at a splice junction in the human beta-globin gene is associated with beta 0-thalassemia. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4218–4221. doi: 10.1073/pnas.78.7.4218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chang J. C., Kan Y. W. A sensitive new prenatal test for sickle-cell anemia. N Engl J Med. 1982 Jul 1;307(1):30–32. doi: 10.1056/NEJM198207013070105. [DOI] [PubMed] [Google Scholar]
  4. Chang J. C., Kan Y. W. Antenatal diagnosis of sickle cell anaemia by direct analysis of the sickle mutation. Lancet. 1981 Nov 21;2(8256):1127–1129. doi: 10.1016/s0140-6736(81)90584-5. [DOI] [PubMed] [Google Scholar]
  5. Conner B. J., Reyes A. A., Morin C., Itakura K., Teplitz R. L., Wallace R. B. Detection of sickle cell beta S-globin allele by hybridization with synthetic oligonucleotides. Proc Natl Acad Sci U S A. 1983 Jan;80(1):278–282. doi: 10.1073/pnas.80.1.278. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Geever R. F., Wilson L. B., Nallaseth F. S., Milner P. F., Bittner M., Wilson J. T. Direct identification of sickle cell anemia by blot hybridization. Proc Natl Acad Sci U S A. 1981 Aug;78(8):5081–5085. doi: 10.1073/pnas.78.8.5081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kan Y. W., Dozy A. M. Antenatal diagnosis of sickle-cell anaemia by D.N.A. analysis of amniotic-fluid cells. Lancet. 1978 Oct 28;2(8096):910–912. doi: 10.1016/s0140-6736(78)91629-x. [DOI] [PubMed] [Google Scholar]
  8. Kan Y. W., Dozy A. M. Evolution of the hemoglobin S and C genes in world populations. Science. 1980 Jul 18;209(4454):388–391. doi: 10.1126/science.7384810. [DOI] [PubMed] [Google Scholar]
  9. Kan Y. W., Dozy A. M. Polymorphism of DNA sequence adjacent to human beta-globin structural gene: relationship to sickle mutation. Proc Natl Acad Sci U S A. 1978 Nov;75(11):5631–5635. doi: 10.1073/pnas.75.11.5631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kan Y. W., Lee K. Y., Furbetta M., Angius A., Cao A. Polymorphism of DNA sequence in the beta-globin gene region. Application to prenatal diagnosis of beta 0 thalassemia in Sardinia. N Engl J Med. 1980 Jan 24;302(4):185–188. doi: 10.1056/NEJM198001243020401. [DOI] [PubMed] [Google Scholar]
  11. Kazazian H. H., Jr, Orkin S. H., Boehm C. D., Sexton J. P., Antonarakis S. E. beta-Thalassemia due to a deletion of the nucleotide which is substituted in the beta S-globin gene. Am J Hum Genet. 1983 Sep;35(5):1028–1033. [PMC free article] [PubMed] [Google Scholar]
  12. Kidd V. J., Wallace R. B., Itakura K., Woo S. L. alpha 1-antitrypsin deficiency detection by direct analysis of the mutation in the gene. Nature. 1983 Jul 21;304(5923):230–234. doi: 10.1038/304230a0. [DOI] [PubMed] [Google Scholar]
  13. Orkin S. H., Little P. F., Kazazian H. H., Jr, Boehm C. D. Improved detection of the sickle mutation by DNA analysis: application to prenatal diagnosis. N Engl J Med. 1982 Jul 1;307(1):32–36. doi: 10.1056/NEJM198207013070106. [DOI] [PubMed] [Google Scholar]
  14. Orkin S. H., Markham A. F., Kazazian H. H., Jr Direct detection of the common Mediterranean beta-thalassemia gene with synthetic DNA probes. An alternative approach for prenatal diagnosis. J Clin Invest. 1983 Mar;71(3):775–779. doi: 10.1172/JCI110826. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Phillips J. A., 3rd, Panny S. R., Kazazian H. H., Jr, Boehm C. D., Scott A. F., Smith K. D. Prenatal diagnosis of sickle cell anemia by restriction and endonuclease analysis: HindIII polymorphisms in gamma-globin genes extend test applicability. Proc Natl Acad Sci U S A. 1980 May;77(5):2853–2856. doi: 10.1073/pnas.77.5.2853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Phillips J. A., 3rd, Scott A. F., Kazazian H. H., Jr, Smith K. D., Stetten G., Thomas G. H. Prenatal diagnosis of hemoglobinopathies by restriction endonuclease analysis: pregnancies at risk for sickle cell anemia and S--O Arab disease. Johns Hopkins Med J. 1979 Aug;145(2):57–60. [PubMed] [Google Scholar]
  17. Pirastu M., Kan Y. W., Cao A., Conner B. J., Teplitz R. L., Wallace R. B. Prenatal diagnosis of beta-thalassemia. Detection of a single nucleotide mutation in DNA. N Engl J Med. 1983 Aug 4;309(5):284–287. doi: 10.1056/NEJM198308043090506. [DOI] [PubMed] [Google Scholar]
  18. Studencki A. B., Wallace R. B. Allele-specific hybridization using oligonucleotide probes of very high specific activity: discrimination of the human beta A- and beta S-globin genes. DNA. 1984;3(1):7–15. doi: 10.1089/dna.1.1984.3.7. [DOI] [PubMed] [Google Scholar]
  19. Tan Z. K., Ikuta S., Huang T., Dugaiczyk A., Itakura K. Solid-phase synthesis of polynucleotides. VIII: A simplified synthesis of oligodeoxyribonucleotides. Cold Spring Harb Symp Quant Biol. 1983;47(Pt 1):383–391. doi: 10.1101/sqb.1983.047.01.045. [DOI] [PubMed] [Google Scholar]
  20. Wallace R. B., Schold M., Johnson M. J., Dembek P., Itakura K. Oligonucleotide directed mutagenesis of the human beta-globin gene: a general method for producing specific point mutations in cloned DNA. Nucleic Acids Res. 1981 Aug 11;9(15):3647–3656. doi: 10.1093/nar/9.15.3647. [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