Skip to main content
PMC home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1981 Jan;33(1):25–35.

Population heterogeneity of the Hpa I restriction site associated with the beta globin gene: implications for prenatal diagnosis.

S R Panny, A F Scott, K D Smith, J A Phillips 3rd, H H Kazazian Jr, C C Talbot Jr, C D Boehm
PMCID: PMC1684869  PMID: 6162380

Abstract

The Hpa I restriction endonuclease site polymorphism that results in some human beta globin genes being contained in a 13-kilobase (kb) DNA restriction fragment rather than in the usual 7.6-kb fragment has been reported to be in linkage disequilibrium with the beta S mutation. The frequency of the 13-kb fragment among Baltimore black sickle cell (SS) disease patients (58%) is lower than that reported for San Francisco black SS disease patients (87%) and similar to that reported for such New York patients (59%). There is, then, considerable heterogeneity among American black populations. Therefore, for the purposes of prenatal diagnosis, the frequency in the particular population at risk should be established. When the frequency of association of the 13-kb fragment and the beta S mutation is low, the linkage phase must also be established. When the linkage phase is known, the Hpa I pattern alone can exclude SS disease 54% of the time for Baltimore AS X AS couples.

Full text

PDF
26

Images in this article

28Fig. 2
on p.28

Selected References

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

  1. Alter B. P., Modell C. B., Fairweather D., Hobbins J. C., Mahoney M. J., Frigoletto F. D., Sherman A. S., Nathan D. G. Prenatal diagnosis of hemoglobinopathies. A review of 15 cases. N Engl J Med. 1976 Dec 23;295(26):1437–1443. doi: 10.1056/NEJM197612232952601. [DOI] [PubMed] [Google Scholar]
  2. Alter B. P. Prenatal diagnosis of hemoglobinopathies and other hematologic diseases. J Pediatr. 1979 Oct;95(4):501–503. doi: 10.1016/s0022-3476(79)80753-2. [DOI] [PubMed] [Google Scholar]
  3. COOPER A. J., BLUMBERG B. S., WORKMAN P. L., MCDONOUGH J. R. BIOCHEMICAL POLYMORPHIC TRAITS IN A U. S. WHITE AND NEGRO POPULATION. Am J Hum Genet. 1963 Dec;15:420–428. [PMC free article] [PubMed] [Google Scholar]
  4. Deisseroth A., Nienhuis A., Lawrence J., Giles R., Turner P., Ruddle F. H. Chromosomal localization of human beta globin gene on human chromosome 11 in somatic cell hybrids. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1456–1460. doi: 10.1073/pnas.75.3.1456. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Feldenzer J., Mears J. G., Burns A. L., Natta C., Bank A. Heterogeneity of DNA fragments associated with the sickle-globin gene. J Clin Invest. 1979 Sep;64(3):751–755. doi: 10.1172/JCI109519. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Flavell R. A., Kooter J. M., De Boer E., Little P. F., Williamson R. Analysis of the beta-delta-globin gene loci in normal and Hb Lepore DNA: direct determination of gene linkage and intergene distance. Cell. 1978 Sep;15(1):25–41. doi: 10.1016/0092-8674(78)90080-6. [DOI] [PubMed] [Google Scholar]
  7. GLASS B., LI C. C. The dynamics of racial intermixture; an analysis based on the American Negro. Am J Hum Genet. 1953 Mar;5(1):1–20. [PMC free article] [PubMed] [Google Scholar]
  8. Hobbins J. C., Mahoney M. J. In utero diagnosis of hemoglobinopathies. Technic for obtaining fetal blood. N Engl J Med. 1974 May 9;290(19):1065–1067. doi: 10.1056/NEJM197405092901908. [DOI] [PubMed] [Google Scholar]
  9. Jeffreys A. J. DNA sequence variants in the G gamma-, A gamma-, delta- and beta-globin genes of man. Cell. 1979 Sep;18(1):1–10. doi: 10.1016/0092-8674(79)90348-9. [DOI] [PubMed] [Google Scholar]
  10. Jeffreys A. J., Flavell R. A. A physical map of the DNA regions flanking the rabbit beta-globin gene. Cell. 1977 Oct;12(2):429–439. doi: 10.1016/0092-8674(77)90119-2. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. Kazazian H. H., Jr, Dover G. L., Lightbody K. L., Park I. J. Prenatal diagnosis in a fetus at risk for hemoglobin S-O Arab disease. J Pediatr. 1978 Sep;93(3):502–504. doi: 10.1016/s0022-3476(78)81179-2. [DOI] [PubMed] [Google Scholar]
  14. Kirby K. S., Cook E. A. Isolation of deoxyribonucleic acid from mammalian tissues. Biochem J. 1967 Jul;104(1):254–257. doi: 10.1042/bj1040254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kunkel L. M., Smith K. D., Boyer S. H., Borgaonkar D. S., Wachtel S. S., Miller O. J., Breg W. R., Jones H. W., Jr, Rary J. M. Analysis of human Y-chromosome-specific reiterated DNA in chromosome variants. Proc Natl Acad Sci U S A. 1977 Mar;74(3):1245–1249. doi: 10.1073/pnas.74.3.1245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kurnit D. M. Evolution of sickle variant gene. Lancet. 1979 Jan;1(8107):104–104. doi: 10.1016/s0140-6736(79)90093-x. [DOI] [PubMed] [Google Scholar]
  17. Kurnit D. M., Hoehn H. Prenatal diagnosis of human genome variation. Annu Rev Genet. 1979;13:235–258. doi: 10.1146/annurev.ge.13.120179.001315. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. 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]
  20. Reed T. E. Caucasian genes in American Negroes. Science. 1969 Aug 22;165(3895):762–768. doi: 10.1126/science.165.3895.762. [DOI] [PubMed] [Google Scholar]
  21. Schachat F. H., Hogness D. S. Repetitive sequences in isolated Thomas circles from Drosophila melanogaster. Cold Spring Harb Symp Quant Biol. 1974;38:371–381. doi: 10.1101/sqb.1974.038.01.040. [DOI] [PubMed] [Google Scholar]
  22. Scott A. F., Phillips J. A., 3rd, Migeon B. R. DNA restriction endonuclease analysis for localization of human beta- and delta-globin genes on chromosome 11. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4563–4565. doi: 10.1073/pnas.76.9.4563. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. WORKMAN P. L., BLUMBERG B. S., COOPER A. J. SELECTION, GENE MIGRATION AND POLYMORPHIC STABILITY IN A U. S. WHITE AND NEGRO POPULATION. Am J Hum Genet. 1963 Dec;15:429–437. [PMC free article] [PubMed] [Google Scholar]
  25. Wilson J. T., Wilson L. B., deRiel J. K., Villa-komaroff L., Efstratiadis A., Forget B. G., Weissman S. M. Insertion of synthetic copies of human globin genes into bacterial plasmids. Nucleic Acids Res. 1978 Feb;5(2):563–581. doi: 10.1093/nar/5.2.563. [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