Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1983 Aug;80(15):4808–4812. doi: 10.1073/pnas.80.15.4808

Recombination within and between the human insulin and beta-globin gene loci.

R V Lebo, A Chakravarti, K H Buetow, M C Cheung, H Cann, B Cordell, H Goodman
PMCID: PMC384134  PMID: 6348773

Abstract

We detected a large number of polymorphic insulin restriction fragments in black Americans. These different size fragments were probably generated by unequal recombination on both sides of the human insulin gene. Population genetic analysis indicates that recombination occurred 33 times more frequently than expected to generate this large number of polymorphic fragments. Specific properties of the unique repeated 14- to 16-base-pair sequences 5' to the insulin gene suggest that this sequence would promote increased unequal recombination. Additional pedigree analysis showed that the recombination rate between the structural insulin and beta-globin gene loci was 14% with strong evidence for linkage. Since both insulin and beta-globin have been mapped to the short arm of human chromosome 11, this study establishes that the genetic map distance between these genes is 14.2 centimorgans.

Full text

PDF
4811

Selected References

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

  1. BAGLIONI C. The fusion of two peptide chains in hemoglobin Lepore and its interpretation as a genetic deletion. Proc Natl Acad Sci U S A. 1962 Nov 15;48:1880–1886. doi: 10.1073/pnas.48.11.1880. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bell G. I., Karam J. H., Rutter W. J. Polymorphic DNA region adjacent to the 5' end of the human insulin gene. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5759–5763. doi: 10.1073/pnas.78.9.5759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bell G. I., Pictet R. L., Rutter W. J., Cordell B., Tischer E., Goodman H. M. Sequence of the human insulin gene. Nature. 1980 Mar 6;284(5751):26–32. doi: 10.1038/284026a0. [DOI] [PubMed] [Google Scholar]
  4. Bell G. I., Selby M. J., Rutter W. J. The highly polymorphic region near the human insulin gene is composed of simple tandemly repeating sequences. Nature. 1982 Jan 7;295(5844):31–35. doi: 10.1038/295031a0. [DOI] [PubMed] [Google Scholar]
  5. Biezunski N. Structure and distribution of inverted repeats (palindromes). II. Analysis of DNA of the mouse. Chromosoma. 1981;84(1):111–129. doi: 10.1007/BF00293366. [DOI] [PubMed] [Google Scholar]
  6. Bridges C B, Olbrycht T M. The Multiple Stock "Xple" and Its Use. Genetics. 1926 Jan;11(1):41–56. doi: 10.1093/genetics/11.1.41. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Craighead J. E. Current views on the etiology of insulin-dependent diabetes mellitus. N Engl J Med. 1978 Dec 28;299(26):1439–1445. doi: 10.1056/NEJM197812282992605. [DOI] [PubMed] [Google Scholar]
  8. Embury S. H., Miller J. A., Dozy A. M., Kan Y. W., Chan V., Todd D. Two different molecular organizations account for the single alpha-globin gene of the alpha-thalassemia-2 genotype. J Clin Invest. 1980 Dec;66(6):1319–1325. doi: 10.1172/JCI109984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ewens W. J. The sampling theory of selectively neutral alleles. Theor Popul Biol. 1972 Mar;3(1):87–112. doi: 10.1016/0040-5809(72)90035-4. [DOI] [PubMed] [Google Scholar]
  10. FORD C. E., HAMERTON J. L. The chromosomes of man. Nature. 1956 Nov 10;178(4541):1020–1023. doi: 10.1038/1781020a0. [DOI] [PubMed] [Google Scholar]
  11. Farabaugh P. J., Schmeissner U., Hofer M., Miller J. H. Genetic studies of the lac repressor. VII. On the molecular nature of spontaneous hotspots in the lacI gene of Escherichia coli. J Mol Biol. 1978 Dec 25;126(4):847–857. doi: 10.1016/0022-2836(78)90023-2. [DOI] [PubMed] [Google Scholar]
  12. Faugeron-Fonty G., Culard F., Baldacci G., Goursot R., Prunell A., Bernardi G. The mitochondrial genome of wild-type yeast cells. VIII. The spontaneous cytoplasmic "petite" mutation. J Mol Biol. 1979 Nov 5;134(3):493–457. doi: 10.1016/0022-2836(79)90365-6. [DOI] [PubMed] [Google Scholar]
  13. Goossens M., Dozy A. M., Embury S. H., Zachariades Z., Hadjiminas M. G., Stamatoyannopoulos G., Kan Y. W. Triplicated alpha-globin loci in humans. Proc Natl Acad Sci U S A. 1980 Jan;77(1):518–521. doi: 10.1073/pnas.77.1.518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Goossens M., Kan Y. Y. DNA analysis in the diagnosis of hemoglobin disorders. Methods Enzymol. 1981;76:805–817. doi: 10.1016/0076-6879(81)76159-7. [DOI] [PubMed] [Google Scholar]
  15. Gusella J., Varsanyi-Breiner A., Kao F. T., Jones C., Puck T. T., Keys C., Orkin S., Housman D. Precise localization of human beta-globin gene complex on chromosome 11. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5239–5242. doi: 10.1073/pnas.76.10.5239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Harper M. E., Ullrich A., Saunders G. F. Localization of the human insulin gene to the distal end of the short arm of chromosome 11. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4458–4460. doi: 10.1073/pnas.78.7.4458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hultén M. Chiasma distribution at diakinesis in the normal human male. Hereditas. 1974;76(1):55–78. doi: 10.1111/j.1601-5223.1974.tb01177.x. [DOI] [PubMed] [Google Scholar]
  18. KIMURA M., CROW J. F. THE NUMBER OF ALLELES THAT CAN BE MAINTAINED IN A FINITE POPULATION. Genetics. 1964 Apr;49:725–738. doi: 10.1093/genetics/49.4.725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. 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]
  21. Kendall A. G., Ojwang P. J., Schroeder W. A., Huisman T. H. Hemoglobin Kenya, the product of a gamma-beta fusion gene: studies of the family. Am J Hum Genet. 1973 Sep;25(5):548–563. [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Lebo R. V., Carrano A. V., Burkhart-Schultz K., Dozy A. M., Yu L. C., Kan Y. W. Assignment of human beta-, gamma-, and delta-globin genes to the short arm of chromosome 11 by chromosome sorting and DNA restriction enzyme analysis. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5804–5808. doi: 10.1073/pnas.76.11.5804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lebo R. V., Kan Y. W., Cheung M. C., Carrano A. V., Yu L. C., Chang J. C., Cordell B., Goodman H. M. Assigning the polymorphic human insulin gene to the short arm of chromosome 11 by chromosome sorting. Hum Genet. 1982;60(1):10–15. doi: 10.1007/BF00281255. [DOI] [PubMed] [Google Scholar]
  25. MORTON N. E. Sequential tests for the detection of linkage. Am J Hum Genet. 1955 Sep;7(3):277–318. [PMC free article] [PubMed] [Google Scholar]
  26. Maniatis T., Fritsch E. F., Lauer J., Lawn R. M. The molecular genetics of human hemoglobins. Annu Rev Genet. 1980;14:145–178. doi: 10.1146/annurev.ge.14.120180.001045. [DOI] [PubMed] [Google Scholar]
  27. Martin S. L., Zimmer E. A., Davidson W. S., Wilson A. C., Kan Y. W. The untranslated regions of beta-globin mRNA evolve at a functional rate in higher primates. Cell. 1981 Sep;25(3):737–741. doi: 10.1016/0092-8674(81)90181-1. [DOI] [PubMed] [Google Scholar]
  28. Mather K. Crossing over and Heterochromatin in the X Chromosome of Drosophila Melanogaster. Genetics. 1939 Apr;24(3):413–435. doi: 10.1093/genetics/24.3.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. McEntee K., Weinstock G. M., Lehman I. R. Initiation of general recombination catalyzed in vitro by the recA protein of Escherichia coli. Proc Natl Acad Sci U S A. 1979 Jun;76(6):2615–2619. doi: 10.1073/pnas.76.6.2615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Mendelsohn M. L., Mayall B. H., Bogart E., Moore D. H., 2nd, Perry B. H. DNA content and DNA-based centromeric index of the 24 human chromosomes. Science. 1973 Mar 16;179(4078):1126–1129. doi: 10.1126/science.179.4078.1126. [DOI] [PubMed] [Google Scholar]
  31. Morton N. E. Analysis of crossingover in man. Cytogenet Cell Genet. 1978;22(1-6):15–36. doi: 10.1159/000130916. [DOI] [PubMed] [Google Scholar]
  32. Müller U. R., Fitch W. M. Evolutionary selection for perfect hairpin structures in viral DNAs. Nature. 1982 Aug 5;298(5874):582–585. doi: 10.1038/298582a0. [DOI] [PubMed] [Google Scholar]
  33. Nei M., Tajima F. DNA polymorphism detectable by restriction endonucleases. Genetics. 1981 Jan;97(1):145–163. doi: 10.1093/genetics/97.1.145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Ott J. Estimation of the recombination fraction in human pedigrees: efficient computation of the likelihood for human linkage studies. Am J Hum Genet. 1974 Sep;26(5):588–597. [PMC free article] [PubMed] [Google Scholar]
  35. Potter H., Dressler D. DNA synaptase: an enzyme that fuses DNA molecules at a region of homology. Proc Natl Acad Sci U S A. 1980 May;77(5):2390–2394. doi: 10.1073/pnas.77.5.2390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Rao D. C., Morton N. E., Lindsten J., Hultén M., Yee S. A mapping function for man. Hum Hered. 1977;27(2):99–104. doi: 10.1159/000152856. [DOI] [PubMed] [Google Scholar]
  37. Riccardi V. M., Sujansky E., Smith A. C., Francke U. Chromosomal imbalance in the Aniridia-Wilms' tumor association: 11p interstitial deletion. Pediatrics. 1978 Apr;61(4):604–610. [PubMed] [Google Scholar]
  38. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  39. Skolnick M. H., Francke U. Report of the committee on human gene mapping by recombinant DNA techniques. Oslo Conference (1981): Sixth International Workshop on Human Gene Mapping. Cytogenet Cell Genet. 1982;32(1-4):194–204. doi: 10.1159/000131699. [DOI] [PubMed] [Google Scholar]
  40. Spritz R. A. Duplication/deletion polymorphism 5' - to the human beta globin gene. Nucleic Acids Res. 1981 Oct 10;9(19):5037–5047. doi: 10.1093/nar/9.19.5037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Ullrich A., Dull T. J., Gray A., Philips J. A., 3rd, Peter S. Variation in the sequence and modification state of the human insulin gene flanking regions. Nucleic Acids Res. 1982 Apr 10;10(7):2225–2240. doi: 10.1093/nar/10.7.2225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Weitkamp L. R. Proceedings: Population differences in meiotic recombination frequency between loci on chromosome 1. Cytogenet Cell Genet. 1974;13(1):179–182. doi: 10.1159/000130267. [DOI] [PubMed] [Google Scholar]
  43. Wyman A. R., White R. A highly polymorphic locus in human DNA. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6754–6758. doi: 10.1073/pnas.77.11.6754. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Yamazaki T. The effects of overdominance of linkage in a multilocus system. Genetics. 1977 May;86(1):227–236. doi: 10.1093/genetics/86.1.227. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES