Skip to main content
PMC home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1991 Nov;49(5):966–971.

Linkage disequilibrium between two highly polymorphic microsatellites.

R Sherrington 1, G Melmer 1, M Dixon 1, D Curtis 1, B Mankoo 1, G Kalsi 1, H Gurling 1
PMCID: PMC1683257  PMID: 1928102

Abstract

The PCR was used to amplify genomic DNA from two microsatellite (dC-dA)n.(dG-dT)n sequences found to be present in the same chromosome 5 genomic clone. Analysis of the haplotype frequencies of these two interspersed repeat sequences in individuals showed strong allelic association or linkage disequilibrium. Six alleles were found for p599 (CA)n with a PIC value of 0.71 and 8 alleles were seen for lambda 599 (CA)n with a PIC value of 0.74. The two microsatellites are separated by approximately 7 kb. Analysis of the length variations for the two microsatellites showed that they were positively correlated, a finding that has no obvious explanation. The strong linkage disequilibrium found demonstrates stability during evolution for these novel markers. Therefore they should be powerful new tools for studying genetic drift and admixture of populations. Furthermore, disequilibrium data from microsatellites can be used in the fine mapping and cloning of disease genes.

Full text

PDF
967

Images in this article

968Figure 1
on p.968

Selected References

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

  1. Chakravarti A., Buetow K. H., Antonarakis S. E., Waber P. G., Boehm C. D., Kazazian H. H. Nonuniform recombination within the human beta-globin gene cluster. Am J Hum Genet. 1984 Nov;36(6):1239–1258. [PMC free article] [PubMed] [Google Scholar]
  2. Dean M., Drumm M. L., Stewart C., Gerrard B., Perry A., Hidaka N., Cole J. L., Collins F. S., Iannuzzi M. C. Approaches to localizing disease genes as applied to cystic fibrosis. Nucleic Acids Res. 1990 Jan 25;18(2):345–350. doi: 10.1093/nar/18.2.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Economou E. P., Bergen A. W., Warren A. C., Antonarakis S. E. The polydeoxyadenylate tract of Alu repetitive elements is polymorphic in the human genome. Proc Natl Acad Sci U S A. 1990 Apr;87(8):2951–2954. doi: 10.1073/pnas.87.8.2951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Estivill X., Farrall M., Scambler P. J., Bell G. M., Hawley K. M., Lench N. J., Bates G. P., Kruyer H. C., Frederick P. A., Stanier P. A candidate for the cystic fibrosis locus isolated by selection for methylation-free islands. 1987 Apr 30-May 6Nature. 326(6116):840–845. doi: 10.1038/326840a0. [DOI] [PubMed] [Google Scholar]
  5. Fujita R., Hanauer A., Sirugo G., Heilig R., Mandel J. L. Additional polymorphisms at marker loci D9S5 and D9S15 generate extended haplotypes in linkage disequilibrium with Friedreich ataxia. Proc Natl Acad Sci U S A. 1990 Mar;87(5):1796–1800. doi: 10.1073/pnas.87.5.1796. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hamada H., Seidman M., Howard B. H., Gorman C. M. Enhanced gene expression by the poly(dT-dG).poly(dC-dA) sequence. Mol Cell Biol. 1984 Dec;4(12):2622–2630. doi: 10.1128/mcb.4.12.2622. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Higgs D. R., Wainscoat J. S., Flint J., Hill A. V., Thein S. L., Nicholls R. D., Teal H., Ayyub H., Peto T. E., Falusi A. G. Analysis of the human alpha-globin gene cluster reveals a highly informative genetic locus. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5165–5169. doi: 10.1073/pnas.83.14.5165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Jeffreys A. J., Royle N. J., Wilson V., Wong Z. Spontaneous mutation rates to new length alleles at tandem-repetitive hypervariable loci in human DNA. Nature. 1988 Mar 17;332(6161):278–281. doi: 10.1038/332278a0. [DOI] [PubMed] [Google Scholar]
  9. Kenter A. L., Birshtein B. K. Chi, a promoter of generalized recombination in lambda phage, is present in immunoglobulin genes. Nature. 1981 Oct 1;293(5831):402–404. doi: 10.1038/293402a0. [DOI] [PubMed] [Google Scholar]
  10. Kmiec E. B., Holloman W. K. Homologous pairing of DNA molecules by Ustilago rec1 protein is promoted by sequences of Z-DNA. Cell. 1986 Feb 28;44(4):545–554. doi: 10.1016/0092-8674(86)90264-3. [DOI] [PubMed] [Google Scholar]
  11. Levinson G., Gutman G. A. Slipped-strand mispairing: a major mechanism for DNA sequence evolution. Mol Biol Evol. 1987 May;4(3):203–221. doi: 10.1093/oxfordjournals.molbev.a040442. [DOI] [PubMed] [Google Scholar]
  12. Litt M., Jorde L. B. Linkage disequilibria between pairs of loci within a highly polymorphic region of chromosome 2Q. Am J Hum Genet. 1986 Aug;39(2):166–178. [PMC free article] [PubMed] [Google Scholar]
  13. Litt M., Luty J. A. A hypervariable microsatellite revealed by in vitro amplification of a dinucleotide repeat within the cardiac muscle actin gene. Am J Hum Genet. 1989 Mar;44(3):397–401. [PMC free article] [PubMed] [Google Scholar]
  14. Luty J. A., Guo Z., Willard H. F., Ledbetter D. H., Ledbetter S., Litt M. Five polymorphic microsatellite VNTRs on the human X chromosome. Am J Hum Genet. 1990 Apr;46(4):776–783. [PMC free article] [PubMed] [Google Scholar]
  15. Morton N. E., Lew R. Mapping genetic systems by the supratype method. Hum Genet. 1985;70(3):231–235. doi: 10.1007/BF00273447. [DOI] [PubMed] [Google Scholar]
  16. Nakamura Y., Leppert M., O'Connell P., Wolff R., Holm T., Culver M., Martin C., Fujimoto E., Hoff M., Kumlin E. Variable number of tandem repeat (VNTR) markers for human gene mapping. Science. 1987 Mar 27;235(4796):1616–1622. doi: 10.1126/science.3029872. [DOI] [PubMed] [Google Scholar]
  17. Ott J. A chi-square test to distinguish allelic association from other causes of phenotypic association between two loci. Genet Epidemiol. 1985;2(1):79–84. doi: 10.1002/gepi.1370020108. [DOI] [PubMed] [Google Scholar]
  18. Ramsay M., Jenkins T. Alpha-globin gene cluster haplotypes in the Kalahari San and southern African Bantu-speaking blacks. Am J Hum Genet. 1988 Oct;43(4):527–533. [PMC free article] [PubMed] [Google Scholar]
  19. Rommens J. M., Iannuzzi M. C., Kerem B., Drumm M. L., Melmer G., Dean M., Rozmahel R., Cole J. L., Kennedy D., Hidaka N. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science. 1989 Sep 8;245(4922):1059–1065. doi: 10.1126/science.2772657. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Slightom J. L., Blechl A. E., Smithies O. Human fetal G gamma- and A gamma-globin genes: complete nucleotide sequences suggest that DNA can be exchanged between these duplicated genes. Cell. 1980 Oct;21(3):627–638. doi: 10.1016/0092-8674(80)90426-2. [DOI] [PubMed] [Google Scholar]
  22. Smeets H. J., Brunner H. G., Ropers H. H., Wieringa B. Use of variable simple sequence motifs as genetic markers: application to study of myotonic dystrophy. Hum Genet. 1989 Oct;83(3):245–251. doi: 10.1007/BF00285165. [DOI] [PubMed] [Google Scholar]
  23. Tautz D., Trick M., Dover G. A. Cryptic simplicity in DNA is a major source of genetic variation. Nature. 1986 Aug 14;322(6080):652–656. doi: 10.1038/322652a0. [DOI] [PubMed] [Google Scholar]
  24. Thompson E. A., Deeb S., Walker D., Motulsky A. G. The detection of linkage disequilibrium between closely linked markers: RFLPs at the AI-CIII apolipoprotein genes. Am J Hum Genet. 1988 Jan;42(1):113–124. [PMC free article] [PubMed] [Google Scholar]
  25. Vogt P. Potential genetic functions of tandem repeated DNA sequence blocks in the human genome are based on a highly conserved "chromatin folding code". Hum Genet. 1990 Mar;84(4):301–336. doi: 10.1007/BF00196228. [DOI] [PubMed] [Google Scholar]
  26. Weber J. L. Informativeness of human (dC-dA)n.(dG-dT)n polymorphisms. Genomics. 1990 Aug;7(4):524–530. doi: 10.1016/0888-7543(90)90195-z. [DOI] [PubMed] [Google Scholar]
  27. Weber J. L., May P. E. Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Am J Hum Genet. 1989 Mar;44(3):388–396. [PMC free article] [PubMed] [Google Scholar]
  28. Weir B. S., Cockerham C. C. Testing Hypotheses about Linkage Disequilibrium with Multiple Alleles. Genetics. 1978 Mar;88(3):633–642. doi: 10.1093/genetics/88.3.633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Zuliani G., Hobbs H. H. A high frequency of length polymorphisms in repeated sequences adjacent to Alu sequences. Am J Hum Genet. 1990 May;46(5):963–969. [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES