Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Juxtaposed regions of extensive and minimal linkage disequilibrium in human Xq25 and Xq28

Abstract

Linkage disequilibrium (LD), or the non-random association of alleles, is poorly understood in the human genome1. Population genetic theory suggests that LD is determined by the age of the markers, population history, recombination rate, selection and genetic drift2. Despite the uncertainties in determining the relative contributions of these factors, some groups have argued that LD is a simple function of distance between markers3,4. Disease-gene mapping studies and a simulation study gave differing predictions on the degree of LD in isolated and general populations5,6. In view of the discrepancies between theory and experimental observations, we constructed a high-density SNP map of the Xq25–Xq28 region7 and analysed the male genotypes and haplotypes across this region for LD in three populations. The populations included an outbred European sample (CEPH males) and isolated population samples from Finland and Sardinia. We found two extended regions of strong LD bracketed by regions with no evidence for LD in all three samples. Haplotype analysis showed a paucity of haplotypes in regions of strong LD. Our results suggest that, in this region of the X chromosome, LD is not a monotonic function of the distance between markers, but is more a property of the particular location in the human genome.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: A plot of pair-wise linkage disequilibrium (r2) versus distance (kb) within the Xq25 (open circle) and Xq28 regions (filled square), in the CEPH population.
Figure 2: Linkage disequilibrium map of targeted regions in Xq25 and Xq28.
Figure 3: A plot of the heterozygosity values for each marker in the three populations across the Xq25 (a) and Xq28 (b) LD regions.

Similar content being viewed by others

References

  1. Chakravarti, A. Population genetics—making sense out of sequence. Nature Genet. 21 (suppl.), 56–60 (1999).

    Article  CAS  PubMed  Google Scholar 

  2. Hartl, D.L. & Clark, A.G. Principles of Population Genetics (Sinauer Associates, Sunderland, 1989).

  3. Watkins W.S. et al. Linkage disequilibrium patterns vary with chromosomal location: a case study from the von Willebrand factor region. Am. J. Hum. Genet. 55, 348–355 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Jorde, L.B. et al. Linkage disequilibrium predicts physical distance in the adenomatous polyposis coli region. Am. J. Hum. Genet. 54, 884–898 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Kruglyak, L. Prospects for whole-genome genome linkage disequilibrium mapping of common disease genes. Nature Genet. 22, 139–144 (1999).

    Article  CAS  PubMed  Google Scholar 

  6. Jorde, L.B., Watkins, W.S., Viskochil, D., O'Connell, P. & Ward, K. Linkage disequilibrium in the neurofibromatosis 1 (NF1) region: implications for gene mapping. Am. J. Hum. Genet. 53, 1038–1050 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Taillon-Miller, P. & Kwok, P.-Y. A high density single nucleotide polymorphism map of Xq25–Xq28. Genomics 65, 195–202 (2000).

    Article  CAS  PubMed  Google Scholar 

  8. Kere, J. et al. Cystic fibrosis in a low-incidence population: two major mutations in Finland. Hum. Genet. 93, 162–166 (1994).

    Article  CAS  PubMed  Google Scholar 

  9. Tahvanainen, E. et al. The gene for a recessively inherited human childhood progressive epilepsy with mental retardation maps to the distal short arm of chromosome 8. Proc. Natl Acad. Sci. USA 91, 7267–7270 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Höglund, P. et al. Fine mapping of the congenital chloride diarrhea gene by linkage disequilibrium. Am. J. Hum. Genet. 57, 95–102 (1995).

    PubMed  PubMed Central  Google Scholar 

  11. Huttley, G.A., Smith, M.W., Carrington, M. & O'Brien, S.J. A scan for linkage disequilibrium across the human genome. Genetics 152, 1711–1722 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Taillon-Miller, P., Piernot, E.E. & Kwok, P.-Y. Efficient approach to unique single nucleotide polymorphism discovery. Genome Res. 9, 499–505 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Taillon-Miller, P. et al. The homozygous complete hydatidiform mole: a unique resource for genome studies. Genomics 46, 307–310 (1997).

    Article  CAS  PubMed  Google Scholar 

  14. Kwok, P.-Y., Carlson, C., Yager, T., Ankener, W. & Nickerson, D.A. Comparative analysis of human DNA variations by fluorescence-based sequencing of PCR products. Genomics 23, 138–144 (1994).

    Article  CAS  PubMed  Google Scholar 

  15. Chen, X., Zehnbauer, B., Gnirke, A. & Kwok, P.-Y. Fluorescence energy transfer detection as a homogeneous DNA diagnostic method. Proc. Natl Acad. Sci. USA 94, 10756–10761 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kwok, P.-Y., Gremaud, M.F., Nickerson, D.A., Hood, L. & Olson, M.V. Automatable screening of yeast artificial-chromosome libraries based on the oligonucleotide-ligation assay. Genomics 13, 935–941 (1992).

    Article  CAS  PubMed  Google Scholar 

  17. Laitinen, T. et al. Genetic control of serum IgE levels and asthma: linkage and linkage disequilibrium studies in an isolated population. Hum. Mol. Genet. 6, 2069–2076 (1997).

    Article  CAS  PubMed  Google Scholar 

  18. Cavalli-Sforza, L.L., Menozzi, P. & Piazza, A. Demic expansions and human evolution. Science 259, 639–646 (1993).

    Article  CAS  PubMed  Google Scholar 

  19. Cao, A., Galanello, R. & Rosatelli, M.C. Genotype-phenotype correlations in β-thalassemias. Blood Rev. 8, 1–12 (1994).

    Article  CAS  PubMed  Google Scholar 

  20. Hedrick, P.W. Gametic disequilibrium measures: proceed with caution. Genetics 117, 331–341 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Lewontin, R.C. On measures of gametic disequilibrium. Genetics 120, 849–852 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank D. Schlessinger for encouragement and support; R.D. Miller for discussions; and P. Buzby and S. Spurgeon for reagents. This work was supported in part by grants from the National Human Genome Research Institute (RO1HG1439, P50HG00201, P50HG00835) and by MH37685 and MH17104.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Pui-Yan Kwok.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Taillon-Miller, P., Bauer-Sardiña, I., Saccone, N. et al. Juxtaposed regions of extensive and minimal linkage disequilibrium in human Xq25 and Xq28. Nat Genet 25, 324–328 (2000). https://doi.org/10.1038/77100

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/77100

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing