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

Nature Genetics volume 25, pages 324–328 (2000)Cite this article

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.

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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.

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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.

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Affiliations

  1. Division of Dermatology, Washington University, St. Louis, Missouri, USA

    Patricia Taillon-Miller, Irma Bauer-Sardiña, Jenna Putzel & Pui-Yan Kwok

  2. Department of Psychiatry, Washington University, St. Louis, Missouri, USA

    Nancy L. Saccone & John P. Rice

  3. IRTAM-CNR, University of Cagliari, Cagliari, Sardinia, Italy

    Antonio Cao & Giuseppe Pilia

  4. Finnish Genome Center, University of Helsinki, Helsinki, Finland

    Tarja Laitinen & Juha Kere

Authors
  1. Patricia Taillon-Miller
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  2. Irma Bauer-Sardiña
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  3. Nancy L. Saccone
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  4. Jenna Putzel
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  5. Tarja Laitinen
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  7. Juha Kere
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  8. Giuseppe Pilia
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  10. Pui-Yan Kwok
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Correspondence to Pui-Yan Kwok.

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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

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