Linkage Disequilibrium Between Microsatellite Markers Extends Beyond 1 cM on Chromosome 20 in Finns

  1. Karen L. Mohlke1,6,
  2. Ethan M. Lange2,6,7,
  3. Timo T. Valle3,
  4. Soumitra Ghosh1,8,
  5. Victoria L. Magnuson1,9,
  6. Kaisa Silander1,
  7. Richard M. Watanabe2,10,
  8. Peter S. Chines1,
  9. Richard N. Bergman4,
  10. Jaakko Tuomilehto3,5,
  11. Francis S. Collins1, and
  12. Michael Boehnke2,11
  1. 1Genetics and Molecular Biology Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA; 2University of Michigan, School of Public Health, Department of Biostatistics, Ann Arbor, Michigan 48109, USA; 3National Public Health Institute, Department of Epidemiology and Health Promotion, Diabetes and Genetic Epidemiology Unit, Helsinki, Finland; 4Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA; 5Department of Public Health, University of Helsinki, Helsinki, Finland

Abstract

Linkage disequilibrium (LD) is a proven tool for evaluating population structure and localizing genes for monogenic disorders. LD-based methods may also help localize genes for complex traits. We evaluated marker–marker LD using 43 microsatellite markers spanning chromosome 20 with an average density of 2.3 cM. We studied 837 individuals affected with type 2 diabetes and 386 mostly unaffected spouse controls. A test of homogeneity between the affected individuals and their spouses showed no difference, allowing the 1223 individuals to be analyzed together. Significant (P < 0.01) LD was observed using a likelihood ratio test in all (11/11) marker pairs within 1 cM, 78% (25/32) of pairs 1–3 cM apart, and 39% (7/18) of pairs 3–4 cM apart, but for only 12 of 842 pairs more than 4 cM apart. We used the human genome project working draft sequence to estimate kilobase (kb) intermarker distances, and observed highly significant LD (P < 10−10) for all six marker pairs up to 350 kb apart, although the correlation of LD with cM is slightly better than the correlation with megabases. These data suggest that microsatellites present at 1-cM density are sufficient to observe marker–marker LD in the Finnish population.

Footnotes

  • ↵6 These authors contributed equally to this work.

  • Present addresses: 7Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1063, USA; 8 The Max McGee National Research Center for Juvenile Diabetes, Children's Hospital of Wisconsin, and Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA; 9Science and Technology Division, Corning Incorporated, Corning, NY 14831, USA; 10Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.

  • ↵11 Corresponding author.

  • E-MAIL boehnke{at}umich.edu; FAX (734) 763-2215.

  • Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.173201.

    • Received November 29, 2000.
    • Accepted April 17, 2001.
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  1. doi: 10.1101/gr.173201 Genome Res. 11: 1221-1226 Cold Spring Harbor Laboratory Press

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