Experimentally-derived haplotypes substantially increase the efficiency of linkage disequilibrium studies (original) (raw)

Nature Genetics volume 28, pages 361–364 (2001)Cite this article

Abstract

The study of complex genetic traits in humans is limited by the expense and difficulty of ascertaining populations of sufficient sample size to detect subtle genetic contributions to disease. Here we introduce an application of a somatic cell hybrid construction strategy called conversion1,2,3,4 that maximizes the genotypic information from each sampled individual. The approach permits direct observation of individual haplotypes, thereby eliminating the need for collecting and genotyping DNA from family members for haplotype-based analyses. We describe experimental data that validate the use of conversion as a whole-genome haplotyping tool and evaluate the theoretical efficiency of using conversion-derived haplotypes instead of conventional genotypes in the context of haplotype-frequency estimation. We show that, particularly when phenotyping is expensive, conversion-based haplotyping can be more efficient and cost-effective than standard genotyping.

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Acknowledgements

We thank B. Vogelstein and H. Yan of Johns Hopkins University for generously donating the somatic cell hybrids. We would also like to acknowledge the technical assistance of T. Dennis and A. Dutra of the National Human Genome Research Institute Cytogenetic and Confocal Microscopy Core. This work was supported in part by a University of Michigan Predoctoral Fellowship to J.A.D. and by National Institutes of Health grants to M.B. (R01 HG00376) and S.B.G. (R01 CA81488).

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Authors and Affiliations

  1. Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA
    Julie A. Douglas
  2. Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA
    Michael Boehnke
  3. Department of Epidemiology, University of Michigan, Ann Arbor, Michigan, USA
    Stephen B. Gruber
  4. Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
    Stephen B. Gruber
  5. Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA
    Julie A. Douglas, Michael Boehnke & Stephen B. Gruber
  6. National Human Genome Research Institute, Bethesda, Maryland, USA
    Elizabeth Gillanders & Jeffrey M. Trent

Authors

  1. Julie A. Douglas
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  2. Michael Boehnke
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  3. Elizabeth Gillanders
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  4. Jeffrey M. Trent
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  5. Stephen B. Gruber
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Corresponding author

Correspondence toMichael Boehnke.

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Douglas, J., Boehnke, M., Gillanders, E. et al. Experimentally-derived haplotypes substantially increase the efficiency of linkage disequilibrium studies.Nat Genet 28, 361–364 (2001). https://doi.org/10.1038/ng582

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