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High-resolution haplotype structure in the human genome

Nature Genetics volume 29, pages 229–232 (2001)Cite this article

Abstract

Linkage disequilibrium (LD) analysis is traditionally based on individual genetic markers and often yields an erratic, non-monotonic picture, because the power to detect allelic associations depends on specific properties of each marker, such as frequency and population history. Ideally, LD analysis should be based directly on the underlying haplotype structure of the human genome, but this structure has remained poorly understood. Here we report a high-resolution analysis of the haplotype structure across 500 kilobases on chromosome 5q31 using 103 single-nucleotide polymorphisms (SNPs) in a European-derived population. The results show a picture of discrete haplotype blocks (of tens to hundreds of kilobases), each with limited diversity punctuated by apparent sites of recombination. In addition, we develop an analytical model for LD mapping based on such haplotype blocks. If our observed structure is general (and published data suggest that it may be), it offers a coherent framework for creating a haplotype map of the human genome.

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Figure 1: Comparison of single-marker LD with haplotype-based LD.
Figure 2: Block-like haplotype diversity at 5q31.

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Acknowledgements

The authors thank D. Reich, D. Altshuler, J. Hirschhorn, K. Lindblad-Toh and M.P. Reeve for many valuable discussions and comments on the manuscript, A. Kirby for informatics support, the technicians in the inflammatory disease research group at the Whitehead Institute Center for Genome Research for their skilled genotyping work and the anonymous referees for their helpful comments. The authors would also like to thank L. Gaffney for her help in the preparation of this manuscript. This work was supported by research grants from Bristol-Myers Squibb, Millennium Pharmaceutical , and Affymetrix.

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Authors and Affiliations

  1. Whitehead Institute/Massachusetts Institute of Technology, Center for Genome Research, Cambridge, Massachusetts, USA

    Mark J. Daly, John D. Rioux, Stephen F. Schaffner, Thomas J. Hudson & Eric S. Lander

  2. Montreal Genome Center, McGill University, Montréal, Québec, Canada

    Thomas J. Hudson

  3. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

    Eric S. Lander

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  1. Mark J. Daly
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  2. John D. Rioux
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Correspondence to Mark J. Daly or Eric S. Lander.

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Daly, M., Rioux, J., Schaffner, S. et al. High-resolution haplotype structure in the human genome. Nat Genet 29, 229–232 (2001). https://doi.org/10.1038/ng1001-229

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