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Chromosome-wide distribution of haplotype blocks and the role of recombination hot spots

Nature Genetics volume 33, pages 382–387 (2003)Cite this article

Abstract

Recent studies of human populations suggest that the genome consists of chromosome segments that are ancestrally conserved ('haplotype blocks'; refs. 1–3) and have discrete boundaries defined by recombination hot spots4,5. Using publicly available genetic markers6, we have constructed a first-generation haplotype map of chromosome 19. As expected for this marker density7, approximately one-third of the chromosome is encompassed within haplotype blocks. Evolutionary modeling of the data indicates that recombination hot spots are not required to explain most of the observed blocks, providing that marker ascertainment and the observed marker spacing are considered. In contrast, several long blocks are inconsistent with our evolutionary models, and different mechanisms could explain their origins.

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Figure 1: Marker allele frequencies and physical spacing on chromosome 19.
Figure 2: Patterns of LD on chromosome 19.
Figure 3: Comparisons of observed block distributions (bars) and evolutionary model expectations (lines) under uniform recombination.
Figure 4: Distribution of block lengths in different marker sets.

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Acknowledgements

The authors thank J. Marcella, J. Ball and R. Tomacelli for advice and guidance during the development of this project at Orchid. R.S. thanks the cancer center at Cold Spring Harbor Laboratory for support. R.L., A.P.M., J.B. and L.R.C. were supported by the Wellcome Trust.

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Authors and Affiliations

  1. Orchid Biosciences Inc., 303A College Road East, Princeton, 08540, New Jersey, USA

    M.S. Phillips, M.A. Donaldson, J.F. Studebaker, W.M. Ankener, S.V. Alfisi, F.-S. Kuo, A.L. Camisa, V. Pazorov, K.E. Scott, B.J. Carey, H.A. Bhatti, J.M. Cyr, V. Derohannessian, C. Elosua, A.M. Forman, N.M. Grecco, C.R. Hock, J.M. Kuebler, J.A. Lathrop, M.A. Mockler, E.P. Nachtman, S.L. Restine, S.A. Varde, M.J. Hozza, C.A. Gelfand & M.T. Boyce-Jacino

  2. Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK

    R. Lawrence, A.P. Morris, J. Broxholme & L.R. Cardon

  3. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA

    R. Sachidanandam, J. Faith & G. Katari

  4. Department of Epidemiology and Public Health, Imperial College Faculty of Medicine, Norfolk Place, London, W2 1PG, UK

    D.J. Balding

  5. University of Michigan, Ann Arbor, 48109, Michigan, USA

    G.R. Abecasis

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Correspondence to L.R. Cardon.

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Authors affiliated with Orchid Biosciences are employed by or have personal financial interests in the company, which specializes in high-throughput genotyping technologies.

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Phillips, M., Lawrence, R., Sachidanandam, R. et al. Chromosome-wide distribution of haplotype blocks and the role of recombination hot spots. Nat Genet 33, 382–387 (2003). https://doi.org/10.1038/ng1100

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