Recombination and linkage disequilibrium in Arabidopsis thaliana (original) (raw)

Nature Genetics volume 39, pages 1151–1155 (2007)Cite this article

Abstract

Linkage disequilibrium (LD) is a major aspect of the organization of genetic variation in natural populations. Here we describe the genome-wide pattern of LD in a sample of 19 Arabidopsis thaliana accessions using 341,602 non-singleton SNPs. LD decays within 10 kb on average, considerably faster than previously estimated. Tag SNP selection algorithms and 'hide-the-SNP' simulations suggest that genome-wide association mapping will require only 40%–50% of the observed SNPs, a reduction similar to estimates in a sample of African Americans. An Affymetrix genotyping array containing 250,000 SNPs has been designed based on these results; we demonstrate that it should have more than adequate coverage for genome-wide association mapping. The extent of LD is highly variable, and we find clear evidence of recombination hotspots, which seem to occur preferentially in intergenic regions. LD also reflects the action of selection, and it is more extensive between nonsynonymous polymorphisms than between synonymous polymorphisms.

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References

  1. Clark, R.M. et al. Common sequence polymorphisms shaping genetic diversity in Arabidopsis thaliana. Science 317, 338–342 (2007).
    Article CAS PubMed Google Scholar
  2. Nordborg, M. et al. The pattern of polymorphism in Arabidopsis thaliana. PLoS Biol. 3, e196 (2005)(doi:10.1371/journal.pbio.0030196).
    Article CAS PubMed PubMed Central Google Scholar
  3. Plagnol, V., Padhukasharam, B., Marjoram, P., Wall, J.D. & Nordborg, M. Relative influences of crossing-over and gene conversion on the pattern of linkage disequilibrium in Arabidopsis thaliana. Genetics 172, 2441–2448 (2006).
    Article CAS PubMed PubMed Central Google Scholar
  4. Nordborg, M. Linkage disequilibrium, gene trees, and selfing: An ancestral recombination graph with partial self-fertilization. Genetics 154, 923–929 (2000).
    CAS PubMed PubMed Central Google Scholar
  5. Hudson, R.R. Two-locus sample distributions and their applications. Genetics 159, 1805–1817 (2001).
    CAS PubMed PubMed Central Google Scholar
  6. Padhukasahasram, B., Wall, J.D., Marjoram, P. & Nordborg, M. Estimating recombination rates from single-nucleotide polymorphisms using summary statistics. Genetics 174, 1517–1528 (2006).
    Article CAS PubMed PubMed Central Google Scholar
  7. Haddrill, P.R., Thornton, K.R., Charlesworth, B. & Andolfatto, P. Multilocus patterns of nucleotide variability and the demographic and selection history of Drosophila melanogaster populations. Genome Res. 15, 790–799 (2005).
    Article CAS PubMed PubMed Central Google Scholar
  8. Przeworski, M. & Wall, J.D. Why is there so little intragenic linkage disequilibrium in humans? Genet. Res. 77, 143–151 (2001).
    Article CAS PubMed Google Scholar
  9. Frisse, L. et al. Gene conversion and different population histories may explain the contrast between polymorphism and linkage disequilibrium levels. Am. J. Hum. Genet. 69, 831–843 (2001).
    Article CAS PubMed PubMed Central Google Scholar
  10. Hagenblad, J. & Nordborg, M. Sequence variation and haplotype structure surrounding the flowering time locus FRI in Arabidopsis thaliana. Genetics 161, 289–298 (2002).
    CAS PubMed PubMed Central Google Scholar
  11. Haubold, B., Kroymann, J., Ratzka, A., Mitchell-Olds, T. & Wiehe, T. Recombination and gene conversion in a 170-kb genomic region of Arabidopsis thaliana. Genetics 161, 1269–1278 (2002).
    CAS PubMed PubMed Central Google Scholar
  12. Hinds, D.A. et al. Whole-genome patterns of common DNA variation in three human populations. Science 307, 1072–1079 (2005).
    Article CAS PubMed Google Scholar
  13. de Bakker, P.I.W. et al. Efficiency and power in genetic association studies. Nat. Genet. 37, 1217–1223 (2005).
    Article CAS PubMed Google Scholar
  14. Johnson, G.C. et al. Haplotype tagging for the identification of common disease genes. Nat. Genet. 29, 233–237 (2001).
    Article CAS PubMed Google Scholar
  15. Zondervan, K.T. & Cardon, L.R. The complex interplay among factors that influence allelic association. Nat. Rev. Genet. 5, 89–100 (2004).
    Article CAS PubMed Google Scholar
  16. International HapMap Consortium. A haplotype map of the human genome. Nature 437, 1299–1320 (2005).
  17. Wall, J.D. & Pritchard, J.K. Haplotype blocks and linkage disequilibrium in the human genome. Nat. Rev. Genet. 4, 587–597 (2003).
    Article CAS PubMed Google Scholar
  18. Arnheim, N., Calabrese, P. & Nordborg, M. Hot and cold spots of recombination in the human genome: The reason we should find them and how this can be achieved. Am. J. Hum. Genet. 73, 5–16 (2003).
    Article CAS PubMed PubMed Central Google Scholar
  19. Drouaud, J. et al. Variation in crossing-over rates across chromosome4 of Arabidopsis thaliana reveals the presence of meiotic recombination hot spots. Genome Res. 16, 106–114 (2006).
    Article CAS PubMed PubMed Central Google Scholar
  20. Schmuths, H., Meister, A., Horres, R. & Bachmann, K. Genome size variation among accessions of Arabidopsis thaliana. Ann. Bot. (Lond.) 93, 317–321 (2004).
    Article CAS Google Scholar
  21. Nordborg, M. & Tavaré, S. Linkage disequilibrium: what history has to tell us. Trends Genet. 18, 83–90 (2002).
    Article CAS PubMed Google Scholar
  22. Hudson, R.R. & Kaplan, N.L. Statistical properties of the number of recombination events in the history of a sample of DNA sequences. Genetics 111, 147–164 (1985).
    CAS PubMed PubMed Central Google Scholar
  23. Andolfatto, P. Adaptive evolution of non-coding DNA in Drosophila. Nature 437, 1149–1152 (2005).
    Article CAS PubMed Google Scholar
  24. Li, N. & Stephens, M. Modeling linkage disequilibrium and identifying recombination hotspots using single-nucleotide polymorphism data. Genetics 165, 2213–2233 (2003).
    CAS PubMed PubMed Central Google Scholar
  25. Hudson, R.R. Generating samples under a Wright-Fisher neutral model. Bioinformatics 18, 337–338 (2002).
    Article CAS PubMed Google Scholar
  26. Andolfatto, P. & Nordborg, M. The effect of gene conversion on intralocus associations. Genetics 148, 1397–1399 (1998).
    CAS PubMed PubMed Central Google Scholar
  27. Barrett, J.C., Fry, B., Maller, J. & Daly, M.J. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21, 263–265 (2005).
    Article CAS PubMed Google Scholar

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Acknowledgements

Support was provided by grants from the US National Institutes of Health (HG002790 to M. Waterman, GM62932 to D.W. and a postdoctoral fellowship to C.T.) and the US National Science Foundation (DEB-0115062 to M.N.) and by funds from the Max Planck Society. D.W. is a director of the Max Planck Institute.

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Author notes

  1. Sung Kim, Vincent Plagnol, Tina T Hu and Christopher Toomajian: These authors contributed equally to this work.

Authors and Affiliations

  1. Molecular and Computational Biology, University of Southern California, Los Angeles, 90089, California, USA
    Sung Kim, Vincent Plagnol, Tina T Hu, Christopher Toomajian & Magnus Nordborg
  2. Cambridge Institute for Medical Research, University of Cambridge, Cambridge, CB2 OXY, UK
    Vincent Plagnol
  3. Department of Molecular Biology, Max Planck Institute for Developmental Biology, Tübingen, 72076, Germany
    Richard M Clark, Stephan Ossowski & Detlef Weigel
  4. Salk Institute Genome Analysis Laboratory, and The Salk Institute for Biological Studies, La Jolla, 92037, California, USA
    Joseph R Ecker
  5. Plant Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, 92037, California, USA
    Joseph R Ecker & Detlef Weigel

Authors

  1. Sung Kim
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  2. Vincent Plagnol
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  3. Tina T Hu
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  4. Christopher Toomajian
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  5. Richard M Clark
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  6. Stephan Ossowski
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  7. Joseph R Ecker
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  8. Detlef Weigel
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  9. Magnus Nordborg
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Contributions

S.K., V.P., T.T.H. and C.T. carried out all the population genetics analyses and assisted with writing the paper. R.M.C. and S.O. analyzed the raw array data. J.R.E. and D.W. directed the array resequencing project. M.N. directed the population genetics analyses and wrote the paper. All authors commented on and revised the manuscript.

Corresponding author

Correspondence toMagnus Nordborg.

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The authors declare no competing financial interests.

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Kim, S., Plagnol, V., Hu, T. et al. Recombination and linkage disequilibrium in Arabidopsis thaliana.Nat Genet 39, 1151–1155 (2007). https://doi.org/10.1038/ng2115

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