Conservation of hotspots for recombination in low-copy repeats associated with the NF1 microdeletion (original) (raw)

Nature Genetics volume 38, pages 1419–1423 (2006)Cite this article

Abstract

Several large-scale studies of human genetic variation have provided insights into processes such as recombination that have shaped human diversity. However, regions such as low-copy repeats (LCRs) have proven difficult to characterize, hindering efforts to understand the processes operating in these regions. We present a detailed study of genetic variation and underlying recombination processes in two copies of an LCR (NF1REPa and NF1REPc) on chromosome 17 involved in the generation of NF1 microdeletions and in a third copy (REP19) on chromosome 19 from which the others originated over 6.7 million years ago. We find evidence for shared hotspots of recombination among the LCRs. REP19 seems to contain hotspots in the same place as the nonallelic recombination hotspots in NF1REPa and NF1REPc. This apparent conservation of patterns of recombination hotspots in moderately diverged paralogous regions contrasts with recent evidence that these patterns are not conserved in less-diverged orthologous regions of chimpanzees.

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Figure 1: Comparison of hotspots of recombination inferred from haplotype and microdeletion data.

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Acknowledgements

The authors thank T. de Ravel for critically reading the manuscript. T.D. is supported by the Emmanuel Vanderschueren Fonds. M.S. is supported by US National Institutes of Health grant 1RO1HG/LM02585-01. E.L. is a part-time clinical researcher of the Fonds voor Wetenschappelijk Onderzoek Vlaanderen (FWO). This work is also supported by research grants from the Fonds voor Wetenschappelijk Onderzoek Vlaanderen (G.0096.02, E.L.; G.0507.04, P.M.); the Interuniversity Attraction Poles (IAP) granted by the Federal Office for Scientific, Technical and Cultural Affairs, Belgium (2002-2006; P5/25) (P.M. and E.L.); by a Concerted Action Grant from the Catholic University of Leuven and by the Belgian Federation against Cancer (SCIE2003-33 to E.L.).

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Authors and Affiliations

  1. Department of Human Genetics, Catholic University Leuven, Leuven, Belgium
    Thomas De Raedt, Ine Heyns, Hilde Brems, Daisy Thijs, Peter Marynen & Eric Legius
  2. Department of Statistics, University of Washington, Seattle, Washington, USA
    Matthew Stephens
  3. Department of Genetics, Laboratory Medical Genetics, University of Alabama, Birmingham, Alabama, USA
    Ludwine Messiaen
  4. Department of Medicine, University of Washington, Seattle, Washington, USA
    Karen Stephens
  5. Institut Catala d'Oncologia–Instituto de Investigación Biomédica de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain
    Conxi Lazaro
  6. Department of Human Genetics, Medical University of Vienna, Vienna, Austria
    Katharina Wimmer
  7. Department of Human Genetics, University of Ulm, Ulm, Germany
    Hildegard Kehrer-Sawatzki
  8. Laboratoire de Génétique Moléculaire, Institut National de la Santé et de la Recherche Médicale U745, Université Paris 5, Paris, France
    Dominique Vidaud
  9. Laboratory for Tumor Biology and Development and Malformation, University Hospital Eppendorf, Hamburg, Germany
    Lan Kluwe

Authors

  1. Thomas De Raedt
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  2. Matthew Stephens
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  3. Ine Heyns
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  4. Hilde Brems
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  5. Daisy Thijs
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  6. Ludwine Messiaen
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  7. Karen Stephens
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  8. Conxi Lazaro
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  9. Katharina Wimmer
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  10. Hildegard Kehrer-Sawatzki
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  11. Dominique Vidaud
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  12. Lan Kluwe
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  13. Peter Marynen
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  14. Eric Legius
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Contributions

This study was coordinated by T.D., P.M. and E.L.; the manuscript was written by T.D., M.S. and E.L.; breakpoint detection was performed by T.D., I.H., H.B., L.M., K.S., C.L., K.W., H.K., D.V. and L.K.; SNP detection and typing was performed by T.D., I.H., H.B. and D.T. and computational analysis was performed by T.D. and M.S.

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Correspondence toEric Legius.

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Raedt, T., Stephens, M., Heyns, I. et al. Conservation of hotspots for recombination in low-copy repeats associated with the NF1 microdeletion.Nat Genet 38, 1419–1423 (2006). https://doi.org/10.1038/ng1920

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