Haplotype Structure, LD Blocks, and Uneven Recombination Within the LRP5 Gene

  1. Rebecca C.J. Twells1,4,
  2. Charles A. Mein1,
  3. Michael S. Phillips2,
  4. J. Fred Hess2,
  5. Riitta Veijola1,
  6. Matthew Gilbey1,
  7. Matthew Bright1,
  8. Michael Metzker2,
  9. Benedicte A. Lie3,
  10. Amanda Kingsnorth1,
  11. Edward Gregory1,
  12. Yusuke Nakagawa1,
  13. Hywel Snook1,
  14. William Y.S. Wang1,
  15. Jennifer Masters1,
  16. Gillian Johnson1,
  17. Iain Eaves1,
  18. Joanna M.M. Howson1,
  19. David Clayton1,
  20. Heather J. Cordell1,
  21. Sarah Nutland1,
  22. Helen Rance1,
  23. Philippa Carr1, and
  24. John A. Todd1
  1. 1JDRF/WT Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 2XY, UK; 2Merck Research Laboratories, Department of Human Genetics, West Point, Pennsylvania 19486, USA; 3Institute of Immunology, Rikshospitalet University Hospital, Oslo, Norway

Abstract

Patterns of linkage disequilibrium (LD) in the human genome are beginning to be characterized, with a paucity of haplotype diversity in “LD blocks,” interspersed by apparent “hot spots” of recombination. Previously, we cloned and physically characterized thelow-density lipoprotein-receptor-related protein 5(LRP5) gene. Here, we have extensively analysed bothLRP5 and its flanking three genes, spanning 269 kb, for single nucleotide polymorphisms (SNPs), and we present a comprehensive SNP map comprising 95 polymorphisms. Analysis revealed high levels of recombination across LRP5, including a hot-spot region from intron 1 to intron 7 of LRP5, where there are 109 recombinants/Mb (4882 meioses), in contrast to flanking regions of 14.6 recombinants/Mb. This region of high recombination could be delineated into three to four hot spots, one within a 601-bp interval. ForLRP5, three haplotype blocks were identified, flanked by the hot spots. Each LD block comprised over 80% common haplotypes, concurring with a previous study of 14 genes that showed that common haplotypes account for at least 80% of all haplotypes. The identification of hot spots in between these LD blocks provides additional evidence that LD blocks are separated by areas of higher recombination.

[Supplementary material: primers are available from our Web site:http://www-gene.cimr.cam.ac.uk/todd/human_data.shtml.]

Footnotes

  • ↵4 Corresponding author.

  • E-MAIL rebecca.twells{at}cimr.cam.ac.uk; FAX (44) 1223 762 102.

  • Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.563703.

    • Received June 28, 2002.
    • Accepted February 18, 2003.
| Table of Contents

This Article

  1. doi: 10.1101/gr.563703 Genome Res. 13: 845-855 Cold Spring Harbor Laboratory Press

Article Category

Share

Preprint Server



Current Issue

  1. March 2024, 34 (3)
  1. Current Issue
  1. Alert me to new issues of Genome Research