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LETTER

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

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

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 the low-density lipoprotein-receptor-related protein 5 (LRP5) gene. Here, we have extensively analysed both LRP5 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. For LRP5, 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.]

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.

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