Haplotype structure, LD blocks, and uneven recombination within the LRP5 gene.

TitleHaplotype structure, LD blocks, and uneven recombination within the LRP5 gene.
Publication TypeJournal Article
Year of Publication2003
AuthorsTwells, RCJ, Mein, CA, Phillips, MS, J Hess, F, Veijola, R, Gilbey, M, Bright, M, Metzker, M, Lie, BA, Kingsnorth, A, Gregory, E, Nakagawa, Y, Snook, H, Wang, WYS, Masters, J, Johnson, G, Eaves, I, Howson, JMM, Clayton, D, Cordell, HJ, Nutland, S, Rance, H, Carr, P, Todd, JA
JournalGenome Res
Date Published2003 May
Keywords3' Flanking Region, 5' Flanking Region, Alleles, Chromosome Mapping, Chromosomes, Human, Pair 11, Diabetes Mellitus, Type 1, Gene Frequency, Genetic Markers, Genetics, Population, Genotype, Haplotypes, Humans, Introns, LDL-Receptor Related Proteins, Linkage Disequilibrium, Low Density Lipoprotein Receptor-Related Protein-5, Microsatellite Repeats, Nuclear Family, Polymorphism, Single Nucleotide, Receptors, LDL, Recombination, Genetic

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.

Alternate JournalGenome Res
PubMed ID12727905
PubMed Central IDPMC430919
Grant List / WT_ / Wellcome Trust / United Kingdom

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