| Title | Haplotype structure, LD blocks, and uneven recombination within the LRP5 gene. |
| Publication Type | Journal Article |
| Year of Publication | 2003 |
| Authors | Twells, 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 |
| Journal | Genome Res |
| Volume | 13 |
| Issue | 5 |
| Pagination | 845-55 |
| Date Published | 2003 May |
| ISSN | 1088-9051 |
| Keywords | 3' 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 |
| 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 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.
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| DOI | 10.1101/gr.563703 |
| Alternate Journal | Genome Res |
| PubMed ID | 12727905 |
| PubMed Central ID | PMC430919 |
| Grant List | / WT_ / Wellcome Trust / United Kingdom |