%0 Journal Article %J Genome Res %D 2003 %T Haplotype structure, LD blocks, and uneven recombination within the LRP5 gene. %A Twells, Rebecca C J %A Mein, Charles A %A Phillips, Michael S %A Hess, J Fred %A Veijola, Riitta %A Gilbey, Matthew %A Bright, Matthew %A Metzker, Michael %A Lie, Benedicte A %A Kingsnorth, Amanda %A Gregory, Edward %A Nakagawa, Yusuke %A Snook, Hywel %A Wang, William Y S %A Masters, Jennifer %A Johnson, Gillian %A Eaves, Iain %A Howson, Joanna M M %A Clayton, David %A Cordell, Heather J %A Nutland, Sarah %A Rance, Helen %A Carr, Philippa %A Todd, John A %K 3' Flanking Region %K 5' Flanking Region %K Alleles %K Chromosome Mapping %K Chromosomes, Human, Pair 11 %K Diabetes Mellitus, Type 1 %K Gene Frequency %K Genetic Markers %K Genetics, Population %K Genotype %K Haplotypes %K Humans %K Introns %K LDL-Receptor Related Proteins %K Linkage Disequilibrium %K Low Density Lipoprotein Receptor-Related Protein-5 %K Microsatellite Repeats %K Nuclear Family %K Polymorphism, Single Nucleotide %K Receptors, LDL %K Recombination, Genetic %X

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.

%B Genome Res %V 13 %P 845-55 %8 2003 May %G eng %N 5 %1 https://www.ncbi.nlm.nih.gov/pubmed/12727905?dopt=Abstract %R 10.1101/gr.563703