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

Genome Res. 2003 May;13(5):845-55. doi: 10.1101/gr.563703.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Flanking Region / genetics
  • 5' Flanking Region / genetics
  • Alleles
  • Chromosome Mapping / methods
  • Chromosomes, Human, Pair 11 / genetics
  • Diabetes Mellitus, Type 1 / genetics
  • Gene Frequency / genetics
  • Genetic Markers / genetics
  • Genetics, Population
  • Genotype
  • Haplotypes / genetics*
  • Humans
  • Introns / genetics
  • LDL-Receptor Related Proteins
  • Linkage Disequilibrium / genetics*
  • Low Density Lipoprotein Receptor-Related Protein-5
  • Microsatellite Repeats / genetics
  • Nuclear Family
  • Polymorphism, Single Nucleotide / genetics
  • Receptors, LDL / genetics*
  • Recombination, Genetic / genetics*

Substances

  • Genetic Markers
  • LDL-Receptor Related Proteins
  • LRP5 protein, human
  • Low Density Lipoprotein Receptor-Related Protein-5
  • Receptors, LDL