Publication:

Haplotype tagging for the identification of common disease genes (2001)

Author(s): Cordell HJ; Smith AN; Johnson GC; Esposito L; Barratt BJ; Heward J; Di Genova G; Ueda H; Eaves IA; Dudbridge F; Twells RC; Payne F; Hughes W; Nutland S; Stevens H; Carr P; Tuomilehto-Wolf E; Tuomilehto J; Gough SC; Clayton DG; Todd JA

  • : Haplotype tagging for the identification of common disease genes

Abstract: Genome-wide linkage disequilibrium (LD) mapping of common disease genes could be more powerful than linkage analysis if the appropriate density of polymorphic markers were known and if the genotyping effort and cost of producing such an LD map could be reduced. Although different metrics that measure the extent of LD have been evaluated, even the most recent studies have not placed significant emphasis on the most informative and cost-effective method of LD mapping-that based on haplotypes. We have scanned 135 kb of DNA from nine genes, genotyped 122 single-nucleotide polymorphisms (SNPs; approximately 184,000 genotypes) and determined the common haplotypes in a minimum of 384 European individuals for each gene. Here we show how knowledge of the common haplotypes and the SNPs that tag them can be used to (i) explain the often complex patterns of LD between adjacent markers, (ii) reduce genotyping significantly (in this case from 122 to 34 SNPs), (iii) scan the common variation of a gene sensitively and comprehensively and (iv) provide key fine-mapping data within regions of strong LD. Our results also indicate that, at least for the genes studied here, the current version of dbSNP would have been of limited utility for LD mapping because many common haplotypes could not be defined. A directed re-sequencing effort of the approximately 10% of the genome in or near genes in the major ethnic groups would aid the systematic evaluation of the common variant model of common disease.

  • Short Title: Haplotype tagging for the identification of common disease genes
  • Date: 01-10-2001
  • Journal: Nature Genetics
  • Volume: 29
  • Issue: 2
  • Pages: 233-237
  • Publisher: Nature Publishing Group
  • Publication type: Article
  • Bibliographic status: Published

Keywords: Base Sequence Dna *Genetic Predisposition to Disease *Haplotypes Humans Linkage Disequilibrium Polymorphism, Single Nucleotide Research Support, Non-U.S. Gov't Sequence Homology, Nucleic Acid

Staff

Professor Heather Cordell
Professor of Statistical Genetics