title: Characterisation of the genomic architecture of human chromosome 17q and evaluation of different methods for haplotype block definition.
abstract: BACKGROUND
  The selection of markers in association studies can be informed through the use of haplotype blocks. Recent reports have determined the genomic architecture of chromosomal segments through different haplotype block definitions based on linkage disequilibrium (LD) measures or haplotype diversity criteria. The relative applicability of distinct block definitions to association studies, however, remains unclear. We compared different block definitions in 6.1 Mb of chromosome 17q in 189 unrelated healthy individuals. Using 137 single nucleotide polymorphisms (SNPs), at a median spacing of 15.5 kb, we constructed haplotype block maps using published methods and additional methods we have developed. Haplotype tagging SNPs (htSNPs) were identified for each map.
  
  
  RESULTS
  Blocks were found to be shorter and coverage of the region limited with methods based on LD measures, compared to the method based on haplotype diversity. Although the distribution of blocks was highly variable, the number of SNPs that needed to be typed in order to capture the maximum number of haplotypes was consistent.
  
  
  CONCLUSIONS
  For the marker spacing used in this study, choice of block definition is not important when used as an initial screen of the region to identify htSNPs. However, choice of block definition has consequences for the downstream interpretation of association study results.
authors.affiliation: Centre for Integrated Genomic Medical Research, University of Manchester, Manchester, UK. elez@well.ox.ac.uk
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Zeggini
authors.forename: Anne
authors.initials: A
authors.lastname: Barton
authors.forename: Stephen
authors.initials: S
authors.lastname: Eyre
authors.forename: Daniel
authors.initials: D
authors.lastname: Ward
authors.forename: William
authors.initials: W
authors.lastname: Ollier
authors.forename: Jane
authors.initials: J
authors.lastname: Worthington
authors.forename: Sally
authors.initials: S
authors.lastname: John
mesh_terms: D002886:Chromosomes, Human, Pair 17; D005787:Gene Frequency; D005819:Genetic Markers; D015894:Genome, Human; D023281:Genomics / Q000379:methods*; D006239:Haplotypes; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D006113:United Kingdom
chemical_list: D005819:Genetic Markers