Human Genetics

, Volume 118, Issue 6, pp 669–679

Evaluating HapMap SNP data transferability in a large-scale genotyping project involving 175 cancer-associated genes

  • Gloria Ribas
  • Anna González-Neira
  • Antonio Salas
  • Roger L. Milne
  • Ana Vega
  • Begoña Carracedo
  • Emilio González
  • Eva Barroso
  • Lara P. Fernández
  • Patricio Yankilevich
  • Mercedes Robledo
  • Ángel Carracedo
  • Javier Benítez
Review Article

Abstract

One of the many potential uses of the HapMap project is its application to the investigation of complex disease aetiology among a wide range of populations. This study aims to assess the transferability of HapMap SNP data to the Spanish population in the context of cancer research. We have carried out a genotyping study in Spanish subjects involving 175 candidate cancer genes using an indirect gene-based approach and compared results with those for HapMap CEU subjects. Allele frequencies were very consistent between the two samples, with a high positive correlation (R) of 0.91 (P<<1×10−6). Linkage disequilibrium patterns and block structures across each gene were also very similar, with disequilibrium coefficient (r2) highly correlated (R=0.95, P<<1×10−6). We found that of the 21 genes that contained at least one block larger than 60 kb, nine (ATM, ATR, BRCA1, ERCC6, FANCC, RAD17, RAD50, RAD54B and XRCC4) belonged to the GO category “DNA repair”. Haplotype frequencies per gene were also highly correlated (mean R=0.93), as was haplotype diversity (R=0.91, P<<1×10−6). “Yin yang” haplotypes were observed for 43% of the genes analysed and 18% of those were identical to the ancestral haplotype (identified in Chimpazee). Finally, the portability of tagSNPs identified in the HapMap CEU data using pairwise r2 thresholds of 0.8 and 0.5 was assessed by applying these to the Spanish and current HapMap data for 66 genes. In general, the HapMap tagSNPs performed very well. Our results show generally high concordance with HapMap data in allele frequencies and haplotype distributions and confirm the applicability of HapMap SNP data to the study of complex diseases among the Spanish population.

Supplementary material

439_2005_94_MOESM1_ESM.pdf (458 kb)
Supplementary material

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Gloria Ribas
    • 1
  • Anna González-Neira
    • 2
  • Antonio Salas
    • 3
    • 4
  • Roger L. Milne
    • 2
  • Ana Vega
    • 4
    • 5
  • Begoña Carracedo
    • 4
  • Emilio González
    • 2
  • Eva Barroso
    • 1
  • Lara P. Fernández
    • 1
  • Patricio Yankilevich
    • 6
  • Mercedes Robledo
    • 7
  • Ángel Carracedo
    • 3
    • 4
    • 5
  • Javier Benítez
    • 1
    • 2
  1. 1.Grupo de Genética Humana Programa de Patología MolecularCentro Nacional de Investigaciones Oncológicas (CNIO)MadridSpain
  2. 2.Centro Nacional de Genotipado (CeGen)Centro Nacional de Investigaciones Oncológicas (CNIO)MadridSpain
  3. 3.Unidade de XenéticaInstituto de Medicina Legal, Facultade de Medicina Santiago de CompostelaSpain
  4. 4.Centro Nacional de Xenotipado (CeGen)Hospital Clínico UniversitarioSantiago de CompostelaSpain
  5. 5.Unidade de Medicina Molecular, Fundación Pública Galega de Medicina Xenómica (FPGMX)Hospital Clínico UniversitarioSantiago de CompostelaSpain
  6. 6.Grupo de BioinformáticaCentro Nacional de Investigaciones Oncológicas (CNIO)MadridSpain
  7. 7.Cáncer Hereditario EndocrinoCentro Nacional de Investigaciones Oncológicas (CNIO)MadridSpain

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