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

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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 (r 2) 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 r 2 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.

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Acknowledgements

EB and LPF are funded by the Comunidad Autónoma de Madrid and by the Spanish Ministry of Science and Technology (MCT), respectively. We thank Christian Torrenteras for Illumina platform support and Fatima Mercadillo and for her expert technical skills. We would also like to thank Christopher Philips and Beatriz Sobrino for their technical support with the SNPlex genotyping platform as well as Jorge Amigo for his assistance with the Genotyping Data Formatter software used to parse SNPlex data and to control genotyping errors. The National Genotyping Centre (CeGen) is funded by the Genome Spain Foundation. This study was partially supported by BFI2003-03852, PI020919, PI041313 and PGIDIT02PXIC20804PN.

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Authors and Affiliations

  1. Grupo de Genética Humana Programa de Patología Molecular, Centro Nacional de Investigaciones Oncológicas (CNIO), C/Melchor Fdz Almagro, 3, E-28029, Madrid, Spain

    Gloria Ribas, Eva Barroso, Lara P. Fernández & Javier Benítez

  2. Centro Nacional de Genotipado (CeGen), Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain

    Anna González-Neira, Roger L. Milne, Emilio González & Javier Benítez

  3. Unidade de Xenética, Instituto de Medicina Legal, Facultade de Medicina , Santiago de Compostela, Galicia, Spain

    Antonio Salas & Ángel Carracedo

  4. Centro Nacional de Xenotipado (CeGen), Hospital Clínico Universitario, Santiago de Compostela, Galicia, Spain

    Antonio Salas, Ana Vega, Begoña Carracedo & Ángel Carracedo

  5. Unidade de Medicina Molecular, Fundación Pública Galega de Medicina Xenómica (FPGMX), Hospital Clínico Universitario, Santiago de Compostela, Galicia, Spain

    Ana Vega & Ángel Carracedo

  6. Grupo de Bioinformática, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain

    Patricio Yankilevich

  7. Cáncer Hereditario Endocrino, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain

    Mercedes Robledo

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  1. Gloria Ribas
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  2. Anna González-Neira
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  3. Antonio Salas
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Correspondence to Gloria Ribas.

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Ribas, G., González-Neira, A., Salas, A. et al. Evaluating HapMap SNP data transferability in a large-scale genotyping project involving 175 cancer-associated genes. Hum Genet 118, 669–679 (2006). https://doi.org/10.1007/s00439-005-0094-9

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