Haplotype tagging for the identification of common disease genes View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2001-10

AUTHORS

Gillian C.L. Johnson, Laura Esposito, Bryan J. Barratt, Annabel N. Smith, Joanne Heward, Gianfranco Di Genova, Hironori Ueda, Heather J. Cordell, Iain A. Eaves, Frank Dudbridge, Rebecca C.J. Twells, Felicity Payne, Wil Hughes, Sarah Nutland, Helen Stevens, Phillipa Carr, Eva Tuomilehto-Wolf, Jaakko Tuomilehto, Stephen C.L. Gough, David G. Clayton, John A. Todd

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 evaluated1,2,3, even the most recent studies2,4 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. More... »

PAGES

233-237

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng1001-233

    DOI

    http://dx.doi.org/10.1038/ng1001-233

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1017573512

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/11586306


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