Published online 14 February 2006
Methods Online |
Genotyping pooled DNA using 100K SNP microarrays: a step towards genomewide association scans
Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London De Crespigny Park, London, SE5 8AF, UK
*To whom correspondence should be addressed. Box Number P082, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK. Tel: +44 20 7848 0748; Fax: +44 20 7848 0895; Email: e.meaburn{at}iop.kcl.ac.uk
Received October 26, 2005. Revised December 6, 2005. Accepted January 27, 2006.
The identification of quantitative trait loci (QTLs) of small effect size that underlie complex traits poses a particular challenge for geneticists due to the large sample sizes and large numbers of genetic markers required for genomewide association scans. An efficient solution for screening purposes is to combine single nucleotide polymorphism (SNP) microarrays and DNA pooling (SNP-MaP), an approach that has been shown to be valid, reliable and accurate in deriving relative allele frequency estimates from pooled DNA for groups such as cases and controls for 10K SNP microarrays. However, in order to conduct a genomewide association study many more SNP markers are needed. To this end, we assessed the validity and reliability of the SNP-MaP method using Affymetrix GeneChip® Mapping 100K Array set. Interpretable results emerged for 95% of the SNPs (nearly 110 000 SNPs). We found that SNP-MaP allele frequency estimates correlated 0.939 with allele frequencies for 97 605 SNPs that were genotyped individually in an independent population; the correlation was 0.971 for 26 SNPs that were genotyped individually for the 1028 individuals used to construct the DNA pools. We conclude that extending the SNP-MaP method to the Affymetrix GeneChip® Mapping 100K Array set provides a useful screen of >100 000 SNP markers for QTL association scans.
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