Published online 8 February 2005
Methods Online |
A central resource for accurate allele frequency estimation from pooled DNA genotyped on DNA microarrays
Department of Neurology, PO43, Institute of Psychiatry London SE5 8AF, UK 1 Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry London SE5 8AF, UK 2 Department of Neuroscience, Institute of Psychiatry London SE5 8AF, UK 3 Department of Psychiatry and Genome Centre, University of Hong Kong Hong Kong
*To whom correspondence should be addressed. Tel: +44 20 7848 5172; Fax: +44 20 7848 5190; Email: ammar{at}iop.kcl.ac.uk
Received October 7, 2004. Revised January 21, 2005. Accepted January 21, 2005.
Analysing pooled DNA on microarrays is an efficient way to genotype hundreds of individuals for thousands of markers for genome-wide association. Although direct comparison of case and control fluorescence scores is possible, correction for differential hybridization of alleles is important, particularly for rare single nucleotide polymorphisms. Such correction relies on heterozygous fluorescence scores and requires the genotyping of hundreds of individuals to obtain sufficient estimates of the correction factor, completely negating any benefit gained by pooling samples. We explore the effect of differential hybridization on test statistics and provide a solution to this problem in the form of a central resource for the accumulation of heterozygous fluorescence scores, allowing accurate allele frequency estimation at no extra cost.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors
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