Simpson, Claire L. and Knight, Joanne and Butcher, Lee M. and Hansen, Valerie K. and Meaburn, Emma and Schalkwyk, Leonard C. and Craig, Ian W. and Powell, John F. and Sham, Pak C. and Al-Chalabi, Ammar (2005) A central resource for accurate allele frequency estimation from pooled DNA genotyped on DNA microarrays. Nucleic Acids Research, 33 (3). ISSN 0305-1048
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Abstract
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.