Simpson Claire L, Knight Joanne, Butcher Lee M, Hansen Valerie K, Meaburn Emma, Schalkwyk Leonard C, Craig Ian W, Powell John F, Sham Pak C, Al-Chalabi Ammar
Department of Neurology, PO43, Institute of Psychiatry London SE5 8AF, UK.
Nucleic Acids Res. 2005 Feb 8;33(3):e25. doi: 10.1093/nar/gni028.
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.
在微阵列上分析混合DNA是对数百名个体进行数千个标记的基因分型以进行全基因组关联研究的有效方法。虽然直接比较病例组和对照组的荧光分数是可行的,但校正等位基因的差异杂交很重要,特别是对于罕见的单核苷酸多态性。这种校正依赖于杂合荧光分数,并且需要对数百名个体进行基因分型以获得校正因子的充分估计,这完全抵消了混合样本所带来的任何益处。我们探讨了差异杂交对检验统计量的影响,并以积累杂合荧光分数的中央资源的形式提供了解决该问题的方案,从而能够在不增加额外成本的情况下准确估计等位基因频率。