title: SNP allele frequency estimation in DNA pools and variance components analysis.
abstract: The estimation of single nucleotide polymorphism (SNP) allele frequency in pooled DNA samples has been proposed as a cost-effective approach to whole genome association studies. However, the key issue is the allele frequency window in which a genotyping method operates and provides a statistically reliable answer. We assessed the homogeneous mass extend assay and estimated the variance associated with each experimental stage. We report that a relationship between estimated allele frequency and variance might exist, suggesting that high statistical power can be retained at low, as well as high, allele frequencies. Assuming this relationship, the formation of subpools consisting of 100 samples retains an effective sample size greater than 70% of the true sample size, with a savings of 11-fold the cost of an individual genotyping study, regardless of allele frequency.
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Downes
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Barratt
authors.forename: Pelin
authors.initials: P
authors.lastname: Akan
authors.forename: Sue J
authors.initials: SJ
authors.lastname: Bumpstead
authors.forename: Stacey D
authors.initials: SD
authors.lastname: Taylor
authors.forename: David G
authors.initials: DG
authors.lastname: Clayton
authors.forename: Panos
authors.initials: P
authors.lastname: Deloukas
mesh_terms: D000465:Algorithms; D004247:DNA / Q000032:analysis* / Q000737:chemistry* / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods*; D005787:Gene Frequency / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D008957:Models, Genetic; D015233:Models, Statistical; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D025341:Principal Component Analysis; D015203:Reproducibility of Results; D018401:Sample Size; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA / Q000379:methods*
chemical_list: D004247:DNA