title: Precise estimation of allele frequencies of single-nucleotide polymorphisms by a quantitative SSCP analysis of pooled DNA.
abstract: We show that single-nucleotide polymorphisms (SNPs) of moderate to high heterozygosity (minor allele frequencies >10%) can be efficiently detected, and their allele frequencies accurately estimated, by pooling the DNA samples and applying a capillary-based SSCP analysis. In this method, alleles are separated into peaks, and their frequencies can be reliably and accurately quantified from their peak heights (SD <1.8%). We found that as many as 40% of publicly available SNPs that were analyzed by this method have widely differing allele frequency distributions among groups of different ethnicity (parents of Centre d'Etude Polymorphisme Humaine families vs. Japanese individuals). These results demonstrate the effectiveness of the present pooling method in the reevaluation of candidate SNPs that have been collected by examination of limited numbers of individuals. The method should also serve as a robust quantitative technique for studies in which a precise estimate of SNP allele frequencies is essential-for example, in linkage disequilibrium analysis.
authors.affiliation: Division of Genome Analysis, Institute of Genetic Information, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sasaki
authors.forename: T
authors.initials: T
authors.lastname: Tahira
authors.forename: A
authors.initials: A
authors.lastname: Suzuki
authors.forename: K
authors.initials: K
authors.lastname: Higasa
authors.forename: Y
authors.initials: Y
authors.lastname: Kukita
authors.forename: S
authors.initials: S
authors.lastname: Baba
authors.forename: K
authors.initials: K
authors.lastname: Hayashi
mesh_terms: D000483:Alleles; D016375:Antisense Elements (Genetics); D001483:Base Sequence; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004252:DNA Mutational Analysis / Q000379:methods*; D005787:Gene Frequency / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D016375:Antisense Elements (Genetics); D004247:DNA