title: Cheap, accurate and rapid allele frequency estimation of single nucleotide polymorphisms by primer extension and DHPLC in DNA pools.
abstract: At present, the cost of genotyping single nucleotide polymorphisms (SNPs) in large numbers of subjects poses a formidable problem for molecular genetic approaches to complex diseases. We have tested the possibility of using primer extension and denaturing high performance liquid chromatography to estimate allele frequencies of SNPs in pooled DNA samples. Our data show that this method should allow the accurate estimation of absolute allele frequencies in pooled samples of DNA and also of the difference in allele frequency between different pooled DNA samples. This technique therefore offers an efficient and cheap method for genotyping SNPs in large case-control and family-based association samples.
authors.affiliation: Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, United Kingdom.
authors.forename: B
authors.initials: B
authors.lastname: Hoogendoorn
authors.forename: N
authors.initials: N
authors.lastname: Norton
authors.forename: G
authors.initials: G
authors.lastname: Kirov
authors.forename: N
authors.initials: N
authors.lastname: Williams
authors.forename: M L
authors.initials: ML
authors.lastname: Hamshere
authors.forename: G
authors.initials: G
authors.lastname: Spurlock
authors.forename: J
authors.initials: J
authors.lastname: Austin
authors.forename: M K
authors.initials: MK
authors.lastname: Stephens
authors.forename: P R
authors.initials: PR
authors.lastname: Buckland
authors.forename: M J
authors.initials: MJ
authors.lastname: Owen
authors.forename: M C
authors.initials: MC
authors.lastname: O'Donovan
mesh_terms: D000483:Alleles; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid / Q000191:economics / Q000379:methods; D002894:Chromosomes, Human, Pair 4; D003365:Costs and Cost Analysis; D004247:DNA / Q000737:chemistry / Q000235:genetics*; D017931:DNA Primers; D005787:Gene Frequency; D030342:Genetic Diseases, Inborn / Q000175:diagnosis / Q000235:genetics; D006720:Homozygote; D006801:Humans; D016133:Polymerase Chain Reaction / Q000191:economics / Q000379:methods; D011110:Polymorphism, Genetic; D015203:Reproducibility of Results; D006113:United Kingdom
chemical_list: D017931:DNA Primers; D004247:DNA