Approaches to allele frequency determination

Hundreds of thousands of candidate single nucleotide polymorphisms (SNPs) are being identified as part of the human genome project. For these markers to be useful in any study their allele frequencies in the study population must be known, or much effort will be wasted when markers with the wrong characteristics are selected for studies involving large-scale genotyping of SNP markers. Because allele frequency estimations by genotyping a representative sample of a population is a costly endeavour, an obvious strategy to reduce the cost is to identify accurate and efficient approaches to allele frequency estimation using DNA pools. There are several allele frequency estimation approaches currently in use, including PCR-RFLP analysis, DNA sequencing, the Taqman assay and kinetic PCR. All these approaches give reasonably good allele frequency estimates. Accurate and efficient allele frequency estimation in DNA pools will reduce the cost and effort needed in genetic and association studies and opens up ways to perform pharmacogenomic and evolutionary studies efficiently.