A well-known finding of functional polymorphisms is that they are usually under strong selective pressure and thus have low minor allele frequencies (5). To validate the results of our prioritization, we compared the output risk rankings of FASTSNP with the allele frequencies from SNP500Cancer (33) to see if SNPs with high predicted risks actually have low allele frequencies. The SNP500Cancer database was selected because it provides sufficient curated disease-causing SNPs with comparable allele-frequency results obtained by sequencing the same 102 subjects of different ethnic groups. FASTSNP successfully prioritized 1569 SNPs and the results, as given in Figure 3, show that high-risk SNPs tend to have low allele frequencies. SNPs with the highest risk have the least mean minor allele frequency (MAF) and MAF increases if the risk is not as high, consistent with Cargill et al.'s finding (5).
