Allele frequencies

Genetic drift is alteration of allele frequencies in small populations by chance events. During times when large populations are reduced to small numbers of individuals, genetic variation is likely to be lost by chance. Genetic drift also occurs when a small number of individuals colonize a new region. The pioneers are unlikely to have all the alleles found in the source population and the frequencies of the ones they do have are likely to differ from those in the source population. 

Parker, P.J.-A. and Callaghan, A. (1997). Esterase activity and allele frequency in field populations of Simulium equinum exposed to organophosphate pollution. Environmental Toxicology and Chemistry 16, 2550-2555. 

One point should be raised that was not dealt with in the Lauranson and Lebreton (1991) paper. It would appear that the authors examined the concentration values of the individual flavonols at face value without considering likely or possible biosynthetic relationships. In particular, isorhamnetin is produced by 0-methylation of quercetin. Total quercetin produced would then be the sum of quercetin per se plus the amount of isorhamnetin present. This value, reflecting total 3, 4 -dioxygenated flavonols, would be the more accurate measure of allele frequency. 

The discrepancies between the results of studies in different ethnic groups may be partially due to differences in allele frequencies. 

Bradford, L. D. (2002). CYP2D6 allele frequency in European Caucasians, Asians, Africans and their descendants. Pharmacogenomics, 3, 229 13. 

Nozawa, T., Nakajima, M., Tamai, I., Noda, K., Nezu, J., Sai, Y., Tsuji, A., Yokoi, T., Genetic polymorphisms of human organic anion transporters OATP-C (SLC21A6) and OATP-B (SLC21A9) allele frequencies in the Japanese population and functional analysis, J. Pharmacol. Exp. Ther. 2002, 302, 804-813. 

Sample sizes required for discovering SNPs associated with drug response depend on a number of factors, among which are the SNP allele frequencies, the number of SNPs being tested and, for LD mapping studies, the strength of LD. A marker... 

For example, if 400 patients were required to find an association by measuring the causative SNP directly, then 816 patients would be required to find the same association using random SNPs in LD with the causative SNP where D is 0.7, and 1,600 patients if D is 0.5. This situation becomes even more complex when large differences in allele frequencies exist between markers and susceptibility SNPs. If marker allele frequencies are substantially different from the susceptibility allele frequency, then the required sample size, the number of markers, or both will need to be dramatically increased [53]. 

Goddard KA, Hopkins PJ, Hall JM, Witte JS. Hnkage disequilibrium and allele frequency distributions for 114 single-nucleotide polymorphisms in five populations. Am J Hum Genet 2000 66 216-234. 

Location Position Allele Effect Allelic frequency m Genotype Genotype frequency m Reference... 

Population Allele frequency Genotype frequency Reference... 

A total of 13 polymorphisms in the gene and its transcriptional regulator beta-upstream peptide (BUP) have been identified [73]. Three closely linked polymorphisms, two coding block SNPs at amino acid positions 16 and 27, and a SNP in the BUP were found to be common (i.e., allele frequency >0.15) in the general Caucasian population [74, 75]. 

Allele frequency Dominant model31 Recessive model4 ... 

Both mode of inheritance (dominant, recessive) and allele frequency can have dramatic effects on required sample sizes (Table 10.2). Even for the best case scenario - a common SNP acting in a dominant fashion - a relatively large sample size of more than 300 cases (a total sample size of >900 subjects) is required at an a of 0.05 (Table 10.2). 

The function of DMEs is also thought to include the detoxification of dietary products and the evolution of plant metabolites, including drugs [11]. The selective forces responsible for the maintenance of different alleles in different populations may include the fact that one allele may enable improved rates of implantation, improved prenatal growth and development, improved postnatal health in response to dietary or environmental selective pressures or improved resistance to bacteria, viruses or parasites [11, 14]. Allele frequencies may also reflect ethnic dietary differences that have evolved over thousands of years [15]. 

---