Blood types and allozymes were historically important as genetic markers used in population genetic studies, and allozymes continue to be used. Increasingly, however, DNA markers are becoming the primary type of genetic marker used in population genetics. A wide range of markers are available and much higher levels of variation can be screened than with allozymes. Variations may be in numbers of short repeats (STRPs, simple tandem repeat polymorphisms) and in single base substitutions. PCR and restriction fragment length polymorphisms (RFLPs) are two ways to detect such variation.
DNA markers can be used in criminal and paternity cases. This relies on high levels of variation available in these markers (e.g., STRPs). In many cases the normal individual in a population will be heterozygous, and many alleles will be present. There is some variation among human population groups in frequencies of particular alleles. This needs to be considered in estimating the probabilties of particular genotypes.
The basic principle of this analysis is that a failure to find a match between a person’s markers and the unknown will exclude a suspect, but a match does not in itself prove a person is guilty. When a match occurs, though, it is helpful to estimate the frequency of that genotype in the population to help the court make a decision. To estimate probabilities, the frequency of the genotype that is found at each marker locus is multiplied across all of the markers tested. For example, if the individual were heterozygous at five markers, and the allele frequency in all cases were 0.1, the likelihood of that specific genotype in the population would be 2pq multiplied five times, or 2(.1)(.1) to the fifth power, or (.02)5 = 8 X 10-6
The following are the assumptions of the Hardy-Weinberg principle. (These are reasonable starting points for using this formula. As we will see, deviations from these assumptions are the basis for genetic change over time (evolution). (1) Random mating- individuals mate at random with respect to genotype and phenotype. (2) No mutation — (over the short term, this is not a bad assumption since mutation is a rare process). (3) No migration- alleles from other groups with other allele frequencies would change the population over time. (4) No selection- If some genotypes survive and reproduce better than others, change will occur. (5) Large population size, no "genetic drift". Genetic drift can change allele frequencies in small populations as a result of sampling effects. Founder effect refers to a situation in which a few individuals found a population and the resulting population has a different allele frequency than the source population.
The Hardy-Weinberg principle has important implications when studying rare alleles and sex-linked genes. For rare alleles, heterozygotes carrying the allele are much more common than the homozygous individuals. This difference is more pronounced the rarer the allele is. For example cystic fibrosis is a genetic disease which is relatively common in Caucasian populations. The frequency is 1/1700 = .00059 = q2. The allele frequency, q, then is the square root of .00059, or .024. The frequency of heterozygotes will then be 2pq = (2) (.976) (.024) = .047 = 1/21. If marriages are at random, 1/21 X 1/21 = 1/444 Caucasian marriages will be between two heterozygotes. In contrast, albinism is a rarer condition, with an even greater proportion of alleles in the heterozygotes. The frequency of albinism among the offspring of unrelated individuals will be 1/20,000 = q2 = 5 X 10-5 . This gives an allele frequency (q) of about 7 X 10-3, for a heterozygote frequency of 1.4 X 10-2, or about 1/70. Comparing the frequency of homozygotes and heterozygotes for the two conditions above illustrates that more of the alleles are in heterozygotes for rarer conditions.
For X linked genes, the frequency in males will be the same as the allele frequency (q), while the frequency in females will be q2 . X-linked color blindness is relatively common. About 1/20 males is colorblind. The expected frequency of colorblind females will be q2 = (.05)2 = .0025. Hemophilia is a rarer X-linked condition. The frequency of the condition in males is 1/10,000 = 10-4 . In females, the frequency will be q2 = (10-4)2 = 10-8. Thus the condition is exceedingly rare among females. Thus, the rarer the condition, the greater the disparity in frequency of affected individuals is between males and females.