Determination of Genotype Frequencies in Well-Defined Populations

A general survey application is to determine the distribution of various genes and alleles in defined populations. While it is an empirical question whether well-constructed and executed population samples will reveal estimates of genotype (allele) frequencies markedly different from more customary sources, such as volunteer populations, clinical populations, blood donors, and newborn screening samples, this use is probably one of the best applications for preexisting and planned general population samples. In addition to their specific sample representativeness, the NIA populations may be attractive because of their broad national coverage, multinational representation, and in some instances access to special populations such as the institutionalized elderly or the oldest old. This access would be particularly valuable as genes are discovered that are associated with late-onset diseases, given the age distribution of many NIA-sponsored survey participants. Several potential specific applications are presented, with examples from the recent scientific literature:

  1. Identification of the age-specific prevalence rates for various alleles to explore hypotheses that these alleles are associated with longevity, at least in cross-sectional designs.
  2. More precise estimation of rare gene/allele population prevalence, because many populations have thousands of participants. This would generally increase the ability to study the biologic behavior of putative, but rarely occurring, gene-disease associations. For an example in population genetic modeling, see Joyce and Tavare (1995). Another example is the population prevalence of the genetic variants of phenylketonuria, a condition that has a frequency of about 1:10,000 (Eisensmith and Woo, 1994).
  3. Determination of allele frequency in multiple ethnic and national groups; this allows assessment of the genetic relatedness of such groups, as well as a comparison of gene frequencies with disease-occurrence rates (Gill and Evett, 1995).
  4. Calculation of population inbreeding coefficients in selected populations to explore the emergence of recessive traits. If genetic determinations are done on available families ascertained from population surveys, it is possible to quantify the degree of population inbreeding, which positively correlates with the emergence rate of hidden (recessive) genetic conditions in that population. This value is sometimes a very important datum in understanding population disease rates (Gill and Evett, 1995).
  5. Assessment of genetic relatedness of migrant and native ethnic, tribal, or national populations. Genetic tools may be useful for tracking the origins of population migration in prehistoric and early historic times (Kalnin et al., 1995).
  6. Provision of high-quality population-referent genetic-marker data for forensic applications. The use of geographically defined populations may offer


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