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greater precision in estimating genetic-marker prevalence, which has many medico-legal uses (van Oorschot et al., 1994).
Geographic searches for original or "founding" populations for various genetic diseases. Sometimes it is useful in understanding the population distribution of important genetic diseases to determine the historical source of the original mutations. This can often be difficult, but variation in allele frequencies among different ethnic groups in a population can offer useful clues, as in familial hypercholesterolemia, which is caused by a major gene (Rubinsztein et al., 1994).
Exploration for certain genes or alleles that may explain geographic differences in individual response to certain medications. For example, a particular allele that alters metabolism of a common class of antihypertensive drugs may be much more common in Chinese than in Caucasian populations (Lee, 1994). In an analogous manner, gene-directed alterations in the metabolism of toxic environmental chemicals may be used to explain population differences in disease risk associated with those exposures. Another example is the possibility of determining population differences in the risk of adverse reactions to blood transfusion based on the genetic characteristics of donor and recipient populations (Shivdasani and Anderson, 1994).
Determination of the risk of specific diseases in individuals. A major hope has been to use population studies to explore the role of various genetic determinations in disease risk for individuals. Earlier attempts at using measurable phenotypes (physical manifestations of gene function such as blood type or eye color) as risk factors for disease occurrence were only modestly successful. Even now, with a host of gene-measurement techniques, determining gene-disease associations in prospective population studies is probably inefficient, although perhaps useful for selected investigations. Most gene-disease associations are sought by other means, such as twin studies, segregation analysis of pedigrees, and case-control studies. Defined populations could also be used to verify gene-disease associations, discovered elsewhere, in a population context and to determine the sensitivity and specificity of particular alleles for predicting disease occurrence. One example is the recent association of the apolipoprotein E alleles with variation in the risk of dementia or cognitive change, which was seen in a cohort study (Hyman et al., in press). Other examples of genetic applications for determining disease risk in populations are the suggestion that there may be genes determining susceptibility to tuberculosis infection (Skamene, 1994) and the emerging demonstration of genetic forces in cardiovascular-disease risk factors, such as obesity and hypertension (Schork et al., 1994). Knowledge of population gene frequency for known disease-causing alleles is also quite useful for planning and executing population-based genetic screening programs, which are becoming more common as disease genes are discovered (Shickle and Harvey, 1993). However, regardless of whether genetic markers predict disease onset, they have other emerging uses, such as predicting the natural history and outcome