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        Models for Determining Genetic Susceptibility and Predicting Outcome

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        In this chapter, we focus on the study of associations between disease and inheritance of particular genetic variants, a field described as genetic epidemiology. Genetic variation based on polymorphism is common in human populations and appears to be a critical factor in determining susceptibility to disease. Polymorphism describes the presence of variant forms of genes (alleles) that are inhherited from parents. Individuals within a population may therefore inherit none (homozygous wild-type), one (heterozygote), or two (homozygous mutant) copies of the variant allele. These combinations are referred to as genotypes. Many types of allelic variation have been described, including deletions and insertions of DNA bases or even whole genes. Recently, genetic variation derived from single nucleotide polymorphisms (SNPs)—single base changes thought to occur every 500–1000 nucleotides—have attracted considerable interest in the context of disease susceptibility. For the purpose of this review, we will use data collected in our laboratories on ploymorphisms in members of the glutathione S-transferase (GST) supergene family of enzymes (see Hayes and Strange [1 ] for a recent review).
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