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Human genetics research has received considerable recent attention as a result of major developments in molecular genetic technologies, large-scale coordinated research initiatives such as the Human Genome Project and the International HapMap Project, and major discoveries concerning the genetic basis of disease. The strategies that human geneticists exploit to identify DNA sequence variations that influence disease susceptibility leverage an understanding of the behavior of sequence variations when transmitted from parents to offspring across generations either within a specific family, among a set of families, or in the population at large. In this brief review we describe the basic principles behind the most widely used human genetic strategies to identify inherited disease susceptibility factors. We also point out the limitations and issues that plague these strategies as well as areas for further study.