Genetic Mapping

T he goal of this chapter is to provide the investigator with sufficient information to undertake the design and perform the initial steps in trait-gene discovery—i.e., in identifying genetic variations that modulate (e.g., increasing or decreasing) the risk of developing a particular human trait or modulate the expression of a particular trait. It covers the stages from initial definition of a trait through identification of the genetic variation that either is the causative, susceptibility, or functional variation, or lies close to it. The approaches presented for ascertainment, and the laboratory procedures presented for genotype generation (also see Chapter 2, “Genotyping”), can be applied to traits with either a simple or a complex genetic etiology. The data analyses presented for the simpler genetic traits provide the basis for understanding approaches to more complex traits. There have been numerous advances in analytical methods for complex genetic traits, but no standard or ubiquitous approach has yet emerged that is successful under all circumstances. This is not surprising, since the underlying genetic architectures of human traits are extremely variable. To understand this chapter, the reader must have a basic understanding of genetics, including meiosis, recombination, and the structure of the genome. A basic understanding of statistics and biostatistics is also recommended for some of the units (see recommended texts in the preface to this manual, and citations below).