ABSTRACT
Genetic association studies are all about the association of various phenotypes with genetic variants. Genetic variation generates variability in phenotypes, including a spectrum of susceptibility to disease. The most common type of genetic variation is sequence differences between the copies of genes on different chromosomes. Genetic variation may also refer to changes in the copy number of short sequences, regions, or genes. Changes in the numbers or structures of chromosomes are gross types of variation, often incompatible with life, and are therefore rare. To be able to modify disease susceptibility, variants should affect either gene function or the structure of the encoded protein. A variant may modify disease risk via changes in genome biology (Figure 1.1). The most common trait or intermediate phenotype that is influenced by genetic variation is gene expression. This chapter provides background information on molecular genetics relevant to the understanding of the outcomes of genetic variation. Such information is important in variant selection for a genetic association study, for interpretation of results, and for designing functional replication experiments as follow-up studies. Very rare variations that are Mendelian disease-causing mutations are important in medical genetics. Other chapters providing background information for the statistical and epidemiologic aspects of genetic association studies follow this chapter.
