Introduction

Several different methodologic approaches are useful to establish that genes are important for the development and manifestation of complex disorders. Historically, twin, adoption, and family studies have been the methods of choice. It is assumed that genetic factors are important in the expression of a disorder if (i) monozygotic twins have a higher concordance rate than do dizygotic twins, (ii) adopted children resembled their biological parents more often than they resemble their adoptive parents, or (iii) a particular condition is more likely to occur among biological relatives of the patient than would be expected by chance. If there is compelling evidence from these types of study, then genetic linkage studies can be initiated to identify regions of the genome that harbor susceptibility genes.

Genetic linkage has long been recognized as one of the most powerful methods for clarifying the role of genetics in the expression of human disorders. Historically, the method has had limited applicability because of the small number of sufficiently polymorphic genetic markers available for study in humans. This situation has changed dramatically. Advances in DNA technology have made it possible to detect many highly polymorphic genetic markers. These genetic markers, based on DNA sequence polymorphisms, have stimulated a renewed interest in linkage approaches to the study of human disorders. As a result, extensive linkage maps of all human chromosomes are available for use in genome wide scans (Gyapay et al., 1994).