Genetic Architecture of Complex Diseases

The rapid development of molecular genetic technologies allows highly detailed examination of genome sequence variation and leads to rapid progress in the understanding of the genetic architecture of complex diseases. This chapter reviews the research approaches that have been used to address the relevant questions and summarizes the current state of knowledge and understanding regarding the genetic architecture of complex diseases that have come out of various studies. Common diseases are highly heterogeneous, with a small proportion of cases having relatively simple etiology dominated by a single genetic mutation, while the vast majority of cases are caused by the combined effect of multiple genetic and environmental factors each contributing a minor influence. The genetics approach to the study of complex diseases is complementary to other research paradigms such as the use of cell culture or animal models. The advantages of the genetics approach are that the finite size and regularity of the genome allows a systematic search for sequence-phenotype relationships, which may unveil novel associations that implicate previously unsuspected biological pathways, and the demonstration of sequence-phenotype relationships offers strong direct evidence for the role of a gene or a pathway in human disease, minimizing the need to perform potentially hazardous experiments on humans.