Mendelian, Non-Mendelian, Multigenic Inheritance, and Epigenetics

Genetics plays a role in the pathophysiology of much of human disease. Approximately one-third of all human genes are expressed in the nervous systems, making neurogenetic phenotypes quite common. In this chapter, we review the modes of inheritance that can be observed in various human neurologic and psychiatric disease: mendelian disorders, wherein mutations in a single disease-causing gene can result in a disease phenotype; nonmendelian disorders, exemplified by uniparental disomy and imprinting; multifactorial inheritance and complex traits, where interactions between various genes and environment are crucial to phenotype manifestation; and epigenetics, involving control of gene expression and gene-gene or gene-environmental interactions. Emphasis is placed on clinical examples of genetic mechanisms, as well as on molecular methods used to identify genetic and genomic variability and mutations underlying neurogenetic phenotypes.