Diametric gene-dosage effects as windows into neurogenetic architecture

Gene expression can be modulated in two opposite directions, towards higher or lower amounts of product. How do diametric changes in gene dosage influence neurological development and function? Recent studies of transgenic and knockout mouse models, genomic copy-number variants, imprinted-gene expression alterations, and sex-chromosome aneuploidies are revealing examples of 'mirror-extreme' brain and behavior phenotypes, which provide unique insights into neurodevelopmental architecture. These convergent studies quantitatively connect gene dosages with specific trajectories and outcomes, with important implications for the experimental dissection of normal neurological functions, the genetic analysis of psychiatric disorders, the development of pharmacological therapies, and mechanisms for the evolution of human brain and behavior.

► Copy-number variants, imprinting, and aneuploidies cause diametric gene dosages. ► Gene dosage changes in opposite directions sometimes cause diametric phenotypes. ► Diametric gene dosage effects can be created with mouse models or occur naturally. ► Diametric gene dosages provide unique insights into neuogenetic architecture.