Translational relevance of forward genetic screens in animal models for the study of psychiatric disease

• Published in: Neuroscience and biobehavioral reviews Vol. 135; p. 104559
• Main Authors: Sheardown, Eva, Mech, Aleksandra M., Petrazzini, Maria Elena Miletto, Leggieri, Adele, Gidziela, Agnieszka, Hosseinian, Saeedeh, Sealy, Ian M., Torres-Perez, Jose V., Busch-Nentwich, Elisabeth M., Malanchini, Margherita, Brennan, Caroline H.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.04.2022
• Subjects: Addiction; Animals; C. elegans; Caenorhabditis elegans - genetics; Core component behaviors; Disease Models, Animal; Drosophila; Forward genetic screen; Humans; Impulse control; Mental Disorders - genetics; Mice; Models, Animal; Psychiatric disease; Zebrafish; Zebrafish - genetics; C. elegans; Addiction; Drosophila; Zebrafish; Mice; Impulse control; Psychiatric disease; Core component behaviors; Forward genetic screen
• ISSN: 0149-7634; 1873-7528; 1873-7528
• DOI: 10.1016/j.neubiorev.2022.104559

Psychiatric disorders represent a significant burden in our societies. Despite the convincing evidence pointing at gene and gene-environment interaction contributions, the role of genetics in the etiology of psychiatric disease is still poorly understood. Forward genetic screens in animal models have helped elucidate causal links. Here we discuss the application of mutagenesis-based forward genetic approaches in common animal model species: two invertebrates, nematodes (Caenorhabditis elegans) and fruit flies (Drosophila sp.); and two vertebrates, zebrafish (Danio rerio) and mice (Mus musculus), in relation to psychiatric disease. We also discuss the use of large scale genomic studies in human populations. Despite the advances using data from human populations, animal models coupled with next-generation sequencing strategies are still needed. Although with its own limitations, zebrafish possess characteristics that make them especially well-suited to forward genetic studies exploring the etiology of psychiatric disorders. •Assays of core component behaviors associated with human psychiatric disease are established.•Behavioral screens in animal models predict loci affecting human behavior.•Next generation sequencing facilitates identification of candidate mutations.•Combining human and animal studies reveals the biology of human psychiatric disease.