title: Identifying genes for neurobehavioural traits in rodents: progress and pitfalls.
abstract: Identifying genes and pathways that contribute to differences in neurobehavioural traits is a key goal in psychiatric research. Despite considerable success in identifying quantitative trait loci (QTLs) associated with behaviour in laboratory rodents, pinpointing the causal variants and genes is more challenging. For a long time, the main obstacle was the size of QTLs, which could encompass tens if not hundreds of genes. However, recent studies have exploited mouse and rat resources that allow mapping of phenotypes to narrow intervals, encompassing only a few genes. Here, we review these studies, showcase the rodent resources they have used and highlight the insights into neurobehavioural traits provided to date. We discuss what we see as the biggest challenge in the field - translating QTLs into biological knowledge by experimentally validating and functionally characterizing candidate genes - and propose that the CRISPR/Cas genome-editing system holds the key to overcoming this obstacle. Finally, we challenge traditional views on inbred versus outbred resources in the light of recent resource and technology developments.
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK abaud@ebi.ac.uk JFlint@mednet.ucla.edu.
authors.forename: Amelie
authors.identifier: 0000-0003-2448-0283
authors.initials: A
authors.lastname: Baud
authors.affiliation: Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90095-1761, USA abaud@ebi.ac.uk JFlint@mednet.ucla.edu.
authors.forename: Jonathan
authors.identifier: 0000-0002-9427-4429
authors.initials: J
authors.lastname: Flint
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D007178:Inbreeding; D051379:Mice; D009420:Nervous System / Q000378:metabolism*; D040641:Quantitative Trait Loci / Q000235:genetics; D019655:Quantitative Trait, Heritable; D051381:Rats; D011995:Recombination, Genetic / Q000235:genetics
keywords: Genetics of behaviour; Quantitative trait loci; Rodent resources