title: Identification of genetic factors that modify motor performance and body weight using Collaborative Cross mice.
abstract: Evidence has emerged that suggests a link between motor deficits, obesity and many neurological disorders. However, the contributing genetic risk factors are poorly understood. Here we used the Collaborative Cross (CC), a large panel of newly inbred mice that captures 90% of the known variation among laboratory mice, to identify the genetic loci controlling rotarod performance and its relationship with body weight in a cohort of 365 mice across 16 CC strains. Body weight and rotarod performance varied widely across CC strains and were significantly negatively correlated. Genetic linkage analysis identified 14 loci that were associated with body weight. However, 45 loci affected rotarod performance, seven of which were also associated with body weight, suggesting a strong link at the genetic level. Lastly, we show that genes identified in this study overlap significantly with those related to neurological disorders and obesity found in human GWA studies. In conclusion, our results provide a genetic framework for studies of the connection between body weight, the central nervous system and behavior.
authors.affiliation: Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Mao
authors.affiliation: Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
authors.forename: Sasha A
authors.initials: SA
authors.lastname: Langley
authors.affiliation: Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
authors.forename: Yurong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Hang
authors.affiliation: Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
authors.forename: Kristofer E
authors.initials: KE
authors.lastname: Bouchard
authors.affiliation: Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Celniker
authors.affiliation: Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
authors.forename: James B
authors.initials: JB
authors.lastname: Brown
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory Richland, WA, USA.
authors.forename: Janet K
authors.initials: JK
authors.lastname: Jansson
authors.affiliation: Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.|Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
authors.forename: Gary H
authors.initials: GH
authors.lastname: Karpen
authors.affiliation: Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
authors.forename: Antoine M
authors.initials: AM
authors.lastname: Snijders
mesh_terms: D000818:Animals; D001835:Body Weight / Q000235:genetics*; D002874:Chromosome Mapping; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000235:genetics*; D009765:Obesity / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D040641:Quantitative Trait Loci / Q000235:genetics*; D012307:Risk Factors