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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:
 [1];  [1];  [1];  [1];  [1];  [1];  [1];  [2];  [3];  [1]
+ Show Author Affiliations
  1. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  2. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
  3. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States)
Publication Date:
Research Org.:
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER)
OSTI Identifier:
1243256
Alternate Identifier(s):
OSTI ID: 1378638
Report Number(s):
PNNL-SA-115429
Journal ID: ISSN 2045-2322
Grant/Contract Number:  
AC05-76RL01830; AC02-05CH11231
Resource Type:
Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 5; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; behavioural genetics

Citation Formats

Mao, Jian -Hua, Langley, Sasha A., Huang, Yurong, Hang, Michael, Bouchard, Kristofer E., Celniker, Susan E., Brown, James B., Jansson, Janet K., Karpen, Gary H., and Snijders, Antoine M. Identification of genetic factors that modify motor performance and body weight using Collaborative Cross mice. United States: N. p., 2015. Web. doi:10.1038/srep16247.
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Mao, Jian -Hua, Langley, Sasha A., Huang, Yurong, Hang, Michael, Bouchard, Kristofer E., Celniker, Susan E., Brown, James B., Jansson, Janet K., Karpen, Gary H., & Snijders, Antoine M. Identification of genetic factors that modify motor performance and body weight using Collaborative Cross mice. United States. https://doi.org/10.1038/srep16247
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Mao, Jian -Hua, Langley, Sasha A., Huang, Yurong, Hang, Michael, Bouchard, Kristofer E., Celniker, Susan E., Brown, James B., Jansson, Janet K., Karpen, Gary H., and Snijders, Antoine M. Mon . "Identification of genetic factors that modify motor performance and body weight using Collaborative Cross mice". United States. https://doi.org/10.1038/srep16247. https://www.osti.gov/servlets/purl/1243256.
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@article{osti_1243256,
title = {Identification of genetic factors that modify motor performance and body weight using Collaborative Cross mice},
author = {Mao, Jian -Hua and Langley, Sasha A. and Huang, Yurong and Hang, Michael and Bouchard, Kristofer E. and Celniker, Susan E. and Brown, James B. and Jansson, Janet K. and Karpen, Gary H. and Snijders, Antoine M.},
abstractNote = {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.},
doi = {10.1038/srep16247},
journal = {Scientific Reports},
number = ,
volume = 5,
place = {United States},
year = {Mon Nov 09 00:00:00 EST 2015},
month = {Mon Nov 09 00:00:00 EST 2015}
}
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https://doi.org/10.1038/srep16247
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