title: Genetic architecture of voluntary exercise in an advanced intercross line of mice.
abstract: Exercise is essential for health, yet the amount, duration, and intensity that individuals engage in are strikingly variable, even under prescription. Our focus was to identify the locations and effects of quantitative trait loci (QTL) controlling genetic predisposition for exercise-related traits, utilizing a large advanced intercross line (AIL) of mice. This AIL (G(4)) population originated from a reciprocal cross between mice with genetic propensity for increased voluntary exercise [high-runner (HR) line, selectively bred for increased wheel running] and the inbred strain C57BL/6J. After adjusting for family structure, we detected 32 significant and 13 suggestive QTL representing both daily running traits (distance, duration, average speed, and maximum speed) and the mean of these traits on days 5 and 6 (the selection criteria for HR) of a 6-day test conducted at 8 wk of age, with many co-localizing to similar genomic regions. Additionally, seven significant and five suggestive QTL were observed for the slope and intercept of a linear regression across all 6 days of running, some representing a combination of the daily traits. We also observed two significant and two suggestive QTL for body mass before exercise. These results, from a well-defined animal model, reinforce a genetic basis for the predisposition to engage in voluntary exercise, dissect this predisposition into daily segments across a continuous time period, and present unique QTL that may provide insight into the initiation, continuation, and temporal pattern of voluntary activity in mammals.
authors.affiliation: Department of Genetics, University of North Carolina at Chapel Hill, 120 Mason Farm Rd., Chapel Hill, NC 27599-7264, USA. scottkelly@unc.edu
authors.forename: Scott A
authors.initials: SA
authors.lastname: Kelly
authors.forename: Derrick L
authors.initials: DL
authors.lastname: Nehrenberg
authors.forename: Jeremy L
authors.initials: JL
authors.lastname: Peirce
authors.forename: Kunjie
authors.initials: K
authors.lastname: Hua
authors.forename: Brian M
authors.initials: BM
authors.lastname: Steffy
authors.forename: Tim
authors.initials: T
authors.lastname: Wiltshire
authors.forename: Fernando
authors.initials: F
authors.lastname: Pardo-Manuel de Villena
authors.forename: Theodore
authors.initials: T
authors.lastname: Garland
authors.forename: Daniel
authors.initials: D
authors.lastname: Pomp
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D005838:Genotype; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009043:Motor Activity / Q000235:genetics; D010805:Physical Conditioning, Animal; D040641:Quantitative Trait Loci
references.citation: Behav Genet. 2006 Mar;36(2):238-47
references.pmid: 16502139
references.citation: Physiol Genomics. 2008 Feb 19;32(3):401-8
references.pmid: 18171721
references.citation: Bioinformatics. 2003 May 1;19(7):889-90
references.pmid: 12724300
references.citation: Eur J Hum Genet. 2007 Dec;15(12):1252-9
references.pmid: 17700629
references.citation: Med Sci Sports Exerc. 2009 Jan;41(1):35-73
references.pmid: 19123262
references.citation: Behav Genet. 1997 May;27(3):201-10
references.pmid: 9210791
references.citation: Nat Genet. 2002 Jan;30(1):97-101
references.pmid: 11731797
references.citation: Genetics. 2009 Aug;182(4):1335-44
references.pmid: 19535546
references.citation: J Exp Biol. 2010 Feb 1;213(3):510-9
references.pmid: 20086137
references.citation: BMC Genet. 2009 Jul 29;10:40
references.pmid: 19638241
references.citation: PLoS One. 2008 Apr 23;3(4):e1977
references.pmid: 18431467
references.citation: Physiol Genomics. 2009 Sep 9;39(1):47-55
references.pmid: 19567786
references.citation: Lancet. 2005 Apr 9-15;365(9467):1333-46
references.pmid: 15823385
references.citation: Nat Genet. 2004 Nov;36(11):1197-202
references.pmid: 15489855
references.citation: Integr Comp Biol. 2005 Jun;45(3):438-55
references.pmid: 21676789
references.citation: Mamm Genome. 2003 Oct;14(10):692-702
references.pmid: 14694905
references.citation: Genetics. 1995 Nov;141(3):1199-207
references.pmid: 8582624
references.citation: J Appl Physiol (1985). 2008 Apr;104(4):1249
references.pmid: 18385304
references.citation: Int J Obes (Lond). 2008 Aug;32(8):1256-63
references.pmid: 18504442
references.citation: J Nutr. 2002 Nov;132(11 Suppl):3456S-3464S
references.pmid: 12421870
references.citation: Genetics. 2001 Sep;159(1):371-87
references.pmid: 11560912
references.citation: Nat Genet. 2004 Nov;36(11):1133-7
references.pmid: 15514660
references.citation: Science. 2004 Apr 16;304(5669):445-8
references.pmid: 15031436
references.citation: Lab Anim (NY). 2001 Jul-Aug;30(7):44-52
references.pmid: 11469113
references.citation: Anim Behav. 1998 Jul;56(1):11-27
references.pmid: 9710457
references.citation: Am J Physiol. 1994 Oct;267(4 Pt 2):R1098-108
references.pmid: 7943421
references.citation: Science. 2000 Apr 7;288(5463):100-6
references.pmid: 10753108
references.citation: J Appl Physiol (1985). 2008 Apr;104(4):1243-5
references.pmid: 18048588
references.citation: J Appl Physiol (1985). 2004 Jan;96(1):3-10
references.pmid: 14660491
references.citation: Am J Physiol Regul Integr Comp Physiol. 2000 Jul;279(1):R1-8
references.pmid: 10896857
references.citation: Physiol Biochem Zool. 2009 Nov-Dec;82(6):662-79
references.pmid: 19799520
references.citation: J Hered. 2010 Jan-Feb;101(1):42-53
references.pmid: 19666993
references.citation: J Hered. 2008 Jul-Aug;99(4):349-54
references.pmid: 18310069
references.citation: Br J Sports Med. 2009 Feb;43(2):80-1
references.pmid: 18927165
references.citation: Curr Protoc Hum Genet. 2009 Jan;Chapter 2:Unit 2.12
references.pmid: 19170031
references.citation: J Comp Physiol Psychol. 1964 Oct;58:159-63
references.pmid: 14215383
references.citation: Behav Genet. 1998 May;28(3):227-37
references.pmid: 9670598
references.citation: J Hered. 2008 Nov-Dec;99(6):679-87
references.pmid: 18544554
references.citation: Evolution. 2002 Jun;56(6):1267-75
references.pmid: 12144025
references.citation: J Exp Biol. 2006 Jun;209(Pt 12):2344-61
references.pmid: 16731811
references.citation: Obesity (Silver Spring). 2006 Sep;14(9):1596-604
references.pmid: 17030971
references.citation: Obes Rev. 2002 Feb;3(1):5-8
references.pmid: 12119660
references.citation: Med Sci Sports Exerc. 2003 Aug;35(8):1355-9
references.pmid: 12900690
references.citation: Physiol Genomics. 2010 Jan 8;40(2):111-20
references.pmid: 19903762
references.citation: Nat Genet. 1998 Jan;18(1):19-24
references.pmid: 9425894
references.citation: J Neural Transm (Vienna). 2006 Dec;113(12):1921-5
references.pmid: 16736243
references.citation: Genetics. 2009 Aug;182(4):1263-77
references.pmid: 19474203
references.citation: Genet Res (Camb). 2009 Apr;91(2):85-99
references.pmid: 19393125
references.citation: Genetics. 2005 Feb;169(2):855-62
references.pmid: 15371360
references.citation: Genetics. 2006 Sep;174(1):481-9
references.pmid: 16783000
references.citation: Mamm Genome. 2003 Nov;14(11):733-47
references.pmid: 14722723
references.citation: Obes Res. 1998 Sep;6 Suppl 2:51S-209S
references.pmid: 9813653
references.citation: Int J Biol Sci. 2008 Apr 29;4(3):126-32
references.pmid: 18449357
references.citation: PLoS One. 2007 Oct 17;2(10):e1036
references.pmid: 17940600
references.citation: Obesity (Silver Spring). 2009 Jul;17(7):1402-9
references.pmid: 19282822
references.citation: MMWR Morb Mortal Wkly Rep. 2003 Aug 22;52(33):785-8
references.pmid: 12931076
references.citation: Nat Methods. 2009 Sep;6(9):663-6
references.pmid: 19668205
references.citation: Genes Brain Behav. 2009 Feb;8(1):13-22
references.pmid: 18721260
references.citation: Mamm Genome. 2006 Feb;17(2):111-8
references.pmid: 16465591
references.citation: Med Sci Sports Exerc. 2007 Aug;39(8):1423-34
references.pmid: 17762377
references.citation: Mamm Genome. 2009 Apr;20(4):224-35
references.pmid: 19306044
references.citation: Nature. 2004 Nov 18;432(7015):345-52
references.pmid: 15549097
references.citation: Physiol Genomics. 2004 Nov 17;19(3):270-6
references.pmid: 15383638
references.citation: Anim Behav. 1999 Mar;57(3):F11-F12
references.pmid: 10196070
references.citation: PLoS One. 2006 Dec 20;1:e22
references.pmid: 17183649