Skip to main content
SpringerLink
Log in

Multivariate analysis of quantitative trait loci influencing variation in anxiety-related behavior in laboratory mice

  • Published:
Mammalian Genome Aims and scope Submit manuscript

Abstract

The number and mode of action of quantitative trait loci (QTL) that contribute to behavioral variation in rodents is still largely unknown. On theoretical grounds, multivariate techniques are expected to yield new insights into this problem, but there are only a few examples of its application in practice. Here we explore the power of multivariate approaches to uncover the genetic architecture of 23 anxiety-related phenotypes in 1636 F2 laboratory mice. We detected QTL with a genome-wide significance threshold of P < 0.05 on 14 chromosomes, of which 10 correspond to those identified by univariate analysis. Novel QTL were found on Chromosomes 3, 9, 13, and 17. Thus, multivariate analyses increased the yield of QTL exceeding a genome-wide significance threshold by 40%. On the basis of these results and by the application of a QTL estimator, we show that the mean number of QTL influencing anxiety-related behavior in mice is 6, with a 95% upper limit of 14.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. CI Amos RC Elston GE Bonney BJB Keats GS Berenson (1990) ArticleTitleA multivariate method for detecting genetic-linkage, with application to a pedigree with an adverse lipoprotein phenotype. Am J Hum Genet 47 247–254 Occurrence Handle1:CAS:528:DyaK3cXmtVKitbw%3D Occurrence Handle2378349

    CAS  PubMed  Google Scholar 

  2. CJ Basten BS Weir Z-B Zeng (1994) QTLCartographer: a suite of programs for mapping quantitative trait loci. C Smith JS Gavora BBJ Chesnais W Fairfull JP Gibson BW Kennedy EB Burnside (Eds) Proceedings of the 5th World Congress on Genetics Applied to Livestock Production: Computing Strategies and Software. Guelph Ontario, Canada 65–66

    Google Scholar 

  3. WD Beavis (1998) QTL analyses: power, precision and accuracy. AH Paterson (Eds) Molecular Analysis of Complex Traits. CRC Press Boca Raton, Fla 123–150

    Google Scholar 

  4. B Costall BJ Jones ME Kelly RJ Naylor DM Tomkins (1989) ArticleTitleExploration of mice in a black and white test box: validation as a model of anxiety. Pharmacol Biochem Behav 32 777–785 Occurrence Handle1:STN:280:BiaB1MjhvVY%3D Occurrence Handle2740429

    CAS  PubMed  Google Scholar 

  5. A Darvasi (1998) ArticleTitleExperimental strategies for the genetic dissection of complex traits in animal models. Nat Genet 18 19–24 Occurrence Handle1:CAS:528:DyaK1cXivFWgtQ%3D%3D Occurrence Handle9425894

    CAS  PubMed  Google Scholar 

  6. JC DeFries JP Hegmann (1970) Genetic analysis of open-field behavior. G Lindzey DD Thiessen (Eds) Contributions to Behavior-Genetic Analysis: The Mouse as a Prototype. Appleton-Century-Crofts New York 23–56

    Google Scholar 

  7. JC DeFries MC Gervais EA Thomas (1978) ArticleTitleResponse to 30 generations of selection for open field activity in laboratory mice. Behav Genet 8 3–13 Occurrence Handle1:STN:280:CSeC2cvitVY%3D Occurrence Handle637827

    CAS  PubMed  Google Scholar 

  8. A Fernandez-Teruel RM Escorihuela JA Gray R Aguilar L Gil et al. (2002) ArticleTitleA quantitative trait locus influencing anxiety in the laboratory rat. Genome Res 12 618–626 Occurrence Handle1:CAS:528:DC%2BD38XivVemt7Y%3D Occurrence Handle11932246

    CAS  PubMed  Google Scholar 

  9. J Flint (2003) ArticleTitleAnalysis of quantitative trait loci that influence animal behavior. J Neurobiol 54 46–77 Occurrence Handle10.1002/neu.10161 Occurrence Handle1:CAS:528:DC%2BD3sXps1Gjuw%3D%3D Occurrence Handle12486698

    Article  CAS  PubMed  Google Scholar 

  10. J Flint R Corley JC DeFries DW Fulker JA Gray et al. (1995) ArticleTitleA simple genetic basis for a complex psychological trait in laboratory mice. Science 269 1432–1435 Occurrence Handle1:CAS:528:DyaK2MXnvFCkt70%3D Occurrence Handle7660127

    CAS  PubMed  Google Scholar 

  11. J Flint JC DeFries ND Henderson (2003) ArticleTitleLittle epistasis for anxiety-related measures in the DeFries strains of laboratory mice. Mamm Genome . .

    Google Scholar 

  12. ND Henderson MG Turri JC DeFries J Flint (2003) ArticleTitleA QTL analysis of multiple behavioural indications of anxiety in mice. Behav Genet . .

    Google Scholar 

  13. C Jiang Z-B Zeng (1995) ArticleTitleMultiple trait analysis of genetic mapping for quantitative trait loci. Genetics 140 1111–1127 Occurrence Handle1:CAS:528:DyaK28Xht1Gjur4%3D Occurrence Handle7672582

    CAS  PubMed  Google Scholar 

  14. AB Korol YI Ronin VM Kirzhner (1995) ArticleTitleInterval mapping of quantitative trait loci employing correlated trait complexes. Genetics 140 1137–1147 Occurrence Handle1:CAS:528:DyaK28Xht1Gjurw%3D Occurrence Handle7672584

    CAS  PubMed  Google Scholar 

  15. AB Korol YI Ronin AM Itskovich J Peng E Nevo (2001) ArticleTitleEnhanced efficiency of quantitative trait loci mapping analysis based on multivariate complexes of quantitative traits. Genetics 157 1789–1803

    Google Scholar 

  16. ES Lander D Botstein (1989) ArticleTitleMapping Mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics 121 185–199 Occurrence Handle1:STN:280:BiaC3sjpsVw%3D Occurrence Handle2563713

    CAS  PubMed  Google Scholar 

  17. B Mangin P Thoquet N Grimsley (1998) ArticleTitlePleiotropic QTL analysis. Biometrics 54 88–99

    Google Scholar 

  18. AE Melchinger HF Utz CC Schon (1998) ArticleTitleQuantitative trait locus (QTL) mapping using different testers and independent population samples in maize reveals low power of QTL detection and large bias in estimates of QTL effects. Genetics 149 383–403 Occurrence Handle1:CAS:528:DyaK1cXks1ektb8%3D Occurrence Handle9584111

    CAS  PubMed  Google Scholar 

  19. SP Otto CD Jones (2000) ArticleTitleDetecting the undetected: estimating the total number of loci underlying a quantitative trait. Genetics 156 2093–2107

    Google Scholar 

  20. S Pellow P Chopin S File M Briley (1985) ArticleTitleValidation of open:closed arms entries in an elevated plus maze as a measure of anxiety in the rat. J Neurosci Methods 14 149–167 Occurrence Handle1:STN:280:BimD3M3pt1E%3D Occurrence Handle2864480

    CAS  PubMed  Google Scholar 

  21. A Ramos P Mormede (1998) ArticleTitleStress and emotionality: a multidimensional and genetic approach. Neurosci Biobehav Rev 22 33–57 Occurrence Handle1:STN:280:DyaK1c7ltV2jsQ%3D%3D Occurrence Handle9491939

    CAS  PubMed  Google Scholar 

  22. YI Ronin VM Kirzhner AB Korol (1995) ArticleTitleLinkage between loci of quantitative traits and marker loci—multi-trait analysis with a single marker. Theor Appl Genet 90 776–786

    Google Scholar 

  23. NJ Schork M Boehnke JD Terwilliger J Ott (1993) ArticleTitleTwo-trait-locus linkage analysis: a powerful strategy for mapping complex genetic traits. Am J Hum Genet 53 1127–1136 Occurrence Handle1:STN:280:ByuD38jgvVU%3D Occurrence Handle8213836

    CAS  PubMed  Google Scholar 

  24. JK Shepherd SS Grewal A Fletcher DJ Bill CT Dourish (1994) ArticleTitleBehavioural and pharmacological characterisation of the elevated “zero-maze” as an animal model of anxiety. Psychopharmacology (Berl) 116 56–64 Occurrence Handle1:CAS:528:DyaK2cXmsVCqsbs%3D

    CAS  Google Scholar 

  25. M Stoll Jr AW Cowley PJ Tonellato AS Greene ML Kaldunski et al. (2001) ArticleTitleA genomic-systems biology map for cardiovascular function. Science 294 1723–1726 Occurrence Handle10.1126/science.1062117 Occurrence Handle1:CAS:528:DC%2BD3MXoslCrsLc%3D Occurrence Handle11721057

    Article  CAS  PubMed  Google Scholar 

  26. PL Toubas KA Abla W Cao LG Logan TW Seale (1990) ArticleTitleLatency to enter a mirrored chamber: a novel behavioral assay for anxiolytic agents. Pharmacol Biochem Behav 35 121–126

    Google Scholar 

  27. MG Turri SR Datta J DeFries ND Henderson J Flint (2001a) ArticleTitleQTL analysis identifies multiple behavioral dimensions in ethological tests of anxiety in laboratory mice. Curr Biol 11 725–734 Occurrence Handle1:CAS:528:DC%2BD3MXjvFSiurw%3D

    CAS  Google Scholar 

  28. MG Turri ND Henderson JC DeFries J Flint (2001b) ArticleTitleQuantitative trait locus mapping in laboratory mice derived from a replicated selection experiment for open-field activity. Genetics 158 1217–1226 Occurrence Handle1:CAS:528:DC%2BD3MXmtVKqtrw%3D

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK

    Maria Grazia Turri & Jonathan Flint

  2. Institute for Behavioral Genetics, University of Colorado, Boulder, Colorado 80309, USA

    John C. DeFries

  3. Oberlin College, Oberlin, Ohio 44074-1086, USA

    Norman D. Henderson

Authors
  1. Maria Grazia Turri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John C. DeFries
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Norman D. Henderson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jonathan Flint
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jonathan Flint.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Grazia Turri, M., DeFries, J.C., Henderson, N.D. et al. Multivariate analysis of quantitative trait loci influencing variation in anxiety-related behavior in laboratory mice . Mamm Genome 15, 69–76 (2004). https://doi.org/10.1007/s00335-003-3032-y

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00335-003-3032-y

Keywords

Search

Navigation