Skip to main content
SpringerLink
Log in

Simultaneous mapping of epistatic QTL in DU6i × DBA/2 mice

  • Published:
Mammalian Genome Aims and scope Submit manuscript

Abstract

We have mapped epistatic quantitative trait loci (QTL) in an F2 cross between DU6i × DBA/2 mice. By including these epistatic QTL and their interaction parameters in the genetic model, we were able to increase the genetic variance explained substantially (8.8%–128.3%) for several growth and body composition traits. We used an analysis method based on a simultaneous search for epistatic QTL pairs without assuming that the QTL had any effect individually. We were able to detect several QTL that could not be detected in a search for marginal QTL effects because the epistasis cancelled out the individual effects of the QTL. In total, 23 genomic regions were found to contain QTL affecting one or several of the traits and eight of these QTL did not have significant individual effects. We identified 44 QTL pairs with significant effects on the traits, and, for 28 of the pairs, an epistatic QTL model fit the data significantly better than a model without interactions. The epistatic pairs were classified by the significance of the epistatic parameters in the genetic model, and visual inspection of the two-locus genotype means identified six types of related genotype–phenotype patterns among the pairs. Five of these patterns resembled previously published patterns of QTL interactions.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Boer MP, ter Braak CJF, Jansen RC (2002) A penalized likelihood method for mapping epistatic quantitative trait loci with one-dimensional genome searches. Genetics 162: 951–960

    PubMed  Google Scholar 

  • Brockmann GA, Haley CS, Renne U, Knott SA, Schwerin M (1998) Quantitative trait loci affecting body weight and fatness from a mouse line selected for extreme high growth. Genetics 150:396–381

    Google Scholar 

  • Brockmann GA, Kratzsch J, Haley CS, Renne U, Schwerin M, et al. (2000) Single QTL effects, epistasis, and pleiotropy account for two-thirds of the phenotypic F(2) variance of growth and obesity in DU6i × DBA/2 mice. Genome Res 10: 1941–1957

    Article  PubMed  Google Scholar 

  • Bünger L, Herrendörfer G, Renne U (1990) Results of long term selection for growth traits in laboratory mice. Proceedings of the 4th World Congress on Genetics Applied to Livestock Production, University of Edinburgh, Edinburgh, Scotland 13, pp 321–324

  • Carlborg Ö (2002) New methods for mapping quantitative trait loci. Ph.D. thesis, Acta Universitatis Agriculturae Sueciae. Veterinaria 121. Swedish University of Agricultural Sciences, Uppsala

  • Carlborg Ö, Andersson L (2002) The use of randomization testing for detection of multiple epistatic QTL. Genet Res 79: 175–184

    Article  PubMed  Google Scholar 

  • Carlborg Ö, Andersson L Kinghorn B (2000) The use of a genetic algorithm for simultaneous mapping of multiple interacting quantitative trait loci. Genetics 155: 2003–2010

    PubMed  Google Scholar 

  • Carlborg Ö, Andersson-Eklund L, Andersson L (2001) Parallel computing in interval mapping of quantitative trait loci. J Hered 92: 449–451

    Article  PubMed  Google Scholar 

  • Carlborg Ö, Kerje S, Schutz K, Jacobsson L, Jensen P, et al. (2003) A global search reveals epistatic interaction between QTLs for early growth in the chicken. Genome Res 13: 413–421

    Article  PubMed  Google Scholar 

  • Carlborg Ö, Burt D, Hocking P, Haley CS (2004) Simultaneous mapping of epistatic QTL in chickens reveals clusters of QTL pairs with similar genetic effects on growth. Genet Res 83: 197–209

    Article  PubMed  Google Scholar 

  • Chase K, Adler FR, Lark KG (1997) Epistat: a computer program for identifying and testing interactions between pairs of quantitative trait loci. Theor Applied Genet 94: 724–730

    Article  Google Scholar 

  • Cheverud JM, Vaughn TT, Pletscher LS, Peripato AC, Adams ES, et al. (2001) Genetic architecture of adiposity in the cross of LG/J and SM/J inbred mice. Mamm Genome 12: 3–12

    Article  PubMed  Google Scholar 

  • Churchill GA, Doerge RW (1994) Empirical threshold values for quantitative trait mapping. Genetics 138: 963–971

    PubMed  Google Scholar 

  • Fijneman RJ, De Vries SS, Jansen RC, Dermant P (1996) Complex interactions of new quantitative trait loci, Sluc1, Sluc2, Sluc3, and Sluc4, that influence the susceptibility to lung cancer in the mouse. Nat Genet 14: 465–467

    Article  PubMed  Google Scholar 

  • Haley CS, Knott SA (1992) A simple regression method for mapping quantitative trait loci in line crosses using flanking markers. Heredity 69: 315–324

    Google Scholar 

  • Haley CS, Knott SA, Elsen J M (1994) Mapping quantitative trait loci in crosses between outbred lines using least squares. Genetics 136: 1195–1207

    PubMed  Google Scholar 

  • Hua J, Xing Y, Wu W, Xu C, Sun X, et al. (2003) Single-locus heterotic effects and dominance by dominance interactions can adequately explain the genetic basis of heterosis in an elite rice hybrid. Proc Natl Acad Sci U S A 100: 2574–2579

    Article  PubMed  Google Scholar 

  • Ihaka R, Gentleman R (1996) R: a language for data analysis and graphics. J Comp Graph Stat 5: 299–314

    Google Scholar 

  • Jannink JL, Jansen RC (2001) Mapping epistatic quantitative trait loci with one-dimensional genome searches. Genetics 157: 445–454

    PubMed  Google Scholar 

  • Kao C-H, Zeng Z-B, Teasdale R (1999) Multiple interval mapping for quantitative trait loci. Genetics 152: 1203–1216

    PubMed  Google Scholar 

  • Leamy LJ, Routman EJ, Cheverud JM (2002) An epistatic genetic basis for fluctuating asymmetry of mandible size in mice. Evolution Int J Org Evolution 56: 642–653

    PubMed  Google Scholar 

  • Levine D (1996) Users Guide to the PGAPack Parallel Genetic Algorithm Library. (Argonne, IL: Mathematics and Computer Science Division, Argonne National Laboratory)

  • Ljungberg K, Holmgren S, Carlborg Ö (2002) Efficient algorithms for quantitative trait loci mapping problems. J Comput Biol 9: 793–804

    Article  PubMed  Google Scholar 

  • Peripato AC, De Brito RA, Vaughn TT, Pletscher LS, Matioli SR, et al. (2002) Quantitative trait loci for maternal performance for offspring survival in mice. Genetics 162: 1341–1353

    PubMed  Google Scholar 

  • Sen S, Churchill GA (2001) A statistical framework for quantitative trait mapping. Genetics 159: 371–387

    PubMed  Google Scholar 

  • Shimomura K, Low–Zeddues SS, King DP, Steeves TDL, Whiteley A, et al. (2001) Genome-wide epistatic interaction analysis reveals complex genetic determinants of circadian behavior in mice. Genome Res 11: 959–980

    Article  PubMed  Google Scholar 

  • Wolf JB, Vaughn TT, Pletscher LS, Cheverud JM (2002) Contribution of maternal effect QTL to genetic architecture of early growth in mice. Heredity 89, 300–310

    Article  PubMed  Google Scholar 

  • Zeng Z-B, Liu J, Stam LF, Kao Z-H, Mercer JM, Laurie CC (2000) Genetic architecture of a morphological shape difference between two Drosophila species. Genetics 154: 299–310

    PubMed  Google Scholar 

Download references

Acknowledgments

ÖC was funded by a fellowship from the Knut and Alice Wallenberg Foundation. CSH is grateful for support from the Biotechnology and Biological Sciences Research Council (BBSRC). GAB acknowledges support from the Deutsche Forschungsgemeinschaft.

Author information

Author notes

  1. Örjan Carlborg

    Present address: Linnaeus Centre for Bioinformatics, Uppsala University, BMC Box 598, Uppsala, SE-751 24, Berlin, Sweden

Authors and Affiliations

  1. Roslin Institute, Roslin, Midlothian, EH25 9PS, United Kingdom

    Örjan Carlborg & Chris S. Haley

  2. Breeding Biology and Molecular Genetics, Institute for Animal Sciences, Humboldt-Universität zu Berlin, Invalidenstrasse 42, 10115, Berlin, Germany

    Gudrun A. Brockmann

Authors
  1. Örjan Carlborg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gudrun A. Brockmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chris S. Haley
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Örjan Carlborg.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Carlborg, Ö., Brockmann, G.A. & Haley, C.S. Simultaneous mapping of epistatic QTL in DU6i × DBA/2 mice. Mamm Genome 16, 481–494 (2005). https://doi.org/10.1007/s00335-004-2425-4

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00335-004-2425-4

Keywords

Search

Navigation