Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Commentary
  • Published:

Analysing complex genetic traits with chromosome substitution strains

Nature Genetics volume 24, pages 221–225 (2000)Cite this article

An Errata/Corrections to this article was published on 01 May 2000

Abstract

Many valuable animal models of human disease are known and new models are continually being generated in existing inbred strains1,2. Some disease models are simple mendelian traits, but most have a polygenic basis. The current approach to identifying quantitative trait loci (QTLs) that underlie such traits is to localize them in crosses, construct congenic strains carrying individual QTLs, and finally map and clone the genes. This process is time-consuming and expensive, requiring the genotyping of large crosses and many generations of breeding. Here we describe a different approach in which a panel of chromosome substitution strains (CSSs) is used for QTL mapping. Each of these strains has a single chromosome from the donor strain substituting for the corresponding chromosome in the host strain. We discuss the construction, applications and advantages of CSSs compared with conventional crosses for detecting and analysing QTLs, including those that have weak phenotypic effects.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Hypothetical composition of inbred strains and their derivatives.
Figure 2: Strategy for constructing CSSs.

References

  1. Bedell, M.A., Jenkins, N.A. & Copeland, N.G. Mouse models of human disease. Part I. Techniques and resources for genetic analysis in mice. Genes Dev. 11, 1–10 (1997).

    Article  CAS  Google Scholar 

  2. Bedell, M.A., Jenkins, N.A. & Copeland, N.G. Mouse models of human disease. Part II. Recent progress and future directions. Genes Dev. 11, 11 –43 (1997).

    Article  Google Scholar 

  3. Lander, E.S. & Botstein, D. Mapping mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics 121, 185–199 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Snell, G.D. Methods for the study of histocompatibility genes. J. Genet. 49, 87–108 (1948).

    Article  CAS  Google Scholar 

  5. Dietrich, W.F. et al. A comprehensive genetic map of the mouse genome. Nature 380, 149–152 ( 1996).

    Article  CAS  Google Scholar 

  6. Steen, R.G. et al. A high-density integrated genetic linkage and radiation hybrid map of the laboratory rat. Genome Res. 9, 1–8 (1999).

    Google Scholar 

  7. Gould, K.A., Dietrich, W.F., Borenstein, N., Lander, E.S. & Dove, W.F. Mom1 is a semi-dominant modifier of intestinal adenoma size and multiplicity in Min/+ mice. Genetics 144, 1769–1776 ( 1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Markel, P. et al. Theoretical and empirical issues for marker-assisted breeding of congenic strains. Nature Genet. 17, 280 –284 (1997).

    Article  CAS  Google Scholar 

  9. Wakeland, E.K., Morel, L., Achey, K., Yui, M. & Longmate, J. Speed congenics: a classic technique in the fast lane (relatively speaking). Immunol. Today 18, 472–477 (1997).

    Article  CAS  Google Scholar 

  10. Darvasi, A. Experimental strategies for the genetic dissection of complex traits in animal models. Nature Genet. 18, 19– 24 (1998).

    Article  CAS  Google Scholar 

  11. Matin, A., Collin, G.B., Asada, Y., Varnum, D. & Nadeau, J.H. Susceptibility to testicular germ cell tumors in 129.MOLF-Chr19 mice. Nature Genet. 23, 237– 240 (1999).

    Article  CAS  Google Scholar 

  12. Darvasi, A. & Soller, M. Advanced intercross lines, an experimental population for fine genetic mapping. Genetics 141, 1199–1207 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Talbot, C.J. et al. High-resolution mapping of quantitative trait loci in outbred mice. Nature Genet. 21, 305– 308 (1999).

    Article  CAS  Google Scholar 

  14. Collin, G.B., Asada, Y., Varnum, D.S. & Nadeau, J.H. DNA pooling as a quick method for finding candidate linkages in multigenic trait analysis: an example involving susceptibility to germ cell tumors. Mamm. Genome 7, 68–70 ( 1996).

    Article  CAS  Google Scholar 

  15. Wang, D.G. et al. Large-scale identification, mapping and genotyping of single-nucleotide polymorphisms in the human genome. Science 280, 1077–1082 (1998).

    Article  CAS  Google Scholar 

  16. Hudgins, C.C., Steinberg, R.T., Klinman, D.M., Reeves, M.J. & Steinberg, A.D. Studies of consomic mice bearing the Y chromosome of the BXSB mouse. J. Immunol. 134 , 3849–3854 (1985).

    CAS  PubMed  Google Scholar 

  17. Scribner, C.L. & Steinberg, A.D. The role of splenic colony-forming units in autoimmune disease. Clin. Immunol. Immunopathol. 49, 133–142 (1988).

    Article  CAS  Google Scholar 

  18. Waters, N.S. & Deneberg, V.H. Analysis of two measures of paw preference in a large population of inbred mice. Behav. Brain Res. 63, 195–204 ( 1994).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

J.B.S. was supported by NHGRI grant F32 HG00195. This work was supported by NIH grant RR12305 and CA75056 to J.H.N., a grant from the Keck Foundation to the Department of Genetics, Case Western Reserve University School of Medicine, a grant from the Howard Hughes Medical Institute to Case Western Reserve University School of Medicine and grants from the NIH to E.S.L.

Author information

Authors and Affiliations

  1. Department of Genetics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA

    Joseph H. Nadeau & Angabin Matin

  2. Center for Human Genetics, University Hospitals of Cleveland, Cleveland, Ohio, USA

    Joseph H. Nadeau

  3. Whitehead Institute for Biomedical Research Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

    Jonathan B. Singer & Eric S. Lander

  4. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

    Eric S. Lander

Authors
  1. Joseph H. Nadeau
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jonathan B. Singer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Angabin Matin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eric S. Lander
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joseph H. Nadeau.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nadeau, J., Singer, J., Matin, A. et al. Analysing complex genetic traits with chromosome substitution strains . Nat Genet 24, 221–225 (2000). https://doi.org/10.1038/73427

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/73427

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing