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.
-
Heart disease in a mutant mouse model of spontaneous eosinophilic myocarditis maps to three loci
BMC Genomics Open Access 11 October 2019
-
The qSAC3 locus from indica rice effectively increases amylose content under a variety of conditions
BMC Plant Biology Open Access 24 June 2019
-
Development of Three Sets of High-Throughput Genotyped Rice Chromosome Segment Substitution Lines and QTL Mapping for Eleven Traits
Rice Open Access 10 May 2019
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
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).
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).
Lander, E.S. & Botstein, D. Mapping mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics 121, 185–199 (1989).
Snell, G.D. Methods for the study of histocompatibility genes. J. Genet. 49, 87–108 (1948).
Dietrich, W.F. et al. A comprehensive genetic map of the mouse genome. Nature 380, 149–152 ( 1996).
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).
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).
Markel, P. et al. Theoretical and empirical issues for marker-assisted breeding of congenic strains. Nature Genet. 17, 280 –284 (1997).
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).
Darvasi, A. Experimental strategies for the genetic dissection of complex traits in animal models. Nature Genet. 18, 19– 24 (1998).
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).
Darvasi, A. & Soller, M. Advanced intercross lines, an experimental population for fine genetic mapping. Genetics 141, 1199–1207 (1995).
Talbot, C.J. et al. High-resolution mapping of quantitative trait loci in outbred mice. Nature Genet. 21, 305– 308 (1999).
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).
Wang, D.G. et al. Large-scale identification, mapping and genotyping of single-nucleotide polymorphisms in the human genome. Science 280, 1077–1082 (1998).
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).
Scribner, C.L. & Steinberg, A.D. The role of splenic colony-forming units in autoimmune disease. Clin. Immunol. Immunopathol. 49, 133–142 (1988).
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).
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
Corresponding author
Rights 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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/73427
This article is cited by
-
Neonatal lethality of mouse A/J-7SM consomic strain is caused by an insertion mutation in the Dchs1 gene
Mammalian Genome (2023)
-
The qSAC3 locus from indica rice effectively increases amylose content under a variety of conditions
BMC Plant Biology (2019)
-
Development of Three Sets of High-Throughput Genotyped Rice Chromosome Segment Substitution Lines and QTL Mapping for Eleven Traits
Rice (2019)
-
Heart disease in a mutant mouse model of spontaneous eosinophilic myocarditis maps to three loci
BMC Genomics (2019)
-
Development and use of chromosome segment substitution lines as a genetic resource for crop improvement
Theoretical and Applied Genetics (2019)