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Originally published in Science Express on 18 March 2004
Science 16 April 2004:
Vol. 304. no. 5669, pp. 445 - 448
DOI: 10.1126/science.1093139
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Reports

Genetic Dissection of Complex Traits with Chromosome Substitution Strains of Mice

Jonathan B. Singer,1,2* Annie E. Hill,3* Lindsay C. Burrage,3,4 Keith R. Olszens,3 Junghan Song,5{dagger} Monica Justice,5 William E. O'Brien,5 David V. Conti,6{ddagger} John S. Witte,6 Eric S. Lander,1,2,7§|| Joseph H. Nadeau3,4,8§||

Chromosome substitution strains (CSSs) have been proposed as a simple and powerful way to identify quantitative trait loci (QTLs) affecting developmental, physiological, and behavioral processes. Here, we report the construction of a complete CSS panel for a vertebrate species. The CSS panel consists of 22 mouse strains, each of which carries a single chromosome substituted from a donor strain (A/J) onto a common host background (C57BL/6J). A survey of 53 traits revealed evidence for 150 QTLs affecting serum levels of sterols and amino acids, diet-induced obesity, and anxiety. These results demonstrate that CSSs greatly facilitate the detection and identification of genes that control the wide diversity of naturally occurring phenotypic variation in the A/J and C57BL/6J inbred strains.

1 The Broad Institute, Cambridge, MA 02142, USA.
2 Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA.
3 Department of Genetics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
4 Center for Computational Genomics and Systems Biology, Case Western Reserve University, Cleveland, OH 44106, USA.
5 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
6 Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH 44106, USA.
7 Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
8 Center for Human Genetics, University Hospitals of Cleveland, Cleveland, OH 44106, USA.



* These authors contributed equally to this work.

{dagger} Present address: Department of Laboratory Medicine, Seoul National University Bundang Hospital 300, Kumidong, Bundang-ku, Sungnam, Kyungki 463-707, Korea.

{ddagger} Present address: Department of Preventive Medicine, University of Southern California, Los Angeles, CA 90089, USA.

§ These authors co-supervised this work.

|| To whom correspondence should be addressed. E-mail: jhn4{at}cwru.edu (J.H.N.); lander{at}broad.mit.edu (E.S.L.)

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