Genetic Dissection of Complex Traits with Chromosome Substitution Strains of Mice

Author:

Singer Jonathan B.12345,Hill Annie E.12345,Burrage Lindsay C.12345,Olszens Keith R.12345,Song Junghan12345,Justice Monica12345,O'Brien William E.12345,Conti David V.12345,Witte John S.12345,Lander Eric S.12345,Nadeau Joseph H.12345

Affiliation:

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.

Abstract

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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