International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


POSTER 120 - CONSTRUCTION AND ANALYSIS OF MOUSE CHROMOSOME SUBSTITUTION LINES

Dr. Jonathan Singer
Whitehead Institute
9 Cambridge Ctr
Cambridge,
MA 02142
USA

Co-Authors: 1) Lander ES, 2) Nadeau JH
Institutions: 1)Whitehead Institute for Biomedical Research, 2)Dept. of Genetics, Case Western Reserve University School of Medicine

We are constructing a panel of mouse "chromosome substitution lines" (CSL lines). Each of these consomic strains will contain a single chromosome derived from the A/J inbred strain in a C57BL/6J background. Chromosome substitution is accomplished by selectively breeding, at each backcross generation, progeny with a non-recombinant chromosome. The resulting panel of lines consists of the 19 autosomes and the X and Y chromosomes. This will provide a system to readily map genes responsible for the many physiological, biochemical, immunological  and behavioral differences which have already been documented between the two strains.

Mapping of traits should be significantly easier, cheaper, faster and more sensitive than with backcrosses or recombinant inbred lines because of the defined parental contribution of each line. Researchers will be able to make measurements of a phenotypic trait in the 21 CSL lines and immediately determine whether a chromosome contains a gene affecting the trait. Fine structure mapping will also be greatly simplified, as the CSL serves as a congenic strain. If desired, more specific congenics can be derived in only two backcross generations. Most importantly, the CSL lines enable non-geneticists to analyze complex genetic traits by phenotype analysis.

As of July, we have completed breeding 19 of the 21 lines. We are now completing the last two lines and analyzing diet-induced obesity, drug preference, anxiety and other phenotypes.


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