International Mammalian Genome Society

The 13th International Mouse Genome Conference
October 31-November 3, 1999

Table of Contents * Structure * Bioinformatics * Sequence * Mapping * New Tools * Gene Discovery * Developmental * Mutagenesis * Functional Genomics

E59 Analyzing Multigenic Traits with Chromosome Substitution Strains

Joe Nadeau1, Jon Singer1, Angabin Matin1, and Eric Lander2. 1Department of Genetics, CWRU School of Medicine, Cleveland Center for Genome Research and 2Whitehead Institute, MIT, Cambridge, MA

Chromosome Substitutions Strains (CSSs) are a new and powerful resource for studying the genetics and biology of multigenic traits. CSSs result from the systematic replacement of each chromosome in a host strain with the corresponding chromosome from a donor strain. A complete panel consists of 21 strains, one for each of the 19 autosomes, one for the X Chromosome, and one for the Y Chromosome. The C57BL/6J.A/J - CHR (abbr. B6.A-CHR) panel is nearly complete with several of the strains currently being homozygosed. Four other panels are under construction: A.B6, B6.129, 129.B6, and B6.CAST. These strains can be used to map genes on the substituted chromosome, map background genes while holding genes on the substituted chromosome constant, make congenic strains quickly, and test for epistasis. We show that CSSs can be used to detect weaker QTLs with fewer animals than is possible with conventional methods. We propose statistical thresholds to account for multiple testing that can be used for general resources such as CSSs that are likely typed for many traits. A series of traits ranging from alcohol consumption to weight gain on a high fat diet and susceptibility to valproate-induced homeotic transformations have been shown to differ between the C57BL/6J and A/J progenitor strains, and will be typed in the CSSs. Finally, the power of CSSs in multigenic trait analysis is illustrated by the first autosomal consomic strain, 129.MOLF-Chr19, that was recently used to discover the first testicular cancer susceptibility gene. This CSS and other CSSs that are under development in mice and other species will greatly enhance our ability to study the genetic basis of complex traits.


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