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Mapping quantitative trait loci for behavioral traits in the mouse

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Abstract

After many years of studying various behavioral characters in the mouse, it is clear that most are heritable and are specified by complexes of genes or quantitative trait loci (QTLs). In order to attain a more complete understanding of the genetic causes of individual differences in behavior, the mechanism of action of these QTLs must be elucidated. The most straightforward approach to determining the mechanism of action of a particular QTL is to identify and molecularly clone the gene; this can be done by positional cloning, which depends on precise knowledge of the genetic map position. As the genetic data base for the mouse genome continues to develop, such strategies will become increasingly easy to perform. Here we suggest a multistage strategy for QTL mapping using recombinant-inbred strains of mice: (1) characterize genomic DNA from parental strains originally used to generate the RI strains; (2) characterize the RI strains for a quantitative character and for DNA markers that differ in the parental strains; and (3) assess the quantitative character in F2 mice derived from crosses between the parental strains, then determine the genotypes of extreme F2 mice for markers that account for at least 5% of the additive genetic variance. Data from these F2 crosses can be used to test hypotheses from the analysis of RI strains, i.e., that a QTL maps to a particular region. Using data from the mouse genome data base, this strategy should allow the molecular identification of the gene based on a candidate-gene approach. We illustrate the approach with examples from our work in mapping QTLs specifying neural sensitivity to the anesthetic effects of ethanol.

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Authors and Affiliations

  1. Institute for Behavioral Genetics and Department of Psychology, University of Colorado, Box 447, 80309, Boulder, Colorado

    Thomas E. Johnson, John C. DeFries & Paul D. Markel

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  1. Thomas E. Johnson
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  2. John C. DeFries
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  3. Paul D. Markel
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Additional information

This work was supported by grants from the National Institutes of Health (R01-AG08332, R01-AG10248, and K04-AG00369), by a gift from the Glenn Foundation for Medical Research, from ADAMHA (P05 AA-03527), by a training grant from the NIMH (MH-16880) to support P.D.M., and by BRSG Grant RR-07013 to the University of Colorado.

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Johnson, T.E., DeFries, J.C. & Markel, P.D. Mapping quantitative trait loci for behavioral traits in the mouse. Behav Genet 22, 635–653 (1992). https://doi.org/10.1007/BF01066635

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