Fine scale mapping of a genetic locus for conditioned fear |
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Authors: | Christopher J Talbot Richard A Radcliffe Jan Fullerton Robert Hitzemann Jeanne M Wehner Jonathan Flint |
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Institution: | (1) Department of Genetics, University of Leicester, University Road, Leicester LE1 7RH, UK,;(2) Institute for Behavioral Genetics, University of Colorado, Boulder, Colorado 80309, USA,;(3) School of Pharmacy, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA,;(4) Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK,;(5) Department of Behavioral Neuroscience, Oregon Health Sciences University, Portland, Oregon 97201-3098, USA, |
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Abstract: | Abstract
Fear conditioning is one of a number of models for investigating the genetic basis of individual variation in emotion and
learning. Genetic mapping using crosses between strains of laboratory mice has identified a locus on chromosome one that appears
to influence not only variation in conditioned fear, but also in other validated tests of fear-related behaviour, (including
the open-field and the elevated-plus maze), suggesting that the rodent locus may act in ways consistent with how a locus influencing
susceptibility to anxiety in humans is believed to operate. Here we use high-resolution mapping in genetically heterogeneous
mice to show that a quantitative trait locus influencing conditioned fear can be separated from loci influencing open-field
activity. Mapping in two different heterogeneous stocks, the Boulder and Northport HS, gave similar map locations for open-field
activity at two positions on the current mouse physical map, one at 162 Mb on chromosome one (negative log P-value 5.4) the other at 173 Mb (negative log P-value 4.8), while mapping of contextual conditioned fear in the Boulder HS identified a locus at 170 Mb (negative log P-value 5.4). Estimates of the 95% confidence intervals show that the locations do not overlap. The region containing a gene
or genes that influence variation in conditioned fear is approximately 1 megabase in size and contains only one gene of known
function, a pre-B cell leukaemia factor. |
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