Marcadors genétics de la conducta ansiosa en rates

Using a F2 sample derived from two inbred rat strains (RHA and RLA, psychogenetically selected for extreme anxious responses) we have recently found that certain loci (QTLs) at chromosomes 1,3,5,6,10,15,19 and X affect an array of anxiety-related behaviours (i.e two types of experimentally learned phobia and several innate defensive responses to novel and theatening situations; Fernandez-Teruel et al (2002) Genome Reserch 12:618-626). Although the results are striking-especially the QTL on Chr 5-[for example, they are consistent with current theories of the neuropsychology of anxiety (gray, J.A and McNaughton, N. (2000). The Neuropsychology of Anxiety OUP, Oxford) we are in a preliminary stage to understand the genetic architecture of anxiety. A further step in this direction consists of replicating and extending these findings with heerogeneous and highly recombinant rats, and using more sophisticated analytic tools now available [Mott, R.; Talbot, Ch. J.; Turri, M.G.; Collins, A.C, and Flint J. (2000). A method for fine mapping quantitative trait loci in outbred animal stocks. PNAS, 97 (23): 12649-12654] that permit us a fine (and high resolution) genetic mapping (QTL mapping with a resolution of about 1cM). By augmenting the resolution power of the genetic markers it could be possible to isolate those genes effectively contributing to anxiety: thereby, a straightfoward research could be carried out toward them. In conclusion, to discern the precise achitecture of the anxious genome it is necessary to define those loci that, with high likelihood, contain target genes for anxiety. To do it, a suitable appoximation is the one advanced in the present project