High-resolution genetic maps, large sets of highly polymorphic markers, and the availability of inbred strains of genetically identical mice can now be combined with transgenic and gene-targeting technologies

that permit the direct manipulation of the mouse genome. The availability of inbred strains eliminates trait variation due to differences in genetic background, and the ability to sample multiple, essentially identical individuals permits assessment of subtle interstrain differences in the expression of complex traits. At the same time, the number of Inhibitors,research,lifescience,medical valid and reliable mouse behavioral testing paradigms is rapidly expanding and these can be used to assess Inhibitors,research,lifescience,medical many aspects of behavioral capability. A number of studies have now indicated that quantitative trait loci on specific chromosomes are associated with heightened emotionality and with fear-conditioning in rodents. For example, Flint et al75 showed that three loci on mouse chromosomes

1,12, and 15 were associated with decreased activity and increased defecation in a novel environment. They concluded that these loci were responsible for heightened “emotionality” and speculated that the genetic basis of emotionality is similar in other species, and may underlie the psychological trait of susceptibility to anxiety in humans. In two studies,76,77 quantitative trait loci on several chromosomes were found to be associated with Inhibitors,research,lifescience,medical contextual fear conditioning in rodents, and chromosome 1 was implicated in both studies. The fact that loci on chromosome 1 have been highlighted in three studies working on such different measures of the same trait is encouraging.78 On the basis of the increasing evidence that genetic variability in expression and Inhibitors,research,lifescience,medical function of proteins that regulate brain neurotransmitter systems (eg, receptors, ion channels,

transporters, Inhibitors,research,lifescience,medical and enzymes) is associated with complex behavioral traits, research is also emphasizing the molecular psych obiological basis of anxiety-related behavior in rodents, and increasingly in nonhuman primates.25 Conclusion Anxiety disorders belong to the category of complex diseases for which intense research efforts are focused on the identification of genetic susceptibility factors. Emerging tools and technologies for genetic analysis will provide the Romidepsin FK228 groundwork for an advanced stage of gene identification and functional studies in anxiety and related disorders. More than 1.4 Brefeldin_A million single nucleotide polymorphisms (SNPs) have been identified in the human genome. This collection should allow the initiation of genome-wide linkage disequilibrium mapping of genes influencing anxiety in the human population. The duplication of part of chromosome 15 is probably a major genetic factor of susceptibility for panic and phobic disorders, and its identification may have important implications for psychiatry and health.