New approaches to the genetic analysis of neuroticism and anxiety.

The completion of the human genome project and the complementary genome projects for other species has broadened the scope for novel bioinformatic approaches to quantitative trait locus (QTL) identification. A key issue for quantitative trait nucleotide (QTN) identification is progressing from a large QTL peak, spanning perhaps 50 cM and many hundreds of genes, to a gene or nucleotide variant which is responsible for that QTL effect. The complementary use of mouse models to dissect large syntenic loci in humans is a powerful method for reducing QTL intervals to the order of 1 Mb. This paper presents an overview of the approaches used in our laboratory to ultra-fine map QTLs for anxiety-related traits, and to identify quantitative trait genes (QTG). As new genetic techniques and statistical approaches arise, we are getting closer to identifying those long sought after QTNs.