anxiety

23 October 2004

Scientists at the Wellcome Trust Centre for Human Genetics in Oxford have found a gene that modulates anxiety, using an innovative approach that could be widely applicable to other complex biological traits.

The search for genes that influence behaviours has always been difficult – particularly because an individual gene is likely to have a very small impact.

In Oxford, Jonathan Flint, Richard Mott and colleagues tried a new approach, using an 'outbred' strain of mice (one of mixed ancestry), rather than the pure-bred, genetically identical mice usually used in research.

They reasoned that the genome of this outbred strain was a composite, or 'mosaic', of the six strains originally used to create it. So the genome of each mouse comprises chunks of DNA all of which can be traced back to one of the original strains.

This approach allowed the group to map in fine detail a region of chromosome previously shown to influence anxiety. They found evidence for three genetic effects within one small chromosomal segment, one of which coincided with a gene known as Rgs2.

To confirm that the association was real, the group used a technique known as 'quantitative complementation' to show that Rgs2 affected anxiety. This technique has been used by fruit fly geneticists but this is its first use in mammals.

Rgs2 codes for a protein that regulates signalling within the cell, though its exact role is uncertain. Further studies will be needed to tease out its role in brain function and behaviour. A better understanding of the biology of anxiety and emotional disorders will open up new possibilities for drug discovery.

More generally, suggests the Oxford team, this approach could be used to study any trait where many genes act together and individually have only a small impact – as in many common diseases.

External links

The research was published in Nature Genetics (36: 1197–202).