Professor, Psychiatry and Biobehavioral Sciences
Member, Neuroscience GPB Home Area
My research has been devoted to understanding how genes influence behaviour, and in particular how genetic variation contributes to disease susceptibility. My first work investigated the genetic basis of mental retardation, showing that small rearrangements involving the ends of chromosomes are detectable in approximately 8% of people with mental retardation of unknown aetiology. Characterizing the ends of human chromosomes led to the first sequence map of a human telomere and advanced understanding of the relationship between chromosome structure and function. I next addressed the challenging question of the genetic basis of complex behaviour, including psychiatric disease. I started by demonstrating that behaviour could be robustly mapped in inbred strains of mice. I then proceeded to show that high resolution mapping could be achieved using mosaic populations of outbred mice, and that mapping down to the gene level was possible in some commercially available outbred mice. I developed methods permitting the identification of genes in which natural variation gives rise to behavioural phenotypes, such as fear-related behaviour. I pioneered the use of mosaic populations for whole genome association mapping, providing the highest resolution genetic map of the mouse genome. Equally important however, this work provided information about the genetic architecture of complex traits, a subject that continues to be of great interest.
My laboratory investigates the genetic basis of common psychiatric disorders, in particular the determination of the genetic basis of anxiety and depression in animal models and in humans. I have used two complementary approaches in the investigation of emotional disorders.
(i) Animal models
I am developing methods that will make straightforward the identification of the relevant genes in mice. This has led to the genetic characterization of outbred stocks, the realization that they can deliver gene level resolution(Yalcin et al. 2010) , and to a fuller understanding of the value of complete genome sequence. Using next generation sequencing I have coordinated a project to obtain genome sequence of 17 inbred strains of mice. The results were published in two articles in Nature(Yalcin et al. 2011).
(ii) Human studies
Over the last five years I have undertaken the largest project of its kind anywhere in the world in the genetics of major depression. In collaboration with 60 hospitals across China I have obtained 6,000 cases and 6,000 controls, with complete genomic sequence. These data have been used to identify the first robust associations between sequence variants and the commonest of all psychiatric illnesses.