Interspecies genetics of eating disorders; of mice and men
01 / 2008 - 01 / 2013
Anorexia is een ziekte waarbij mensen dwangmatig te weinig eten. Naast psychologische heeft dit gedrag ook biologische oorzaken, waarbij erfelijkheid een rol speelt. Met een nieuwe methode worden chromosomen systematisch onderzocht om beter inzicht te verkrijgen in het ziektebeeld en behandelingsmogelijkheden.
Eating disorders are complex psychiatric disorders in which patients display a variety of behavioral traits, including obsessionality, increased anxiety, hyperactivity and altered appetitive motivation. These traits are also seen in other psychiatric disorders, such as in obsessive-compulsive disorders and depression, which are often co-morbid with eating disorders. Family and twin studies have revealed that genetic factors play a major role in eating disorders, but attempts to find susceptibility genes through linkage and association studies have been largely unsuccessful. Thus, novel approaches are required to deal with both phenotypic and genetic heterogeneity and with gene-environment interactions underlying these disorders. Recent studies have shown that genetic variation associated with psychiatric disorders affect analogous neuro-anatomical and behavioral traits in mice and men, demonstrating that mouse models can contribute to systematic searches for genetic determinants of psychiatric disorders. Therefore, by combining mouse phenotyping methods that dissect complex behavior into distinct behavioral domains and an innovative and powerful genetic strategy, this project aims to identify novel genetic loci and associated genetic pathways regulating mouse behavioral traits related to eating disorders. To establish this, new and sensitive mouse genetic mapping and inbred populations will be exposed to a comprehensive animal model of eating disorder traits. In an initial screen using this method, specific behavioral eating disorder traits were linked to mouse chromosomes that are syntenic with human linkage regions for anorexia nervosa and obsessive-compulsive disorders. Further genetic fine-mapping of these chromosomes, haplotype mapping, and genome-wide gene expression profiling, will reveal novel genetic loci and associated pathways for these behavioral traits in mice. Homologous candidate genes will then be tested in already available DNA samples from well-characterized eating disorder patients.