Causal genomic duplications in patients with mental retardation: role of overexpression of genes on cognition.

Previously, genetic causes for constitutional diseases such as mental retardation (MR) have solely been related to gene interruption, mutation or deletion resulting in the lack of protein or a reduced or abrogated function. We recently identified several causal duplications on the X chromosome in MR patients identifying a novel mechanism in mental diseases. As such, a two-fold increase in gene dosage can disturb normal brain development and/or function. We also found small duplications containing only a few genes in patients but the role of the increased dosage is not clear. Therefore, we want to investigate the functional relevance of an increased copy number of some candidate genes in two models; overexpression of these genes in primary rat hippocampal neurons and overexpression in the mushroom bodies of the fruitfly. We aim to functionally correlate the increased dosage of genes within a duplication withthe MR phenotype observed in the patients. At the same time, we will continue our screen for the identification of novel microduplications in order to explain the mental handicap.

Keywords:Mental retardation, Overexpression

Disciplines:Genetics, Systems biology, Molecular and cell biology

Project type:PhD project