Project description:Non-syndromic mental retardation is one of the most important unresolved problems in genetic health care. Autosomal forms are far more common than X-linked ones, but in contrast to the latter, they are still largely unexplored. Here we report on a complex mutation in the ionotropic glutamate receptor 6 gene (GRIK2, GLUR6), which co-segregates with moderate to severe non-syndromic autosomal recessive mental retardation in a large consanguineous Iranian family1. The predicted gene product lacks the first ligand-binding domain, the two adjacent transmembrane domains and the putative pore-forming loop of the GLUK6 protein, suggesting a complete loss of function, which is supported by electrophysiological data. This finding provides the first irrefutable proof that GLUK6 is indispensable for higher brain functions in man, and future studies of this and other ionotropic kainate receptors will shed more light on the pathophysiology of mental retardation. Keywords: array CGH
Project description:We have analysed a family with an autosomal recessive type of tetraplegic cerebral palsy with mental retardation, reduction of cerebral white matter, and atrophy of the cerebellum in an inbred sibship. Homozygosity mapping using SNPs was performed to identify the chromosomal locus for the disease. In the 14 Mb candidate region on chromosome 7q22, RNA expression profiling was used to select among the 203 genes in the area.
Project description:Down syndrome is the most common form of genetic mental retardation. How Trisomy 21 causes mental retardation remains unclear and its effects on adult neurogenesis have not been addressed. To gain insight into the mechanisms causing mental retardation we used microarrays to investigate gene expression differences between Ts1Cje (a mouse model of Down syndrome) and C57BL/6 littermate control neurospheres. The neurospheres were generated from neural stem cells and progenitors isolated from the lateral walls of the lateral ventricles from adult mice.
Project description:Down syndrome is the most common form of genetic mental retardation. How Trisomy 21 causes mental retardation remains unclear and its effects on adult neurogenesis have not been addressed. To gain insight into the mechanisms causing mental retardation we used microarrays to investigate gene expression differences between Ts1Cje (a mouse model of Down syndrome) and C57BL/6 littermate control neurospheres. The neurospheres were generated from neural stem cells and progenitors isolated from the lateral walls of the lateral ventricles from adult mice. RNA was extracted for hybridization to arrays from 3 pairs of Ts1Cje and disomic C57BL/6 littermate control 7-day old adult neurosphere cultures.
