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Two autism susceptibility genes identified




Strand of DNAA new study led by researchers at the University of Oxford, England, has identified two genes involved in brain development that appear to be associated with the chances of children developing autism spectrum disorders.

The study, involving 661 families, found variations in the genes that encode for the production of two specific brain proteins were significantly associated with susceptibility for autism spectrum disorders (ASD).

The research was led by Anthony Monaco from the Wellcome Trust Centre for Human Genetics at the University of Oxford who collaborated with an international team of researchers to study four candidate genes in families from the UK, the Netherlands, Italy and Germany.

The results of the study are published in the newly launched journal Molecular Autism - published by BioMed Central the journal is a peer-reviewed, online open access journal that publishes high-quality basic, translational and clinical research into the molecular basis of autism and related neurodevelopmental conditions.

The brain proteins that the two genes identified influence are known as LRRN3 and LRRTM3. Monaco said, "To our knowledge, this is one of the most comprehensive genetic analyses of association between these important genes in brain connections and ASD risk". The proteins encoded by these two genes have been implicated in brain development, which is often impaired in autistic individuals. In particular, LRRN3 is thought to play a role in the development and maintenance of the nervous system, while LRRTM3 is part of a family of proteins thought to organize synaptic connections.

Synapses are the tiny gaps between nerve cells where the electrical signal which the pre-synaptic nerve carries is converted to a chemical signal, in the form of neurotransmitters such as serotonin and dopamine, and then back to an electrical signal in a post-synaptic nerve after the neurotransmitters attach to receptors on its membrane.

According to Monaco, " A focused candidate gene study was carried out using association approaches to identify common variants in the UK cohort and in additional European populations. This study covered four brain-enriched leucine-rich repeat candidates and taken together, there is converging evidence that common genetic variants in LRRTM3 and LRRN3 confer susceptibility to ASD. Future studies of these genes and their function will provide valuable insights into their role in ASD pathogenesis".

If further studies confirm an important role for these genes and the proteins they encode for in ASD they may become the traget for therapeutic interventions and further research may reveal any environmental influences that play a role in the expression of these gene variants.

Source: Sousa I Clark TG Holt R Pagnamenta AT Mulder EJ Minderaa RB Bailey AJ Battaglia A Klauck SM Poustka F Monaco AP International Molecular Genetic Study of Autism Consortium (2010) Polymorphisms in leucine-rich repeat genes are associated with autism spectrum disorder susceptibility in populations of European ancestry Molecular Autism 1:7 doi:10.1186/2040-2392-1-7


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