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Congruent Changes in Cortical Gene Expression in Duplication 15q Syndrome and Idiopathic Autism


T. Grant Belgard, DPhil
Thursday, November 20, 2014
12 pm
Link Auditorium

Autism is a highly heritable and heterogeneous neurodevelopmental disorder with a wide variety of genetic contributors.  We have previously demonstrated a convergent gene expression signature in postmortem brains from autistic individuals.  Using RNA-seq we find that Duplication 15q Syndrome – a syndrome with a known genetic etiology – has highly congruent gene expression changes to those seen in idiopathic autism, except that these changes are even more consistently present in Dup15q Syndrome.  This gene expression signature is uncorrelated with history of seizures or estimated intelligence.  The remarkable overlap in the molecular phenotypes of Dup15q and idiopathic autism suggests that these differences in gene expression could reflect the shared clinical phenotypes and that research into the neurological differences in one of these disorders may therefore be informative for both.  We propose that Dup15q be used as a tractable model to investigate the neurological changes underlying gene expression differences in idiopathic autism.  Expression in the duplicated region is highly complex, including genes positively correlated, uncorrelated and negatively correlated with copy number, and that some genes in the region have notable correlations to the strength of the wider gene expression effects among individuals.  Finally, we speculate as to the biological interpretations of these changes, in which several glial markers are increased and neuronal markers are decreased.

T. Grant Belgard, DPhil studies the spatiotemporal patterning and evolution of brain gene expression and how this is disrupted in neurological disorders such as autism.  He works remotely from Ohio as a research scientist at Oxford University, where he focuses on single cell transcriptomics in neuroscience.  Grant completed a postdoctoral fellowship at UCLA, a doctorate jointly at Oxford University and the National Institutes of Health as a Marshall Scholar, and bachelor’s degrees in physics,