Sepp Hochreiter, Djork-Arné Clevert,
"Copy number aberrations affecting adhesion genes involved in the development of the cerebellar vermis are associated with autism spectrum disorders"
: 12th International Congress of Human Genetics and the American Society of Human Genetics, 10-2011
Original Titel:
Copy number aberrations affecting adhesion genes involved in the development of the cerebellar vermis are associated with autism spectrum disorders
Sprache des Titels:
Englisch
Original Buchtitel:
12th International Congress of Human Genetics and the American Society of Human Genetics
Original Kurzfassung:
We investigated neurodevelopmental dysfunctions in autism
spectrum disorders (ASD) by a integrative analysis including the two largest
genome-wide studies on associations between copy number aberrations
(CNA) and ASD, the BioGPS tissue atlas, the Allen brain atlas, and in
situ hybridization histochemistry data from the developing mouse brain. In
contrast to the original association studies, we considered ?ASD candidate
genes? each of which is the only CNA-impaired gene in an ASD case,
therefore, presumably causing ASD. For extracting ASD candidate genes,
we developed an analysis pipeline for rare and small CNAs. Rare CNAs
are supposed to be more disease-specific, because CNAs that cause ASD
with high probability are assumed to be de novo and quickly vanish in the
population due to their low reproductive fitness. Small CNAs affect only
few genes and, therefore, are very specific concerning the genes they are
impairing. Results: ASD candidate genes that are indentified independently
in both CNA studies include the neurexins CNTNAP2 and NRXN1, the
catenin CTNNA3, the cadherin CDH13, and the contactins CNTN5 and
CNTN6. Gene set enrichment analysis of ASD candidate genes showed
that significant biological processes are all related to cell and synaptic adhesion
the postsynaptic density, membrane and synapse. At data from the
BioGPS, the Cancer Genome Anatomy Project, and the Allen brain atlas,
ASD candidate genes have significantly different variations in their expression
values in cerebellum compared to other genes, where at the Allen brain
atlas cerebellar vermis lobes I-II, III, VI, and VIII where most significant. In
situ hybridization histochemistry data indicate that ASD candidate genes
are primarily expressed in the developing mouse cerebellum.