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considerable phenotypic variability seen in these emerging disease–common variant hypothesis in psychiatric disorders. From
genomic disorders remain to be elucidated. Possible explanations a genetic perspective, recent studies suggest that autism,
include genetic variation in the remaining copy of genes within the schizophrenia and other psychiatric conditions may in fact be an
deletion region, variation in other interacting genes or the presence amalgamation of numerous different genomic disorders. ■
of additional CNVs. Alternatively, epigenetic or environmental
factors may play a role.
Alistair T Pagnamenta is a Post-doctoral Research
Scientist at the Wellcome Trust Centre for Human
CNVs such as those described in this article typically contain
Genetics. His current work involves fine-mapping of
numerous genes. Analysis of gene expression changes resulting from
genetic susceptibility factors underlying autism.
Particular interests include genomic architecture of
such genomic imbalance, together with functional studies, should help
autism, in particular 15q13.3 microdeletion. He
identify the dosage-sensitive genes involved in synaptic interactions
received a PhD from the University College London
and other pathways in brain development that may contribute to
after working on the genetics of mitochondrial
disorders. Prior to this, he worked as a Development
these psychiatric phenotypes. Identifying the rare cases where
Scientist for Amersham Biosciences.
deletions may result in stable fusion-gene transcripts with potential
Anthony P Monaco is Pro-Vice Chancellor of Planning
will be important. It will also be instructive to
and Resources at Oxford University and a Professor of
compare the disrupted genetic pathways that appear shared between
Human Genetics and Fellow at Merton College. He
psychiatric disorders with those such as SHANK3-neuroligin, which
directs the Neurogenetics Group at the Wellcome
Trust Centre for Human Genetics, with a focus on
currently appear to be more specific to autism.
neurodevelopmental disorders such as autism,
dyslexia and specific language impairments.
In contrast to common conditions such as obesity and diabetes,
there is limited well-replicated evidence to date for the common
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