HGM 2011 - Dubai, UAE
Arthur L.Beaudet - Abstract
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Arthur L. Beaudet
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Haploinsufficiency for individual genes or chromosomal regions is known to be capable of causing autism or schizophrenia. In addition to the known copy number mutations causing schizophrenia and autism, we have identified novel copy number variations at substantial frequency in the DNA of patients with combined schizophrenia and epilepsy. By analogy, epigenetic silencing of an allele should be the functional equivalent of deletion or loss-of-function point mutation in that allele. We hypothesize that some fraction of autism and schizophrenia cases might be caused by epimutations. A genome-wide analysis of DNA methylation was performed on brain samples from 44 normal individuals, 13 patients with autism and 22 with schizophrenia using the Illumina Infinium human 27 methylation bead chip platform. The CpG island at the 5?-end of SERHL was hypermethylated in cerebellum of one autism patient. The CpG island at the 5?-end of LOC652276, a hypothetical gene, was hypermethylated in the BA8 region of cerebral cortex of one schizophrenia case. In both instances, the Infinium data were consistent with the interpretation that all controls and other cases were unmethylated at these loci and that heterozygous methylation was present in these two cases. Bisulfite treatment of DNA followed by PCR and sequencing of clones yielded approximately equal numbers of highly methylated and unmethylated clones for each locus which is consistent with the possibility of methylation of one allele but not the other for each locus. No similar cases of gain of methylation were observed in control brain samples. In addition, we also identified more than 100 sites showing hypomethylation in both disease sample sets. This work is being extended using the Illumina Human Methylation 450 DNA Analysis BeadChip and additional autism and schizophrenia samples. |
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Sheikh Hamdan Bin Rashid Al Maktoum |
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Human Genome Organisation |
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Centre for Arab Genomic Studies |
