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Genome Institute of Singapore Release: Novel Genomic Sequencing Reveals Potential Causes Of Autism



11/18/2016 3:00:16 PM

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Finding could lead to new treatments which include development of drugs

SINGAPORE – Scientists studying autism have applied a novel epigenomic sequencing approach to find possible causes of the disorder, discovering that thousands of gene control regions are consistently altered in autism patients. The epigenome refers to the layer of molecular features that allows cells in the body to have diverse properties, despite having the same genomic DNA. Although autism is generally believed to be a heterogeneous collection of distinct diseases, the scientists found that epigenomic aberrations in the brain cells of autistic individuals were surprisingly homogeneous, thus opening up new avenues for treatment. This finding is published in the scientific journal Cell.

Autism is an umbrella term for several brain disorders that have three symptoms in common: altered thought and imagination processes, social impairment and communication deficits. Despite massive worldwide DNA sequencing of autism patients, the causes of this disorder are still poorly understood due to its complexity. With no common disease mechanism known, it has been difficult to develop effective drugs that could treat the majority of autism patients.

In this study, the researchers used a method, known as “epigenome profiling”, to characterise thousands of gene control elements across the genome in both healthy individuals and autism patients. Uniquely, they focussed on epigenomic changes to DNA packaging molecules in specific regions of the brain. By comparing these two groups, the team discovered for the first time that thousands of control regions behave differently from those of healthy subjects. These elements act as an autism-specific signature and could explain how autism develops in the majority of patients. Importantly, this finding opens up the possibility of treating autistic individuals with “epigenetic drugs” that alter the epigenomic profiles of cells.

“We now have a method with which we can basically investigate any disease, and find the aberrant gene control regions. This development took six years,” said one of the study’s lead authors Dr Sun Wenjie, Research Associate, Computational & Systems Biology at A*STAR’s Genome Institute of Singapore (GIS).

Led by GIS, this multi-national, multi-institutional project also involved researchers at the University of California at Los Angeles (UCLA, US), the University of Exeter (UK) and King’s College London (UK). The US team was led by Prof Daniel Geschwind, Director of the UCLA Center for Autism Research and Treatment, and the UK team was led by Jonathan Mill, Professor of Epigenetics at the University of Exeter.

“We could not have done this without our collaborators. For this study, we had to combine deep knowledge of the biology of autism with cutting edge experimental techniques and highly precise data analysis methods,” added Dr Shyam Prabhakar, the study’s senior author and Associate Director of Integrative Genomics at the GIS.

GIS Executive Director Prof Ng Huck Hui said, “This is a major breakthrough for the research community because the method can now also be applied to other diseases. This work on epigenomics clearly illustrates the importance of epigenetic signatures in linking the critical genome regulatory loci to disease states."

This international collaboration was funded by the PsychENCODE program of the US National Institutes Health and Singapore’s A*STAR. Furthermore, this study was performed as part of the International Human Epigenome Consortium (IHEC).

“Being part of such multi-national consortia enables us to significantly impact on research while sharing our findings with scientists throughout the world,” noted joint lead author Dr Jeremie Poschmann, Research Fellow, University of Exeter. This is part of a collection of 41 publications in Cell, Cell Press-associated and other high-impact journals by IHEC scientists#.

Notes to Editor:

The research findings described in this media release can be found in the scientific journal Cell, under the title, “Histone Acetylome-wide Association Study of Autism Spectrum Disorder” by Wenjie Sun1,6, Jeremie Poschmann1,6, Ricardo Cruz-Herrera del Rosario2, Neelroop N. Parikshak3, Hajira Shreen Hajan1, Vibhor Kumar1, Ramalakshmi Ramasamy1, T. Grant Belgard3, Bavani Elanggovan1, Chloe Chung Yi Wong4, Jonathan Mill4,5, Daniel H. Geschwind3,*, Shyam Prabhakar1,7,*

1Computational and Systems Biology, Genome Institute of Singapore, Singapore

2Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA

3Program in Neurogenetics, Department of Neurology, Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA

4Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London SE5 8AF, United Kingdom

5University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK

6Co-first author

7Lead Contact

*Correspondence: prabhakars@gis.a-star.edu.sg (S.P.), dhg@ucla.edu (D.H.G.)

Read at BioSpace.com


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