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Results of largest ever genome scan for autism out

The genomes of the largest collection of families with multiple cases of autism ever assembled have been scanned and the preliminary results published in Nature Genetics (February 18, 2007). They provide new insights into the genetic basis of autism.

The research was performed by more than 120 scientists from more than 50 institutions representing 19 countries. In the UK, work was carried out at The University of Manchester, the Institute of Psychiatry at King’s College, London and the University of Oxford.

The international collaboration started in 2002 when researchers from around the world decided to come together and share their samples, data, and expertise to facilitate the identification of autism susceptibility genes. They formed the Autism Genome Project.

The world-wide consortium of scientists made the most of its large sample of 1,200 families, using “gene chip” technology to look for genetic similarities in autistic people. The AGP also scanned DNA from these families for copy number variations (CNV), or sub-microscopic genomic insertions and deletions that scientists believe might be involved with this and other common diseases.

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The innovative combination of these two approaches implicates a previously unidentified region of chromosome 11, and neurexin 1 - a member of a family of genes believed to be important in the contact and communication of neurons. The neurexin finding in particular highlights a special group of neurons called glutamate neurons and the genes affecting their development and function, suggesting they play a critical role in autism spectrum disorders.

The first phase of the effort – the assembly and scanning of the largest autism DNA collection ever – was funded by Autism Speaks, a non-profit organisation dedicated to increasing awareness of autism and raising money to fund autism research, and the US National Institutes of Health.

Phase two of the project, which will build on the success of the linkage scan, is now being launched. It represents a £7.44 million investment over three years by Autism Speaks, the UK Medical Research Council (MRC), the Health Research Board of Ireland (HRB), Genome Canada and partners, Canadian Institutes for Health Research (CIHR), Southwest Autism Research and Resource Center (SARRC), and the Hilibrand Foundation. This unique combination of international, public and private partners funding a consortium of clinicians and scientists is unprecedented in the field of autism research.

Professor Tony Monaco from the University of Oxford’s Wellcome Trust Centre for Human Genetics led the funding bid, and the International Molecular Genetic Study of Autism Consortium (IMGSAC), led by Professors Monaco and Anthony Bailey (both University of Oxford), is a major contributor to both phases of the Autism Genome Project. The Manchester team for phase 2 includes autism genetics expert Dr Janine Lamb, who had a central role in IMGSAC’s genetic analysis, statistician Professor Andrew Pickles who is a leading international researcher in the autism field, and child psychiatrist Professor Jonathan Green, who led the clinical fieldwork in Manchester. The work links to a wider significant programme of autism research in Manchester led by Professors Pickles and Green; including national and international developmental studies and trials of autism interventions.

Professor Green said: “Autism is a very difficult condition for families – communication is taken for granted by parents of healthy children but is so greatly missed by those with autistic children. We are working now in Manchester to investigate the basic science and develop and test new treatments for the condition. We hope that these exciting results may represent a step on the way to further new treatments in the future.”

Autism Speaks co-founder and board chair, Bob Wright, said: “The identification of susceptibility genes will provide profound new insight into the basis of autism offering a route to breakthroughs in new treatments in support of families.”

Jon Keighren | alfa
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