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.
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.”
For more information or to arrange an interview please contact:
University of Manchester Media Relations Officers Jo Nightingale or Mikaela Sitford on 0161 275 8156 or 2111 (for Dr Janine Lamb, Professor Jonathan Green or Professor Andrew Pickles)
University of Oxford Press Officer Ruth Collier 01865 280 532 (for Professor Anthony Monaco or Professor Anthony Bailey)
Editors Note:
Autism is a complex brain disorder that inhibits a person’s ability to communicate and develop social relationships, and is often accompanied by extreme behavioural challenges. Autism Spectrum Disorders are diagnosed in one in 166 children in the United States, affecting four times as many boys as girls. The diagnosis of autism has increased tenfold in the last decade. The Centres for Disease Control and Prevention have called autism a national public health crisis whose cause and cure remain unknown.
Speakers: Dr Janine Lamb (University of Manchester) will discuss the genetics of the study. Professor Jonathan Green (University of Manchester) will discuss the clinical implications of the study, and Professor Andrew Pickles (University of Manchester) will discuss its links to other autism research. Professor Anthony Bailey (University of Oxford) is also available for comment.
The International Molecular Genetic Study of Autism Consortium (IMGSAC) was established in 1994 and includes scientific researchers and clinicians from a number of European countries and the United States. It is led by Professors Tony Monaco and Anthony Bailey at the University of Oxford. Professor Bailey previously led from the Institute of Psychiatry (based at King’s College, London) before moving to Oxford. The Consortium has generated an extensive collection of families with autism, and has led the field using sophisticated technology to examine these families for genes underlying autism susceptibility. The Consortium is funded in part by project grants from the Medical Research Council (UK), The Wellcome Trust and The NLM Foundation.
The University of Manchester’s Faculty of Medical and Human Sciences boasts an annual research income of £51m, almost a third of the University’s total research income. There are 7,600 undergraduate students and 1,600 postgraduates on award-bearing courses. More students graduate each year from the School of Medicine than from any other medical school in the UK. For more information see www.manchester.ac.uk/
The Institute of Psychiatry is the largest academic community in Europe devoted to the study and prevention of mental health problems. It provides post-graduate education and carries out research in psychiatry, psychology, and allied disciplines, including basic and clinical neurosciences. The Institute, world renowned for the quality of its research, became a school of King's College, London, in August 1997.
Oxford University’s Medical Sciences Division is one of the largest in Europe. It represents almost one third of University income and expenditure and two thirds of external research income. It has 2,500 staff, a budget of £200m and over £107m in external research income.
The Wellcome Trust Centre for Human Genetics is funded by the Wellcome Trust and based at the University of Oxford. The scientific objective of the Centre is to explore all aspects of the genetic susceptibility of disease. The Centre houses multi-disciplinary research teams in human genetics, functional genomics, bioinformatics, statistical genetics and structural biology. See www.well.ox.ac.uk.
The Medical Research Council (MRC) is dedicated to improving human health through excellent science. It invests on behalf of the UK taxpayer. Its work ranges from molecular level science to public health research, carried out in universities, hospitals and a network of its own units and institutes. The MRC liaises with the Health Departments, the National Health Service and industry to take account of the public’s needs. The results have led to some of the most significant discoveries in medical science and benefited the health and wealth of millions of people in the UK and around the world. www.mrc.ac.uk
Autism Speaks is dedicated to increasing awareness of autism spectrum disorders, to funding research into the causes, prevention, treatments and cure for autism, and to advocating for the needs of affected families. It was founded in February 2005 by Suzanne and Bob Wright, the grandparents of a child with autism. Bob Wright is Vice Chairman and Executive Officer, General Electric. Autism Speaks has merged with both the National Alliance for Autism Research (NAAR) and Cure Autism Now (CAN), bringing together the nation’s three leading autism advocacy organizations. For more information see www.autismspeaks.org
Journal
Nature Genetics