On July 19, a luncheon was held in Los Angeles to honor actor Ed Asner and his son Matt. Phillip Hain, Executive Director of the Los Angeles Chapter opened the program by giving an overview of what the chapter does in the community and talked about some of the local events. Attendees then heard from Dr. Clara Lajonchere, Vice President of Clinical Programs, who talked about the advances in science that have been made by Autism Speaks and its predecessor, Cure Autism Now, and how the Autism Genetic Resource Exchange (AGRE) has helped researchers be more efficient and collaborative with their studies. Marianne Toedtman, Associate Director of Family Services, talked about her challenges as a mother of a son on the spectrum, Family Services programs, and the current state of Family Services at Autism Speaks, particularly the Baker Summer Camp Program.
Ed talked about his involvement with Autism Speaks and how much work has been done since his son Charlie was diagnosed more than two decades ago. He implored the guests there to support Autism Speaks’ efforts in advocacy, family services, and science.
Matt told the attendees that when he was a teenager he was mad at his dad a lot, because his dad was the kind of guy who always took a stand on something and stuck to it, no matter what the cost was, to himself or others. And often the price he paid was very high. But now he realizes that his father set an example. Having both a brother and son affected by autism, Matt has become a passionate voice for our kids on the autism spectrum, fighting for their right to a fair and equal education in Los Angeles public schools. He noted that attending the Los Angeles Walk Now for Autism Speaks a few years ago gave him the feelings of hope and empowerment to help others.
Councilman Tom LaBonge presented Ed with a proclamation from the city of Los Angeles and Phillip gave Matt a piece of artwork created by a teen with autism, as a thank you for his continuing efforts and support.
By Geri Dawson, Chief Science Officer, Autism Speaks
Science moves so slowly and is so labor-intensive that we don’t often have moments to celebrate an achievement or breakthrough that has resulted from our investments. With this week’s announcement of Phase 2 results from the Autism Genome Project, we are celebrating such an achievement.
Several years ago, when I was a professor at the University of Washington, I remember a phone call from Andy Shih, Ph.D. (Autism Speaks VP, Scientific Affairs) who asked if he could take my colleague, Jerry Schellenberg, and me out to breakfast. Over coffee, Andy described to us an idea he had: Would we be willing to collaborate with other scientists around the world and add the genetic data we have been collecting to a combined database? While each of us at that time had been working independently to try to discover autism risk genes, we knew that ultimately we would need much larger samples to deal with the significant heterogeneity that exists in autism spectrum disorder. After a lot of discussion and questions, Andy convinced us that this would be a worthwhile effort and thus we became part of what became known as the “Autism Genome Project,” or the AGP. Eventually, Andy talked with over 50 groups worldwide and cajoled each of them to join the effort. What ensued was a series of monthly conference calls, complex negotiations and agreements that Andy helped broker, the creation of a combined database, and yearly meetings during which the goals for analysis and future data collection would be discussed. Today, the AGP is considered a driving force in autism genetic research.
Meanwhile, Clara Lajonchere, Ph.D. (Autism Speaks VP, Clinical Programs) was spearheading an effort to create a database of multiplex families called the Autism Genetic Resource Exchange (AGRE). She was leaving most of us collecting similar samples in the dust as she quickly assembled the largest private genetic individual data base that exists. Her ability to form partnerships with families, engaging them in the process of scientific discovery, was a model for us all. Not surprisingly, Clara readily agreed to join the AGP since AGRE’s basic premise was “collaboration and data sharing.”
Fast forward to this week when the AGP published the largest and most comprehensive study of copy number variations (CNV) – small deletions or duplications in our genome that can disrupt gene function – in autism families. By comparing CNVs found in 1,000 individuals with autism with those from 1,300 individuals without autism, the AGP reported the following:
- Several novel ASD genes were discovered, and many genes previously implicated by other studies were confirmed. Some of these genes are involved with communication between neurons, while others help regulate cell growth and how they respond to environmental stimuli.
- It was confirmed that autism risk genes are rare variants in our genome that occur very infrequently or not at all in the general population, and each person with ASD may have a unique risk gene or set of risk genes. Some of these genes are “highly penetrant” meaning that, if you carry this risk gene, you very likely will develop ASD, whereas other only raise the risk for ASD and need to combine with other genetic and/or environmental risk factors to cause ASD. Some of these are inherited, but many appear “de novo” meaning that they only exist in the child and not the parents.
- In the not-so-distant future, we will start to see more comprehensive genetic testing being conducted in the clinic to provide parents with information about whether their child may be at risk for ASD, so they can watch for signs or better understand the cause of their child’s ASD. It will be important to consider carefully what tests are appropriate and interpret them in a manner that is responsible and helpful for parents.
- Although the fact that so many rare genes can be related to risk for autism seems to form an overwhelmingly complex picture of autism, there is a path forward: These genes appear to cluster around specific biochemical pathways in the brain and, thus, point to new directions for developing drugs that could potentially help recover function of these pathways. This is good news for families.
Most of all, I see the publication of this report as a celebration of the fruitful partnership between the families and the scientific community. While Autism Speaks staff like Andy and Clara helped create and implement unique and productive scientific endeavors like the AGP, ultimately, it is the families who contributed their time and literally a part of themselves that is helping us put together this puzzle called autism piece by piece.
Genetic research is one of the exciting avenues of investigation that was highlighted at this year’s IMFAR meeting. The section on human genetics started with a description of the largest study of autism twins to date. This study, described by Dr. Joachim Hallmayer, has concluded the data collection phase and is beginning to shed new light on how much autism can be explained by genes and how much by environment. Because identical twins share 100% of their DNA while fraternal twins share only approximately 50%, geneticists can compare the relative contribution of genes and environment, since it is assumed that for each twin pair, the environment is the same. Clearly, both environment and genes are involved but this study may help to identify to what extent.
Dr. David Ledbetter described his effort to gather anonymous genetic information on chromosomal microarays from hundreds of thousands of patients with autism spectrum disorder and developmental delay. He is doing this by forming partnerships with over 120 clinical labs throughout the U.S. Dr. Ledbetter, a world-reknown expert in cytogenetics, has the knowledge and respect of the scientific community to achieve the goal of creating data standards and pooling information to show which chromosomal changes are most often identified in these groups. Deletions in regions on chromosomes 16 and 22 are identified consistently. Although still rare, an understanding of altered genes in these regions may lead us to identify new subtypes of autism.
Other talks focused on studies of brain and face development (since these happen at the same time) in families with autism from the Autism Genetic Resource Exchange, an update from the Autism Genome Project, and a fascinating talk from Sun-Chiao Chang (working with Dr. Susan Santangelo) on sex-specific effects in autism spectrum disorder. Ms. Chang identified several genes which seem to have an effect only in males, possibly helping to explain the common finding that there are four times as many males with autism as there females.
To read complete coverage from IMFAR, please visit http://www.autismspeaks.org/science/science_news/imfar_2010.php.
In honor of the anniversary of Autism Speaks’ founding on Feb 25, for the next 25 days we will be sharing stories about the many significant scientific advances that have occurred during our first five years together. Our seventh item, AGRE Reaches Milestones, is from Autism Speaks’ Top 10 Autism Research Events of 2007.
Created in 1997 by Cure Autism Now/Autism Speaks, the Autism Genetic Resource Exchange (AGRE) remains one of the most powerful resources for autism research. AGRE is a nation-wide family registry and biomaterials repository that recruits families with at least two members with an autism spectrum disorder. Biological samples (blood, plasma and DNA) are collected along with the accompanying clinical data and made available to AGRE-approved researchers all over the globe. As of December 2007, this open-access, collaborative resource contained information on over 1600 families with autism, making it the largest privately maintained autism repository in the world.As parents know, the research process can be frustratingly slow. AGRE significantly speeds up the process by providing researchers with the necessary materials and information to test a diversity of hypotheses without having to recruit families or collect their own data. Furthermore, having such a large database of sample data provides researchers with more meaningful insight into the disorder. The impact has been enormous. This summer AGRE reached a publication milestone, when the 100th paper citing use of the resource was released. As recognition of this remarkable contribution and the pivotal role of AGRE in advancing autism research, in September 2007 the National Institute of Mental Health awarded an $8.4 million grant to the University of Southern California that will provide funding to support AGRE with the next five years of data collection.
The AGRE program provides families with a means to get involved and positively contribute to autism research. A better understanding of autism will require different scientific approaches and even greater numbers of families. This year scientists studying other complex disorders such as diabetes and heart disease found that sample sizes on the order of tens of thousands of affected individuals were required before common disease genes could be detected. Continued expansion of AGRE and other collections like it will be necessary to reach these goals as fast as possible.
Did you know?: The AGRE collection continues to be the largest private source of genetic and clinical information for autism research available to scientists worldwide, containing information on over 2100 families with autism as of January 2010. AGRE is now responsible for 162 peer-reviewed publications and has been used in most of the major autism genetic discoveries to date. It is currently facilitating 11 collaborations with outside researchers and supports six federal grants. One of these grants was awarded to Autism Speaks by the NIH as part of the 2009 stimulus funding. This new grant will allow AGRE and the NIH to enter a partnership to help build a larger and more flexible national database for autism research.