In 2003, I moved to California from my native Hawaii. I’d just graduated from college, and I immediately accepted a job with Autism Genetic Resource Exchange (AGRE) with one goal in mind: Start building my career in research!
I didn’t know that this job would become so much more.
Autism quickly became my passion. As I learned more about the complexities of autism, I knew I wanted to make a difference in the lives of affected families. My interactions with AGRE parents and grandparents have been amazing. They have remarkable stories about their children and how each is wonderfully unique.
At the same time, I find it a great challenge to address some of their greatest concerns. I understand their urgent need for answers. But as someone trained in science, I also know that real answers sometimes take years to deliver. I remind our parents to never give up hope.
One of my most memorable interactions occurred at a Defeat Autism Now (DAN) conference several years ago. Autism Speaks had just started to become a prominent player within the autism community, and there was still apprehension about us. Unfortunately, I was not well equipped to answer some of the challenging political questions people asked me that day! I felt like a moving target and was left confused because I had thought we were all working towards the same goal: helping people with autism!
Just as I was packing up for the day, a man came over to the Autism Speaks table to talk with me. “I’ve been meaning to come over here all day,” he said. “I just want to thank you for being here. It means so much to us that you’re here to support us. Thank you.” To this day, whenever I feel lost in the politics and paperwork, I remember that moment and am reminded by why I’m here at AGRE.
Ultimately, I think the future of autism research lies in collaboration with scientists and families around the world. So it is very exciting to see AGRE’s mission begin to expand outside of North America. We know that autism is a global issue, and I think diversity is the glue that autism research needs to put all the pieces together.
In closing I want to thank all our supporters – those who Walk, those who participate in research, and everyone who cares about our mission to improve the lives of all who struggle with autism. Thank you so much. I love being part of this community.
On a day to day basis, I can get so immersed in the mechanics, data and details of what I do that I sometimes forget to step back and see the bigger picture: The tremendous value of the research information systems that Autism Speaks has created within its Autism Genetic Resource Exchange (AGRE).
I am feeling particularly sensitive to this “big picture” with this week’s announcement of the historic addition of AGRE information to the National Database for Autism Research (NDAR), which is supported and maintained by the National Institutes of Health.
I’m reminded that the goal of all my work is to increase the availability and usefulness of the vital information that we collect—information that can advance the scientific understanding of autism and speed the development of better treatments.
I promise to spare you the technical details. Suffice it to say, our role is to take the anonymous information (de-identified data) we gather from our participating families and put it in an easy-to-use format that autism researchers can use to increase the power and accuracy of their scientific findings and insights.
In joining our data with NDAR’s, we are making more comprehensive data available to the broader scientific community and also linking data collected on participants within AGRE with additional data on the same participants across a variety of other research studies (all anonymous). This is adding significantly to the autism field’s body of scientific knowledge. And this is our obligation to our families: To maximize their contributions and make sure their de-identified data will always be available to qualified scientists who are working to improve the lives of those who struggle with autism. We take pride in providing researchers with the most comprehensive and highest quality of data possible, so that they can do what they do best: science.
Special thanks go to Reinis Berzins, our AGRE data projects coordinator, whose position was made possible by the $1 million National Institutes of Health grant we received to integrate the AGRE and NDAR databases. To learn more about AGRE, please visit its website. To learn more about the AGRE-NDAR federation, please see this week’s related news item.
Read more science news and perspective on the Science Page.
Beijing Genomics Institute (BGI), the world’s largest genome sequencing organization got its start a little more than a decade ago at a moment when idealism, patriotic fervor and more than a little chutzpah converged to create what one of its founders, Huanming Yang, Ph.D., recently acknowledged was “a Mission Impossible.”
Yang, then with the Chinese Academy of Sciences, promised to complete 1 percent of the Human Genome Project–at the time the biological equivalent of the moon shot of the 1960s. There was just one problem: He didn’t have a gene-sequencing machine!
What followed was one of the most thrilling rags-to-riches stories in modern science. Yang and his colleagues overcame immense technical, financial and political obstacles to deliver the DNA sequence of their portion of human chromosome 3. In doing so, they changed Chinese science forever and built a scientific-industrial juggernaut that now represents 20 percent of the world’s capacity for genome sequencing.
That same can-do spirit was clearly on display when I and Autism Speaks-funded Duke University researcher Yong-hui Jiang, M.D., Ph.D., visited BGI in Shenzhen after the Autism Research Collaboration Development Meeting, co-hosted by Children’s Hospital of Fudan University in Shanghai and Autism Speaks. Not coincidentally, Yang gave the keynote address to the meeting, which ended last weekend.
Today most of BGI is housed in a former shoe factory on a small campus that includes several high-rise dormitories for nearly 4,000 employees. In recent years, the institute has produced such high-impact scientific accomplishments as complete genome sequences of rice and potato plants and the human gut microbiome (our digestive microbes). Through genetic sequencing, it also identified the culprit behind this summer’s deadly E. coli outbreak in Germany. In the face of this public health crisis, BGI marshaled the staff and technology to sequence the entire genome of the toxic bacterial strain in less than three days.
In visiting BGI, I was impressed by more than the arrays of cutting-edge automated sequencers, which run 24/7. I was struck by BGI’s eclectic leadership.
BGI cofounder, Jian Wang, Ph.D., recently scaled Mount Everest, after three attempts over a two-month period. For inspiration he credits BGI’s landmark collaboration with U.S. and European scientists in documenting the rapid evolution of the Tibetan human genome to accommodate life at high altitudes.
BGI executive director Jun Wang, Ph.D., joined the institute when he was 23 and went on to amass 36 publications in Science and Nature over 12 years. For your average researcher, having 1 or 2 publications in Science or Nature is sufficient to secure a tenured position at a top U.S. or European university.
At age 25 years, Yirui Li is leading the bioinformatics efforts of BGI’s recently announced collaboration with Autism Speaks to sequence 10,000 autism genomes. With 16 Science and Nature publications to his name, Li dropped out of China’s elite Tsing Hua University at age 19.
Despite their intellectual firepower, drive and personal and professional accomplishments, they were a down-to-earth group. They thought nothing of coming in on a Sunday to meet with us. Sporting what appeared to be their regular uniform of T-shirts, jeans and flip-flops or running shoes, they looked more like grad students than high-profile executives of a leading international research institute.
Yang and his colleagues also have a refreshingly progressive view on science and its end game. Impatient with traditional distinctions among scientific disciplines–such as genetics versus environmental sciences–they advocate a “trans-omics” approach to scientific development. In their view, decoding the genome is part of a continuum of activities that includes epigenetics, proteomics, cell biology, systems biology and computer science.
Most importantly, perhaps, they see all these activities as integrated and dedicated to “advancing the science of medicine” and “improving the effectiveness of healthcare.” Clearly, they remain driven by the sense of urgency that allowed them to identify and decipher a deadly pathogen by sequencing its entire DNA sequence in three days.
I left BGI inspired by what I saw and heard. The BGI team seemed refreshingly unencumbered by the petty divisions and willful near-sightedness we too often encounter in science and society. They are pursuing a grander vision that I, too, have lost at times. More than ever, I am hopeful that with enough idealism, ambition and even a little chutzpah, Autism Speaks collaborations like this one will soon deliver a better future for all of our families.
After a few drinks and a dinner of simple and very spicy local fare in the BGI canteen, Yang leaned over to me and said matter-of-factly, “We’ll get it done.”
Please visit our science pages for more news and perspective.
As head of clinical programs at Autism Speaks, I oversee a number of vital resources for researchers studying the causes and treatment of autism. Today brought the publication of a new and revealing study made possible by Autism Speaks’ Autism Genetic Resource Exchange (AGRE).
Autism researchers have been studying twins for years for insights into the genetic and nongenetic factors that influence the development of autism. One of the most powerful ways to do so is to study twins (both identical and non-identical) where at least one of the pair has autism. This approach allows us to look at how often both twins receive a diagnosis of autism. Study of identical twins, who share 100 percent of their genes, then helps us determine the degree to which autism is inherited, or genetic; and comparison to fraternal twins, who share around 50 percent of their DNA, allows us to understand how environmental influences add to the risk of autism spectrum disorder (ASD).
But until now we’ve had only three, small twin studies, which together looked at just 66 twin pairs–a number too small to produce reliable conclusions. Still, these studies were the best we had, and theysuggested that when one identical twin develops an ASD, the chance of the other twin developing the disorder is as high as 90 percent. These same studies showed little to no overlap among fraternal twins – leading to the conclusion that inherited genes alone produced the risk.
Now comes the game changer. The California Autism Twins Study (CATS) is the largest ever study of twins with ASD, with scientifically reliable information on 192 twin pairs, both identical and fraternal. It was conducted by a group of renowned researchers in collaboration with the AGRE team. AGRE clinical staff collected DNA and helped perform the home-based diagnostic and cognitive testing on many of the participants, using scientifically validated research measures for diagnosing ASD.
So what were its dramatic findings?
It found that when one identical twin develops autism, the chance of the other twin developing the disorder is 70 percent. More surprisingly, it documented a whopping 35 percent overlap among fraternal twins. This is strong evidence that environmental influences are at play. Moreover, the 35 percent “both twins affected” rate is higher than the 3 percent to 14 percent overlap between different age siblings. (i.e. If one child in a family has autism, there is a 3 percent to 14 percent chance that a younger sibling will develop it.) This suggests that there are environmental influences uniquely shared by twins–for instance, in the womb and perhaps during birth.
In other words, we now have strong evidence that, on top of genetic heritability, a shared prenatal environment may have a greater than previously realized role in the development of autism in twins
This has important implications for future research. For instance, is there a particular time period during the pregnancy when a child’s brain development is particularly vulnerable to environmental influences? And what might these influences be? Already we have evidence implicating such factors as advanced parental age, maternal nutrition, maternal infections (especially flu) during pregnancy, and premature and/or underweight birth. Indeed, multiple-birth pregnancies are themselves associated with increased risk of developmental disorders such as cerebral palsy and autism.
Only by further studying these issues can we begin to provide parents and parents-to-be with the reliable guidance they seek and need. Autism Speaks is currently investing in several studies that are exploring how environmental factors increase the risk for ASD. As we go forward in these endeavors, we greatly value your input. So please write and share your comments on our blog and website. For more on the study, read The Womb as Environment.
On July 5th, NBC Nightly News came to Andy Shih, Autism Speaks’ vice president of scientific affairs, for perspective on the game-changing California Autism Twins study. To view the clip please visit here.
More national television media coverage of the ground-breaking results of the California Autism Twin study–research made possible by the Autism Speaks Autism Genetic Resource Exchange (AGRE) and Autism Speaks’ supporters such as you.
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.