Autism Speaks MSSNG study expands understanding of autism's complex geneticsAugust 04, 2016
A new study from Autism Speaks' MSSNG program expands understanding of autism's complex causes and may hold clues for the future development of targeted treatments. The report, appearing in npj Genomic Medicine is the largest-ever whole genome study of autism, involving 200 children with the condition and both their unaffected parents.
The new research focuses on newly arising, or de novo, gene changes in the germline cells that produce a parent's eggs or sperm. Previous studies have shown that these mutations can be major contributors to autism through their effects on early brain development.
The 600 fully sequenced genomes came from MSSNG (pronounced "missing"), the world's largest collection of autism genomes and a collaborative effort of Autism Speaks and The Hospital for Sick Children (SickKids), in Toronto. More than halfway to its goal of sequencing more than 10,000 autism genomes, MSSNG has made this unprecedented resource freely available for worldwide research into the causes and personalized treatments for autism.
Geneticists Stephen Scherer and Ryan Yuen, of SickKids, led the study team, which also included scientists with the University of Toronto, Google, BGI-Shenzhen (China) and Autism Speaks.
The researchers found:
- An abundance of autism-linked changes in DNA outside of the gene-coding regions of the genome. Traditional genetic testing largely ignores the non-coding regions of the genome -- which make up 98 percent of our DNA. Coding DNA spells out our genes. Non-coding DNA had long been considered "junk," with no known function. Geneticists now appreciate that it helps regulate the activity of our genes. This regulation is particularly crucial for healthy brain development, which involves genes turning on and off at precisely the right times.
"This represents the most comprehensive assessment to date on the contribution of non-coding variants to autism," Dr. Yuen says. "As such, it provides an important road map on how whole genome sequencing can advance autism research in the future."
- A clear difference between the de novo mutations that come from the mother versus the father. The study confirmed previous findings that most autism-linked de novo mutations come from the father and tend to increase with his age.
However, the researchers also found that clustered, or concentrated, stretches of de novo mutations tend to come from the mother. "This new finding may be evidence that different types of gene-change and gene-repair mechanisms are at work in men versus women," Dr. Yuen says. Indeed, the clustered mutations from the mother tended to occur near stretches of deleted or repeated DNA called copy number variations (CNVs) -- a type of mutation that the research team had previously linked to autism.
In addition to genetic changes in egg and sperm, the analysis turned up autism-associated mutations that likely occurred in the embryo soon after fertilization. "These genetic changes can arise due to environmental insults [such as exposure to toxic chemicals]," Dr. Yuen says.
- A new way to explore epigenetic risk factors for autism. The team also developed new methods to look at changes in the epigenetic control of gene expression. Epigenetics is the study of proteins that wrap around our DNA to help regulate gene activity. These epigenetic controls can be disrupted by some -- perhaps many -- of the environmental influences suspected of increasing autism risk. Examples include exposure to certain pollutants, nutritional deficiencies and inflammation during pregnancy. Using their new test, the researchers found significantly disrupted epigenetic patterns in just over 1 percent of the genomes they analyzed.
- A cascade effect, with one altered gene affecting the expression of many other genes involved in brain development. "Using new statistical methods and the whole genome sequence as a framework, we found genes with mutations that led to a cascade of changes in gene expression," Dr. Yuen says. This may help explain how the hundreds of rare gene changes associated with autism may converge to affect a few vital pathways in early brain development, he notes.
"These findings advance our efforts to improve diagnostics and precision healthcare for autism," says geneticist Mathew Pletcher, Autism Speaks interim chief science officer and a co-author on the report. "There's so much about the causes of autism that we would miss if we focused only on the gene-coding regions of the genome. This demonstrates again why whole genome sequencing is so important."
"These findings represent a step toward better understanding the interplay between the genetic and non-genetic factors that contribute to autism risk," Dr. Scherer adds. "But we need to analyze many more whole genomes - such as the number being sequenced through MSSNG - to fully understand these intriguing findings." Dr. Scherer is project director for the Autism Speaks MSSNG program and directs the Centre for Applied Genomics at Toronto's Sick Children's Hospital. Dr. Yuen's research was supported by an Autism Speaks Meixner Postdoctoral Fellowship in Translational Research. Read more about Autism Speaks research fellowships here.
Autism is a general term used to describe a group of complex developmental brain disorders - autism spectrum disorders - caused by a combination of genes and environmental influences. These disorders are characterized, in varying degrees, by communication difficulties, social and behavioral challenges, and repetitive behaviors. An estimated 1 in 68 children in the U.S. is on the autism spectrum.
About Autism Speaks
Autism Speaks is the world's leading autism science and advocacy organization. It is dedicated to funding research into the causes, prevention, treatments and a cure for autism; increasing awareness of autism spectrum disorders; and advocating for the needs of individuals with autism and their families. Autism Speaks was founded in February 2005 by Suzanne and Bob Wright, the grandparents of a child with autism. Since its inception, Autism Speaks has committed more than $570 million to its mission, the majority in science and medical research. On the global front, Autism Speaks has established partnerships in more than 70 countries on five continents to foster international research, services and awareness. To learn more about Autism Speaks, please visit AutismSpeaks.org.
About The Hospital for Sick Children
The Hospital for Sick Children (SickKids) is recognized as one of the world's foremost paediatric health-care institutions and is Canada's leading centre dedicated to advancing children's health through the integration of patient care, research and education. Founded in 1875 and affiliated with the University of Toronto, SickKids is one of Canada's most research-intensive hospitals and has generated discoveries that have helped children globally. Its mission is to provide the best in complex and specialized child and family-centred care; pioneer scientific and clinical advancements; share expertise; foster an academic environment that nurtures health-care professionals; and champion an accessible, comprehensive and sustainable child health system. SickKids is proud of its vision for Healthier Children. A Better World. For more information, please visit http://www.sickkids.ca. Follow us on Twitter (@SickKidsNews) and Instagram (@SickKidsToronto).
Related Autism Articles:
Exposure to ozone in the environment puts individuals with high levels of genetic variation at an even higher risk for developing autism than would be expected just by adding the two risk factors together, a new analysis shows.
An algorithm based on levels of metabolites found in a blood sample can accurately predict whether a child is on the autism spectrum of disorder (ASD), based upon a recent study.
Autism spectrum disorders (ASD) affect around one percent of the world's population and are characterized by a range of difficulties in social interaction and communication.
A new study from Autism Speaks' MSSNG program expands understanding of autism's complex causes and may hold clues for the future development of targeted treatments.
A new report in Biological Psychiatry reports that brain alterations in infants at risk for autism may be widespread and affect multiple systems, in contrast to the widely held assumption of impairment specifically in social brain networks.
Humans are resilient, even facing the toughest of life's challenges.
Recognizing a need to better understand the biology that produces Autism Spectrum Disorder (ASD) symptoms, scientists at Duke-NUS Medical School (Duke-NUS) and the National Neuroscience Institute (NNI), Singapore, have teamed up and identified a novel mechanism that potentially links abnormal brain development to the cause of ASDs.
Using a visual test that is known to prompt different reactions in autistic and normal brains, Harvard researchers have shown that those differences were associated with a breakdown in the signaling pathway used by GABA, one of the brain's chief inhibitory neurotransmitters.
The release of oxytocin leads to an increase in the production of anandamide, which causes mice to display a preference for interacting socially.
The Autism Science Foundation, a not-for-profit organization dedicated to supporting and funding autism research, today announced the launch of the Autism Sisters Project, a new initiative that will give unaffected sisters of individuals with autism the opportunity to take an active role in accelerating research into the 'Female Protective Effect.'
Related Autism Reading:
Uniquely Human: A Different Way of Seeing Autism
by Barry M. Prizant (Author)
Winner of the Autism Society of America’s Dr. Temple Grandin Award for the Outstanding Literary Work in Autism
A groundbreaking book on autism, by one of the world’s leading experts, who portrays autism as a unique way of being human—this is “required reading....Breathtakingly simple and profoundly positive” (Chicago Tribune).
Autism therapy typically focuses on ridding individuals of “autistic” symptoms such as difficulties interacting socially, problems in communicating, sensory challenges, and repetitive behavior patterns. Now Dr. Barry M. Prizant... View Details
The Reason I Jump: The Inner Voice of a Thirteen-Year-Old Boy with Autism
by Naoki Higashida (Author), KA Yoshida (Translator), David Mitchell (Translator)
The Reason I Jump View Details
A Parent's Guide to High-Functioning Autism Spectrum Disorder, Second Edition: How to Meet the Challenges and Help Your Child Thrive
by Sally Ozonoff (Author), Geraldine Dawson (Author), James C. McPartland (Author)
Many tens of thousands of parents have found the facts they need about high-functioning autism spectrum disorder (ASD), including Asperger syndrome, in this indispensable guide. Leading experts show how you can work with your child's unique impairments--and harness his or her capabilities. Vivid stories and real-world examples illustrate ways to help kids with ASD relate more comfortably to peers, learn the rules of appropriate behavior, and succeed in school. You'll learn how ASD is diagnosed and what treatments and educational supports really work. Updated with the latest research and... View Details
The Survival Guide for Kids with Autism Spectrum Disorders (And Their Parents)
by Elizabeth Verdick (Author), Elizabeth Reeve M.D. (Author)
This positive, straightforward book offers kids with autism spectrum disorders (ASDs) their own comprehensive resource for both understanding their condition and finding tools to cope with the challenges they face every day. Some children with ASDs are gifted; others struggle academically. Some are more introverted, while others try to be social. Some get "stuck" on things, have limited interests, or experience repeated motor movements like flapping or pacing ("stims"). The Survival Guide for Kids with Autism Spectrum Disorders covers all of these areas, with an emphasis on... View Details
I See Things Differently: A First Look at Autism (A First Look At...Series)
by Pat Thomas (Author)
Psychotherapist and counselor Pat Thomas puts her gentle, yet straightforward approach to work in this new addition to Barron's highly acclaimed A First Look At...Series. This book will help children understand what autism is and how it affects someone who has it. A wonderful catalyst for discussion that will help children to better understand and support autistic classmates or siblings. The story line is simple and easily accessible to younger children, who will learn that exploring the personal feelings around social issues is a first step in dealing with them. Full-color... View Details
Autism Breakthrough: The Groundbreaking Method That Has Helped Families All Over the World
by Raun K. Kaufman (Author)
As a boy, Raun Kaufman was diagnosed by multiple experts as severely autistic, with an IQ below 30, and destined to spend his life in an institution. Years later, Raun graduated with a degree in Biomedical Ethics from Brown University and has become a passionate and articulate autism expert and educator with no trace of his former condition.
So what happened?
Thanks to The Son-Rise Program, a revolutionary method created by his parents, Raun experienced a full recovery from autism. (His story was recounted in the best-selling book Son-Rise: The Miracle Continues and in the... View Details
Ten Things Every Child with Autism Wishes You Knew: Updated and Expanded Edition
by Ellen Notbohm (Author), Veronica Zysk (Editor)
A bestseller gets even better! Every parent, teacher, social worker, therapist, and physician should have this succinct and informative book in their back pocket. Framed with both humor and compassion, the book describes ten characteristics that help illuminate—not define—children with autism.
Neurotribes: The Legacy of Autism and the Future of Neurodiversity
by Steve Silberman (Author), Oliver Sacks (Foreword)
This New York Times bestselling book upends conventional thinking about autism and suggests a broader model for acceptance, understanding, and full participation in society for people who think differently. What is autism? A lifelong disability, or a naturally occurring form of cognitive difference akin to certain forms of genius? In truth, it is all of these things and moreand the future of our society depends on our understanding it. Wired reporter Steve Silberman unearths the secret history of autism, long suppressed by the same clinicians who became famous for discovering it, and finds... View Details
Eating for Autism: The 10-Step Nutrition Plan to Help Treat Your Child’s Autism, Asperger’s, or ADHD
by Elizabeth Strickland (Author)
What your child eats has a major impact on his brain and body function. Eating for Autism is the first book to explain how an autism, Asperger's, PDD-NOS, or ADHD condition can effectively be treated through diet.
Eating for Autism presents a realistic 10-step plan to change your child's diet, starting with essential foods and supplements and moving to more advanced therapies like the Gluten-Free Casein-Free diet. Parents who have followed Strickland's revolutionary plan have reported great improvements in their child's condition, from his mood, sleeping patterns, learning... View Details
An Early Start for Your Child with Autism: Using Everyday Activities to Help Kids Connect, Communicate, and Learn
by Sally J. Rogers (Author), Geraldine Dawson (Author), Laurie A. Vismara (Author)
Cutting-edge research reveals that parents can play a huge role in helping toddlers and preschoolers with autism spectrum disorder (ASD) connect with others and live up to their potential. This encouraging guide from the developers of a groundbreaking early intervention program provides doable, practical strategies you can use every day. Nearly all young kids—including those with ASD—have an amazing capacity to learn. Drs. Sally Rogers, Geraldine Dawson, and Laurie Vismara make it surprisingly simple to turn daily routines like breakfast or bath time into fun and rewarding learning... View Details