Yes, another type of mutation in autism was revealed this week. Those that are evident after the sperm and egg meet to form the zygote but still very early, during embryonic development. Because it occurs after the original zygote is formed, the mutation is not found in every cell or every region of the body, called post-zygotic. A collaboration of three major genetic consortia studied and collaborated on these types of mutations and revealed that they consist of about 7.5% of all de novo mutations in people with autism. They affect autism risk genes and selectively target brain regions associated with autism. Learn more about what this means for family planning and cognitive ability in people with autism.
On May 4th, Dr. Janine LaSalle from UC Davis and (the soon to be Dr.) Keith Dunaway presented on recent research investigating the role of environmental factors in individuals with Dup15 Syndrome. Individuals with a mutation on chromosome 15 are often diagnosed with autism and previously it had been assumed that these individuals were destined to have a diagnosis due to their genetics. Dr. LaSalle shows that many of the genes in a critical region of chromosome 15 are tied to turning genes on and off via a process called methylation. Environmental chemicals or other exposures may also work on these genes to turn on or off gene expression epigenetically. The first half of the webinar reviews crucial ideas in gene x environment interactions and epigenetics, the second half describes experiments using brain tissue of those with Dup15 Syndrome and autism, as well as cell lines, to understand the role of PCBs in gene expression.
On March 13th, Dr. Mark Zylka from UNC gave a 60 minute overview of how researchers are using autism-relevant genetic mutations in cells to start to understand the interactions between genetics and thousands of environmental factors on gene expression. He pointed out the convergence of pathways in how genes and these environmental factors worked in the brain, and they included: neuroinflammation, early brain development, turning neurons on and off, and cell signaling. Dr. Valerie Hu from George Washington University commented on the important impact of these results and perspective from her lab studying epigenetically modified genes, like RORA, which also may be sensitive to common chemicals found in our environment. The entire webinar, including the questions that they were able to answer from participants, is found here.
With hundreds of genes, thousands of environmental factors, and now sex being variables in determining risk for autism, where should science start? Over the decades researchers have been able to start narrowing down the combinations based on specific behaviors of interest, genes, and mechanisms which may narrow down which gene, which environmental factor and which sex. Dr. Sara Schaafsma and Dr. Donald Pfaff from Rockefeller University combined the three, and found that epigenetic changes in an autism risk gene called contact in associated protein like 2 contributed to elevation of risk for autism behaviors following maternal infection. In other words, being male and having the mutation produced small changes, increased by the environmental factor. In another separate study, Dr. Keith Dunaway and Dr. Janine LaSalle at UC Davis used brain tissue to look at a rare variant for autism on chromosome 15. Typically, mutations of this area of the genome are thought to cause autism. However, the effects of these mutations are also increased when environmental factors are present, leading to more de novo mutations. These are all examples of scientific breakthroughs that are helping better understand what causes autism. Even when it looks like one thing, it’s multiple things.
The year 2016 was eventful for many reasons. In this 20 minute podcast, we review some of the scientific discoveries that highlighted findings in causes, understanding, and treating ASD. Featured more this year is studies on the sibling of individuals with ASD, so we are calling 2016 “The Year of the Sibling” This review includes genetics, gene x environment interactions, diagnosis, the broader autism phenotype, and early interventions and the role of parent-delivered interventions in long term outcome. It also highlights the important role of studying brain tissue from individuals with autism to better understand people with autism across the lifespan, including those with known causes and unknown causes of ASD. We hope you find it informative – please send comments to email@example.com
On Tuesday November 15th, Tracy Bale from University of Pennsylvania provided an insightful analysis of sex differences in behavioral, physiological and molecular outcomes following prenatal stress. She outlined the potential epigenetic markers that may lead to resilience in female offspring which has direct implications for autism. However, prior to Dr. Bale’s presentation, Donna Werling from UCSF briefly outlined the genetic and behavioral data so far about females with autism and why there is a 4:1 ratio in males to females getting a diagnosis. This webinar is part of the Environmental Epigenetics of Autism Webinar Series co-organized by Autism Science Foundation, Autism Speaks and the Escher Family Fund for Autism.
This week’s podcast is inspired by a new study in PNAS thatlooked at the role of methylation of the oxytocin receptor in social behavior in people without autism. Together with studies of the brains of people with autism, it suggests that filling the brains with oxytocin may not be the best approach for treating social impairments. Instead, compounds that turn on or turn off the genes that control oxytocin may be more appropriate, and it also may help explain variability in why some people respond to oxytocin treatment, and why others do not. Also, scientific technology has a new way of studying the influence of the environment on brain development.
What was impactful this year in autism research? This last podcast of 2015 explores the year of the female, highlighting the relatively new exploration into what makes females with ASD different and what they can tell us about everybody with autism and their families. Some of what is discussed was highlighted in other podcasts, but not all of it. The summary is organized so that what may initially be interpreted as small, nonsignificant discoveries, are viewed as progress. Everything from genetics to getting laws passed is included.
On Thursday October 1st, Autism Science Foundation, Autism Speaks and the Escher Fund for Autism co-organized an online symposium which examined the possibility that early mutations in cells that pass along genetic information from generation to generation (sperm and egg and cells that make the sperm an egg) has a role in the causes of autism. This symposium is on the ASF podcast feed, but a quick summary is presented on this week’s podcast. Jill Escher from the Escher Fund for Autism and Mat Pletcher from Autism Speaks provide their perspective. Also, a quick rundown on the study that caused so much monkeying around in the press.