Breaking News
December 13, 2018 - Drug repositioning strategy identifies potential new treatments for epilepsy
December 13, 2018 - Chronic rhinitis associated with hospital readmissions for asthma and COPD patients
December 13, 2018 - Food poisoning discovery could save lives
December 13, 2018 - Cloned antibodies show potential to treat, diagnose life-threatening fungal infections
December 13, 2018 - Exercise may reduce colorectal cancer risk after weight loss
December 13, 2018 - Russian scientists create hardware-information system for brain disorders treatment
December 13, 2018 - Moderate alcohol consumption linked with lower risk of hospitalization
December 13, 2018 - Nurturing Healthy Neighborhoods | NIH News in Health
December 13, 2018 - Rise in meth and opioid use during pregnancy
December 13, 2018 - Researchers gain new insights into pediatric tumors
December 13, 2018 - FSU study finds racial disparity among adolescents receiving flu vaccine
December 13, 2018 - Drug cocktail induces cancer cell death by switching off energy supply
December 13, 2018 - Baculovirus virion completely eliminates liver-stage parasites in mouse model
December 13, 2018 - Researchers create noninvasive technology that detects when nerve cells fire
December 13, 2018 - Treating patients with hypertension induced albuminuria
December 13, 2018 - New substance could improve efficacy of established breast cancer treatments
December 13, 2018 - Scientists develop new stem cell line to study conversion of stem cells into muscle
December 13, 2018 - Re-programming the body’s energy pathway boosts kidney self-repair
December 13, 2018 - Research findings could help improve treatment of anxiety and post-traumatic stress disorders
December 13, 2018 - The Microbiome Movement announce Microbiotica as official industry partner
December 13, 2018 - New study reveals potential benefits of cEEG monitoring for infant ICU patients
December 13, 2018 - Whole-body imaging PET/MRI offers information to guide treatment options for prostate cancer
December 13, 2018 - International investigators fight against the negative campaign on benzodiazepines
December 13, 2018 - Targeting biochemical pathway may lead to new therapies for alleviating symptoms of anxiety disorders
December 13, 2018 - FDA Approves Tolsura (SUBA®-itraconazole capsules) for the Treatment of Certain Fungal Infections
December 13, 2018 - Are scientists studying the wrong kind of mice?
December 13, 2018 - Computer memory: A scientific team builds a virtual model of a key brain region
December 13, 2018 - Visual inspection alone is insufficient to diagnose skin cancer
December 13, 2018 - Paternal grandfather’s access to food associated with grandson’s mortality risk
December 13, 2018 - Our brain senses angry voices in a flash, study shows
December 13, 2018 - PM2.5 Exposure Linked to Asthma Rescue Medication Use
December 13, 2018 - Can’t exercise? A hot bath may help improve inflammation, metabolism, study suggests
December 13, 2018 - Can artificial intelligence help doctors with the human side of medicine?
December 13, 2018 - Virginia Tech and UC San Diego researchers team up to develop nonopioid drug for chronic pain
December 13, 2018 - NIH offers support for HIV care and prevention research in the southern United States
December 12, 2018 - Activating brain region could revive the urge to socialize among opioid addicts
December 12, 2018 - Relationship impairment appears to interfere with seeking mental health treatment in men
December 12, 2018 - Sleep, Don’t Cram, Before Finals for Better Grades
December 12, 2018 - Effective treatments for urticarial vasculitis
December 12, 2018 - Gun violence is a public health issue: One physician’s story
December 12, 2018 - The Science of Healthy Aging
December 12, 2018 - Yes to yoghurt and cheese: New improved Mediterranean diet
December 12, 2018 - Researchers uncover a number of previously unknown insecticide resistance mechanisms
December 12, 2018 - Regulating the immune system’s ‘regulator’
December 12, 2018 - In breaking bad news, the comfort of silence
December 12, 2018 - Study finds upward link between alcohol consumption and physical activity in college students
December 12, 2018 - FDA issues warning letter to Zhejiang Huahai Pharmaceutical involved in valsartan recall
December 12, 2018 - Weight history at ages 20 and 40 could help predict patients’ future risk of heart failure
December 12, 2018 - Presence of antiphospholipid antibodies tied to first-time MI
December 12, 2018 - DNA analysis finds that stethoscopes are teaming with bacteria
December 12, 2018 - New study could help inform research on preventing falls
December 12, 2018 - Women and men with heart attack symptoms receive different care from EMS
December 12, 2018 - Disrupted biological clock can contribute to onset of diseases, USC study shows
December 12, 2018 - New publications generate controversy over the value of reducing salt consumption in populations
December 12, 2018 - New data from TAILORx trial confirms lack of chemo benefit regardless of race or ethnicity
December 12, 2018 - Specific class of biomarkers can accurately indicate the severity of cancer
December 12, 2018 - Meds Taken Do Not Vary With ADL Impairment in Heart Failure
December 12, 2018 - Long-term study shows that HIV-2 is deadlier than previously thought
December 12, 2018 - People living near oil and gas wells show early signs of cardiovascular disease
December 12, 2018 - IONTAS founder and pioneer in phage display technology attends Nobel Prize Award Ceremony
December 12, 2018 - People who eat red meat have high levels of chemical associated with heart disease, study finds
December 12, 2018 - New method uses water molecules to unlock neurons’ secrets
December 12, 2018 - Genetics study offers hope for new acne treatment
December 12, 2018 - New computer model predicts prostate cancer progression
December 12, 2018 - Nobel Laureates lecture about immune checkpoint therapy for cancer treatment
December 12, 2018 - More Illnesses From Tainted Romaine Lettuce Reported
December 12, 2018 - Aspirin could reduce HIV infections in women
December 12, 2018 - The EORTC Brain Tumor Group and Protagen AG collaborate to study immuno-competence of long-term glioblastoma survivors
December 12, 2018 - Insights into magnetotactic bacteria could guide development of biological nanorobots
December 12, 2018 - Sacrificial immune cells alert body to infection
December 12, 2018 - Low-salt diet may be more beneficial for females than males
December 12, 2018 - Major soil organic matter compound battles chronic wasting disease
December 12, 2018 - Findings may open up new ways to treat dwarfism and other ER-stress-related conditions
December 12, 2018 - New computational model provides clearer picture of shape-changing cells’ structure and mechanics
December 12, 2018 - 10 Facts on Patient Safety
December 12, 2018 - Poorest dying nearly 10 years younger than the rich in ‘deeply worrying’ trend for UK
December 12, 2018 - Innovative care model for children with ASD reduces use of behavioral drugs in ED
December 12, 2018 - Spending time in and around Hong Kong’s waters linked to better health and wellbeing
December 12, 2018 - Simple measures to prevent weight gain over Christmas
December 12, 2018 - Research advances offer hope for patient-tailored AML treatment
Epigenetics study helps focus search for autism risk factors

Epigenetics study helps focus search for autism risk factors

image_pdfDownload PDFimage_print
Lucia Peixoto of Washington State University led a team that found several DNA regions, including a genetic mutation, associated with an increased risk of autism. Credit: Washington State University

Scientists have long tried to pin down the causes of autism spectrum disorder. Recent studies have expanded the search for genetic links from identifying genes toward epigenetics, the study of factors that control gene expression and looks at chemical modifications of DNA and the proteins associated with it. The challenge is knowing where to look, given that our genome is comprised of more than three billion nucleotides, or building blocks, of DNA.

Now, a breakthrough study by researchers at Washington State University and elsewhere has brought focus to the search for epigenetic mechanisms related to autism. Published in the Jan. 16 issue of Science Signaling, their work identifies more than 2,000 regulatory regions (DNA regions that control gene expression) involved in learning that are strongly associated with autism. Further study within one of those regions revealed a genetic mutation that is associated with increased risk of developing autism.

“Our proof-of-concept study demonstrates the feasibility of going after genetic components of autism that are outside of genes and may eventually lead to improvements in the diagnosis and treatment of autism,” said study co-author Lucia Peixoto, an assistant professor in the WSU Elson S. Floyd College of Medicine who conducted the study and analyzed the data.

She said that the majority of human-disease-causing mutations are thought to be outside of genes, which make up only 2 percent of our genome.

Looking beyond genes

An estimated two million Americans are affected by autism. About half of them have learning disabilities, which is why the research team looked toward learning and memory to address their research question. It is known that learning requires epigenetic regulation—changes in the regulatory regions of DNA that lead to changes in gene expression that guide the formation of long-term memories. To identify regulatory regions associated with autism, they hypothesized that the same regulatory regions involved in learning and memory may also be linked to autism.

Researchers conducted a classical conditioning experiment in which mice were placed in a box and given a small shock. Upon being placed in the same box after 24 hours, the mice had learned to associate the box with the unpleasant shock and would freeze. The researchers then analyzed DNA from the hippocampus—a brain area critical to memory—to identify learning-induced changes in chromatin accessibility.

Chromatin helps package the long strands of DNA into a compact, dense shape so it fits inside cells. It opens and closes to allow access to certain genes during transcription, essentially controlling the activity of these genes.

Results from the experiments suggested that learning increases chromatin accessibility at specific places in the genome. To determine the regions where these changes were occurring, the researchers conducted a second experiment using the same design and analyzed the data for gene expression levels. They then developed a new bioinformatics tool called Differential Enrichment Scan. The tool allowed them to look at the combined data sets to pinpoint, with a high degree of confidence, 2,365 regions regulated by learning.

Further analysis using data from the Encyclopedia of DNA Elements consortium confirmed that the regions made accessible during learning are also for the most part accessible during development. Next, the team looked for genes near the identified regions and found that many of them are known risk genes for autism spectrum disorder.

Finally, they tried to find a genetic risk factor for autism within one of the regulatory regions, selecting one that is associated with a well-known autism risk gene, Shank3. Within the Shank3 promoter 6 region they identified a single nucleotide polymorphism (or SNP, a common type of genetic variation) known as rs6010065. Analyzing genomic data from a clinical study of 554 children with autism and 214 healthy controls, they found that rs6010065 is indeed associated with autism spectrum disorder.

“One of the major challenges in the genetics of disease is understanding the role of the vast portions of the genome that regulate gene expression. Our work suggests that studying activity-dependent changes in chromatin accessibility may hold the key to understanding the function of this ‘dark matter’ of the genome and may provide novel insights into the nature of autism and other neurodevelopmental disorders,” said Ted Abel, Roy J. Carver Chair of Neuroscience and director of the Iowa Neuroscience Institute at the University of Iowa. Abel and Peixoto collaborated on these studies, which were started when both were at the University of Pennsylvania.

Easing the burden on family, individuals

Peixoto said their work opens the door for scientists to delve farther into the other regulatory regions identified in the study, increasing our understanding of the genetic factors involved in autism with learning disability. She said the same approach could also be used to identify regulatory regions that are involved in other behaviors that are disturbed in autism—such as sleep and social interaction—and to look for mutations in those areas.

Down the line, the researchers’ work could lead to accelerated diagnoses; better predictions of severity; improved timing and effectiveness of behavioral interventions; and the development of drugs that could mitigate the effects of genetic mutations linked to autism.

“Ultimately, our goal is to find ways to reduce the burden on families and help individuals with autism to be more functional and have a better, happier experience,” Peixoto said.


Explore further:
Signaling pathway may be key to why autism is more common in boys

More information:
“Learning-dependent chromatin remodeling highlights noncoding regulatory regions linked to autism,” Science Signaling (2018). stke.sciencemag.org/lookup/doi … 26/scisignal.aan6500

Journal reference:
Science Signaling

Provided by:
Washington State University

Tagged with:

About author

Related Articles