Breaking News
January 23, 2019 - Short interval between last meal of the day and bedtime may not affect blood glucose levels
January 23, 2019 - Still Too Many Highway Deaths Tied to Speeding
January 23, 2019 - Prenatal valproate exposure linked to increased ADHD risk
January 23, 2019 - Compound identified that may help treat heart failure
January 23, 2019 - Undiagnosed Asthma in Urban Adolescents May Be Common
January 23, 2019 - Study describes metabolism of intestinal microbiota in babies for the first time
January 22, 2019 - Study links concussions to development of epilepsy
January 22, 2019 - Specialist-led hospital bereavement service may help restrain legal action after difficult deaths
January 22, 2019 - Genetic study reveals possible new routes to treating osteoarthritis
January 22, 2019 - Blood test may detect early signs of lung-transplant rejection
January 22, 2019 - Blood marker could aid in early prediction of Alzheimer’s progression
January 22, 2019 - Orthodontic treatment does not guarantee future dental health
January 22, 2019 - Rutgers researchers discover cause of bone loss in people with joint replacements
January 22, 2019 - Diversity among rural Africans extends to their gut microbiomes
January 22, 2019 - Newly developed biological system lets cells to create self-curving cornea
January 22, 2019 - VTv Therapeutics Announces Publication of Comprehensive Data in Science Translational Medicine Detailing the Discovery and Clinical Development of TTP399, including Results of Phase 2 AGATA Study
January 22, 2019 - about one in three adults with prediabetes has arthritis
January 22, 2019 - A look at how data is democratizing health care
January 22, 2019 - Alcohol-Linked Disease Overtakes Hep C As Top Reason For Liver Transplant
January 22, 2019 - Researchers identify new genes linked with age-related macular degeneration
January 22, 2019 - MPFI researchers identify synaptic logic for connections between two brain hemispheres
January 22, 2019 - New study extends our knowledge of the link between miRNAs and cancer
January 22, 2019 - Asthma, eczema are not barriers to active lifestyle in teenagers
January 22, 2019 - Genetic changes may predict likelihood of relapse in breast cancer patients
January 22, 2019 - Antiepileptic drug use by people with Alzheimer’s disease linked to accumulation of hospital days
January 22, 2019 - IUPUI researcher receives $2.85 million grant to find ways to improve bone strength
January 22, 2019 - Precision medicine can help keep astronauts healthy during deep space missions
January 22, 2019 - Detecting signs of neurodegeneration earlier and more accurately
January 22, 2019 - Mouse studies challenge ‘inhibition’ theory of autism
January 22, 2019 - SSB launches BIOSTAT RM TX single-use bioreactor for producing consistent quality cellular products
January 22, 2019 - Experimental drug can positively modify key characteristic behavior in FXS patients
January 22, 2019 - Low-Income Women Lack Menstrual Hygiene Supplies
January 22, 2019 - Better mouse model built to enable precision-medicine research for Alzheimer’s
January 22, 2019 - Molecular profiling of precancerous lung lesions could lead to early detection and new treatments
January 22, 2019 - Genetic factors influence where fat is stored in our bodies
January 22, 2019 - The Psychology Behind Sticking to Your New Year’s Resolutions
January 22, 2019 - Scientists aim to find genetic causes of developmental abnormalities in the vagina and uterus
January 22, 2019 - New survey reveals scale of preventative healthcare challenge in the UK
January 22, 2019 - Looming Global Crisis Means People’s Diets Must Change: Experts
January 22, 2019 - Excessive social media use is comparable to drug addiction
January 22, 2019 - Researchers show how mechanical stress affects bone development
January 22, 2019 - Study takes a step closer to understanding the body’s response to opioid painkillers
January 22, 2019 - Unexpected connection found between feeding and memory centers of the brain
January 22, 2019 - A revolutionary approach transforms bone trauma treatment
January 22, 2019 - Early studies and recent clinical trials on nerve growth factor
January 22, 2019 - Dry Mouth and Older Adults: Information for Caregivers
January 22, 2019 - Are your grandparents getting tipsy at the holiday party?
January 22, 2019 - New machine learning algorithms identify early symptoms of urinary tract infections
January 22, 2019 - Young women skipping the Pap smear test due to embarrassment
January 22, 2019 - A global influenza pandemic high on the WHO’s agenda
January 22, 2019 - Amgen Makes All Repatha (evolocumab) Device Options Available In The US At A 60 Percent Reduced List Price
January 22, 2019 - Elastronics—hydrogel-based microelectronics for localized low-voltage neuromodulation
January 22, 2019 - Branched-chain amino acids in tumors can be targeted to prevent and treat cancer
January 22, 2019 - Fueling macrophages with energy to attack and eat cancer cells
January 22, 2019 - Amgen And UCB Receive Positive Vote From FDA Advisory Committee In Favor Of Approval For Evenity (romosozumab)
January 22, 2019 - Does being bilingual make children more focused? Study says no
January 22, 2019 - Study reveals new genes and biological pathways linked to osteoarthritis
January 22, 2019 - FSU study provides better understanding of spinal cord injuries
January 22, 2019 - Delaying bath for newborn babies increases breastfeeding rates, finds study
January 21, 2019 - WHO identifies non-communicable diseases as major threat to human health
January 21, 2019 - Many parents still try non-evidence-based cold prevention methods for children
January 21, 2019 - High Levels of Activity, Motor Ability Linked to Better Cognition
January 21, 2019 - Killer blows? Knockout study of pair of mouse MicroRNA provides cancer insight
January 21, 2019 - Buffalo researchers receive grant to quicken development of generic equivalents of contraceptives
January 21, 2019 - One-third of pregnant women do not believe cannabis is harmful to their fetus
January 21, 2019 - Fiderstat could be used as chemopreventative drug for intestinal cancers caused by APC gene mutations
January 21, 2019 - Modifying healthcare delivery practices may improve discussions between youth and healthcare providers
January 21, 2019 - UNIST researcher named as recipient of Merck’s 2018 Life Science Awards
January 21, 2019 - How Getting a Flu Shot Could Save Your Life
January 21, 2019 - Surgical adhesions can be treated, prevented in mice
January 21, 2019 - Increased physician-targeted marketing associated with higher opioid overdose deaths
January 21, 2019 - Researchers uncover specific microbial signatures of intestinal disease
January 21, 2019 - Researchers discover new blood vessel system in bones
January 21, 2019 - Simple blood test reliably detects signs of Alzheimer’s damage before symptoms
January 21, 2019 - Study to investigate new targeted oral treatments for severe asthma
January 21, 2019 - Plan Your Plate | NIH News in Health
January 21, 2019 - Fecal occult blood test may improve CRC outcomes in some
January 21, 2019 - Blood test detects Alzheimer’s disease years before symptoms develop
January 21, 2019 - Mount Sinai joins with Paradigm and ReqMed to repurpose drug for treatment of MPS
January 21, 2019 - FDA Advisory Committee Votes on Zynquista (sotagliflozin) as Treatment for Adults with Type 1 Diabetes
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