Breaking News
April 20, 2019 - Parenteral Antimicrobial Tx at Home Burdens Children’s Caregivers
April 20, 2019 - Diabetes treatment may keep dementia, Alzheimer’s at bay
April 20, 2019 - New bandage-like biosensor collects and analyzes sweat
April 20, 2019 - A comprehensive, centralized database of bovine milk compounds
April 20, 2019 - Two new epigenetic regulators maintain self-renewal of embryonic stem cells
April 20, 2019 - New Evidence That Veggies Beat Steak for Heart Health
April 20, 2019 - Study reveals genes associated with heavy drinking and alcoholism
April 20, 2019 - Texas A&M AgriLife becomes the newest member of NutriRECS international consortium
April 20, 2019 - In most states, insurance won’t cover addiction treatments
April 20, 2019 - Computer-based memory games may be beneficial for individuals with fragile X syndrome
April 20, 2019 - Timing of food intake influences molecular clock in the liver of mice
April 20, 2019 - Precise decoding of breast cancer cells paves way for new treatment option
April 20, 2019 - Scientists use 3D imaging to help model complex processes performed by placenta
April 20, 2019 - MediciNova Announces Plans to Move Forward with a Phase 3 Trial of MN-166 (ibudilast) in ALS
April 20, 2019 - Genetic variants that protect against obesity could aid new weight loss medicines
April 20, 2019 - New technology developed for microscopic imaging in living organisms
April 20, 2019 - when quitting cigarettes, consider using more nicotine, not less
April 20, 2019 - Key proteins can block Listeria without triggering the death of host cells
April 20, 2019 - Researchers create a working model of cerebral tract to study brain function
April 20, 2019 - New study shows that microbes can help break toxic chemical in dust
April 20, 2019 - Scientists use NIR light and injected DNA nanodevice to guide stem cells to injury
April 20, 2019 - Microbial Features ID’d for Pediatric Irritable Bowel Syndrome
April 20, 2019 - Study reveals patterns of drug intoxication deaths, organ donors across the US
April 20, 2019 - Scientists deploy CRISPR gene-editing tool to engineer multiple edits
April 20, 2019 - AHA News: Here’s How Middle-Aged People — Especially Women — Can Avoid a Heart Attack
April 20, 2019 - Charcot foot: MedlinePlus Medical Encyclopedia
April 20, 2019 - France to ban popular breast implants over cancer risk: media
April 20, 2019 - Researchers explore whether time of day can affect the body’s response to physical exertion
April 20, 2019 - CPAP brings longer life for obese people with sleep apnea: Study
April 20, 2019 - New discovery transforms conventional microfluidics into open-space microfluidics
April 20, 2019 - An accurate estimation of the overall cost of bacterial resistance in French hospitals during 2015 and 2016
April 20, 2019 - ‘PRO-cision Medicine’ approach helps personalize care for patients with cancer
April 19, 2019 - TG Therapeutics Receives Orphan Drug Designation for Umbralisib from the U.S. Food and Drug Administration for the Treatment of Marginal Zone Lymphoma
April 19, 2019 - Screen time—even before bed—has little impact on teen well-being: study
April 19, 2019 - Cytosurge’s first FluidFM User Conference
April 19, 2019 - New study finds that previously described differences among endoscopists are not true
April 19, 2019 - Study compares effectiveness and cost of gene therapy and HSCT in major beta-thalassemia
April 19, 2019 - Scientific breakthrough provides new hope for people living with multiple sclerosis
April 19, 2019 - New Virtual Reality Therapy game could offer relief for patients with chronic pain, mobility issues
April 19, 2019 - Emergency medicine doctors find better way to treat severe epileptic seizures in children
April 19, 2019 - MedlinePlus: Cholesterol Good and Bad
April 19, 2019 - For busy medical students, two-hour meditation study may be as beneficial as longer course
April 19, 2019 - Music therapy helps young patients feel better
April 19, 2019 - Molecular target UNC45A is essential for cancer cell proliferation and tumor growth
April 19, 2019 - Crackling and wheezing could be the sounds of a progressing lung disease
April 19, 2019 - Key research takeaways from ECCMID 2019
April 19, 2019 - AI Can Identify Model of Cardiac Rhythm Device From Chest X-Ray
April 19, 2019 - New way to combat childhood anxiety: treat the parents
April 19, 2019 - Women getting C-sections best judge of own pain medication needs | News Center
April 19, 2019 - Light-intensity physical activity associated with healthy brain aging
April 19, 2019 - Immune responses that prevent fungal infections may eliminate Trichinella spiralis
April 19, 2019 - Exercising in the morning, rather than at night, may yield better results, shows study
April 19, 2019 - Why eating ‘right’ could cause you to stray from your diet
April 19, 2019 - Health Tip: Antidepressant Precautions – Drugs.com MedNews
April 19, 2019 - Bigger portions lead to preschoolers eating more over time
April 19, 2019 - Specific strains of Staphylococcus aureus linked to wounds that do not heal
April 19, 2019 - Morning exercise may burn more calories
April 19, 2019 - Nominations invited for prestigious awards at Pittcon Conference & Expo 2020
April 19, 2019 - Revolutionary discovery paves new way for treatment of necrotizing enterocolitis
April 19, 2019 - Drug that treats high blood pressure shows promise against neurodegenerative diseases
April 19, 2019 - More care is needed for patients after kidney transplantations, reports research
April 19, 2019 - Virtual reality offers benefits for Parkinson’s disease patients
April 19, 2019 - Liver Illness Strikes Latino Children Like A ‘Silent Tsunami’
April 19, 2019 - Disruptive behaviors in autistic children linked to reduced brain connectivity
April 19, 2019 - New insights into how vitamin D affects immune system
April 19, 2019 - Microfluidic-based drug screening chip identifies antibiotic interactions in eight hours
April 19, 2019 - Research sheds light on how hepatitis B virus establishes chronic infection
April 19, 2019 - New scoring system based on genetic markers predicts obesity risk at birth
April 19, 2019 - Pfizer Announces Presentation of Data from a Phase 2 Study of its 20-Valent Pneumococcal Conjugate Vaccine Candidate Being Investigated for the Prevention of Invasive Disease and Pneumonia in Adults Aged 18 Years and Older
April 19, 2019 - Exercise can improve non-motor symptoms of Parkinson’s disease
April 19, 2019 - Phasefocus to launch new cell imaging system
April 19, 2019 - KZFPs play a key role in the regulation of human genome
April 19, 2019 - DWK Life Sciences offers Workflow Solutions to improve productivity
April 19, 2019 - Bedfont wins 2nd accolade at the South East FSB Awards 2019
April 19, 2019 - Extracts of ginkgo seeds show antibacterial activity on pathogens that cause skin infections
April 19, 2019 - Groundbreaking experiment in pigs challenges the notion about brain damage
April 19, 2019 - Improving the quality of digital pathology imaging
April 19, 2019 - Scientists get closer to injecting artificial lymph nodes into people to fight disease
April 19, 2019 - Exercises and swimming goggles may reduce adverse effects on eye during long spaceflights
April 19, 2019 - Review suggests a reciprocal relationship between obesity and self-control
Research team uncovers critical new clues about what goes awry in autistic brains

Research team uncovers critical new clues about what goes awry in autistic brains

image_pdfDownload PDFimage_print
UCLA-led team uncovers critical new clues about what goes awry in autistic brains
The research of UCLA professors Xinshu (Grace) Xiao, Dr. Daniel Geschwind and their team is the first comprehensive study of RNA editing in autism spectrum disorder. Credit: Reed Hutchinson/UCLA

A team of UCLA-led scientists has discovered important clues to what goes wrong in the brains of people with autism—a developmental disorder with no cure and for which scientists have no deep understanding of what causes it.

The new insights involve RNA editing—in which genetic material is normal, but modifications in RNA alter nucleotides, whose patterns carry the data required for constructing proteins.

“RNA editing is probably having a substantial physiologic effect in the brain, but is poorly understood,” said co-author Dr. Daniel Geschwind, UCLA’s Gordon and Virginia MacDonald distinguished professor of human genetics, neurology and psychiatry and director of UCLA’s Institute for Precision Health. “RNA editing is a mysterious area whose biological implications have not been much explored. We know what only a handful of these RNA editing sites do to proteins. This study gives a new critical clue in understanding what has gone awry in the brains of autism patients.”

More than 24 million people worldwide are estimated to have autism. In developed countries, about 1.5 percent of children have been diagnosed with autism spectrum disorder as of 2017. The disorder affects communication and behavior, and is marked by problems in social communication and social interaction, and repetitive behaviors.

“We need to understand how a panoply of genetic and environmental factors converges to cause autism,” Geschwind said. “RNA editing is an important piece of the autism puzzle that has been totally under-appreciated.”

The researchers analyzed brain samples from 69 people who died, about half of whom had autism spectrum disorder (which includes autism and related conditions), and about half of whom did not and served as a control group.

Xinshu (Grace) Xiao, the senior author of the research and UCLA’s Maria R. Ross professor of integrative biology and physiology, and her research team analyzed seven billion nucleotides for each brain sample.

Xiao’s team discovered reduced editing in the group members with autism. Specifically, they identified 3,314 editing sites in the brain’s frontal cortex in which the autism patients had different levels of RNA editing from the control group. In 2,308 of those sites, the individuals with autism had reduced RNA editing, said lead author Stephen Tran, a graduate student in UCLA’s bioinformatics interdepartmental program who works in Xiao’s laboratory. In the 1,006 others, they had increased levels of RNA editing, he added.

In the brain’s temporal cortex, the people with autism had different levels of RNA editing from the control group in 2,412 editing sites, with 1,471 of those sites showing reduced editing levels, Tran said. In the brain’s cerebellum, the autism group members had different levels of RNA editing from control group members in 4,340 sites, of which 3,330 sites in the autistic brain had decreased levels. All three of these brain regions are very important in autism.

The research, published in the journal Nature Neuroscience, is the first comprehensive study of RNA editing in autism spectrum disorder.

Xiao said RNA editing can be thought of as RNA mutations, analogous to the DNA mutations that are linked to many diseases.

“The same piece of DNA can generate multiple versions of RNA, and possibly lead to different protein sequences,” said Xiao, director of UCLA’s bioinformatics interdepartmental graduate program. “RNA editing allows cells to create novel protein sequences that are not written in the DNA.”

Scientists had long assumed that a sequence of RNA is a faithful copy of a gene’s DNA sequence—and that RNA is merely the cellular messenger that carries out DNA’s instructions to other parts of the cell. “This assumption was proved to be wrong when RNA editing was first discovered in the 1980s,” Xiao said, “and we are finding many examples where the genetic codes we inherit from our parents are edited in our cells.”

In another major finding, the researchers identified two proteins, called FMRP and FXR1P, that regulate abnormal RNA editing in autism spectrum disorder. FMRP increases RNA editing and FXR1P decreases RNA editing, Tran discovered. The autism group had reduced editing levels regulated by FMRP, as well as reduced RNA editing overall.

“This is the first strong data showing a broad and direct functional role for FMRP and FXR1P in the human brain and autism,” Xiao said.

“Something about what FMRP does is clearly critical to autism pathogenesis,” Geschwind said. “Grace and her team show that these two related proteins are likely responsible for the reduced RNA editing, as well as the occasional increased RNA editing.”

It is currently unknown, he said, whether the changes the people with autism had in RNA editing caused their autism, contributed to the disorder or were a result of it. “We can’t assign causality,” said Geschwind, who praised the research of Xiao’s team as “elegant and brilliant.”

RNA editing may also be disrupted in schizophrenia, bipolar disorder and major depression. The research team plans to continue to study this as well as other brain diseases.

Xiao and Tran replicated their findings by analyzing the frontal cortex from a different group of 22 people who had autism spectrum disorder and a control group of 23 without the disorder. They found the same pattern of editing reduction as they found originally, Tran said.

The researchers found RNA editing alterations in genes of critical neurological relevance to autism, including CNTNAP2 and CNTNAP4, NRXN1 and NRXN3, ANK2, NOVA1 and RBFOX1.

Xiao and Tran used powerful methods of bioinformatics and statistics to identify the RNA editing sites, including a method similar to GIREMI that Xiao designed in 2015 with Qing Zhang, a former postdoctoral scholar in her laboratory.

In searching for causes of diseases, most research has focused on searching for mutations in the DNA. “What was missing, until recently,” Xiao said, “is to look for RNA mutations that are not coded in the DNA. These changes in the RNA could have similar impact as DNA mutations.”

This study may eventually lead to new treatments for autism, but likely not for many years, the researchers said.


Researchers devise new method to identify disease markers


More information:
Stephen S. Tran et al, Widespread RNA editing dysregulation in brains from autistic individuals, Nature Neuroscience (2018). DOI: 10.1038/s41593-018-0287-x


Provided by
University of California, Los Angeles

Citation:
Research team uncovers critical new clues about what goes awry in autistic brains (2019, January 30)
retrieved 21 March 2019
from https://medicalxpress.com/news/2019-01-team-uncovers-critical-clues-awry.html

This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no
part may be reproduced without the written permission. The content is provided for information purposes only.

Tagged with:

About author

Related Articles