Autism blurs distinctions between brain regions
A module of co-expressed genes that code for neurons and their connections tend to be under-expressed in many individuals with autism (red), compared to controls (gray).
Autism blurs the molecular differences that normally distinguish different brain regions, a new study suggests. Among more than 500 genes that are normally expressed at significantly different levels in the front versus the lower middle part of the brains outer mantle, or cortex, only 8 showed such differences in brains of people with autism, say researchers funded in part by the National Institutes of Health.
"Such blurring of normally differentiated brain tissue suggests strikingly less specialization across these brain areas in people with autism," explained Daniel Geschwind, M.D., Ph.D., of the University of California, Los Angeles, a grantee of the NIHs National Institute of Mental Health. "It likely reflects a defect in the pattern of early brain development."
He and his colleagues published their study online May 26, 2011 in the journal Nature. The research was based on postmortem comparisons of brains of people with the disorder and healthy controls.
In fetal development, different mixes of genes turn on in different parts of the brain to create distinct tissues that perform specialized functions. The new study suggests that the pattern regulating this gene expression goes awry in the cortex in autism, impairing key brain functions.
"This study provides the first evidence of a common signature for the seemingly disparate molecular abnormalities seen in autism," said NIMH director Thomas R. Insel, M.D. "It also points to a pathway-based framework for understanding causes of other brain disorders stemming from similar molecular roots, such as schizophrenia and ADHD."
In an earlier study, the researchers showed that genes that turn on and off together at the same time hold clues to the brains molecular instructions. These modules of co-expressed genes can reveal genetic co-conspirators in human illness, through what Geschwind and colleagues call "guilt by association." A gene is suspect if its expression waxes and wanes in sync with others in an illness-linked module.
Using this strategy, the researchers first looked for gene expression abnormalities in brain areas implicated in autism genes expressed at levels different than in brains of healthy people. They found 444 such differently expressed genes in the cortexes of postmortem brains of people with autism.
Most of the same genes turned out to be abnormally expressed in the frontal cortex as in the temporal cortex (lower middle) of autistic brains. Of these, genes involved in synapses, the connections between neurons, tended to be under-expressed when compared with healthy brains. Genes involved in immune and inflammatory responses tended to be over-expressed. Significantly, the same pattern held in a separate sample of autistic and control brains examined as part of the study.
Autistic and healthy control brains were similarly organized -- modules of co-expressed genes correlated with specific cell types and biological functions.
Yet normal differences in gene expression levels between the frontal and temporal cortex were missing in the modules of autistic brains. This suggests that the normal molecular distinctions the tissue differences between these regions are nearly erased in autism, likely affecting how the brain works. Strikingly, among 174 genes expressed at different levels between the two regions in two healthy control brains, none were expressed at different levels in brains of people with autism.
An analysis of gene networks revealed two key modules of co-expressed genes highly correlated with autism.
One module was made up of genes in a brain pathway involved in neuron and synapse development, which were under-expressed in autism. Many of these genes were also implicated in autism in previous, genome-wide studies. So, several different lines of evidence now converge, pointing to genes in this M12 module (see picture below) as genetic causes of autism.
A second module of co-expressed genes, involved in development of other types of brain cells, was over-expressed in autism. These were determined not to be genetic causes of the illness, but likely gene expression changes related to secondary inflammatory, immune, or possible environmental factors involved in autism.
This newfound ability to see genes in the context of their positions in these modules, or pathways, provides hints about how they might work to produce illness, according to Geschwind and colleagues. For example, from its prominent position in the M12 module, the researchers traced a potential role in creating defective synapses to a gene previously implicated in autism.
More information: Transcriptomic analysis of autistic brain reveals convergent molecular pathology. Voineagu I, Wang X, Johnston P, Lowe JK, Tian Y, Horvath S, Mill J, Cantor RM, Blencowe BJ, Geschwind DH. Nature. 2011 May 25. PMID:21614001
Provided by National Institutes of Health
- Autism changes molecular structure of the brain, study finds May 25, 2011 | not rated yet | 0
- Study adds to evidence that autism has genetic basis May 02, 2010 | not rated yet | 0
- Multiple genes implicated in autism Feb 09, 2009 | not rated yet | 0
- Recurrent genetic deletion linked to autism Jan 08, 2008 | not rated yet | 0
- Researchers identify gene variant associated with both autism and gastrointestinal dysfunction Mar 02, 2009 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Classical and Quantum Mechanics via Lie algebras
Apr 15, 2011 I'd like to open a discussion thread for version 2 of the draft of my book ''Classical and Quantum Mechanics via Lie algebras'', available online at http://lanl.arxiv.org/abs/0810.1019 , and for the...
- More from Physics Forums - Independent Research
More news stories
Northwestern University scientists have shown a gene involved in neurodegenerative disease also plays a critical role in the proper function of the circadian clock.
Genetics May 16, 2013 | 3 / 5 (1) | 1 |
Informed consent is the backbone of patient care. Genetic testing has long required patient consent and patients have had a "right not to know" the results. However, as 21st century medicine now begins to use the tools of ...
Genetics May 16, 2013 | 5 / 5 (1) | 3 |
Ethicists provide framework supporting new recommendations on reporting incidental findings in gene sequencing
In a paper published in Science Express, a group of experts led by bioethicists in the Center for Medical Ethics and Health Policy at Baylor College of Medicine provide a framework for the new American College of Medical Geneti ...
Genetics May 16, 2013 | not rated yet | 0
The use of genome-wide analysis (GWA), where the entirety of an individual's DNA is examined to look for the genomic mutations or variants which can cause health problems is a massively useful technology for diagnosing disease. ...
Genetics May 16, 2013 | not rated yet | 0
DNA databases might help identify victims of crime and human trafficking, but how do we safeguard the personal privacy of innocent victims and family members? A new report online May 15 in the Cell Press journal Trends in ...
Genetics May 15, 2013 | not rated yet | 0
A new study conducted by researchers at the Child Study Center at NYU Langone Medical Center found men diagnosed as children with attention-deficit/hyperactivity disorder (ADHD) were twice as likely to be obese in a 33-year ...
54 minutes ago | not rated yet | 0 |
New research from the University of Southampton has shown that blind and visually impaired people have the potential to use echolocation, similar to that used by bats and dolphins, to determine the location of an object.
10 minutes ago | not rated yet | 0 |
A novel vaccine study from South Dakota State University (SDSU) will headline the groundbreaking research that will be unveiled at the American Association of Pharmaceutical Scientists' (AAPS) National Biotechnology Conference ...
32 minutes ago | not rated yet | 0
Parkinson's disease (PD) is a degenerative neurological disorder marked by a progressive loss of motor control. Despite intensive research, there are currently no approved therapies that have been demonstrated to alter the ...
32 minutes ago | not rated yet | 0
Women are less likely than men to receive care in a trauma center after severe injury, according to a new study of almost 100,000 Canadian patients.
57 minutes ago | not rated yet | 0
Over the past few decades, neuroscientists have made much progress in mapping the brain by deciphering the functions of individual neurons that perform very specific tasks, such as recognizing the location ...
2 hours ago | 5 / 5 (3) | 0 |