Mutations in autism susceptibility gene increase risk in boys
Researchers at Emory University School of Medicine have identified five rare mutations in a single gene that appear to increase the chances that a boy will develop an autism spectrum disorder (ASD).
Mutations in the AFF2 gene, and other genes like it on the X chromosome, may explain why autism spectrum disorders affect four times as many boys as girls.
The mutations in AFF2 appeared in 2.5 percent (5 out of 202) of boys examined. Mutations in X chromosome genes only affect boys, who have one X chromosome. Girls have a second copy of the gene that can compensate.
The results were published July 5 in the journal Human Molecular Genetics.
"Our data suggest that AFF2 could be one of the major X-linked risk factors for ASD's," says senior author Michael Zwick, PhD, assistant professor of human genetics at Emory University School of Medicine.
The finding bolsters a growing consensus among geneticists that rare variants in many different genes contribute significantly to risk for autism spectrum disorders. The mutations in the AFF2 gene probably do not cause ASDs all by themselves, Zwick says.
"We do not think that the variants we have identified are monogenic causes of autism," he says. "Our data does support the idea that this is an autism susceptibility gene."
In some situations, mutations in a single gene are enough by themselves to lead to a neurodevelopmental disorder with autistic features, such as fragile X syndrome or tuberous sclerosis complex. But these types of mutations are thought to account for a small number of ASD cases.
Recent large-scale genetic studies of autism spectrum disorders have identified several "rare variants" that sharply increase ASD risk. Scientists believe rare variants could explain up to 15 or 20 percent of ASD cases. However, until now no single variant has been found in more than one percent of ASD cases.
Working with Zwick, postdoctoral fellow Kajari Mondal and her colleagues read the sequence of the AFF2 gene in DNA from 202 boys diagnosed with autism spectrum disorders. The patient samples came from the Autism Genetic Resource Exchange and the Simons Simplex Collection.
Tests showed that in four cases, the affected boys had inherited the risk-conferring mutations from their mothers. One boy had a "de novo" (not coming from the parents) mutation. Compared with X-linked genes in unaffected people, mutations in AFF2 were five times more abundant in the boys with ASDs.
The AFF2 gene had already been identified as responsible for a rare inherited form of intellectual disability with autistic features. This effect is seen when the AFF2 gene is deleted or silenced completely.
AFF2 has some similarity to FMR1, the gene responsible for fragile X syndrome. Like FMR1, it can be silenced by a triplet repeat. In these cases, the presence of the triplet repeat (three genetic bases repeated dozens of times) triggers a change in chromosomal structure that prevents the gene from being turned on.
In contrast, the mutations Zwick's team found are more subtle, slightly changing the sequence of the protein AFF2 encodes. Little is known about the precise function of the AFF2 protein (more?). A related gene in fruit flies called lilliputian also appears to regulate the development of neurons.
Zwick says one of his laboratory's projects is to learn more about the function of the AFF2 gene, and to probe how the mutations identified by his team affect the function. His team is also working on gauging the extent to which other genes on the X chromosome contribute to autism risk.
More information: K. Mondal, D. Ramachandran, V.C. Patel, K.R. Hagen, P. Bose, D.J. Cutler and M.E. Zwick. Excess variants in AFF2 detected by massively parallel sequencing of males with autism spectrum disorder. Hum. Mol. Genet. Advance access. (2012). doi: 10.1093/hmg/dds267
Journal reference: Human Molecular Genetics
Provided by Emory University
- Mutations in 3 genes linked to autism spectrum disorders Apr 04, 2012 | not rated yet | 0
- Further support for a role of synaptic proteins in autism spectrum disorders Feb 09, 2012 | not rated yet | 0
- X marks the spot -- TBL1X gene involved in autism spectrum disorder Nov 04, 2011 | not rated yet | 0
- Study explains functional links between autism and genes Jun 21, 2012 | not rated yet | 0
- More gene mutations linked to autism risk Jun 25, 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
Bubbles in a Pre-Boiling/Boiling pot of water
20 minutes ago How is it that bubbles form on the bottom of a surface of a pot of boiling water? I think that there is probably an elementary answer to this...
Assumptions of Griffith's fracture theory
10 hours ago Any experts on Griffith's fracture theory? I am studying the subject and I am having hard time finding out if the theory is valid for all possible...
Current leading voltage or vice versa concept
12 hours ago Hello, I was wondering if there is a conceptual explanation for when current leads voltage or vice versa for capacitors or inductors with AC...
Angular Frequency of AC voltage
15 hours ago Hello, I am wondering, what is the physical interpretation of the angular frequency of AC voltage? I don't see the physicality of what the angle...
Modeling Rigid Body - Unsure about Euler angles and angular velocity
15 hours ago I'm modeling a single 3D rigid body in preparation for some more complicated modeling in order to gain a better understanding of Euler angles, the...
Function for a bullet's path
17 hours ago I've been mulling this over all weekend, and I've decided to get some help on this. The problem is writing a function to describe a bullet's path....
- More from Physics Forums - Classical Physics
More news stories
Research by Victoria University PhD education graduand Larah van der Meer highlights the importance of understanding the communication preferences of children with developmental disabilities such as autism.
Autism spectrum disorders May 14, 2013 | 3.3 / 5 (3) | 1
Children with autism see simple movement twice as quickly as other children their age, and this hypersensitivity to motion may provide clues to a fundamental cause of the developmental disorder, according ...
Autism spectrum disorders May 08, 2013 | not rated yet | 0 |
(AP)—Autism scientists are seeking more brain samples for research.
Autism spectrum disorders May 02, 2013 | 5 / 5 (1) | 0
(HealthDay)—An experimental drug for autism did not improve levels of lethargy and social withdrawal in children who took it, but it did show some other benefits, a new study finds.
Autism spectrum disorders May 02, 2013 | 4 / 5 (1) | 0
Young adults with an autism spectrum disorder (ASD) are more likely to never see friends, never get called by friends, never be invited to activities and be socially isolated.
Autism spectrum disorders May 02, 2013 | 5 / 5 (1) | 0
You're standing near an airport luggage carousel and your bag emerges on the conveyor belt, prompting you to spring into action. How does your brain make the shift from passively waiting to taking action when ...
23 minutes ago | not rated yet | 0 |
Widely available in pharmacies and health stores, phosphatidylserine is a natural food supplement produced from beef, oysters, and soy. Proven to improve cognition and slow memory loss, it's a popular treatment for older ...
47 minutes ago | 5 / 5 (1) | 0 |
Children who are exposed to secondhand smoke in early childhood are more likely to grow up to physically aggressive and antisocial, regardless of whether they were exposed during pregnancy or their parents have a history ...
7 minutes ago | not rated yet | 0
Youth who had a schoolmate die by suicide are significantly more likely to consider or attempt suicide, according to a study in published in CMAJ (Canadian Medical Association Journal). This effect can last 2 years or mo ...
57 minutes ago | not rated yet | 0
Most elite athletes consider doping substances "are effective" in improving performance, while recognising that they constitute cheating, can endanger health and entail the obvious risk of sanction. At the same time, the ...
57 minutes ago | not rated yet | 0
(Medical Xpress)—Native peoples in regions where cameras are uncommon sometimes react with caution when their picture is taken. The fear that something must have been stolen from them to create the photo ...
1 hour ago | 3.5 / 5 (2) | 0 |