Navigation Links
Mutations in autism susceptibility gene increase risk in boys
Date:7/12/2012

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.


'/>"/>
Contact: Quinn Eastman
qeastma@emory.edu
404-727-7829
Emory University
Source:Eurekalert

Related biology news :

1. Interacting mutations promote diversity
2. Gene mutations cause massive brain asymmetry
3. BRG1 mutations confer resistance to hormones in lung cancer
4. Hunting for autisms chemical clues
5. Brain scans detect early signs of autism
6. Autism Speaks awards nearly $2.9 million to fund autism research
7. MindSpec develops Autism Quiz app
8. Fish show autism-like gene expression in water with psychoactive pharmaceuticals
9. New treatment for irritability in autism
10. MindSpec launches online Autism Reading Room
11. Common genetic variants identify autism risk in high risk siblings of children with ASD
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/29/2017)... 29, 2017  higi, the health IT company that ... North America , today announced a Series B ... of EveryMove. The new investment and acquisition accelerates higi,s ... to transform population health activities through the collection and ... higi collects and secures data today on behalf ...
(Date:3/27/2017)... ROCKVILLE CENTRE, N.Y. , March 27, 2017 ... by Healthcare Information and Management Systems Society (HIMSS) ... Analytics Outpatient EMR Adoption Model sm . In ... top 12% of U.S. hospitals using an electronic ... recognized CHS for its high level of EMR ...
(Date:3/24/2017)... Research and Markets has announced the addition of the "Global ... to 2025" report to their offering. ... The Global Biometric Vehicle Access System Market ... the next decade to reach approximately $1,580 million by 2025. ... for all the given segments on global as well as regional ...
Breaking Biology News(10 mins):
(Date:9/20/2017)... ... ... Diversity focused business accelerator, The Refinery , announced today they are ... top technology-driven, women-led startups in Boston, MA, New Haven/Hamden, CT, and Newark, NJ. ... on that week – in Boston, it will be part of the City of ...
(Date:9/20/2017)... ... September 20, 2017 , ... From industry leaders, sports stars, and Hollywood icons ... Many of these people had lost all hope. Their stories are told ... (pdf) , “Neil takes readers on a riveting journey through the past, ...
(Date:9/19/2017)... , ... September 19, 2017 , ... ... standard fume hood and a high-performance fume hood. Along with the advantages and ... applications for ductless vs. ducted hoods in the laboratory. , Attendees will learn ...
(Date:9/19/2017)... Washington, D.C. (PRWEB) , ... September 19, 2017 ... ... care during an biological outbreak is about to be eliminated, said Lyle Probst, ... makes ExcitePCR’s FireflyDX™ technologies different than other pathogen detection solutions, Probst ...
Breaking Biology Technology: