Copy Number Variations

NIMH’s Top 10 Research Advances of 2011

Source: 
NIMH
Date Published: 
December 23, 2011
Abstract: 

Director of the NIMH Dr. Tom Insel shares the NIMH's Top 10 Research Advances for 2011.

Researchers debut SHANK2 mouse, SHANK3 rat

Source: 
SFARI
Abstract: 

Researchers debut the SHANK2 mouse and SHANK3 rat at the 2011 Society for Neuroscience annual meeting. SHANK2 belongs to the same family as SHANK3, a well-established autism candidate gene.

Evidence found for the genetic basis of autism: Models of autism show that gene copy number controls

Source: 
Science Daily
Date Published: 
October 5, 2011
Abstract: 

Scientists at Cold Spring Harbor Laboratory (CSHL) have discovered that one of the most common genetic alterations in autism -- deletion of a 27-gene cluster on chromosome 16 -- causes autism-like features. By generating mouse models of autism using a technique known as chromosome engineering, CSHL Professor Alea Mills and colleagues provide the first functional evidence that inheriting fewer copies of these genes leads to features resembling those used to diagnose children with autism.

Attention deficit, autism share genetic risk factors

Source: 
SFARI
Date Published: 
August 22, 2011
Abstract: 

People with autism and attention deficit hyperactivity disorder (ADHD) share some of the same underlying genetic risk factors, according to a study published this month in Science Translational Medicine. This is one of the first studies to find risk variants that are common to both disorders.
In searching for rare copy number variations (CNVs) — deletions and duplications in genetic material — in people with ADHD, the researchers found more than a dozen regions that include genes implicated in bipolar disorder, schizophrenia, intellectual disability and autism.

Rare De Novo and Transmitted Copy-Number Variation in Autistic Spectrum Disorders

Source: 
Neuron
Date Published: 
June 9, 2011
Year Published: 
2011

A study of the genetic causes of autism confirmed that spontaneous or de novo mutations are present in a substantial number of families with only one child on the spectrum. These de novo mutations are not inherited from parents' DNA, arising instead in their egg or sperm or very early in embryonic development. Researchers compared the DNA of children with ASD to that of their unaffected sibling(s) and identified a diverse array of rare genetic abnormalities that may contribute to autism. Recent advances in technology have allowed researchers to identify genetic mutations on a finer scale than was previously possible. Some of thede novo mutations, known as copy number variations (CNVs) because they contain deleted or duplicated sections of DNA, were located in regions known to be associated with ASD, while others implicate new regions. Many of the mutations are thought to affect genes or gene networks involved in brain development. The study confirmed that these non-inherited CNVs are more common in children with ASD compared to their non-affected siblings; however, each unique variant is exceedingly rare, some found in only one family. In addition, researchers found evidence that inherited "ultrarare" genetic duplications may also contribute to autism. Based on the results of the study, the authors note that females have a greater resistance to autism from genetic causes, raising questions about the fate of female carriers. The study findings emphasize the diversity of rare genetic variations that contribute to ASD and suggest the possibility that a treatment for one form of autism may not have value for the majority of cases. The DNA samples analyzed in the study were part of the Simons Simplex Collection, a repository of over 1,000 families in the U.S. and Canada with only one child on the spectrum.

--IACC 2011 Summary of Advances in ASD Research

Multiple Recurrent De Novo CNVs, including Duplications of the 7q11.23 Williams Syndrome Region, are Strongly Associated with Autism

Source: 
Pediatrics
Date Published: 
May 2011
Year Published: 
2011

A recent collaborative study identified six genetic mutations that are strongly associated with autism spectrum disorder, including an area of DNA that likely holds clues to understanding the nature of human social behavior. The researchers estimate that these mutations represent only a few of the hundreds of spontaneously arising variants that are likely to increase autism risk. Using gene chip or microarray technology, the researchers analyzed the genomes of over 1,100 families with a single child on the autism spectrum, and compared the results of affected and unaffected siblings. The DNA samples analyzed in the study were part of the Simons Simplex Collection. The scan revealed a variety of copy number variants (CNVs) -- genetic mutations that can range from micro-deletions and duplications to large sequences of missing or additional DNA. Notably, one of the non-inherited or de novo CNVs was located on a genetic region linked to Williams-Beuren syndrome, a rare disorder that causes people to be extremely social, overly trusting, and highly empathetic.While loss of DNA from the area results in Williams-Beuren syndrome, gain of extra DNA in this area is associated with autism, which is marked by difficulty with social interaction and lack of empathy. This region's connection with both disorders suggests its importance in understanding the nature of the social brain. The study also supports earlier findings of higher rates of de novo CNVs in people with autism compared to their unaffected siblings. Uncovering the genetic basis of autism is critical to understanding the neurobiology underlying the disorder and may aid in developing targeted treatment approaches for different subtypes.

--IACC 2011 Summary of Advances in ASD Research

Researchers Reveal 18 Novel Subtype-Dependent Genetic Variants for Autism Spectrum Disorders and Identify Potential Genetic Markers for Diagnostic Screening

Source: 
Science Daily
Date Published: 
April 28, 2011
Abstract: 

By dividing individuals with autism spectrum disorders (ASD) into four subtypes according to similarity of symptoms and reanalyzing existing genome-wide genetic data on these individuals vs. controls, researchers at the George Washington University School of Medicine and Health Sciences have identified 18 novel and highly significant genetic markers for ASD. In addition, ten of the variants were associated with more than one ASD subtype, providing partial replication of these genetic markers. This study thus identifies candidate genes for ASD and potential subtype-dependent genetic markers for diagnostic screening.

Autism Spectrum Disorder Linked to Genetic Synaptic Behaviors

Source: 
Medical News Today
Date Published: 
April 21, 2011
Abstract: 

It seems that the place where your brain transfers electricity between synapses and how your genes determine how these processes function, are tied to autism in one way or another. There can be genetically driven disturbances in this process that lead to varying levels of autism according to a new study of DNA from approximately 1,000 autistic children and their kin.

Gene Variants in Autism Linked to Brain Development

Source: 
Science Daily
Date Published: 
March 7, 2011
Abstract: 

New research on the genomics of autism confirms that the genetic roots of the disorder are highly complicated, but that common biological themes underlie this complexity. In the current study, researchers have implicated several new candidate genes and genomic variants as contributors to autism, and conclude that many more remain to be discovered. While the gene alterations are individually very rare, they mostly appear to disrupt genes that play important functional roles in brain development and nerve signaling.

Gene Variants in Autism Linked to Brain Development

Source: 
Journal of Molecular Psychiatry, Gai et al.
Date Published: 
March 2011
Year Published: 
2011

This research on the genomics of autism confirms that the genetic roots of the disorder are highly complicated, but that common biological themes underlie this complexity. In the current study, researchers have implicated several new candidate genes and genomic variants as contributors to autism, and conclude that many more remain to be discovered. While the gene alterations are individually very rare, they mostly appear to disrupt genes that play important functional roles in brain development and nerve signaling. While an association between genomic variants in certain nervous system processes and autism has been hypothesized in the past, this research definitively links these biological functions to autism. 

"This large study is the first to demonstrate a statistically significant connection between genomic variants in autism and both synaptic function and neurotransmission," said senior author Peter S. White, Ph.D., a molecular geneticist and director of the Center for Biomedical Informatics at The Children's Hospital of Philadelphia. Synapses are the contact points at which nerve cells communicate with other nerve cells, while neurotransmitters are the chemical messengers carrying those signals.

"Prior genomic studies of autism have successfully identified several genes that appear to confer risk for autism, but each gene appears to contribute to only a small percentage of cases," said the lead author, Xiaowu Gai, Ph.D. "Our approach considered whether groups of genes with common biological functions collectively accounted for a greater percentage of autism risk."

-- via Science Daily http://www.sciencedaily.com/releases/2011/03/110301111243.htm.