Genetics

Transcriptome Analysis Reveals Dysregulation of Innate Immune Response Genes and Neuronal Activity-Dependent Genes in Autism

Source: 
Nature
Date Published: 
December 10, 2014
Abstract: 

Using resources from the Autism BrainNet, a new study in brains affected by autism revealed a common factor of activated immune cells. Led by Dr. Dan Arking at Johns Hopkins, the project analyzed dats collected from 72 individuals, both with and without autism The findings compared gene expression across these two groups and from different brain banks. It also utilized a large dataset that contains data on existing autism risk genes. This represents the largest dataset so far in studying gene expression in the brains of autism. Previous studies have been too small to make meaningful conclusions, because of the lack of tissue available.

The team, which also included the University of Alabama at Birmingham, saw that in individuals with ASD, a type of immune cell called microglia was always active, with genes for inflammation always being turned on. Arking noted that he did not think that the inflammation itself as the root cause of autism, but that it is the marker of a downstream effect.

“This type of inflammation is not well understood but it highlights the lack of current understanding about how innate immunity controls neural circuits,” Dr. Andrew West, associated professor of neurology at the University of Alabama at Birmingham said.

Future of Autism Genetics Should Learn from its Past

Source: 
Simons Foundation Autism Research Initiative
Date Published: 
December 9, 2014
Abstract: 

The results of sequencing studies are helping autism researchers narrow down what genes to look for and where. They can now put forth a statistically sound estimate of the overall genetic contribution of de novo mutations of different categories to autism. However, they still cannot pinpoint the causal mutations for many cases of autism because the genomic background noise remains high.

Massive Sequencing Studies Reveal Key Autism Genes

Source: 
Simons Foundation Autism Research Initiative
Date Published: 
October 29, 2014
Abstract: 

Analyzing the sequences of more than 20,000 people, researchers have unearthed the largest and most robust list of autism genes so far, they reported in the journal Nature.These 50 ‘high-confidence’ autism genes may help researchers understand the biological underpinnings of autism. The researchers found these genes by scouring the exomes, the protein-coding regions of the genome, looking for rare genetic glitches unique to people with autism.

Expansion of the Clinical Phenotype Associated with Mutations in Activity-Dependent Neuroprotective Protein

Source: 
Journal of Medical Genetics
Date Published: 
July 23, 2014
Abstract: 

A new study has identified a genetic change in a recently identified autism-associated gene, which may provide further insight into the causes of autism. The study, now published online in the Journal of Medical Genetics, presents findings that likely represent a definitive clinical marker for some patients' developmental disabilities. Researchers identified a genetic change in a newly recognized autism-associated gene, Activity-Dependent Neuroprotective Protein (ADNP), in a girl with developmental delay. This change in the ADNP gene helps explain the cause of developmental delay in this patient. This same genetic change in ADNP was also found in a boy who was diagnosed with autism.

Age Alters Patterns of Chemical Tags on Sperm DNA

Source: 
Simons Foundation Autism Research Initiative
Date Published: 
August 18, 2014
Abstract: 

The configuration of methyl tags that modify DNA in sperm change as men get older, according to a study published PLOS Genetics. These alterations may help explain why children of older fathers are at increased risk for neuropsychiatric disorders such as autism. Researchers at the University of Utah collected sperm from 17 men, once in the 1990s and again in 2008. They found that the distribution of methyl tags, a particular kind of DNA modification, shows relatively consistent changes over time in the sperm. However, the study does not necessarily prove that these altered patterns survive past fertilization or influence the risk of disorders such as autism.

Disruptive CHD8 Mutations Define a Subtype of Autism Early in Development

Source: 
Cell
Date Published: 
July 7, 2014
Abstract: 

A variation in the CHD8 gene has a strong likelihood of leading to a type of autism accompanied by digestive problems, a larger head and wide-set eyes, a study in Cell reports. This discovery is part of an emerging approach to studying the underlying mechanisms of autism and what those mean for people with the condition. Many research teams are trying to group subtypes of autism based on genetic profiles. This is the first time researchers have shown a definitive cause of autism from a genetic mutation.

Large Study Underscores Role of Gene Copy Number in Autism

Source: 
Simons Foundation Autism Research Initiative
Date Published: 
June 2, 2014
Abstract: 

People with autism tend to carry mutations that duplicate or delete several genes at once, according to a large study published in the American Journal of Human Genetics. Previous studies have shown that people with autism have more large deletions or duplications of DNA, also known as copy number variations (CNVs), than controls do. The new study, the largest to look at CNVs in people with autism thus far, confirms this finding. It also found that in people with autism, the CNVs are more likely to affect genes linked to intellectual disability and fragile X syndrome.

Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism

Source: 
Cell
Date Published: 
November 21, 2013

"As techniques for studying the human genome have advanced, an increasing number of genes are being associated with ASD; it is important to find the connections between these ASD-linked genes in order to understand how they may contribute to ASD. A new resource called the BrainSpan1 atlas provides researchers with three dimensional maps showing when and where genes turn on and off in the human brain, from embryonic stages through older adulthood. This study used the BrainSpan atlas to identify commonalities in when and where ASD-associated genes are expressed.By using the shared characteristics of different gene mutations implicated in ASD, this study creates a picture of the developmental processes that are changed in these cases. This image provides a sharper focus for the development of targeted treatments, and even holds potential for the development of personalized interventions based on genotype."

Mothers of Children with Autism Share Their Sensory Problems

Source: 
Simons Foundation Autism Research Initiative
Date Published: 
May 2, 2014
Abstract: 

A small study published 3 April in Molecular Autism found that 98 percent of mothers of children with autism have unusual responses to sensory stimuli, including light, sound and touch. Up to 90 percent of children with autism show sensory problems, fixating on or avoiding certain smells, sounds or textures. As a result, the newest edition of the Diagnostic and Statistical Manual of Mental Disorders lists abnormal sensitivity in one or more of the five senses as a core diagnostic feature of autism. It’s unclear whether genetics contributes to these sensory patterns, but a larger study examining the relationship between unusual sensory response, autism traits and additional disorders in family members may clarify the link.

Repeats in Human DNA may Aggravate Autism Symptoms

Source: 
Simons Foundation Autism Research Initiative
Date Published: 
April 21, 2014
Abstract: 

Certain DNA repeats that increased exponentially during human evolution are directly related to the severity of autism symptoms, according to a preliminary study published in PLoS Genetics. The repeats each span 65 amino acids and are collectively referred to as DUF1220, for ‘domain of unknown function.’ There are six types of these repeats, each with a slightly different sequence and all of which diverged from a common ancestor.