Genomics

Whole-Genome Sequencing Reveals New Types of Autism Risk

Source: 
Simons Foundation Autism Research Initiative
Date Published: 
October 20, 2014
Abstract: 

Much of the genetic risk for autism may reside in regulatory regions of the genome, hidden from traditional methods of sequencing analysis. That's the upshot of preliminary results from three studies presented at the 2014 American Society of Human Genetics Annual Meeting in San Diego. Together, the findings from these new studies show the promise of looking for autism risk in unusual places.

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."

Genome-Editing Tools Compose New Models of Autism

Source: 
Simons Foundation Autism Research Institute
Date Published: 
September 5, 2013
Abstract: 

New synthetic biology tools have allowed for great advances in genetic testing of many mutations. This technology known as CRISPR (clustered regularly interspaced short palindromic repeats) allows researchers to create molecular scissors that cut and paste essentially any mutation into the genome of any cell, including a human stem cell.

Neuronal Connectivity as a Convergent Target of Gene-environment Interactions that Confer Risk for Autism Spectrum Disorders

Source: 
Neurotoxicology and Teratology
Date Published: 
March, 2013
Abstract: 

This review briefly summarizes the evidence implicating dysfunctional signaling via Ca2 +-dependent mechanisms, extracellular signal-regulated kinases (ERK)/phosphatidylinositol-3-kinases (PI3K) and neuroligin–neurexin–SHANK as convergent molecular mechanisms in ASD, and then discusses examples of environmental chemicals for which there is emerging evidence of their potential to interfere with normal neuronal connectivity via perturbation of these signaling pathways.

Sporadic Autism Exomes Reveal a Highly Interconnected Protein Network of De Novo Mutations

Source: 
Nature
Date Published: 
April 4, 2012
Abstract: 

Researchers demonstrate that de-novo point mutations are overwhelmingly paternal in origin (4:1 bias) and positively correlated with paternal age, consistent with the modest increased risk for children of older fathers to develop ASD.

Patterns and Rates of Exonic De Novo Mutations in Autism Spectrum Disorders

Source: 
Nature
Date Published: 
April 4, 2012
Abstract: 

Results support polygenic models in which spontaneous coding mutations in any of a large number of genes increases risk by 5 to 20-fold. Despite the challenge posed by such models, results from de novo events and a large parallel case-control study provide strong evidence in favor of CHD8 and KATNAL2 as genuine autism risk factors.

Levels of Select PCB and PBDE Congeners in Human Postmortem Brain Reveal Possible Environmental Involvement in 15q11-q13 Duplication Autism Spectrum Disorder.

Source: 
Environmental and Molecular Genetics
Date Published: 
August 29, 2012
Abstract: 

These results demonstrate a novel paradigm by which specific POPs may predispose to genetic copy number variation of 15q11-q13.

CNVs: Harbingers of a Rare Variant Revolution in Psychiatric Genetics.

Source: 
Cell
Date Published: 
March 16, 2012
Abstract: 

A proportion of risk for schizophrenia, bipolar disorder, and autism can be explained by rare mutations. Alleles can have specific effects on behavioral and neuroanatomical traits; however, expressivity is variable, particularly for neuropsychiatric phenotypes

Rate of De Novo Mutations and the Importance of Father’s Age to Disease Risk

Source: 
Nature
Date Published: 
August 23, 2012
Abstract: 

The diversity in mutation rate of SNP's is dominated by the age of the father at conception of the child. The effect is an increase of about two mutations per year.

A Novel Approach of Homozygous Haplotype Sharing Identifies Candidate Genes in Autism Spectrum Disorder

Source: 
Human Genetics
Date Published: 
April, 2012
Abstract: 

A large scale analysis identifies candidate genes which may contain low-frequency recessive variations contributing to ASD