Genetics

Genetic and Functional Analyses of SHANK2 Mutations Suggest A Multiple Hit Model of Autism Spectrum Disorders

Source: 
PLOS Genetics
Date Published: 
February 2012
Abstract: 

"Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n = 396 patients and n = 659 controls). We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4%) patients and in 16 of 1,090 (1.5%) controls (P = 0.004, OR = 2.37, 95% CI = 1.23-4.70). In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P = 0.0013). Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11-q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the "multiple hit model" for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD."

Predicting the Diagnosis of Autism Spectrum Disorder Using Gene Pathway Analysis

Source: 
Molecular Psychiatry
Date Published: 
September 11, 2012
Abstract: 

"The current investigation interrogated single-nucleotide polymorphisms (SNPs) of individuals with ASD from the Autism Genetic Resource Exchange (AGRE) database. SNPs were mapped to Kyoto Encyclopedia of Genes and Genomes (KEGG)-derived pathways to identify affected cellular processes and develop a diagnostic test. "

An Integrated Encyclopedia of DNA Elements in the Human Genome

Source: 
Nature
Date Published: 
September 6, 2012
Abstract: 

"The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research."

Autism Genetic Testing: A Qualitative Study of Awareness, Attitudes, and Experiences among Parents of Children with Autism Spectrum Disorders.

Source: 
Genetics in Medicine
Date Published: 
January 3, 2013
Abstract: 

This study provides insight into awareness, perspectives and experiences of ASD genetic testing among parents of autistic children.

The Autism Sequencing Consortium: Large-Scale, High-Throughput Sequencing in Autism Spectrum Disorders

Source: 
Neuron
Date Published: 
December 20, 2012
Abstract: 

Dr. Joseph Buxbaum and team discuss the current state of ASD gene discovery and the benefits of a genomic technology called high-throughput sequencing.

Whole-Genome Sequencing in Autism Identifies Hot Spots for De Novo Germline Mutation

Source: 
Cell
Date Published: 
December 21, 2012
Abstract: 

UCSD researchers suggest genes linked to autism have higher mutation rates than other genes.

Genomic Technology Reveals Hundreds of Autism Gene Mutations

Source: 
Laboratory Equipment
Date Published: 
December 20, 2012
Abstract: 

ASF SAB member Dr. Joe Buxbaum on his new gene discoveries using high-throughput sequencing:
"By identifying the many genetic roots of this disorder, we can better understand its biology, which in turn will allow us to develop more tailored treatments for individuals. It is a transformative time for genetic research in autism."

FMRP Targets Distinct mRNA Sequence Elements to Regulate Protein Expression

Source: 
Nature
Date Published: 
December 12, 2012
Abstract: 

Researchers link Fragile X syndrome protein to 93 genes that have been implicated in ASD. Lead investigator says the findings may lead to more detailed genetic tests.

Decreased Levels of Adhesion Molecules Involved in Immune Cell Migration Found in Children with ASD

Source: 
Biological Psychiatry
Date Published: 
June 21, 2012
Abstract: 

Researchers at the M.I.N.D Institute found decreased levels of adhesion molecules involved in immune cell migration in children with ASD. Reduced levels were associated with increased repetitive behaviors, abnormal brain growth, and impaired cognition.