Genetics

Sex Differences in Autism Spectrum Disorders

Source: 
Current Opinion in Neurology
Date Published: 
February 13, 2013
Abstract: 

A review of current research shows that ASD affects females less frequently than males and suggests this difference may be due to several sex-differential genetic and hormonal factors.

Astroglial FMRP-Dependent Translational Down-regulation of mGluR5 Underlies Glutamate Transporter GLT1 Dysregulation in the Fragile X Mouse

Source: 
Human Molecular Genetics
Date Published: 
February 7, 2013
Abstract: 

This paper discusses the role fragile X mental retardation protein (FMRP) plays in protein expression in astrocytes, and suggests that FMRP loss in astrocytes may contribute to the development of fragile X.

Sequencing Studies Implicate Inherited Mutations in Autism

Source: 
SFARI
Date Published: 
January 23, 2013
Abstract: 

SFARI: Rare, inherited mutations contribute to a significant proportion of autism cases according to two new studies published in Neuron.

Identification of Rare Recurrent Copy Number Variants in High-Risk Autism Families and Their Prevalence in a Large ASD Population

Source: 
PLOS One
Date Published: 
January 14, 2013
Abstract: 

Researchers discover 25 new autism-linked copy number variants.

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.