- About ASF
- What is Autism?
- How Common is Autism?
- Early Signs of Autism
- Autism Diagnosis
- Following a Diagnosis
- Treatment Options
- Beware of Non-Evidence-Based Treatments
- Autism and Vaccines
- Autism Science
- Quick Facts About Autism
- What We Fund
- Baby Siblings Research Consortium
- Resources for Grantees
- Funding Calendar
- ASF Funded Research
- ASF Supported Findings
- Apply for a Fellowship
- Apply for a Research Accelerator Grant
- Apply for an Undergraduate Summer Research Grant
- Apply for INSAR Annual Meeting Travel Grant
- Get Involved
- Day of Learning
- Research Recap of 2017
- Contact Us
Research by Topic: Genomics
A Novel Approach of Homozygous Haplotype Sharing Identifies Candidate Genes in Autism Spectrum DisorderPublished April 8, 2015 in Human Genetics
A large scale analysis identifies candidate genes which may contain low-frequency recessive variations contributing to ASD
Neuronal Connectivity as a Convergent Target of Gene-environment Interactions that Confer Risk for Autism Spectrum DisordersPublished March 8, 2015 in Neurotoxicology and Teratology
This review briefly summarizes the evidence implicating dysfunctional signaling via Ca2 +-dependent mechanisms, extracellular signal-regulated kinases (ERK)/phosphatidylinositol-3-kinases (PI3K) and neuroliginneurexinSHANK 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.
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 autismPublished November 21, 2013 in Cell
"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 […]
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.
Researchers at UCLA observed hyperactive firing rates in the brains of FMR1 knockout mice; mice engineered to have symptoms similar to those in ASD and Fragile X syndrome.
Methylomic Analysis of Monozygotic Twins Discordant for Autism Spectrum Disorder and Related Behavioural TraitsPublished April 23, 2013 in Molecular Psychiatry
This study suggests environmentally driven changes to the epigenome may contribute to the development of ASD and ASD-related behaviors. The study, which involved identical twins who were discordant for ASD and related traits, is the first large-scale examination of the role of genome-wide DNA methylation in ASD.
Penn State researchers link autism to increased genetic change in “hotspots”, regions of the genome that are highly susceptible to mutation.
A mother with two sons with autism helps advance research on neuroligin-4 mutations.
SFARI Gene is an integrated resource for the autism research community. It is a publicly available, curated, web-based, searchable database for autism research. This resource is built on information extracted from the studies on molecular genetics and biology of Autism Spectrum Disorders (ASD). The genetic information includes data from linkage and association studies, cytogenetic abnormalities, and specific mutations associated with ASD.
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.
Stem Cell Research Focusing on Autisms Genetic Mysteries Earns $2.125 Million Grant at Robert Wood Johnson Medical SchoolPublished February 12, 2013 in Newswise
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 PopulationPublished January 14, 2013 in PLOS One
Researchers discover 25 new autism-linked copy number variants.
Autism Genetic Testing: A Qualitative Study of Awareness, Attitudes, and Experiences among Parents of Children with Autism Spectrum Disorders.Published January 3, 2013 in Genetics in Medicine
This study provides insight into awareness, perspectives and experiences of ASD genetic testing among parents of autistic children.
UCSD researchers suggest genes linked to autism have higher mutation rates than other genes.
The Autism Sequencing Consortium: Large-Scale, High-Throughput Sequencing in Autism Spectrum DisordersPublished December 20, 2012 in Neuron
Dr. Joseph Buxbaum and team discuss the current state of ASD gene discovery and the benefits of a genomic technology called high-throughput sequencing.
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.”
De novo mutations in six genes may contribute to 1% of simplex ASD cases.
Unpublished data presented at the 2012 Society for Neuroscience annual meeting show at least 30 genes show altered expression in brain tissue of people with autism. The ongoing study aims to include more samples than previous postmortem studies, and includes samples lost in Harvards freezer malfunction.
Using Large Clinical Data Sets to Infer Pathogenicity for Rare Copy Number Variants in Autism CohortsPublished October 9, 2012 in Molecular Psychiatry
Copy number variants (CNVs) have a major role in the etiology of autism spectrum disorders (ASD), and several of these have reached statistical significance in casecontrol analyses. Nevertheless, current ASD cohorts are not large enough to detect very rare CNVs that may be causative or contributory (that is, risk alleles).
“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. “
“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.”
Levels of Select PCB and PBDE Congeners in Human Postmortem Brain Reveal Possible Environmental Involvement in 15q11-q13 Duplication Autism Spectrum Disorder.Published August 29, 2012 in Environmental and Molecular Genetics
These results demonstrate a novel paradigm by which specific POPs may predispose to genetic copy number variation of 15q11-q13.
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.
UCLA researchers compare the genes of children with autism and their typically-developing siblings to better understand the role of gene expression in the development of autism.
Researchers at MIT use zebrafish to better understand the genetics of autism.
“Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far. We found the diversity and abundance of each habitat’s signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81-99% of the genera, enzyme families and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology and translational applications of the human microbiome.”
A Common X-linked Inborn Error of Carnitine Biosynthesis May be a Risk Factor for Nondysmorphic Autism.Published May 22, 2012 in Proceedings of the National Academy of Sciences of the United States of America
These data suggest that dysregulation of carnitine metabolism may be important in nondysmorphic autism; that abnormalities of carnitine intake, loss, transport, or synthesis may be important in a larger fraction of nondysmorphic autism cases; and that the carnitine pathway may provide a novel target for therapy or prevention of autism.
Copy Number Variations suggest that the distinction between milder neuropsychiatric conditions from those of severe developmental impairment may be a consequence of increased mutational burden affecting more genes
Negative Allosteric Modulation of the mGluR5 Receptor Reduces Repetitive Behaviors and Rescues Social Deficits in Mouse Models of AutismPublished April 25, 2012 in Science Translational Medicine
Using a mouse model with behaviors relevant to the three diagnostic behavioral symptoms of autism, researchers used a genetic approach to reduce repetitive behaviors and partially reverse the striking lack of sociability in these mice.
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.
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.
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
A new study published in PLoS Genetics uses a combination of genetic and neurobiological approaches to confirm that synaptic mutations increase the risk of autism spectrum disorders (ASDs) and underlines the effect for modifier genes in these disorders.
A team led by researchers at the University of California, San Diego School of Medicine reports that newly discovered mutations in an evolved assembly of genes cause Joubert syndrome, a form of syndromic autism.
Director of the NIMH Dr. Tom Insel shares the NIMH’s Top 10 Research Advances for 2011.
TBL1X Gene Involved In Autism Spectrum Disorder: Dr. Eden Martin from the Hussman Institute explains, “The SNP in TBL1X is associated with an increase in risk for ASD of about 15%.
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.
With the help of two sets of brothers with autism, Johns Hopkins scientists have identified a gene associated with autism that appears to be linked very specifically to the severity of social interaction deficits. The gene, GRIP1 (glutamate receptor interacting protein 1), is a blueprint for a traffic-directing protein at synapses — those specialized contact points between brain cells across which chemical signals flow.
The Autism Tissue Program (ATP) is a postmortem brain tissue program created by the National Alliance for Autism Research (NAAR) for the purpose of supplying research scientists with neurological tissue samples of deceased Autistic individuals. Scientists, however, are not supplied with tissue samples from any other parts of the deceased individual, leading to frustration over […]
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.
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 […]
Researchers have uncovered a prominent genetic risk factor for autism spectrum disorders and schizophrenia is a small genomic deletion. Remarkably, they found the same deletion on chromosome 17 in 24 separate patients. This CNV was absent in 52,448 controls, making the finding statistically significant. Someone with this deletion is 13.58 times more likely to develop ASD or schizophrenia than is someone lacking this CNV. This gene mutation is also known to cause kidney disease (renal cysts and diabetes syndrome, RCAD).
Mutations in a single gene can cause several types of developmental brain abnormalities that experts have traditionally considered different disorders. With support from the National Institutes of Health, researchers found those mutations through whole exome sequencing ? a new gene scanning technology that cuts the cost and time of searching for rare mutations. Whole exome sequencing can be applied to dozens of other rare genetic disorders where the culprit genes have so far evaded discovery. Such information can help couples assess the risk of passing on genetic disorders to their children. It can also offer insights into disease mechanisms and treatments.
DNA for each individual contains variants that are more or less common in the overall population.Some gene variations are actually genetic deletions, where sections of DNA ‘code’ are missing entirely. These variants are likely to have important effects on gene function and, therefore, likely to contribute to diseases associated with that gene. But what happens when multiple genes are disrupted in a single family?
Together with colleagues from an international research group, autism researcher Christopher Gillberg of the University of Gothenburg, Sweden, has found in a new study that autism can be partially explained by abnormalities in certain genes. The group’s results could, in the long run, pave the way for more appropriate treatments for autism.In the article the group reveals that a survey of 1,000 individuals with autism and 1,300 without showed that Copy Number Variants (CNVs) sub-microscopic abnormalities in the chromosomes are heavily over-represented in autistic people.
A genome-wide analysis reveals that people with ASDs carry a higher load of rare copy-number variants — segments of DNA for which the copy number differs between individual genomes — which are either inherited or arise de novo. The results implicate several novel genes as ASD candidates and point to the importance of cellular proliferation, […]
Mount Sinai researchers and the Autism Genome Project Consortium (AGP) announced that they have identified new autism susceptibility genes that may lead to the development of new treatment approaches. These genes, which include SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus, primarily belong to synapse-related pathways, while others are involved in cellular proliferation, projection and motility, and intracellular signaling
This study analysed the genome-wide characteristics of rare (
Schizophrenia involves some of the same genetic variations as autism and attention deficit disorders, a new whole-genome study has confirmed. In an effort to assess some of the common genetic variations that might underpin this fairly common but thorny mental illness, researchers sequenced DNA from 1,735 adults with schizophrenia and 3,485 healthy adults. Across the patients that had the disease, the researchers found many frequent variations related to copying or deleting genes, known as copy-number variations.
New research from the lab of Michael Greenberg, Nathan Marsh Pusey professor and chair of neurobiology at HMS, in collaboration with bioinformatics specialist and neuroscientist Gabriel Kreiman, assistant professor of ophthalmology at Children’s Hospital, Boston, has found that a particular set of RNA molecules widely considered to be no more than a genomic oddity are actually major players in brain development – and are essential for regulating the process by which neurons absorb the outside world into their genetic machinery.
A large study from Children’s Hospital Boston and the Boston-based Autism Consortium finds that a genetic test that samples the entire genome, known as chromosomal microarray analysis, has about three times the detection rate for genetic changes related to autism spectrum disorders (ASDs) than standard tests.
Researchers at the University of North Carolina at Chapel Hill School of Medicine have found that the 22q11 gene deletion — a mutation that confers the highest known genetic risk for schizophrenia — is associated with changes in the development of the brain that ultimately affect how its circuit elements are assembled.The researchers would now like to figure out how these alterations in the circuitry of the brain affect the behavior of the mouse. They also hope that understanding the “mis-wiring” of the brain in a genetic animal model of schizophrenia would help them understand the causes of the disease in the general population
In one of the first studies of its kind, an international team of researchers has uncovered a single-letter change in the genetic code that is associated with autism. The finding, published in the October 8 issue of the journal Nature, implicates a neuronal gene not previously tied to the disorder and more broadly, underscores a role for common DNA variation. In addition, the new research highlights two other regions of the genome, which are likely to contain rare genetic differences that may also influence autism risk.
Genome-Wide Analyses of Exonic Copy Number Variants in a Family-Based Study Point to Novel Autism Susceptibility GenesPublished June 1, 2009 in PLOS Genetics, Bucan M, Abrahams BS, Wang K, Glessner JT, Herman EI, et al.
The study identified 27 different genetic regions where rare copy number variations – missing or extra copies of DNA segments – were found in the genes of children with autism spectrum disorders, but not in the healthy controls. The researchers, including geneticists from the University of Pennsylvania School of Medicine and The Children's Hospital of […]
A Common Genetic variant in the neurexin superfamily member CNTNAP2 increases Familial Risk of AutismPublished December 1, 2008 in American Journal of Human Genetics, Arking, Cutler, et al
Autism is a childhood neuropsychiatric disorder that, despite exhibiting high heritability, has largely eluded efforts to identify specific genetic variants underlying its etiology. We performed a two-stage genetic study in which genome-wide linkage and family-based association mapping was followed up by association and replication studies in an independent sample. We identified a common polymorphism in […]
Schizophrenia is an etiologically heterogeneous psychiatric disease, which exists in familial and nonfamilial (sporadic) forms. Here, we examine the possibility that rare de novo copy number (CN) mutations with relatively high penetrance contribute to the genetic component of schizophrenia. We carried out a whole-genome scan and implemented a number of steps for finding and confirming […]
Structural variation (copy number variation [CNV] including deletion and duplication, translocation, inversion) of chromosomes has been identified in some individuals with autism spectrum disorder (ASD), but the full etiologic role is unknown. We performed genome-wide assessment for structural abnormalities in 427 unrelated ASD cases via single-nucleotide polymorphism microarrays and karyotyping. With microarrays, we discovered 277 […]
Autism is a childhood neurodevelopmental disorder with a strong genetic component, yet the identification of autism susceptibility loci remains elusive. We investigated 180 autism probands and 372 control subjects by array comparative genomic hybridization (aCGH) using a 19K whole-genome tiling path bacterial artificial chromosome microarray to identify submicroscopic chromosomal rearrangements specific to autism. We discovered […]
We have identified a novel, recurrent microdeletion and a reciprocal microduplication that carry substantial susceptibility to autism and appear to account for approximately 1% of cases. We did not identify other regions with similar aggregations of large de novo mutations. Among the AGRE families, we observed five instances of a de novo deletion of 593 […]
Autism is a profound disorder of neurodevelopment with poorly understood biological origins. A potential role for maternal autoantibodies in the etiology of some cases of autism has been proposed in previous studies To investigate this hypothesis, maternal plasma antibodies against human fetal and adult brain proteins were analyzed by western blot in 61 mothers of […]