Identification Of Candidate Asd Risk Genes
Following the classification of autism by Kanner, research efforts were undertaken to determine the disease etiology. Though it was initially assumed to be of environmental origin, an improved understanding of the role of genetics in human health soon suggested otherwise. In 1977, Folstein and Rutter conducted twin studies upon the observation that incidence among siblings was 50× higher than average. They found that monozygotic twins were more likely to share a diagnosis than dizygotic twins, suggesting a genetic influence. Bailey et al. supported this finding, documenting 60% concordance for monozygotic twins versus no concordant dizygotic pairs. In addition, risk of a child having ASD was found to be proportional to the percentage of the genome they shared with an affected sibling or parent . By the turn of the century, ASD was established to have some genetic component, though which genes were involved remained a mystery.
Somatic Mosaicism and ASD Risk
CNVs Contribute to ASD Susceptibility
Epigenetic Regulation and ASD
Where Does Autism Come From When It Doesnt Run In The Family
Autism genetics expert Ivan Iossifov breaks down recent research that sheds light on how unaffected parents can pass autism onto their child.
A quick Google search for autism causes is all it takes to learn that scientists believe the disorder has a strong genetic component. So if theres no genetic history in the family, where does a childs autism come from?
A key fact has come to light within the last couple of years: many autism-causing genetic mutations are spontaneous. They occur in the affected child, but in neither parent. Mutations in this category are not directly inherited from the parents, explains Assistant Professor Ivan Iossifov, one of several CSHL scientists who has pioneered the study of the role of spontaneous mutations in autism causation.
A childs genome is a patchwork stitched together from the genetic cloth contained in the mothers egg and fathers sperm. In theory, that means that children are cut from exactly the same cloth as their parents. But in reality, there are virtually always small factory defects in that clothmutations that spontaneously arise during the sperm or eggs creation.
Spontaneous mutations cause as much as half of all autism in situations in which only one child in the family has autism. This and other analysis comes from a study Iossifov published in 2015. He and his team looked at about 2,500 families with a single affected child and investigated the causal link to spontaneous mutations.
Is Genetic Testing For Autism Reliable
The short version is not always. Genetic testing cannot diagnose or detect autism as over 100 genes can be linked to autism, but no single instance is repeatable among those who have it. What it can do is help identify markers or concerns, and it can help autism research. These markers, when identified between siblings or parent and child, can help future researchers know what to look for and can help concerned caregivers have an explanation of the condition, but not a direct cause.
Genetic testing is evolving and changing rapidly, and in the future we may discover a solid connection between genetics and DNA. For now, we only know they are connected somehow.
What Autistic People Have To Say
Through our Stories from the Spectrum series, weve spoken to several autistic people, who have shared their thoughts on this topic, what being autistic is like for them, and some of the positive aspects of being autistic.
“I just seem to see and think about people and the world in a different way. It’s part of who I am.” John Clark
John Clark, autistic filmmaker, told us:“I just seem to see and think about people and the world in a different way. For instance, I am both confused and fascinated by idioms. Its part of who I am. I used to be very self-conscious about people liking and accepting me, but now, I just think, take me or leave me. Were all different. Some people seem to find live and let live a difficult mantra to grasp though.”
Patrick Samuel, autistic artist and musician, said: “My autism makes it easy for me to do things a lot of non-autistic people may struggle with. I work intensely when Im painting, writing, composing or doing anything creative. I think being autistic also contributes to my aptitude in problem solving and pattern recognition, which can help me research a highly specialised subject and give talks on it.”
Evidence For Converging Molecular Pathways
Several recent studies have suggested that in addition to convergent brain pathways, that there may as well be convergence at the level of molecular mechanisms in ASD. One class of such studies has asked whether putative ASD susceptibility genes are enriched in members for specific molecular or biological processes more than expected by chance. The value of this approach depends on the level of experimental support for the specific genes tested and the degree to which current pathway annotations represent reality . For genes identified within CNV this can be particularly problematic, as most known pathological CNV contain more than one gene and it is not expected that all genes within the CNV contribute to ASD, potentially increasing noise in this analysis. One recent study reduced such background by using a new phenotype-driven method to group genes within high confidence de novo CNV , identifying significant enrichment for several categories of genes, including axon outgrowth, synaptogenesis, cell-cell adhesion, GTPase signaling, and the actin cytoskeleton. These results replicate and extend earlier composite pathway analysis of putative ASD susceptibility genes compiled from the literature , and CNV pathway analysis in the Autism Genetic Resource Exchange and other cohorts . Still, these studies place ASD genes within a multiplicity of pathways, several of which are broad and do not necessarily demonstrate convergence on final common molecular processes in individuals.
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Diagnostic Models Based On Imaging Genetics
Imaging genetics in ASD has proven useful, and pathways that include common genetic variation in TD individuals at risk of developing ASD have been characterized. Prenatal transcription regulation and synapse formation in the developing brain is impacted by the genes associated with ASD . Alteration in frontal WM connectivity and structure and disturbance in the frontal, temporal, and occipital circuits involved in visual and language processing was found to be associated with NRXN superfamily genes. Neuropeptide signaling and emotional functioning was found to be influenced by the oxytocin and arginine vasopressin receptor genes via structural and functional modification in the amygdalahypothalamus circuitry. One study showed a relationship between frontal lobe connectivity and common genetic variants in CNTNAP2 using a functional neuroimaging study and the study found that ASD and TD individuals who were nonrisk allele carriers showed more reduction in the activation of mPFC during an fMRI task as compared to risk allele carriers. Another study showed decreased functional connectivity in the prefrontal cortex, cortical spinal tract, corpus callosum, and decreased integrity of WM in children and adolescents carrying MET rs1858830, C risk allele. Such studies suggest that the genes affect the brain regions that are involved in social and emotional processing.
Indirect Evidence Suggesting A Contribution Of Environmental Factors
Prevalence studies of autism spectrum disorders conducted in recent years have been the source of an important debate because of a steady and highly significant increase of estimates of the total prevalence of pervasive developmental disorders. Indeed, while the prevalence was estimated at 6 per 1000 in a population of school children in 2005,52 recent studies have gone so far as to estimate the prevalence to be one child in 38.59The last prevalence estimates in the United States, released by the Centers for Disease Control recently,60 reached 1 in 88 child in 2008, while their previous estimate was one in 110 in 2006. However, most of the studies are not comparable in method or in the populations studied. One hypothesis is that this increase is the result of enlargement of diagnostic criteria, and the growing importance of screening for ASDs. The results of an epidemiological study from England, based on a national sample from 2007, support this hypothesis. Indeed the authors found a rate of about 1% in adults across the entire age range, without a significant reduction in the older part of the sample, as one would expect if the prevalence had increased in recent years.61 However, another study suggested that diagnostic substitution, especially for the most severe cases, and better ascertainment, especially for children at the less severe end of the spectrum, explain only a part of the linear increase observed in the California registry.62
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Some Known Genetic Traits Among Asd Cases
Listed below are scientific facts that can determine the risks associated to having an autistic child:
- There is no singular ethnic or socioeconomic discrimination in autism
- Parental age is a risk factor, especially the male partner fathers tend to pass on 4 times as many genetic defects as mothers.
- Maternal infections such as rubella may increase risks around genome deficiencies
- Oxygen Deprivation at the time of birth can kill a few brain neurons
- Premature babies this aspect is still inconclusive
- Mothers exposure to chemicals such as valproic acid and thalidomide
A lot of help is available today to help you cope with Autism. There are people, organizations, teachers, schools and therapists well trained in handling Autism Spectrum Disorders. Early diagnosis and intervention are the keys.
Should it Impact my decision to have a Child?.
With cases of Autism Spectrum Disorders rising, parents have a few concerns: What causes autism? Or is autism hereditary? Is there any possibility that I may possess the genome deficiencies and may transmit autism unknowingly to my child? is pregnancy one of the causes of autism? And do early infant vaccines cause autism?
Anne Sue from Autism Rehabilitation says, Working with children on the Autism Spectrum and their families encourage me to let parents know that having a child is the greatest joy one can experience. There is so much we know now to help bring a healthy and happy child into this beautiful world.
Genetic Testing For Autism Spectrum Disorder
In todays world, unfortunately, there is no genetic testing to detect autism spectrum disorder before birth, when the baby is in the womb.
We need to know that autism spectrum disorder is first and foremost a genetic disorder. Most of the risk of autism comes from genes. Mutation in genes causes this condition. While there are four types of tests that can detect these mutations, there is no definite specific test that can diagnose autism.
Genetic tests used to detect other genetic disorders in the womb cannot be used to diagnose autism. Because environmental factors are involved in autism and a situation after the test can change the result. It does not mean that there are hundreds of mutations that lead to this situation, but not every gene mutated causes autism.
Lets say the genetic test was applied and you got a negative result. But after your baby was born and raised, you learned that he had autism. This is a very livable scenario. The genetic tests in question may not be receiving a particular mutation, or there is no relationship with autism at the time of the test. For this reason, most genetic testing facilities reanaly the results once a year based on the latest findings.
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What Is The Treatment For Autism
There is currently no cure for autism. However, autism can be managed and shaped at a young age, even as early as pre-school. Early intensive therapy can have a positive effect on development later in life.
Treatment of autism involves medical and behavioral therapies to help children with conversational language and social interactions. Treatment also involves helping children decrease their repetitive, self-stimulatory behaviors, tantrums and self-injurious behavior.
Medications can help treat specific symptoms such as aggressive or self-injurious behavior, inattention, poor sleep and repetitive behaviors. However, no medications are autism specific and medications should be used in conjunction with a family-centered, behavioral and educational program.
Treatment For Your Child With Autism
At Therapeutic Pathways, our therapists and behavior technicians follow the most up-to-date practices extensively researched and backed by leaders in the scientific community. After your child has been diagnosed with an autism spectrum disorder, come to Therapeutic Pathways for individualized treatment. We provide family training and support as well as comprehensive Applied Behavior Analysis treatment for children, adolescents, and adults.
For more information, call 422-3280.
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Issues In Extracting Target Genes For Analysis
Simons Foundation Autism Research Initiative , which is one of the most famous research institutes, provides a gene database of the human and animal genetics of ASD, as funded by Simons Foundation. They encourage research in three areas of genomics: 1) risk gene discovery and systems biology, 2) functional analysis of variants associated with ASD risk genes, and 3) genetic therapies. SFARI also selects approximately 50 genes as strong candidates for the development of translational research. On the other hand, the American Academy of Pediatrics selected another subset consisting of 22 ASD risk genes identified or confirmed in whole-exome studies, such as KDM5B . However, KDM5B is not in the top 50 genes of the SAFRI database . Thus, Schaaf et al. suggested that there are some differences among research groups , emphasizing the importance of providing an evidence-based framework for curation of neurodevelopmental disorder genes supported by the clinical association between ASD and risk genes .
Table 1 Approximately 50 genes from the SPARS gene list prioritized by SFARI
Get To Know Your Dna With Our At
So, is autism hereditary? Your family genetics can play a key role in whether your child develops ASD or not, but when you get the right testing done you can better prepare for diagnosis like ASD and other rare diseases. Knowledge is key to knowing what works best for you and your family.
If youre interested in getting to know more about your DNA and any genetic predispositions you might have, then Sequencing is your go-to. We offer clinical-grade, safe and secure kits to test your DNA in the privacy of your own home. Sequencings Rare Disease Screening package includes an assessment for rare causes of autism, but it cant detect a genetic cause in the majority of people diagnosed with autism.
Its as simple as a mouth swab and you could learn a plethora of information about your health. Find out more about how it works, here.
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Direct Evidence For The Contribution Of Environmental Factors
There has been much discussion about the initial suggestion that MMR vaccine.79 However there is now a scientific consensus that the evidence favors rejection of a causal relationship between thimerosal-containing vaccines and autism, based on multiple epidemiologic studies which did not support a link between thimerosal-containing vaccines and ASD . However, other environmental factors are likely to contribute to a significant proportion of ASD risk.
Prenatal and perinatal factors
In another meta-analysis focusing on the perinatal and neonatal period,83 the same authors identified several potential risk factors, the main being fetal presentation, umbilieal-cord complications, fetal distress, birth injury or trauma, multiple birth, maternal hemorrhage, summer birth, low birth weight, small for gestational age, low 5minute Apgar score, meconium aspiration, neonatal anemia, ABO or Rh incompatibility, and hyperbilirubinemia. Feeding difficulties and congenital malformation that are also mentioned should rather be considered as symptoms of an underlying cause of autism. The identification of summer birth as a risk factor is consistent with the results of a recent study showing that maternal infection in the first trimester increases autism risk.84
Drugs and toxic exposure
Discovery Of Genetic Root Of Son’s Autism Gives Calgary Family Hope For A Cure
A Calgary family has learned a rare genetic mutation is the root of their son’s severe autism, and now they hope the discovery will lead to a cure.
Mousumee Dutta and Ian Holloway have struggled over the years to make life better for their son.
Ishaan Holloway, 17, was diagnosed with severe autism when he was a young boy.
The family hopes pinpointing the cause could help eventually treat and maybe even cure it.
In many cases, treatments and therapies can lead to behavioural changes or reduce health deterioration. They tried various treatments, but Ishaan’s condition did not improve. His parents were eager to find out if a genetic mutation was blocking the treatments of his neurological pathways.
“I knew there had to be more,” Dutta said.
They wanted to try whole genome sequencing that they had heard about on Facebook from other parents of autistic children.
From 2013 up until 2018, the family did not have access to the testing. Ishaan was not eligible for the testing because he was not diagnosed with a syndrome.
His parents were adamant about finding answers for Ishaan’s severe medical condition.
After years of advocating, doctors finally found out that Ishaan has epilepsy and seizures every 10 seconds. This opened the door to an application for funding for whole genome testing. It was discovered Ishaan has a rare NLGN4 X mutation.
“Is it rare because it has not been studied well, it is not accessible, or is it actually rare? We don’t know,” Mousumee said.
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Current Research On Genetic Autism
Autism is an active area of research with over 6,000 articles and over 700 reviews catalogued in PubMed in 2020.
In 2017, Sleep in Children with Autism Spectrum Disorder provided an overview of the relationship between sleep and children with ASD.
Association of Genetic and Environmental Factors With Autism in a 5-Country Cohort is a study published in the journal JAMA Psychiatry in July 2019 that discovered that autism spectrum disorders are 80% caused by inherited genes. This is the largest study of its kind to date.
Researchers are also investigating conditions that tend to be comorbid with the disorder. In 2020, there is some evidence to suggest CRISP technology may lessen symptoms of Angelman syndrome and that a type of gene therapy may curb deadly seizures in certain forms of epilepsy.
Spectrum, a division of the Simons Foundation Autism Research Initiative, continues to highlight new research, such as this recent study from April 2021 suggesting that progress in treatment shows a strong tendency to level off in many children at age 6.
For more recent research, you can also check out Autism Speaks top 10 studies of 2020. Here, scientific staff and advisors summarize what they believe to be the most impactful autism studies of the year, including those that focus on interventions and health disparities. The United States Department of Health and Human Services also shares recent research and resources.