Genetics of Autism
Sharing doesn't necessarily mean I agree (and certainly not with the ableist/pathologicalization wordings), and and I'd love to hear what folks who are more familiar with genetics/biology and such have to say about these (especially autistic folks)!
And obviously his is in NO way a comprehensive list, as I'm trying not to lose my whole morning by hyperfocusing on this, so these are just a few things googled this morning!
Some Autism Genetics News Articles:
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Autistic children may inherit DNA mutations from their fathers
(Science Mag, 2018)
Reporting on: "Paternally inherited cis-regulatory structural variants are associated with autism" (Science, 2018)
‣ "Research into the genetic risk for autism has mainly focused on how mutations that arise spontaneously in an individual’s genome—rather than being inherited from a parent—disrupt protein-coding regions and lead to the condition. That’s because these sporadic mutations have relatively large effects and studies have shown that such mutations, although individually rare, together contribute to about 25% to 30% of cases, says Jonathan Sebat, a geneticist at the University of California, San Diego." ‣ "Each individual has thousands of structural variants in their genome, so the researchers narrowed down their analysis to examine just a handful of regulatory regions where genetic variation seemed most likely to cause disruption. They chose these by finding regions where the general population has less variation than expected, suggesting that genetic changes there could be detrimental. These included sites involved in regulating gene activity during brain development and initiating the transcription of genes." ‣ "The team found that mothers passed only half of their structural variants on to their autistic children—a frequency that would be expected by chance alone—suggesting that variants inherited from mothers were not associated with autism. But surprisingly, fathers did pass on substantially more than 50% of their variants. This suggests that autistic children might have inherited risk variants in regulatory regions from their fathers but not their mothers, the researchers report today in Science." ‣ "Based on these results, Sebat proposes a more complex model of how autism arises, in which mothers pass on mutations affecting coding regions, which have large effects that women are protected from, while fathers pass on variants affecting noncoding regions; their effects are much more moderate and may only cause symptoms when combined with risk variants from mothers."
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Nature of risk mutations varies with families’ history of autism
(Spectrum News, 2016)
Reporting on: "Rare Inherited and De Novo CNVs Reveal Complex Contributions to ASD Risk in Multiplex Families" (AJHG, 2016)
‣ "Large autism-linked mutations tend to be inherited in families with a history of the condition. By contrast, they often arise spontaneously in families with a single affected person, suggests a new study." ‣ "The findings validate something researchers have long assumed: Studying multiplex families — those in which two or more siblings have autism — yields clues about autism’s heritability, whereas simplex families point to spontaneous, or de novo, mutations.
“The kinds of families you pick will influence what kinds of genetic variation you find,” says lead investigator Daniel Geschwind, distinguished professor of neurology, psychiatry and human genetics at the University of California, Los Angeles." ‣ "In the new study, his team found that large deletions or duplications of DNA tend not to occur spontaneously in multiplex families. These large mutations are called copy number variants (CNVs). They are known to be enriched in people with autism from simplex families, but their role in multiplex families was unclear." ‣ "Even though CNVs in multiplex families tend to be inherited, not all the siblings with autism in those families carry the same CNV. The finding suggests that other factors besides the CNV contribute to their condition.
“The take-home message is, if you just focus on one particular flavor of genetic variation, you don’t get the whole story,” says Jonathan Sebat, chief of the Beyster Center for Genomics of Neuropsychiatric Diseases at the University of California, San Diego." ‣ "Of the 1,532 families with autism they looked at, 78 percent have more than one child with the condition; the rest are simplex families." ‣ "Only 27 of the children with autism (about 2 percent) and 1 unaffected sibling carry a spontaneous CNV. By contrast, a 2015 study of 2,591 simplex families found spontaneous CNVs in nearly 4 percent of children with autism." ‣ "Unexpectedly, the researchers found that siblings with autism rarely share the same autism-linked CNV. In 21 multiplex families, the mutation the researchers found is not present in all children with autism in the family." -
Sequencing thousands of whole genomes yields new autism genes
(Spectrum News, 2017)
Reporting on: "Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder" (Science, 2018)
‣ "The new work identified 61 genes associated with autism, 43 of which turned up in previous studies." ‣ "People with autism carry an average of 74 spontaneous, or de novo, mutations, the researchers found. They also have an average of about 13 large DNA duplications or deletions, called copy number variations (CNVs). ‣ "One of the 15 new genes, MED13, is related to the intellectual disability gene MED13L. MED13L emerged as an autism candidate in the study published last month. The new study identified harmful MED13 mutations in three families." ‣ "Harmful mutations in another new candidate, PHF3, appeared in four families. PHF3 is related to PHF2, which has been linked to autism in previous studies. PHF3 encodes a protein that regulates the structure of chromatin — the coiled complex of DNA and protein." ‣ "Of the 61 genes unearthed in the new study, 49 play a role in chromatin remodeling, RNA processing or building connections between neurons. These findings are in line with those of previous studies. They highlight the fact that these genes are functionally related and tend to work together." ‣ "The study identified CNVs across coding and noncoding parts of the genome. About 7.2 percent of participants with autism carry one or more harmful CNVs, the researchers found.
They identified three new autism-linked CNVs that were too small to be picked up by standard sequencing techniques. They also uncovered five CNVs linked to autism that land in noncoding regions of the genome." ‣ "Participants with autism who carry a harmful CNV have lower intelligence quotients than those who carry a harmful mutation in a candidate gene. But they score higher on a test of adaptive functioning, which measures daily-living skills.
This finding suggests that mutations in genes give rise to autism’s behavioral features, whereas CNVs underlie problems with cognition." -
Study identifies 69 genes that increase the risk for autism
(MedicalXpress, 2019)
Reporting on: "Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks" (Cell, 2019)
‣ "Researchers from UCLA, Stanford University and three other institutions used a technique called whole genome sequencing to map the DNA of 2,300 people from nearly 500 families. They found 69 genes that increase the risk for autism spectrum disorder, or ASD; 16 of those genes were not previously suspected to be associated with a risk for autism." ‣ "Researchers also identified several hundred genes they suspect may increase the risk of autism based on their proximity to genes that were previously identified to carry an increased risk. The study further revealed several new biological pathways that had not previously been identified in studies of autism." ‣ ""We show a substantial difference between the types of mutations that occur in different types of families, such as those that have more than one affected child versus those having only one child with ASD," said Geschwind, who also is director of the UCLA Center for Autism Research and Treatment and director of the Institute of Precision Health at UCLA." ‣ "The research also found that the 16 genes newly determined to be associated with an increased risk for autism form a network with previously identified genes that are associated with a risk for autism spectrum disorder. The way they interact with one another further heightens the risk, said Dennis Wall, the study's co-senior author, a Stanford University School of Medicine associate professor of pediatrics and of biomedical data science.
"They associate with each other more tightly than we'd expect by chance," he said. "These genes are talking to each other, and those interactions appear to be an important link to autism spectrum disorder."" ‣ "The nearly 600 genes researchers suspect to carry an increased risk of autism were identified through "guilt by association," meaning through their interactions with other genes that already had been shown to carry an increased autism risk, Ruzzo said. Although not all of those genes will be found to increase the risk for autism, the analysis indicated that future studies will provide support for many of these genes." -
Genetics By Far The Biggest Factor In Autism Risk, Study Says
(HuffPost, 2019)
Reporting on: "Association of Genetic and Environmental Factors With Autism in a 5-Country Cohortm" (JAMA Psychiatry, 2019)
‣ "Now, a sweeping new study looking at more than 2 million people from five countries (Denmark, Finland, Sweden, Israel and Australia) found that about 80% of an individual’s risk of developing autism comes from inherited genetic factors and not from “environmental” influences, meaning anything other than changes to a gene’s DNA." ‣ "“What’s immense about this study is the number of children across the world that were [included] — two million in the study population — and the large span of time, of a 16-year follow-up,” Dr. Wendy Sue Swanson, a pediatrician with Seattle Children’s who did not work on the study, told HuffPost. “It’s hard to argue with the kind of tonnage of that number.”" ‣ “There is a lot of work that still needs to be done,” Sandin told HuffPost. “We still do not know which specific genes contribute to risk. Also, there are numerous potential environmental factors that could be related to ASD either directly or acting together with genes. We have, so far, only been scratching the surface.” ‣ "Although they’re often called “environmental” influences in the scientific literature, these factors go beyond things like the potential impact of chemical exposures on a person’s likelihood of developing autism. Researchers are probing the possible role that everything from diet to infection during pregnancy might play. For now, the studies are ongoing. There just is not much that autism researchers and pediatricians can say in the way of, “If you avoid XYZ, you will decrease your child’s risk of developing autism.”" ‣ "In an editorial that accompanied the new study, a team of three autism and psychiatry experts said the media has focused disproportionately on those environmental factors, perhaps because they are modifiable. An understandable pull exists to focus on the things that parents might be able to control to a certain extent. But that may have contributed to an incorrectly skewed sense of how much nature versus nurture contributes to the autism risk."
