A group of researchers found ultra rare inherited variants passed from parents without autism to their children with autism and determined that they are more important in families “multiplex”With more than one family member involved on the spectrum.
The results of the new study have been published in the scientific journal Nature Genetics.
Ultra Rare Hereditary Variants: Here’s What The New Research Says
The search for the genes involved has always been the subject of study, now everything is more accessible thanks to the technology and the considerably lower costs that allow the aggregation of thousands of genomes of people with autism and their families. Knowing precisely which genes and particularly the ultra-rare inherited variants that are at play will allow for a greater understanding of the condition known as autism and could eventually lead to targeted therapies for those who want them.
This new study takes on some significance because most of the autism genes discovered to date have been identified through studies of de novo mutations, genetic differences that arise for the first time in the individual with autism but are not present in any of the his parents.
The research findings highlighted that researchers should not assume that the set of autism genes altered by de novo mutations are the same genes as these newly identified inherited ultra-rare variants.
According to the lead author Amy B. Wilfert, Ph.D., of the University of Washington, along with his team, after observing 10.905 people with autism, have identified and replicated a rare class of genetic variants that are passed on (over-transmitted) from parents without autism to children with autism.
“While most autism studies focus on de novo mutations, this study focuses on rare inherited mutations, which are often under-studied in autism,” says Dr. Wilfert. “We find that these variants are individually less harmful than de novo mutations, but have the potential to contribute nearly as much as risk and impact the same molecular pathways, through a distinct set of genes. These variants, however, are only able to persist in the general population for a few generations before being selected by evolution.“
“It is widely known that de novo mutations cannot and do not explain all the genetic causes of autism, a phenomenon sometimes referred to as ‘missing inheritance'”, he claims Pamela Feliciano, Ph.D., Scientific Director, SPARK (Simons Powering Autism Research). The SPARK Consortium contributed more than 50 percent of the genetic data analyzed in this study, including the exomes of 21,331 SPARK participants, 6,539 of them individuals with autism spectrum disorder (ASD).
The number of genomes accessible to scientists at this time allows for the search for certain categories of genetic changes, such as de novo changes and ultra-rare inherited variants, but not all. As more genomes go online, broader categories of variants will be accessible for analysis.
“Interestingly, the vast majority of these variants (95%) are not found in genes already known to be autism genes, which indicates that there is much more to be learned about autism genetics.“, Says Dr. Feliciano, noting that this study is the first step in a much broader investigation. “While the current study isn’t large enough to confidently identify the individual genes that have these rare inherited variants, we are learning more about these genes. Future research focusing on multiplex families is increasingly important to provide new insights ”.
The researchers also claimed that the study confirmed their expectations that this class of rare inherited variants is more prominent in multi-member families with autism than in single-person families hit. Consistent with this result, i children with ASD in these families are more likely to carry two of these variants than their non siblings affected.
The study also highlighted the need for one greater diversity in conducting research of this type, because the researchers were less able to detect rare variants in people belonging to ancestral groups who are underrepresented in genomic research, including people of African, East Asian and South Asian descent.
Ultra Rare Hereditary Variants – Here’s What Previous Studies Say
A major international study by the Autism Sequencing Consortium, with the participation of researchers from the Danish psychiatric project iPSYCH, recently mapped 102 new autism genes. The new findings highlighted a new understanding of the biology behind autism that could be used tomorrow to achieve earlier, more accurate diagnosis and better targeted therapies.
Since the first diagnosis of autism was made in 1938, researchers have been trying to clarify the origin of the disorder. There have been a lot of suggestions, along with a lot of disagreements. But one thing was clear for a while: genetics owns an important role with an inheritance of up to eighty percent.
The largest study so far of rare genetic variants has now identified 102 new so-called risk genes for autism: “Generally, there are two types of genetic variants that play a role in autism. There are uncommon genetic variants that few people have, although these can have a great effect, and then there are frequent variants of which we all carry some, and each of which contributes very little to the risk “, says the associate professor Jakob Grove ofAarhus University, which is one of the driving forces behind the Danish contribution and a member of the iPSYCH research project.
In the study, the experts mapped the building blocks of DNA into the genes of 35,584 individuals, including 11,986 with autism. The researchers then determined how many times each gene is affected by variants with “consequences of protein destruction “, as the researcher states. “If a gene is more often affected by these mutations among people with autism than among people without it, this indicates that the gene is involved in the processes that lead to autism, and is therefore designated as a risk gene“Explains Jakob Grove. Most of the mutations that destroy the identified genes are new mutations found only in the person with autism and not in the parents.
The genetic findings offer an entirely new perspective on the biological processes involved in the development of autism. Some of the genes identified largely alter early development, while others appear to be more specific to autism. Most genes help determine how neurons communicate with each other or regulate the expression of other genes.
“This new knowledge could provide a better basis for understanding autism. For example, it could help us make a diagnosis earlier, which we already know makes life easier for people with autism and their relatives. It is also conceivable that it can contribute to the development of personalized medicine for those who wish“Says Jakob Grove. In other words, the study’s findings could prove crucial for the treatment of psychiatric disorders in the future
It should also be emphasized that the new findings may only explain some cases of autism as these genetic variants are present in only a few individuals. “For this reason, iPSYCH continues to study both rare and more frequent genetic variants“, Concludes the scientist.