Autism, or autism spectrum disorder, is a developmental disorder that often appears in adolescents by the age of three. Intellectual disabilities occur in 40 percent of autism spectrum disorder cases. It has long been established that some people have a genetic predisposition toward autism. However, autism's inheritability, from parents to children, is not yet clear.
A new study has analyzed the DNA of more than 2,100 children with autism who were born into families where neither their parents nor a sibling has an autism disorder. Researchers looked at all of their DNA for any indication of what could indicate a mental disability like autism. They compared "runs of homozygosity" (ROH) between affected children and their siblings. These runs are just inherited genetic material from both parents that is homozygous, or the same, across all of the children of one pair of parents. If something were inherited, it would likely be located here. Their reasoning was that these ROH of genetic material are inherited from both parents and should be very similar between siblings, as they have the same parents. Upon comparison, researchers figured they would find which specific piece of genetic information was altered in the children with autism.
It has been established that autism can come from a genetic disposition and much of the disease's symptoms are based on changes to neurological development due to the changes made to genetic material. A 2008 study found that changes to the gene that creates a protein, called fragile X mental retardation protein (FMRP), can stop the body from making this protein altogether and alter neuronal growth. A 2011 study found that the protein's loss of function, characteristic of autism, can stop neurons from communicating with each other if they develop properly. However, little work has been done to indicate whether this issue with FMRP is inherited; it is understood as a random mutation, leading to autism.
Inheritance of traits like diseases depends on how many are inherited and whether they are dominant or recessive. Genetic disorders tend to be recessive, and in order to be affected by them, one must receive two copies of the gene deciding the disease in order to have the disease or disorder. If someone inherits just one recessive gene for the disease, he or she becomes a carrier and may pass the trait onto his or her children. The researchers have scanned the DNA of their patients and families to establish which gene exactly is the one deciding autism.
Researchers could not identify a particular location in the ROH that differed between children with autism and their siblings without it. However, they did find that children with autism and intellectual disabilities, or an IQ of 70 or less, often had longer ROH than unaffected children. Children with autism had 1.32 times more runs of homozygosity than their unaffected siblings. This suggests that in the ROH, disease fate can be decided, aside from a child just having inherited the recessive trait for the disease.
"At the highest level, the importance of this paper is to refocus on runs of homozygosity as an element of the genetic variation that can contribute to the susceptibility to disease," said Eric Morrow, assistant professor of biology, geneticist, psychiatrist, and leader of this study. "This new sort of variant looks like it is important in a subset of autism." When asked about the significance of what they found, he explained, "Autism is a very broad, heterogeneous condition," Morrow said. "With genomics, we've begun to be able to dissect the heterogeneity into smaller groupings. We find an association between runs of homozygosity and those with co-occuring intellectual disability and autism, but not in so-called 'higher functioning' autism."
Morrow's findings suggests that autism and related intellectual disabilities occur as a result of a number of genetic changes, not just one part of the ROH being altered or one recessive gene being inherited. Similalry, when there are more changes to the ROH, autism and intellectual disability seem to worsen, suggesting that the amount of change certainly affects autism's severity, but it is not one single piece of genentic material deciding it.
Morrow and his colleagues are excited to continue their work and discussion of how autism is inherited. Finding a specific gene that decides someone's fate of having autism or not could be therapeutically useful in helping the children with autism now and in the future. Morrow hopes that his "refocus" on the ROH will allow more researchers to delve into what causes intellectual disabilities in children with autism.
Source: Gamsiz ED, Viscidi EW, Frederick AM, et al. Intellectual disability is associated with increased runs of homozygosity in simplex autism. American Journal of Human Genetics. 2013.