Autism And Other Disorders May Be Caused By Genetic Hotspot Mutations
December 21, 2012

Genetic Mutations Lead To Autism And Other Disorders

[ Watch the Video: Mutation Hotspots in Autism Genes ]

Connie K. Ho for — Your Universe Online

A group of international researchers led by a team of investigators from the School of Medicine at the University of California, San Diego (UCSD), recently revealed a new study that provides signals as to the causes of autism and other related disorders. With the findings, it is possible that there are elevated mutation rates in specific parts of the genome that adds to the disease risk in humans.

In particular, the research centered on how genes associated with autism and other human diseases run the risk of having frequent mutations.

"Some disease-related genes are gluttons for punishment," explained the study´s senior author Jonathan Sebat, a professor of psychiatry and cellular and molecule medicine at UCSD, in a prepared statement. "Despite the fact that these genes are important for normal human development, they appear to be getting hammered with mutations."

In the past, neurodevelopment disorders, such as autism, have been linked to deletions or duplicates of DNA in specific areas of the genome that have a likelihood of mutating at a higher rate. However, up until now, it wasn´t known if the autism genes had many mutations and if autism was the result of “hotspots of nucleotide substitutions.” The scientists decided to investigate this issue and completed a whole-genome sequence of identical twins that were diagnosed with autism spectrum disorder and completed the same analysis on their parents.

When they compared the genomes of the twin and the parents, the researchers discovered nucleotide substitutions in different parts of the genome and saw that mutation rates could range as much as 100 times in the genome. They believe that the multitude of rates could be due to the intrinsic qualities of genetic material, including the characteristics on how the DNA is packed and facets of the DNA sequence. Genes that were related to autism had a higher chance of undergoing mutation than the average gene, demonstrating some of the reason behind the mutation “hotspots” in autism.

"This is truly the first chance anyone has had to explore the landscape of mutability in humans because an unbiased look at patterns of mutation in the genome was impossible before the development of high-throughput sequencing technologies," continued Sebat, who also serves as the chief of the Beyster Center for Molecular Genomics of Neuropsychiatric Diseases at UCSD, in the statement.

In addition, an average of 60 mutations was found in each child.

"The total number of mutations that we found was not surprising," remarked Sebat in the statement. "It's exactly what we would expect based on the normal human mutation rate."

The scientists also found it interesting that the mutations clustered in certain areas of the genome, with some regions more “hot” while others were cold.

"Mutability could be explained by intrinsic properties of the genome," commented the study´s´ lead author Jacob Michaelson, a postdoctoral researcher at UCSD, in the statement. "We could accurately predict the mutation rate of a gene based on the local DNA sequence and its chromatin structure, meaning the way that the DNA is packaged."

The team of investigators believe that the “hotspots” are not special to the autism genome, but are a central factor to the human genome.

"Our findings provide some insights into the underlying basis of autism–that, surprisingly, the genome is not shy about tinkering with its important genes," noted Sebat in the statement. "To the contrary, disease-causing genes tend to be hypermutable."

Moving forward, the researchers plan to continue this trend for other disease genes.

"We plan to focus on these mutation hotspots in our future studies," concluded Sebat in the statement. "Sequencing these regions in larger numbers of patients could enable us to identify more of the genetic risk factors for autism."

The results of the study were recently published in the journal Cell.