The cover of the July 11 edition of Science magazine highlights research on a complex and increasingly prevalent disease autism. Assistant Professor of Biology Russell Ferland is coauthor of the study that offers some exciting new clues about the elusive origins of the disease.
The research team uncovered small deletions in the genomes of children with autism that are strongly correlated to brain function. Isolating these missing sections of DNA could help researchers narrow down the search for the genetic causes of the disorder.
“If you examine the brain of a person with autism and compare it to the brain of a person without autism, they look virtually identical,” Ferland said. “This suggests there is a molecular process or mechanism in the neurons of the brain that is abnormal that then alters the larger brain network.”
In their paper, the researchers provide evidence for this cellular hypothesis. The research team uncovered small deletions in the genomes of children with autism that are strongly correlated to brain function. According to the researchers, these missing pieces of DNA may contribute to abnormal brain function in people with autism. Isolating these missing sections of DNA could help researchers narrow down the search for the genetic causes of the disorder.
“With these findings, we are beginning to build up the number of genes that might be involved and we may be able to start to wrap our heads around this complex disorder,” Ferland said.
To discover the patients’ missing genes, the researchers started with a population mapping method known as homozygosity mapping. Homozygosity occurs when both parents pass on a specific gene sequence to their child, which results in the child having two identical copies of the sequence. In some cases, the sequence being passed on by each parent is a deletion.
In their study of children with autism and their unaffected siblings and parents, the researchers discovered that on a specific region of both of the parents’ DNA only one half of the normal genetic information was encoded. Because half of the genetic material is present in each of the parents, the parents still have normally functioning cells. If only one copy of the two genomic regions is passed on to a child, this child will also be unaffected. But when this identical deleted portion of their parent’s DNA is passed down to a child in a homozygous fashion, the child will have neither half and is missing the entire region of this part of his or her genetic code. Such homozygous deletions were found in the autistic children of these parents.
Based on these results, the researchers hypothesize that the inherited missing pieces in their study’s subjects may be a part of the underlying cause of their autism.
Finding parents with such similar DNA sequences can be difficult, so to narrow down the search, the researchers used data from parents who share a common, close ancestor. This greatly increases the chances that these parents have inherited many of the same genetic sequences, including the same genetic deletions.
Once the deletions were found, the researchers worked to link them to specific genes. Genes are encoded by various segments of our DNA. When an entire segment of the DNA is missing, as is the case with many of the children with autism studied, the molecular instructions to encode certain genes are missing and those genes are not expressed in the individual. The researchers hypothesized that the missing genes in the children with autism could be related to the outward symptoms of their disease and indeed their findings support this idea.
The researchers discovered that some of the genes likely missing in the children with autism are related to neural or brain activity. According to Ferland, a lack of these genes could possibly lead to abnormal brain functions, a hallmark of autism.
Ferland is hopeful that researchers are getting closer to pinpointing the causes of the disorder. “The findings are beginning to suggest that the genes critical for controlling neural activity and plasticity, at the molecular level in the cell, could be important in autism,” he said.
The research team has been working on this study for nearly a decade. The first author of the paper was Eric Morrow and the corresponding author was Christopher Walsh, both of Harvard Medical School.
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