Medical DevicesFurther Gene Mutations Linked To Autism Risk
Pieces in the complex autism inheritance puzzle are emerging in the latest study from a research team including geneticists from the University of
Pennsylvania School of Medicine and The Children"s Hospital of Philadelphia (CHOP). The study identified 27 different genetic regions where rare
copy number variations - missing or extra copies of DNA segments - were found in the genes of children with autism spectrum disorders, but not in
the healthy controls. The findings are published June 26 in the open-access journal PLoS Genetics.
Autism spectrum disorders (ASDs) are common neurodevelopmental syndromes with a strong genetic component. ASDs are characterized by disturbances in
social behavior, impaired verbal and nonverbal communication, repetitive behaviors and/or a restricted range of interests. The genetics underlying
ASDs is complex and remains poorly understood.
The researchers compared genetic samples of 3,832 individuals from 912 families with multiple autistic children against genetic samples of 1,070
disease-free children. Besides the identification of 27 regions harboring rare variants in children with ASDs, the study also uncovered two novel
genes where variations were found, BZRAP1 and MDGA2 - thought to be important in synaptic function and neurological development, respectively.
Interestingly, key variants on these genes were passed down in some, but not all, of the affected individuals in families.
"We focused on changes in the exons of DNA-protein-coding areas in which deletions or duplications are more likely to directly disrupt biological
functions," said study leader Hakon Hakonarson. "We identified additional autism susceptibility genes, many of which belong to the neuronal cell
adhesion molecule family involved in the development of brain circuitry in early childhood." He added that the team discovered many "private"
gene mutations, those found only in one or a few individuals or families-an indication of genetic complexity, in which many different gene changes
may contribute to an autism spectrum disorder.
Hakonarson and co-author Maja Bucan said the latest findings reinforce the view that multiple gene variants, both common and rare, may be interacting
to cause the heterogeneous group of disorders included under autism spectrum disorders. "We are finding that both inherited and new, or de novo,
genetic mutations are scattered throughout the genome, and it is becoming clear that different combinations of these variations contribute to autism
susceptibility," said Bucan.
The Autism Genetic Re Exchange (AGRE), a program of Autism Speaks, provided genetic biomaterials and clinical data from families that have more
than one family member diagnosed with an Autism Spectrum Disorder. Blood samples donated by children and their families at CHOP were used as healthy
controls. AGRE makes data publicly available to qualified researchers worldwide.
CITATION:
"Genome- Wide Analyses of Exonic Copy Number Variants in a Family-Based
Study Point to Novel Autism Susceptibility Genes."
Bucan M, Abrahams BS, Wang K, Glessner JT, Herman EI, et al. (2009)
PLoS Genet 5(6): e1000536. doi:10.1371/journal.pgen.1000536
Public Library of Science
USA