Using the Autism Speaks Autism Genetic Resource Exchange (AGRE), researchers from the Boston-based Autism Consortium reported in the January 9 issue of the New England Journal of Medicine that a submicroscopic deletion or duplication on chromosome 16 is strongly associated with autism spectrum disorders (ASD).
Individuals with this genetic variation experience a hundredfold risk of developing autism in contrast to those without it. The involved region of chromosome 16 contains 25 genes. Since some of these genes are involved in communication between neurons, they appear to be promising autism susceptibility genes. To understand how these genes potentially contribute to an autism phenotype would require further research, but this discovery could be very significant as we move toward creating better treatments and diagnostics.
A research team lead by Dr. Mark Daly at the Broad Institute in Boston identified a recurrent de novo deletion or duplication on chromosome 16 in approximately 1% of the multiplex families obtained from AGRE. These findings were also observed independently in approximately 1% of subjects in two samples of children; one from the Children's Hospital Boston and the other from a research group at deCODE Genetics in Iceland.
Submicroscopic deletions and duplications or copy number variations (CNVs) have attracted increasing attention from autism geneticists over the past few years. Advances in genomic technologies have only recently allowed researchers to identify CNVs that were previously undetectable. Recently, Dr. Jonathan Sebat and his colleagues at Cold Spring Harbor Laboratory have found many CNVs in the genome of individuals with autism. Since some of these CNVs are found only in affected individuals but not in their parents or the general population, they represent de novo, or non-inherited genetic mutations that may contribute to autism susceptibility.
"It's just one piece of the puzzle," said Daly, "but one which we hope uncovers an underlying biological mechanism which may be relevant to many other families."
The general significance of the report is further underscored by a related study led by Dr. Stephen Scherer of The Hospital for Sick Children in Toronto to be published next week that reports similar results of changes on chromosome 16 in 1% of Canadian families affected by autism. In addition, a similar finding was recently described by Dr. Susan Christian and colleagues at the University of Chicago in a smaller study also using AGRE samples.
The convergence of results from these independent studies raises the possibility of gene-based autism diagnosis. By screening for chromosome 16 deletions, duplications and other robust de novo mutations, scientists may develop DNA diagnostic tests that could enable biological diagnosis for this subgroup of the population. Such tests could lead to early and perhaps targeted intervention that promises better prognosis and improved quality of life.