Providing a cure for autism is always on the forefront of our minds. Why then do we pursue genetics, which at first blush seems so remote from treatment? The answer is that uncovering the genetic predispositions to autism can be one of the quickest ways to reveal those pathways that are altered and in need of treatment.
Genes are pieces of DNA that contain the instructions for making proteins. Proteins carry out various specialized functions that are required for the human body to work. To do this, individual proteins interact with each other in complex networks to form biochemical pathways that serve specific needs.
In order to logically treat and cure autism, we need to know what biological pathways are disrupted in affected individuals. Studying genes can give us this information. Decades of research have taught us that variations in gene sequences can create variations in proteins, some of which may function better than others. Because researchers know how to read the sequences of genes, pinpointing one that is strongly linked to autism would immediately reveal a protein whose function must play a role in the development of autism. And again, because researchers have studied the functions of protein pathways for decades, they can leverage existing knowledge to jump to an understanding of which biological pathways are weakened in individuals with autism.
Thus, establishing the genes linked to autism produces the knowledge of what autism involves, biologically-speaking. This points us to the areas that require targeted interventions-- knowledge that is currently lacking. It is with this in mind that Cure Autism Now has funded a Genomics Initiative award to a team of geneticists from UCLA, so they can immediately pursue one of the current best leads in autism genetics.
The search for autism genes has not been as easy as predicted, based on the high rate of heritability of the disorder. This is due to considerable heterogeneity, both in the actual clinical syndrome (the huge variability in symptoms), and at the genetic level (many different genes contribute, and their contributions may be to provide susceptibility to a variety of environmental factors rather than direct causation). One approach to expedite gene identification involves separating autism into more homogeneous subtypes based upon clinical features, so called “endophenotypes.” Endophenotypes are components of a disorder -- such as brain structure, language characteristics, or social behavior -- that are more specific than the general category of “autism,” and thus allow more precise study of the disorder.
UCLA team narrows search for autism genes.
A team of scientists from UCLA, led by Dan Geschwind, M.D., Ph.D, Stan Nelson, Ph.D., and Rita Cantor, Ph.D., has been working to identify autism genes by dividing subjects into subsets using a variety of autism related endophenotypes, including language characteristics, social behavior and gender. The work on gender has been driven by the observation that males are affected 4 times more frequently than females. The researchers reasoned that this might mean that males have different genetic risk factors than females. In a series of published papers using the AGRE collection, they have identified and confirmed a locus on chromosome 17q that contributes to autism in families where autism occurs primarily in males. Since this is the first confirmed autism locus discovered through a whole genome scan, it offers a unique and exciting opportunity to identify a gene that contributes to the risk of developing autism. This new study was so important that Discover magazine has ranked it as one of the overall top 100 scientific findings in 2005!
The Genomics Initiative award from Cure Autism Now will allow these researchers to finely comb through the Chromosome 17q genomic region to determine if any of the approximately 100 genes in the area may be responsible for autism susceptibility. Within the next several months, the UCLA group will test every gene within the chromosomal region, narrowing the hunt to a few genes. This will be accomplished using the most cost effective and efficient methodology currently available for this size project, the Illumina Bead Array System, testing nearly 3 million genetic variants in male-containing families in AGRE. If gene(s) are identified, we will have an improved sense of what altered protein or pathway contributes to the development of autism. As explained above, this knowledge could then provide the basis for clearly targeted treatments and the possibility of definitive diagnostic tests.
It should be noted that this study was made possible by the large number of new families in the AGRE database. Without their participation we would not be poised for this next big step. Although there can never be guarantees in biology, taking the chance to allow this genetic study to progress to the next stage is what Cure Autism Now is all about –accelerating mechanisms that can lead to interventions for individuals affected with autism, as soon as possible.