Genetics

Pinpointing the genes for autism and schizophrenia

Among the 25,000 genes that make up the human genome, which ones carry the blueprint for autism and schizophrenia? This is the question that Guy Rouleau and his team will attempt to answer. They have just received $17.8 million for this major four-year project involving some 20 researchers as well as the regular staff at his Université de Montréal laboratory. When the project is completed, five to 10 genes should be identified for each disease.

This is not a run-of-the-mill project for Dr. Rouleau — a leading geneticist who has been behind several major discoveries over the last 15 years, such as the gene for type 2 neurofibromatosis; the first and second genes of amyotrophic lateral sclerosis; a dozen genes responsible for hereditary diseases, including several major diseases in Quebec. The reality is that searching for genetic predispositions to brain diseases is bold and fraught with obstacles. But the Université de Montréal researcher has an approach all his own. “We will study all of the genes associated with the development of synapses in order to identify those that come into play in these diseases. This is a major departure from traditional methods that consist of targeting a small number of potentially active genes,” explains Dr. Rouleau.

Certain conditions, however, must co-exist in order to embark on this path. First, thanks to the work of British researcher Seth Grant, Dr. Rouleau has a list of 1024 genes from the human genome linked to the development and functioning of synapses which are the connections between two neurons that enable the transmission of nerve signals. “Our research will focus on this because I’m convinced that these diseases involve a breakdown of synapses,” explains Dr. Rouleau.

The sequencing of isolated genes among the 288 research subjects from four continents (144 with severe autism and the other half with schizophrenia) will enable the precious genes to be identified. Each gene can contain 4000 to 10,000 base pairs, that is, more than three billion adenine, cytosine, guanine and thymine (ACGT) pairs that will scroll through the CHUM’s computers. Less than a hundred genes should make it past this step, and will serve as the basis for experiments on animal models. If all goes well, Dr. Rouleau will identify several genetic mutations responsible for these two diseases, which would be a first worldwide.

Autism and schizophrenia are not genetic diseases in the traditional sense of the term, explains Dr. Rouleau in his office at Notre Dame Hospital. Although it is known that the immediate environment (family, physical and social, education) is a factor in the development of these diseases, the role of heredity is accepted today. “The genetic component of some severe forms of disease is certain. And we know that several genes are involved. Once we’ve identified them, the social and commercial applications could be very interesting,” explains Dr. Rouleau.

By developing drugs better adapted to each patient’s profile, the pharmaceutical industry could benefit from the scientific knowledge generated by Dr. Rouleau’s research. Basic research will be the big winner. “At the moment, teams are targeting a limited number of genes before testing them, whereas we want to sequence as many genes as possible. This method of investigation is extremely expensive, which is why it is so rare. But in 10 or 20 years, it will be widely used,” predicts Dr. Rouleau.