Research Project

Summary

Autism, a severe neurodevelopmental disorder affecting thousands of Canadians, is characterized by impairments in social communication and a preference for repetitive activities. Although a strong genetic basis seems to underlie the condition, the causes remain unknown. According to project leader Dr. Stephen Scherer, senior scientist in the Department of Genetics and Genomic Biology at SickKids, characterizing the human genome should aid in the search for autism-susceptibility genes and the mechanisms governing their action.

This unprecedented initiative brings together many leading clinicians, geneticists, and genome scientists undertaking autism research in Canada and involves 170 scientists from 10 other countries. 

This project will screen the genomes from over 6000 members of 1600 families to locate susceptibility genes on the chromosomes. Researchers will then use advanced genomic methods to assess the DNA in these chromosome regions in order to identify disease-associated genes.

This project will incorporate genetic information about autism into healthcare delivery and policy development and eventually lead to new and more accurate diagnostic tests.

This project includes integrated GE³LS research on the communication of genomics research results to research participants. For more information, click here.

Significant Outcomes to Date

• The project has developed the Autism Chromosome Rearrangement Database, which houses breakpoint data from all published sources as well as unpublished data generated in the laboratory.  A Genome Browser track is also included, which allows for the visualization of Copy Number Variants (CNVs) identified as part of Marshall et al’s 2008 publication in the American Journal of Human Genetics (see full citation below).
• The project has developed software, entitled SAFIRE2 (Software for Autism Formulation, Integrative Reports and Electronic Export), for the real-time scoring of the Autism Diagnostic Interview (ADI) and Autism Diagnostic Observation Schedule (ADOS) assessment tools.
• The project has identified a CNV at chromosome 16p11.2 that is associated with autism. The 16p11.2 microdeletion is highly-penetrant with a phenotypic spectrum that includes autism spectrum disorder (ASD), mental retardation/developmental delay and possibly other primary psychiatric disorders.
• In Pinto et al’s 2010 publication in Nature (see full citation below), the project provided evidence for the involvement of multiple genic rare CNVs both genome-wide and at specific loci inASD. The group was the first to report that individuals with ASD carry a greater burden of rare CNVs affecting genes across their genome. Their evidence indicates that rare CNVs account for a proportion of the heritability in ASD.

Notable Publications

Pinto D, et al. 2010. Functional impact of global rare copy number variation in autism spectrum disorders. Nature. [Epub ahead of print]. 

Cook EH Jr, Scherer SW. 2008. Copy-number variations associated with neuropsychiatric conditions. Nature 455(7215):919-23.

Liu XQ, et al.  Autism Genome Project Consortium. 2008. Genome-wide linkage analyses of quantitative and categorical autism subphenotypes. Biol Psychiatry 64(7):561-70.

Marshall CR, et al. Structural variation of chromosomes in autism spectrum disorder. Am J Hum Genet 82(2):477-88.

Autism Genome Consortium.  2007.  Mapping autism risk loci using genetic linkage and chromosomal rearrangements.  Nature Genetics 39(3): 319-28.

Moessner R, et al. Contribution of SHANK3 mutations to autism spectrum disorder.  Am J Hum Genet 81(6): 1289.

Dr. Scherer and his team at SickKids, as well as international scientists, have uncovered key changes in DNA in individuals with autism. The Phase 2 results of the multinational Autism Genome Project Consortium published in the June 9 advance online edition of Nature, substantiate the importance of genes as susceptibility factors in autism spectrum disorders.

To find out more, watch the below video.