Recessive genes for autism and mental retardation
Christopher Walsh, M.D., Ph.D.
Children's Hospital Boston
The many mutations that underlie autism have different impacts on neuronal development and activity, making the genetics of the disorder a complicated puzzle. Some mutations can be so disruptive that a single copy is directly linked to a greater risk of developing autism, whereas other mutations may be recessive
— meaning that the disorder only occurs in individuals who have two copies of the mutated gene, one from each parent. This type of heritability is more difficult to trace, as the mutations are often rare, and the parents do not show symptoms.
Christopher Walsh and his colleagues at Harvard University propose to find these elusive recessive mutations in regions of the world where marriage between blood relatives — such as cousins — is common. Rare recessive mutations are often shared by many members of a family, and families in more isolated regions share other genetic similarities that boost the researchers’ chances of mapping rare disease-linked mutations.
Walsh and his colleagues are collaborating with doctors in Middle Eastern countries to identify families that have multiple individuals with autism. The researchers have enrolled more than 150 families in Kuwait, Oman, Pakistan, Turkey and Saudi Arabia. They have traveled to distant towns and villages to evaluate children for autism using standard tests, and then collected DNA samples from the children and their parents to identify autism-linked genes.
In addition to using traditional genetic methods, the researchers are also capitalizing on advances in genome sequencing, including methods that sequence whole genomes and whole exomes — the protein-encoding regions of the genome — to detect mutations that traditional techniques may not uncover.
The first report from this study, published in Science in 2008, identified several new autism-linked mutations. Analysis of these genes suggests that some of the mutations may have a common mechanism in disrupting changes in the synapse, the junction between neurons, after neuronal activity.