Three independent research groups have identified a large genetic deletion that causes mental retardation. "They've broken open a bubble of something that's going to lead to a lot of follow up," comments William Dobyns, a developmental neurogeneticist at the University of Chicago, who was not affiliated with any of the studies.
Mental retardation comes in a baffling diversity of conditions and could be caused by hundreds of underlying genetic triggers, only a few of which have been identified. One glimmer of hope is the advent of detailed scans of individuals' genomes, which are powerful tools in the search for mutations. However, they yield a deluge of data. Focusing in, researchers in the Netherlands, the United Kingdom, and at the University of Washington (UW) in Seattle decided to take aim at "hot spots" on the genome. These regions are flanked by duplicated genetic sequences prone to rearrangement, which can lead to the accidental loss of genes.
Each team examined a different population of people, ranging in size from 50 to 1200, with various kinds of mental retardation. They found that a small number were missing the same six genes on chromosome 17. Two of these genes, when deleted, are thought to be involved with mental retardation. The data suggest that the deletion could be involved in about 1% of all cases of mental retardation, the researchers report online 13 August in a trio of papers in Nature Genetics.
All three teams found these deletions in children, so they decided to check their parents' genomes. The region turned out to be inverted in all the parents. This suggests that the children of parents with inversions are predisposed to the deletion, says Evan Eichler, a human geneticist who led the UW effort.
Although other studies suggest that one out of every five Caucasians of European ancestry may have this inversion, just how many will have children with the deletion is unknown. One problem is the small size of the studies, Eichler notes. To learn more about the deleted genes and their function, scientists need to study more people with the genomic deletion, he says, which is something his team is addressing now.