Investigating the effects of chromosome 22q11.2 deletions
Maria Karayiorgou, M.D., Ph.D.
One copy of 22q11.2, a segment of chromosome 22 that includes several genes, is missing in 1 of every 4,000 individuals. This non-inherited genetic abnormality results in some physical abnormalities, most of which can be repaired surgically early in life. But the most pernicious deficits associated with this microdeletion are cognitive, including severe learning disabilities and a high risk for mental illness, such as autism and schizophrenia. An improved understanding of the mechanisms that contribute to these psychiatric and cognitive symptoms is essential for providing better treatments.
By taking a simple skin biopsy, Maria Karayiorgou and her colleagues at Columbia University produced human induced pluripotent stem (iPS) cells via direct reprogramming of these skin cells. This provides a robust approach, which promises to be a facile source of patient-derived cell lines.
Karayiorgou and her group obtained and derived iPS cell lines from individuals carrying 22q11.2 microdeletions who have mental illness, as well as from their healthy siblings who do not carry the microdeletion. They differentiated these cells into forebrain neurons in order to study the possible mechanisms underlying the disease in human tissue. The researchers found deficits in neuronal development, which they characterized in detail. By using human-derived neurons from individuals suffering from 22q11.2-linked cognitive deficits, their findings illuminate the underlying mechanisms reliably and provide an excellent vehicle for testing potential therapies for autism and schizophrenia.