CREA - Research and Clinical Center is a scientific research  and cultural-scientifc evolution project for Fondazione San Sebastiano of the Misericordia di Firenze.

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A group of researchers at Cold Spring Harbor Laboratory (CSHL), directed by Johnathan Sebat, have discovered that a mutation of chromosome 16, already linked with autism, is responsible for a sharp increase in the risk of developing schizophrenia.
In the past an increased risk of schizophrenia was linked to some deletions on chromosomes 1, 15 and 22. This time, the mutation in question is a variation of the copy number (CNV) in the region identified as 16p11.2.
The sequencing of human DNA has shown that about 5% consists of segmental duplications, from repetitions of sections of variable length of the genome. In some individuals the number of these repetitions can vary significantly from the average population.
The mutation identified by Sabat and colleagues is quite rare and seems to be associated with the increased risk of developing schizophrenia by more than eight times that that of people with standard gene sequences.
“This is not the first time that region 16p11.2 has caught our attention”, said Sebat. In a 2007 study conducted by Sebat and Michael Wigler, in CSHL, a deletion was noted in the same region in a girl affected with autism, an association has also been confirmed by other studies that have documented a higher risk of autism related to the loss of one copy of 16p11.2.
These studies suggest that some genes in this area of the chromosome can influence schizophrenia and autism. “In a certain sense we can consider the two disorders as opposite ends of the same neurobiological process” ,adds Shane McCarthy, the author of several important works on the subject.
A hypothesis is that the loss of 16p11.2 leads to deprivation of key genes in the development of the brain, especially rational, while an extra copy would produce effects of dysregulation.
In other studies, prior to the deletion of a neighboring area of the short arm of chromosome 16, the p12.1, proved to be an independent risk factor for the development of intellectual disability.
In individuals with intellectual disabilities, the prevalence of schizophrenia is 3-4 times higher than that of the general population and many studies suggest that this comorbidity is in continuity with the tendency of schizophrenia to determine cognitive disorders. About 70% of people with intellectual disorders have autism.
The high presence of cognitive impairment, schizophrenia and autism, and the underlying phenotypic variability reported for various recurrent microdeletions can be explained by a multifactorial model, which also includes an environmental conditioning on the structure of the gene.


- Girirajan S, Rosenfeld JA, Cooper GM, et al. A recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delay. Nature genetics, 2010 Mar;42(3):203-9.
- Turner TH. Schizophrenia and mental handicap: an historical review, with implications for further research. Psychological medicine, 1989;19:301-14.
- Sanderson TL, Best JJ, Doody GA, Owens DG, Johnstone EC. Neuroanatomy of comorbid schizophrenia and learning disability: a controlled study. Lancet, 1999;354:1867-71.
- Woodberry KA, Giuliano AJ, Seidman LJ. Premorbid IQ in schizophrenia: a meta-analytic review. American journal of Psychiatry, 2008;165:579-87.
- Stefansson H, et al. Large recurrent microdeletions associated with schizophrenia. Nature, 2008;455:232-6.

To quote this article:
Bertelli M.O. Autismo, schizofrenia e disabilità intellettiva: un crocevia al braccio corto del cromosoma 16. CREA Website, Dic 2010; (visit date of the quoting person).

Marco O. Bertelli