Genetics of Intellectual Disabilities

The 16p11.2 region encompasses several distinct genomic structural variants in human. The recurrent deletion of a ~600kb region containing 29 genes has a prevalence of 1/2000, and reaches 0.5% in autism spectrum disorders (ASD). It was also linked to macrocephaly and predisposes to morbid obesity. In contrast, the reciprocal duplication, with a similar frequency, was associated with schizophrenia, microcephaly and a high risk of being underweight. Modeling in Zebrafish, human cells and mice will give us a better insight on the functional causes of these mirror phenotypes.