Validation phase of copy number variants (CNVs) associated with major mental disorder identified in families in the north of Mallorca in order to demonstrate their pathogenicity and their potential founding effect

Abstract

[eng] Psychotic major mental disorders – schizophrenia, bipolar disorder and schizoaffective disorder – are heritable diseases caused by a complex interplay between genetic and environmental factors and have a pathology consisting, from a genetic point of view, of the combined effect of common and rare variants. In this work, we have checked previously identified rare copy number variants (CNVs), Insertions and Deletions (INDELS) and single nucleotide variants (SNVs) in new recruited patients from the same geographical regions of the two originally previous studied families with high prevalence (Family 1 and Family 2) in order to replicate results that allow us to demonstrate their pathogenicity and to prove founder effects. SNVs and INDELS genotyping were performed by PCR amplification of DNA extracted from peripheral blood, followed by DNA electrophoresis, PCR purification and Sanger sequencing. CNVs were analyzed by droplet digital PCR. As our results show evidence of the presence of the genotyped CNVs in subjects from the same geographical regions as the previous studied families, we conclude that these CNVs are pathogenic and that they have originated a founder effect.