In a study of a cohort of 427 individuals with autism we identified that ~7% carried de novo CNVs, some of which encompassed megabase-sized genomic regions. In order to study the effect of these large de novo CNVs (~3-20 MB) on the expression levels of genes they encompass and also on global genes expression, we carefully selected 8 individuals with large de novo deletions. The criteria for selection included: 1) having de novo deletions confirmed by qPCR on blood DNA, 2) presence of functionally interesting genes and/or miRNAs at the CNV region, and 3) presence of ultra conserved elements with potential regulatory functions at the CNV region. Included in this study is an individual with ~2.8 Mb de novo deletion at chromosome 22q11.21 region. This genomic segment and the genes it harbours have been associated with Schizophrenia in a number of studies. Lymphoblstoid cell lines from the selected individuals and their available parents and siblings were cultured under controlled conditions in three biological replicates. RNA was extracted and run on Illumina gene and miRNA expression arrays. Statistic analysis of the data indicated approximately one-half reduction in gene expression of the majority of the expressed genes directly encompassed by the deletion. Moreover, several genes located distant to the deletions and on different chromosomes also showed significant variation in individuals carrying the deletions compared to their family members. For instance, in the individual with deletion of 22q11.21, genes involved in the TP53 network were found dysregulated as indicated by Ingenuity pathway analysis tool. The data is further being mined to evaluate/identify gene networks affected by these large CNV alterations.

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