Downregulation of genes outside the deleted region in individuals with 22q11.2 deletion syndrome

Abstract

The 22q11.2 deletion syndrome (22q11.2DS) is caused by recurrent hemizygous deletions of chromosome 22q11.2. The phenotype of the syndrome is complex and varies widely among individuals. Little is known about the role of the different genes located in 22q11.2, and we hypothesized that genetic risk factors lying elsewhere in the genome might contribute to the phenotype. Here, we present the whole-genome gene expression data of 11 patients with approximately 3 Mb deletions. Apart from the hemizygous genes mapped to the 22q11.2 region, the TUBA8 and GNAZ genes, neighboring the deleted interval but in normal copy number, showed altered expression. When genes mapped to other chromosomes were considered in the gene expression analysis, a genome-wide dysregulation was observed, with increased or decreased expression levels. The enriched pathways of these genes were related to immune response, a deficiency that is frequently observed in 22q11.2DS patients. We also used the hypothesis-free weighted gene co-expression network analysis (WGCNA), which revealed the co-expression gene network modules with clear connection to mechanisms associated with 22q11.2DS such as immune response and schizophrenia. These findings, combined with the traditional gene expression profile, can be used for the identification of potential pathways and genes not previously considered to be related to the 22q11.2 deletion syndrome.

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Acknowledgements

This work was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (Grant Nos. 2014/11572-8, 2014/26768-5).

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Dantas, A.G., Santoro, M.L., Nunes, N. et al. Downregulation of genes outside the deleted region in individuals with 22q11.2 deletion syndrome. Hum Genet 138, 93–103 (2019). https://doi.org/10.1007/s00439-018-01967-6

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