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

  • Anelisa Gollo Dantas
  • Marcos Leite Santoro
  • Natalia Nunes
  • Claudia Berlim de Mello
  • Larissa Salustiano Evangelista Pimenta
  • Vera Ayres Meloni
  • Diogo Cordeiro Queiroz Soares
  • Sintia Nogueira Belangero
  • Gianna Carvalheira
  • Chong Ae Kim
  • Maria Isabel MelaragnoEmail author
Original Investigation
  • 128 Downloads

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.

Notes

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).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

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© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Genetics DivisionUniversidade Federal de São PauloSão PauloBrazil
  2. 2.Interdisciplinary Laboratory of Clinical Neurosciences (LiNC), Psychiatry DepartmentUniversidade Federal de São PauloSão PauloBrazil
  3. 3.Psychobiology DepartmentUniversidade Federal de São PauloSão PauloBrazil
  4. 4.Genetics Department, Instituto da CriançaUniversidade de São PauloSão PauloBrazil

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