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

Author(s):Show less -

Dantas, Anelisa Gollo ^[1] ; Santoro, Marcos Leite ^[2] ; Nunes, Natalia ^[1] ; de Mello, Claudia Berlim ^[3] ; Evangelista Pimenta, Larissa Salustiano ^[4] ; Meloni, Vera Ayres ^[1] ; Queiroz Soares, Diogo Cordeiro ^[4] ; Belangero, Sintia Nogueira ^{[2, 1]} ; Carvalheira, Gianna ^[1] ; Kim, Chong Ae ^[4] ; Melaragno, Maria Isabel ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Div Genet, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Dept Psychiat, Interdisciplinary Lab Clin Neurosci LINC, Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Dept Psychobiol, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Inst Crianca, Dept Genet, Sao Paulo - Brazil

• Document type: Journal article
• Source: Human Genetics; v. 138, n. 1, p. 93-103, JAN 2019.
• Web of Science Citations: 0

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 3Mb 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. (AU)

• FAPESP's process: 14/11572-8 - Chromosomal rearrangements and their relevance in the etiology of genetic disorders: cytogenomic and molecular investigation
• Grantee: Maria Isabel de Souza Aranha Melaragno
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/26768-5 - Investigation of patients with 22q11.2 deletion syndrome: Gene expression profile and evaluation of regulatory elements.
• Grantee: Anelisa Gollo Dantas
• Support Opportunities: Scholarships in Brazil - Doctorate