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

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art_DANTAS_Downregulation_of_genes_outside_the_deleted_region_in_2019.PDF (1.18 MB)
Citações na Scopus
6
Tipo de produção
article
Data de publicação
2019
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
SPRINGER
Autores
DANTAS, Anelisa Gollo
SANTORO, Marcos Leite
NUNES, Natalia
MELLO, Claudia Berlim de
MELONI, Vera Ayres
BELANGERO, Sintia Nogueira
CARVALHEIRA, Gianna
Citação
HUMAN GENETICS, v.138, n.1, p.93-103, 2019
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
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.
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URI
https://observatorio.fm.usp.br/handle/OPI/30885
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MPE
Artigos e Materiais de Revistas Científicas - LIM/03
Artigos e Materiais de Revistas Científicas - LIM/36
Artigos e Materiais de Revistas Científicas - ODS/03