A transcriptome meta-analysis of ethanol embryonic exposure: Implications in neurodevelopment and neuroinflammatory genes - 22/07/22

Doi : 10.1016/j.neuri.2022.100094 
Vinícius Oliveira Lord a, b, 1, Giovanna Câmara Giudicelli a, c, 1, Mariana Recamonde-Mendoza d, e, Fernanda Sales Luiz Vianna a, c, f, g, Thayne Woycinck Kowalski a, b, c, e, f,
a Laboratory of Genomic Medicine, Center of Experimental Research, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil 
b Centro Universitário CESUCA, Cachoeirinha, Brazil 
c Post-Graduation Program in Genetics and Molecular Biology, Genetics Department, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil 
d Institute of Informatics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil 
e Bioinformatics Core, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil 
f National Institute of Medical Population Genetics (INAGEMP), Porto Alegre, Brazil 
g Post-Graduation Program in Medical Sciences, Medical College, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil 

Corresponding author at: (current address) Laboratory of Genomic Medicine, Center of Experimental Research, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.Laboratory of Genomic MedicineCenter of Experimental ResearchHospital de Clínicas de Porto Alegre (HCPA)Porto AlegreBrazil

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Abstract

Fetal Alcohol Spectrum Disorder (FASD) comprises the phenotypes induced by prenatal alcohol exposure. Understanding the molecular mechanisms of FASD is needed since it is a public health problem. This study aimed to evaluate the impact of ethanol in the differential gene expression (DGE) of embryonic cells and fetal tissues by performing a transcriptome meta-analysis in microarrays datasets publicly available. The datasets were obtained in the GEO database and DGE was evaluated, followed by meta-analysis. DGE was also analyzed in a RNA-Seq dataset, although it was not included in the meta-analysis. To filter the main candidate genes, a database and literature review was performed, followed by ontologies enrichment analyses. In the meta-analysis, 1,938 genes were deregulated and 487 were perturbed in the RNA-Seq. Calcium homeostasis and neuroinflammation genes were overrepresented in the meta-analysis and RNA-Seq, respectively. After the database and literature review, DOCK8, FOXG1, IL1RN, and PRKN genes were proposed as new candidates for FASD; they are associated with neurodevelopment and neuroinflammation. BDNF and SLC2A1, previously associated to FASD, were also suggested in meta-analysis as candidate genes. It is known neuroinflammation reduction might help to minimize the alcohol damage. Hence, there is an urgent need to understand FASD molecular mechanisms to help in strategies aimed at preventing ethanol-induced neurologic damage.

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Highlights

Fetal Alcohol Spectrum Disorder (FASD) is a public-health problem with an urgent need to understand its molecular mechanisms.
We performed a transcriptome meta-analysis to identify potential genes related to ethanol-induced neurological damage.
DOCK8, FOXG1, IL1RN, and PRKN genes are proposed as new candidates for FASD, being associated with neurophenotypes.
BDNF and SLC2A1, previously associated to FASD, were also suggested in the transcriptome meta-analysis.

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Abbreviations : CTD, DGE, FASD, FAS, FDR, GEO, PCA, ReGEO, REM, RMA, ROS

Keywords : Prenatal ethanol exposure, Fetal alcohol spectrum disorder, Differential gene expression, Neurophenotypes, Random effect model, Microarray, RNA-Seq, Ontology, Bioinformatics


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Vol 2 - N° 3

Article 100094- septembre 2022 Retour au numéro
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