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Identifying Copy Number Variations (CNVs) and Epigenetic Changes in Patients with Stroke

Grant number: 13/24932-0
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): April 01, 2014
Effective date (End): January 31, 2016
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Iscia Teresinha Lopes Cendes
Grantee:Amanda Donatti
Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:13/07559-3 - BRAINN - The Brazilian Institute of Neuroscience and Neurotechnology, AP.CEPID


Stroke is an heterogeneous multifactorial disease, responsible for disturbance in blood supply to the brain. This disease can be classified in two groups: hemorrhagic and ischemic. Studies in twins and families have demonstrated the presence of genetic factors at stroke. Two larges studies of metanalysis have shown 19 associated genes to stroke, but functional variants have not being identified at 8 of those candidates genes (HDAC9, CDKN2B-AS1, PDE4D, PITX2, ZFHX3, ANGPT1, AGTRL1 e ALOX5AP). At in vivo experiments, some methylation patterns at DNA were observed and can act on stroke development or modifying the proteins involved on this process. Those methylations can be responsible for increase the stroke risk. Hemorrhagic stroke studies are demonstrating intense genetic influence on occurrence and recovery. Due to this type low frequency on population and increased death rate, the genetic studies of hemorrhagic stroke are less frequent. Copy number variantion (CNVs) are one of the most common types of mutation occurring in the human genome and they have being shown to cause significant changes in gene expression due to variation in the number of gene copies present or disruption in gene(s) sequences. Investigations are describing a relation among some genes and CNVs on patients with ischemic and hemorrhagic stroke. The purposes of this study are: identifying epigenetic variants on promoter region of candidate genes in patients with ischemic stroke; and identifying CNVs in patients with hemorrhagic stroke. We will use DNA samples of patients and control individuals provided from Joinville/SC. Through EMBOSS CpGPlot and MethPrimer software analysis, only three candidate genes to ischemic stroke (ANGPT1, CDKN2B-AS1 e HDAC9) had regions with potential methylation. The promoter of those genes will be analyzed by the methylation-specific PCR (MS-PCR). To analyze CNVs in patients with hemorrhagic stroke, there were realized microarray chips based on SNPs (Genome-WideHuman SNP Array 6.0; Affymetrix Inc.) and the results were analyzed on Genotyping Console® software (Affymetrix Inc.). Until this moment, we analyzed 35 patients with HS, as well as 31 controls (individuals without stroke). Regions with genomic loss and gain were identified. The main genes found at this analysis are: ANXA8, CYP2E1, DEFB4B, DEFB103B, HGSNAT, NOMO1, PRODH e ZNF92. Thoses genes are related to anticoagulation, thrombosis, edema and blood pressure regulation. Additional analysis are need to better understand the CNVs influences and the genes potentially envolved with the stroke mechanisms.

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Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
DONATTI, Amanda. Identification of structural variants (CNVs) and epigenetic changes in patients with stroke. 2016. Master's Dissertation - Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas Campinas, SP.

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