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| Author(s): |
Gabriel do Nascimento Santos
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Biociências (IBIOC/SB) |
| Defense date: | 2024-08-16 |
| Examining board members: |
Michel Satya Naslavsky;
Gerson Shigeru Kobayashi;
Renata Elaine Paraizo Leite
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| Advisor: | Michel Satya Naslavsky; Luciana Amaral Haddad |
| Abstract | |
The APOE gene has been identified as the main risk factor for the late manifestation of Alzheimer\'s disease (AD) and has three functional common alleles, ε 2, ε 3 and ε 4, defined by two non-synonymous substitutions. The presence of the ε 4 allele confers an increased risk of the disease, in a dose-dependent manner (in Europeans, odds ratio 12.9 for homozygous individuals and between 3.2 and 4.2 for heterozygous individuals). The most prevalent form of AD has a multifactorial etiology, where, besides APOE, various genetic and environmental factors influence its pathology. Recent studies indicate that local ancestry around the APOE gene is also relevant to the risk of the disease. Individuals with African ancestry have a reduced risk of developing the disease compared to Europeans and Asians. These regions may act in a cis-regulatory manner in modulating gene expression. The Brazilian population results from admixture Indigenous Native-American, African, and European populations offering an opportunity to study the effects of different ancestries on AD. The present study aims to quantitatively characterize the role of the different local ancestries across APOE genotypes by associating them with its expression in brain tissue of this gene through RT-qPCR. We identified a heterogeneous expression among the different ancestries, with a reduction in the quantification of allele-specific transcripts in individuals with African allele ε 3 compared to the expression in the group with European allele ε 3. These results suggest a role local ancestry specific haplotype modulating APOE gene expression. (AU) | |
| FAPESP's process: | 21/13421-0 - Expression of APOE gene allele-specific brain transcripts of European and African ancestries |
| Grantee: | Gabriel do Nascimento Santos |
| Support Opportunities: | Scholarships in Brazil - Master |