Banca de QUALIFICAÇÃO: JÉSSICA NAYARA GÓES DE ARAÚJO

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : JÉSSICA NAYARA GÓES DE ARAÚJO
DATE: 24/03/2022
TIME: 13:30
LOCAL: ONLINE
TITLE:

A DEFINIR

KEY WORDS:

Familial hypercholesterolemia; Regulatory variant; Bioinformatics analysis; Next-generation sequencing; LDLR; APOB; PCSK9;

PAGES: 71
BIG AREA: Ciências Biológicas
AREA: Genética
SUMMARY:

Familial hypercholesterolemia (FH) is a hereditary disorder of cholesterol metabolism, characterized by prolonged exposure to high serum concentrations of low-density lipoprotein cholesterol (LDL-c), which leads to a significant increase in the risk of early cardiovascular morbidity and death. The main causes of FH are variants found in genes involved in LDL uptake and catabolism (LDLR, APOB and PCSK9), however, causal variants are not identified in a significant number of individuals clinically diagnosed with FH. Thus, variants in non-coding regions, which are not usually included in diagnostic panels, could be altering the expression of those genes, and contributing to phenotype. The present study aims to identify genetic variants in the upstream/promoter regions of LDLR, APOB and PCSK9 genes of individuals clinically diagnosed with FH, but no confirmation of molecular diagnosis. 25 volunteers were selected for targeted sequencing of 3 kb upstream regions (Chr19:11086362-11089361; Chr2:21044074-21047073; Chr1:55036476-55039475 - GRCh38) using the AmpliSeq for Illumina method. Computational analysis of sequencing results identified 34 single nucleotide variants (SNV) approved in quality filtering (6 in LDLR, 15 no APOB e 13 no PCSK9). 5 variants were prioritized as potentially regulatory (rs36218923 e rs538300761 in LDLR; rs934197 e rs9282606 in APOB, g.55038486A>G in PCSK9) based on regulatory supporting evidence found in public databases, online tools for annotation and effects prediction of variants and literature. Only rs934197, which had the highest regulatory probability score, was previously described as functional. Thus, the next steps of this study include performing luciferase reporter assays to confirm the regulatory role observed by in silico analyses.

BANKING MEMBERS:
Externo à Instituição - MARCELO ARRUDA NAKAZONE
Externo à Instituição - MARCELO ALEX DE CARVALHO - INCA
Presidente - 2085604 - SUSANA MARGARIDA GOMES MOREIRA