Banca de QUALIFICAÇÃO: WASHINGTON CANDEIA DE ARAUJO

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : WASHINGTON CANDEIA DE ARAUJO
DATE: 23/06/2023
TIME: 16:00
LOCAL: Videoconferencia
TITLE:

Computational analysis using exome and RNA-Seq: genetic and infectious diseases approaches

KEY WORDS:

whole exome sequencing, runs of homozygosity, kidney diseases, collagen type IV

PAGES: 142
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Several computational tools have been used in the analysis of genomic data from complex and infectious diseases, allowing an increase in speed and performance, in addition to analytical accuracy. The present studies were focused on evaluating the exome of people with Alport syndrome (Chapter 1) and determining the gene expression profile in people infected with arboviruses when the Zika virus (ZIKV) was introduced in the state of Rio Grande do Norte, Brazil (Chapter 2). Alport syndrome is a hereditary progressive kidney disease, in addition to extra-renal manifestations such as hearing loss and ophthalmological abnormalities. Its inheritance includes autosomal dominant or recessive patterns (variants in COL4A3 and COL4A4, chromosome 2) linked to the X chromosome (COL4A5). These genes encode type IV collagen alpha chains. In this sense, two families with cases of this syndrome in the State of Rio Grande do Norte were evaluated for whole exome sequencing (WES). DNA sequences were mapped against the human genome (GRCh38/hg38 construct) to identify associated mutations. New deleterious variants at the COL4A3 and COL4A4 loci on chromosome 2 have been identified. Two variants were detected in probands with mutant alleles in the homozygous state, a premature stop codon at position 481 of the COL4A3 protein and a frameshift mutation leading to a stop codon at position 786 of the COL4A4 protein. For both Alport cases, the putative variants were surrounded by broad homozygous sequences (ROH). In summary, two new deleterious autosomal recessive genetic variants of Alport syndrome were identified in Northeastern Brazil. Both mutations are within stretches of homozygosity, as well as genes associated with other hereditary nephropathies. Known candidate loci were identified using families with a history of Alport syndrome, allowing for familial genetic counseling. In another part of this work, modern computational tools were used to analyze samples of individuals infected with ZIKV and those who developed Guillain-Barré. Here, we performed RNA-seq (High Throughput Sequencing data) from from individuals recovered from ZIKV infection, those who developed Guillain-Barré syndrome and asymptomatic. The results indicate that developmental pathways (eye morphogenesis, ciliary movement), pathways linked to inflammation and innate immune system, and upregulated synaptic transmission pathways in recovered GBS and recovered from ZIKV, 400 days after infection. In GBS patients, cell cycle and neurogenesis pathways are upregulated, with mitophagy and neuronal maturation downregulated. Therefore, the recovery of normal functions is due to the decrease in the expression of genes in these pathways. Regarding ZIKV, pathways linked to viral RNA recognition, cell cycle, and host defense responses are overregulated. Pathways linked to biosynthesis, ribosome production and cellular signaling during inflammatory processes are downregulated, indicating cellular processes that lead to normality and correction of modification processes during infection by these viruses. These new computational methods have helped to increase the processing of reads, genomic sequences and data analysis, with speed, accuracy and robustness, helping scientists to explain the underlying biological processes, obtained through massive sequencing data.

COMMITTEE MEMBERS:
Presidente - 1549705 - ADRIANA FERREIRA UCHOA
Interno - 2195251 - HUGO ALEXANDRE DE OLIVEIRA ROCHA
Interna - 1453487 - KATIA CASTANHO SCORTECCI