Banca de DEFESA: Vanessa Sodré de Souza

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : Vanessa Sodré de Souza
DATE: 30/08/2023
TIME: 14:00
LOCAL: Híbrido (Laboratório de Genética - Faculdade de Medicina ) e Plataforma Microsoft Teams
TITLE:

Contribution of the main methodologies of classical and molecular cytogenetics in the investigation of structural chromosomal rearrangements.

 

KEY WORDS:

Structural chromosomal variations; Karyotype; Microarray; Optical Genome Mapping

PAGES: 100
BIG AREA: Outra
AREA: Defesa
SUMMARY:

Structural chromosomal alterations are an important source of sequence variation that contribute to phenotypic differences between individuals. The human genome has an average of 18.4 Mb of structural variants (SVs), which has been shown to impact gene expression and be associated with human diseases. SVs lead to two main consequences: changes in gene dosage and DNA order, which can lead to gene fusions and chimeric proteins, in addition to affecting the interaction between genes and regulatory elements. Consequently, the characterization of chromosomal rearrangements and the identification of breakpoints are essential to understand the phenotypic impacts generated by these alterations. This work aimed to investigate how karyotype, microarray and optical genomic mapping methodologies can contribute to the investigation of structural chromosomal rearrangements. Ten cases of carriers of chromosomal variations attended at the Medical Genetics Service of the University Hospital of Brasília were selected. To characterize the chromosomal rearrangements, karyotype analysis, Chromosomal Microarray Analysis (CMA) and Optical Genomic Mapping (OGM) were performed. The ten selected patients were clinically evaluated to characterize them phenotypically. Through the karyotype methodology, it was possible to identify four cases of translocation, three cases of inversion, one case of marker chromosome and one case of derivative chromosome from maternal translocation. In three of the ten cases were identified copy number variations (CNVs) by the CMA technique, with the remaining rearrangements being balanced. In two siblings with normal karyotypes, a microduplication was detected which was later characterized by OGM. Of the ten selected cases, eight proceeded to GMO analysis. In seven cases gene interruptions were identified and the identification of possible candidate genes at the breakpoints or in nearby regions, they are: DLGAP2, DLGAP4 and BIRC6 in cases of ID and ASD; HMGA2 in a Silver-Russell Syndrome case; PTPRZ1 and TAFA4 in cases of learning difficulties and behavioral changes. Furthermore, the OGM showed that some rearrangements were more complex than the karyotype suggested. It is concluded that the karyotype remains an excellent screening method for structural chromosomal variations. CMA was effective in identifying CNVs, however most cases were balanced rearrangements that are not detected by the technique. With OGM it was possible to identify all types of rearrangements, define the breakpoints and have a refinement of the chromosomal segments involved, proving to be a great tool in the investigation of SVs with the potential to replace other methodologies.

COMMITTEE MEMBERS:
Externo à Instituição - NILO SAKAI JUNIOR - SARAH
Externa à Instituição - MARIA ISABEL DO SOUZA ARANHA MELARAGNO - UNIFESP
Externo à Instituição - TÁRSIS ANTONIO PAIVA VIEIRA - UNICAMP
Interna - 2329402 - ANGELICA AMORIM AMATO
Interna - 2731816 - JULIANA FORTE MAZZEU DE ARAUJO