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Investigation of mechanisms of formation of intrachromosomal rearrangements and its relation with the phenotype

Grant number: 19/26175-8
Support type:Scholarships in Brazil - Master
Effective date (Start): March 01, 2020
Effective date (End): February 28, 2022
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Maria Isabel de Souza Aranha Melaragno
Grantee:Bruna Ferreira Burssed dos Santos
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated research grant:14/11572-8 - Chromosomal rearrangements and their relevance in the etiology of genetic disorders: cytogenomic and molecular investigation, AP.TEM

Abstract

Structural chromosomal variations arise from breaks and rearrangements in the chromosomes. This can result in the alteration of the amount of genetic material present in the cell. Interchromosomal rearrangements are the ones that involve more than one chromosome whereas intrachromosomal rearrangements involve a single one. Examples of intrachromosomal rearrangements include inversions, ring chromosomes and intra-arm rearrangements, such as intra-arm insertions and inverted duplications associated with terminal deletions, a rearrangement known as inv dup del. A number of mechanisms of chromosomal rearrangement formation have been proposed and they can be appointed through the analysis of the DNA sequence at the breakpoint junctions of the chromosomal alterations. Breakpoint sequencing is also capable of revealing signatures of diverse DNA repair mechanisms that shape human chromosome rearrangements. In the present study, six patients with complex rearrangements involving intrachromosomal deletions and duplications will be studied using chromosomal microarray, fluorescent in situ hybridization (FISH) and breakpoint sequencing in order to characterize and connect the rearrangements with possible mechanisms of formation. Since the results will allow a better understanding of the genetic basis involved in altered phenotypes, an investigation of the karyotype-phenotype correlation will be carried out in order to identify possible candidate genes for the anomalies. (AU)