The majority of carriers of apparently balanced chromosomal rearrangements are phenotypically normal, but about 7% of these rearrangements are associated with clinical abnormalities at birth. Intragenic break, variable expression of genes near the breakpoint due to position effect, generation of chimeric genes and uniparental disomy are pathogenic mechanisms classically proposed. Recently it was shown that submicroscopic deletions and duplications in the rearranged chromosomes could be the underlying cause of phenotypic abnormalities. Cryptic genomic imbalances were also identified as de novo mutations in patients who inherited the balanced rearrangement from a phenotypically normal parent. In the present study we aim at contributing to the understanding of mechanisms that lead to phenotypic abnormalities in carriers of balanced chromosomal rearrangements. Disclosing the mechanism of formation of these chromosomal rearrangements is another objective of the study. Apparently balanced de novo rearrangements and balanced rearrangements inherited from a phenotypically normal parent in patients with developmental anomalies of unknown etiology will be studied. The study will also include phenotypically normal individuals with balanced rearrangements. The differences between balanced rearrangements in phenotypically normal and abnormal cohorts can reveal characteristics of balanced chromosomal rearrangements that cause phenotypic abnormalities. The breakpoints of the rearrangements will be mapped by fluorescence in situ hybridization (FISH) and the presence of cryptic genomic imbalances will be investigated by array comparative genomic hybridization (a-CGH). The parental origin of the imbalances will be determined by microsatellite genotyping.
News published in Agência FAPESP Newsletter about the scholarship:
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MEHRJOUY, MANA M.;
FONSECA, ANA CAROLINA S.;
MENCARELLI, MARIA ANTONIETTA;
ABE, KIKUE TERADA;
SPECK-MARTINS, CARLOS EDUARDO;
VIANNA-MORGANTE, ANGELA M.;
Regulatory variants of FOXG1 in the context of its topological domain organisation.
European Journal of Human Genetics,
Web of Science Citations: 4.