Genomic study of apparently balanced chromosomal rearrangements in individuals with abnormal phenotype

Abstract

Balanced chromosomal rearrangements (BCR) occur in approximately 1 in 2000 newborns. The array genomic hybridization (aGH) techniques detected genomic imbalances related or not to chromosome breakpoints in 30 to 50% of BCR cases with abnormal phenotype. Recently, insertions or deletions of few base pairs at breakpoints were identified by Next Generation Sequencing (NGS). The aim of this study is to investigate genomic imbalances, relate or not to breakpoints of rearrangements, in individuals with BCR and abnormal phenotype. Initially, patients from the Clinical Genetics Service of Medical Science Faculty/Unicamp will be studied; individuals from others Brazilian centers of clinical attendance could also be included. As first analyses, cases with BCR detected by karyotype will be investigated using aGH technique. To confirm the results of causative genomic imbalances, FISH analyses will be performed of propositus and, if necessary, of parents as well. When genomic imbalances were not detected, chromosomes microdissection and analyses of theirs sequences by NGS with Illumina Genome Analyzer will be performed in order to investigate base pairs alterations. All laboratorial structure necessary is viable at Unicamp and Brazilian Synchrotron Light Laboratory. Results of this project might be helpful to understand genomic mechanisms involved in abnormal phenotype in individuals with BCR. Also, the use of modern technologies will contribute for the implementation of a new area of research at Medical Genetics Department of MSC/Unicamp.