Use of Next Generation Sequencing to study karyotypes with different number of X chromosome

• Grant number: 14/17132-0
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): November 01, 2014
• Effective date (End): October 31, 2019
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Carla Rosenberg
• Grantee: Darine Christina Maia Villela
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center, AP.CEPID
• Associated scholarship(s): 17/23448-8 - Genome-wide cell-free DNA copy number investigation in non-invasive prenatal test, BE.EP.PD

Abstract

In 1997, Dennis Lo and colleagues described the presence of free fetal DNA (ffDNA) in maternal plasma for the first time. Nearly ten years have passed since two independent groups proved that even with a small fraction of fetal DNA in the maternal bloodstream it is possible to detect, through next generation sequencing, aneuploidy fetuses early in pregnancy. Non-invasive prenatal test (NIPT) using ffDNA for screening of aneuploidies became clinically available in 2011 and is rapidly changing the standard of care in obstetric practice. Although current sequencing methods are effective in detecting the most common autosomal aneuploidies, the sensitivity and specificity of NIPT for identification of sex chromosomes aneuploidies are decreased. Several biological factors are pointed out as cause for the challenge in accurate determine X chromosome copy number. However, there is one unique phenomenon related to this chromosome that has not been investigated. The X inactivation, which is regulated by specific histone variants, could result in differential degradation and, consequently, representation of this chromosome in the fetal fraction may be altered. Thus, the main aim of this project is to study the impact of X chromosome in the accurate detection of sex chromosome aneuploidies, which should contribute to the development of new analytical models to help determine precisely the X chromosome copy number. (AU)

Scientific publications

(4)

(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)

VILLELA, DARINE; COSTA, SILVIA SOUZA; VIANNA-MORGANTE, ANGELA M.; KREPISCHI, ANA C. V.; ROSENBERG, CARLA. Efficient detection of chromosome imbalances and single nucleotide variants using targeted sequencing in the clinical setting. EUROPEAN JOURNAL OF MEDICAL GENETICS, v. 60, n. 12, p. 667-674, DEC 2017. (14/17132-0, 13/08028-1)

VILLELA, DARINE; MAZZONETTO, PATRICIA C.; MIGLIAVACCA, MICHELE P.; PERRONE, EDUARDO; GUIDA, GUSTAVO; MILANEZI, MARIA FERNANDA G.; JORGE, ALEXANDER A. L.; RIBEIRO-BICUDO, LUCILENE A.; KOK, FERNANDO; CAMPAGNARI, FRANCINE; et al. Congenital chromoanagenesis in the routine postnatal chromosomal microarray analyses. AMERICAN JOURNAL OF MEDICAL GENETICS PART A, v. 185, n. 8, p. 2335-2344, AUG 2021. (13/08028-1, 14/17132-0, 12/50981-5)

VILLELA, DARINE; SUEMOTO, CLAUDIA K.; LEITE, RENATA; PASQUALUCCI, CARLOS AUGUSTO; GRINBERG, LEA T.; PEARSON, PETER; ROSENBERG, CARLA. Increased DNA Copy Number Variation Mosaicism in Elderly Human Brain. NEURAL PLASTICITY, 2018. (14/17132-0, 13/08028-1)

VILLELA, DARINE; DE BARROS, JULIANA SOBRAL; DA COSTA, SILVIA SOUZA; AGUIAR, TALITA F. M.; CAMPAGNARI, FRANCINE; VIANNA-MORGANTE, ANGELA M.; KREPISCHI, ANA C. V.; ROSENBERG, CARLA. Detection of mosaicism for segmental and whole chromosome imbalances by targeted sequencing. ANNALS OF HUMAN GENETICS, v. 85, n. 1, AUG 2020. (16/04785-0, 13/08028-1, 14/17132-0)