Functional analyses of novel nucleotides variations in the NR5A1 gene identified in patients 46,XY with disorders of sex development

• Grant number: 13/24333-9
• Support type: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): March 01, 2014
• Effective date (End): November 30, 2014
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal researcher: Maricilda Palandi de Mello
• Grantee: Helena Fabbri Scallet
• Supervisor abroad: Sven Olaf Hiort
• Home Institution: Centro de Biologia Molecular e Engenharia Genética (CBMEG). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Research place: Universität zu Lübeck, Germany
• Associated to the scholarship: 13/05603-5 - Functional analyses of new nucleotide variations in NR5A1 gene in patients 46,XY with disorders of sex development, BP.DR

Abstract

The objective of this project is to analyze the functional role of the mutations p.Cis65Tir, p.Arg39Cis, p.Ser32Asn and p.Cis247* in NR5A1 protein, as well as the effect of nucleotide variations (c.-133G>A, c.-156_-136ins18pb, c.-413G>A, c.-208C>A, and c.-762C>T) identified in NR5A1 5'UTR and exon 1, which are non-coding regions but are important for NR5A1 transcriptional regulation. This investigation will focus in the ability Sp1 protein binding since those nucleotide variations localize in putative Sp1 binding sites. The methodology for the study will include: cloning and expression of normal and mutants NR5A1 gene, electrophoretic mobility sift and supershift assays (EMSA), Western Blotting, expression of gene reporter assays using luciferase as marker and two-hybrid system assays. (AU)

Scientific publications

(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)

FABBRI-SCALLET, HELENA; DE MELLO, MARICILDA PALANDI; GUERRA-JUNIOR, GIL; MACIEL-GUERRA, ANDREA TREVAS; RIBEIRO DE ANDRADE, JULIANA GABRIEL; COSTA DE QUEIROZ, CAMILA MAIA; MONLLEO, ISABELLA LOPES; STRUVE, DAGMAR; HIORT, OLAF; WERNER, RALF. Functional characterization of five NR5A1 gene mutations found in patients with 46,XY disorders of sex development. Human mutation, v. 39, n. 1, p. 114-123, JAN 2018. Web of Science Citations: 5.