Functional analysis of MBD5 gene: characterization of the biological role of a gene in neurodevelopment

• Grant number: 13/11781-3
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: November 01, 2013
• End date: October 31, 2014
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Síntia Iole Nogueira Belangero
• Grantee: Vanessa Kiyomi Ota Kuniyoshi
• Supervisor: Gustavo Turecki
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Institution abroad: McGill University, Montreal, Canada
• Associated to the scholarship: 10/19176-3 - Gene expression and DNA methylation analysis in drug-naive first episode of psychosis patients, BP.DR

Abstract

Schizophrenia is a neurodevolpmental disorder with high heritability. Thus, multiple studies have been conducted to elucidate the genetic factors associated with the disease. Nowadays, with the development of genome-wide association studies, we can investigate thousands of genetic variants without a priori hypothesis of the neurobiology of the disease, allowing the search for new genes and pathways in schizophrenia. The first genetic variant to be associated with schizophrenia with GWAS significance level is located in ZNF804A gene of unknown function. It is known that this gene has C2H2 domain, which is associated with the family of zinc finger proteins, which are known to participate in transcription. Furthermore, ZNF804A appears to be the target of HOX family proteins, known for their involvement in embryonic development. Thus, although some later studies have sought to understand the biological function of the gene, further studies are needed in order to delineate its route and provide new hypotheses and pathways related to neurodevelopmental disorders. The aim of this study is to evaluate the functional effects of reduced expression of the ZNF804A gene in neurons derived from human stem cells. Therefore, we will induce a knockdown of ZNF804A by virus in stem cells. Then these cells will be differentiated into neurons. After some time, cells at different stages of development will be used for RNA extraction and conversion to cDNA, which will be submitted to the transcriptome analysis by RNAseq. So in addition to pinpoint genes involved in the function of ZNF804A and therefore, proteins and pathways involved and integrated in the susceptibility of certain phenotypes, genetic findings may provide new hypotheses about the nosological models involved in neurodevelopment disorders and major psychoses. (AU)