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Retroelements: a driving force generating genetic novelties in the human and mouse genome

Abstract

The origin of new gene regions is a preponderant factor in the evolution of several species. Retrocopies (gene duplicates generated from mRNAs) have been classified as non-functional since 1980s. However, it is currently accepted that this type of gene duplication is one of the main driving forces in generating genetic novelties in many species. In humans and mice, have been identified ~8000 and ~7200 retrocopies (RTC), respectively. However, many of them still remain understudied. Only dozens of RTC have been described as functional (retrogenes) in human and mouse. Here, we aim to perform a comprehensive study focusing on the functional characterization of all RTCs found in the human and mouse genome. To perform this, we will use robust computational methods, sequence conservation and several "omics" data, as well as in-house experimental validations focused on answering functional aspects of RTC. We will develop the project on four main lines: i) we will evaluate the fixed RTC potentially creating novel genic regions (encoding or not) in human and mouse. ii) we will evaluate the polymorphic RTC creating novel genic regions in the human population; iii) In tumors, we will evaluate the occurrence of abnormalities in gene expression involving retrocopies; iv) we will also develop and provide a web based platform capable of classifying RTCs into (potentially) functional or not. In the end, we strongly believe that we will contribute to elucidating the functional role of these genic duplicates, which have most of their features still neglected or as anecdotal in the literature. More broadly, this JP-2 will push the growing and establishment of research in bioinformatics, genomics and cancer in my group and in collaborating groups. (AU)

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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)
SEQUEIRA BARREIRO, RODRIGO ARAUJO; SABBAGA, JORGE; ROSSI, BENEDITO M.; ACHATZ, MARIA ISABEL W.; BETTONI, FABIANA; CAMARGO, ANAMARIA A.; ASPRINO, PAULA F.; GALANTE, PEDRO A. F. Monoallelic deleterious MUTYH germline variants as a driver for tumorigenesis. JOURNAL OF PATHOLOGY, v. 256, n. 2 NOV 2021. Web of Science Citations: 0.
MILLER, THIAGO L. A.; REGO, FERNANDA ORPINELLI; BUZZO, JOSE LEONEL L.; GALANTE, PEDRO A. F. sideRETRO: a pipeline for identifying somatic and polymorphic insertions of processed pseudogenes or retrocopies. Bioinformatics, v. 37, n. 3, p. 419-421, FEB 1 2021. Web of Science Citations: 0.
GUARDIA, GABRIELA D. A.; CORREA, BRUNA R.; ARAUJO, PATRICIA ROSA; QIAO, MEI; BURNS, SUZANNE; PENALVA, LUIZ O. F.; GALANTE, PEDRO A. F. Proneural and mesenchymal glioma stem cells display major differences in splicing and lncRNA profiles. NPJ GENOMIC MEDICINE, v. 5, n. 1 JAN 16 2020. Web of Science Citations: 0.

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