Study of the contribution of retrocopies in the origin of new genetic regions

• Grant number: 18/13613-4
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: March 01, 2019
• End date: May 31, 2023
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Pedro Alexandre Favoretto Galante
• Grantee: Helena Beatriz da Conceição
• Host Institution: Hospital Sírio-Libanês. Sociedade Beneficente de Senhoras (SBSHSL). São Paulo , SP, Brazil

Abstract

Retrocopies of coding genes have long been classified as processed and non-functional pseudogenes. However, today it is known that gene retroduplication, the mechanism of generation of these retrocopies, plays an important role in the genesis of novel genes in humans and other organisms. However, this role is confined to specific examples, and studies that systematically analyze the functional role of retrocopies are rare. For example, about 8,000 retrocopies of coding genes have been identified in humans, of which a minority (<10%) has evidence of transcription and functional indicators. Two seminal examples are the PTENP1 retrocopy (from the PTEN, a tumor suppressor) and the BRAFP1 retrocopy (from the BRAF gene, a proto-oncogene), which were studied in detail and had their functions shown. Nowadays, the study of the origin of new genes and gene regions is on the rise thanks to the new technologies in the various "omics", the large-scale DNA/RNA sequencing and the computational tools. All this methodological repertoire provides us with more accurate, deep and robust information to be systematically integrated and analyzed. In this project, we propose to elucidate part of the functional role of retrocopies by studying in details their contributions to the generation of new genes and gene regions in the human genome under normal and tumor conditions. Such a study will be carried out by analyzing and integrating several datasets of fixed and polymorphic retrocopies present in the human genome. In general, as a result, we hope to obtain a most complete repertoire about the functional role of retrocopies in the origin of new genes, gene regions and, if any, their importance in the process of tumorigenesis. (AU)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

CONCEIÇÃO, Helena Beatriz da. Origins andfunctional potential of retrocopies in the genome of humans and other animals: a large-scale approach to identify retrocopies in diverse animal genomes and study their expression pattern in normal human tissues.. 2023. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Matemática e Estatística (IME/SBI) São Paulo.