| Grant number: | 12/24731-1 |
| Support Opportunities: | Research Grants - Young Investigators Grants |
| Start date: | May 01, 2013 |
| End date: | December 31, 2017 |
| Field of knowledge: | Biological Sciences - Biochemistry - Molecular Biology |
| Principal Investigator: | Pedro Alexandre Favoretto Galante |
| Grantee: | Pedro Alexandre Favoretto Galante |
| Host Institution: | Hospital Sírio-Libanês. Sociedade Beneficente de Senhoras (SBSHSL). São Paulo , SP, Brazil |
| Associated researchers: | Anamaria Aranha Camargo ; Fabiana Bettoni ; Raphael Bessa Parmigiani |
| Associated research grant(s): | 18/15579-8 - Retroelements: a driving force generating genetic novelties in the human and mouse genome, AP.JP2 |
Abstract
The improvement of DNA sequencing and large-scale data analyses have allowed the study of genomic features still not or under explored. Amongst these characteristics, those related to gene duplication deserve a special attention. For example, we know that gene duplication, which can generate genomic variations, is related to the emergence of species-specific characteristics and may be in the genesis of some genetic diseases. Among the molecular mechanisms responsible to these events, the gene duplication mediated by mRNA retrocopies is understudied and most of its features and functions are still unknown. Overall, we now know that: i) retroduplicação events were frequent in the evolution of certain species, such as rodents and primates; ii) some retrocopies are functional and important for a cellular health state and; ii) there are retrocopies related to tumorigenesis, such as PTENP1. However, all these features need to be studied deeply and in details. Based on those, we have proposed this project, which aims to make a systematic and extensive study of retrocopies through the analysis of their evolutionary characteristics, their polymorphisms in the human populations, and their role in diseases, especially in some human tumors. To perform these analyses, we will use an enormous repertoire of publicly available data, such as the human reference genome, genomes of other organisms, and genomes from 1000 Genomes, TCGA and ICGC projects. We will also use some genomes and transcriptomes sequenced locally. All these huge amounts of data will be integrated and analyzed by bioinformatics pipelines, which will be built specifically to the identification of retroposition events. We will also develop a strategy to the identification of somatic retrocopies through a sequence capture platform and submit some candidates to experimental validations. In conclusion, we expected to contribute to a deep and better understanding of the retrocopies roles in our and other primate genomes, as well as the retrocopies evolutionary history, their polymorphic characteristics, and their roles in some human tumors. (AU)
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