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SAMARA YASMIM SILVA RIOS
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COMPARATIVE GENOMICS: A TOOL IN THE MODELING OF NEURODEVELOPMENT DISORDERS
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Advisor : VANESSA RODRIGUES PAIXAO CORTES
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COMMITTEE MEMBERS :
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LUCIANA TOVO RODRIGUES
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RENATA LUCIA LEITE FERREIRA DE LIMA
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VANESSA RODRIGUES PAIXAO CORTES
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Data: Jun 29, 2018
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Show Abstract
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Psychiatric neurodevelopmental disorders are complex diseases that have important genetic contribution and their etiology is still inconclusive. As a result, animal modeling has been a great ally in the search for the elucidation of these disorders. Although many animals are available, most researchers choose to use the mouse, but is it the best animal to study all disorders? The aim of this work was to identify, among the possible animal models, the most genetically suitable one to investigating neurodevelopmental diseases. We searched for genes associated with neurodevelopmental disorders using the MGI browser and the Sfari database. Further, we retrieved protein sequences from Ensembl and Uniprot of human (Homo sapiens), rhesus monkey (Macaca mulatta), marmoset (Callithrix jacchus), mouse (Mus musculus), rat (Rattus norvegicus), guinea pig (Cavia porcellus), rabbit (Oryctolagus cuniculus), dog (Canis lupus familiaris), pig (Sus scrofa), chicken (Gallus gallus), frog (Xenopus tropicalis), and zebrafish (Danio rerio). We chose the canonical sequence and, if it was absent, the longest isoform for each gene. After, we compared the proteins’ similarity using the LALIGN browser, and the medium value was plotted in Excel. We used Genomicus v84.01 –PhyloView and UCSC Genome Browser (Human Dec. 2013 (GRCh38/hg38) to quantifying homologous genes and to getting the synteny table of all candidate genes. The table was converted in numerics of 0 (different genes), and 1 (genes shared with human) by using the Rstudio. Finally, we obtained the interaction networks of each gene by using the STRING browser. After analyzing the gene pool for each disease, some animals stood out as follows: rhesus monkey for schizophrenia, obsessive compulsive disorder and Tourette's syndrome; dog for autism; and mouse for the study of attention deficit hyperactivity disorder. However, considering a broad genomic comparison of all genes, the guinea pig stood out as the most suitable for all the neurodevelopmental disorders studied here. Nevertheless, it is known that each gene set has its specificities and each gene and/or gene family has its evolutionary history, therefore, a detailed analysis is required to choosing the most appropriate model. We suggest the results obtained here as a good starting point.
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VALDENIR DOS SANTOS MEIRA
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MOLECULAR EVOLUTION OF THE GENE FAMILY OF AXONAL PROTEIN RECEPTORS ROUNDABOUT (ROBO)
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Advisor : VANESSA RODRIGUES PAIXAO CORTES
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COMMITTEE MEMBERS :
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VANESSA RODRIGUES PAIXAO CORTES
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RODRIGO BARBAN ZUCOLOTO
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PAMELA LAIZ PARE DA ROSA
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Data: Nov 30, 2018
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Show Abstract
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It is undeniable that the knowledge about the neurodevelopment progressed a lot over the last two decades, but is still insufficient to understanding how evolution acted for the acquisition of memory and intelligence, as well as to the emergence of human neurological diseases that challenging scientists. Understanding how the genetic and molecular information processing in the brain development is of great interest to science, because in them supposedly the answer key to the etiology of the brain disorders and to the evolutionary genesis of the vertebrates. The present work aimed to reconstruct the evolutionary history of the ROUNDABOUT (ROBO) gene family, implicated in neurological development. In this study the four genes belonging to this family (ROBO1, ROBO2, ROBO3 and ROBO4) were analyzed in 63 species, 61 of vertebrates and two of invertebrates. We constructed synteny maps through the public data banks Genomicus v84.01 and UCSC Genome Browser, verifying the presence and number ofROBO´sorthologs. We retrieve the sequences available in the Ensembl, NCBI, and UCSC Browser databases. The sequences were aligned through the MAFFT algorithm on the GUIDANCE 2.0 server. The synonymous and non-synonymous substitution rates (dN/dS) were estimated according to the evolutionary models (M0, M1, M2, M8 and M8a) using the program CODEML, part of the PAML_4.8a package. Synthetic analyzes show conservation only in phylogenetically closer groups.There is an apparent genetic loss in the ROBO family, but it still needs more genomic coverage to be confirmed.It was established that the best evolutionary model that describes the evolution of the ROBO´s is the neutral model (M8a), but a small percentage of sites is with relaxation of the functional constriction (ω = 1) 0.6%, 1.3%, 4% and 12% for ROBO1, ROBO2, ROBO3 and ROBO4, respectively.
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