Programa de Pós-graduação em Ciências Biológicas
URI Permanente desta comunidade
Navegar
Navegando Programa de Pós-graduação em Ciências Biológicas por Por Orientador "Castelli, Erick da Cruz"
Agora exibindo 1 - 3 de 3
Resultados por página
Opções de Ordenação
Item Variabilidade e história evolutiva do gene HLA-E(Universidade Federal de Goiás, 2013-01-31) Felício, Leandro Prado; Castelli, Erick da Cruz; http://lattes.cnpq.br/0992559318175235; Castelli, Erick da Cruz; Telles, Mariana Pires de Campos; Mendes Júnior, Celso TeixeiraThe HLA-E locus is a Human Major Histocompatibility Complex (MHC) gene associated with immune-modulation and suppression of the immune response by the interaction with specific NK and T cell receptors. The HLA-E gene is considered the most conserved locus in the human HLA; however, this low variability might be a consequence of the scarce number of studies focusing this subject. In this mastering thesis we assessed the HLA-E coding and 3’ untranslated region variability in a group of individuals from Brazil and the results were evaluated together with data from the 1000Genomes Consortium. Altogether, only 28 variation sites were found in approximately 2724 bp evaluated. These variation sites were arranged into 33 haplotypes, most of them (98.2%) encoding one of the two HLA-E molecules found worldwide, i.e., the molecules associated with the allele groups E*01:01 and E*01:03. Interestingly, 85% of all haplotypes were represented by only three different sequences, each of them associated with one of the main known HLA-E coding alleles, E*01:01:01, E*01:03:01 and E*01:03:02, all of them found worldwide. This phenomenon, together with the comparisons with other primate sequences, reveals that these two main allele groups (and molecules) arose early before human speciation, and indicates that E*01:03:01 might be the oldest allele. In addition, the low nucleotide diversity found for the HLA-E coding and 3’UTR in worldwide populations suggests that the HLA-E gene is in fact a conserved gene, which might be a consequence of its key role in the modulation of the immune system.Item Inferência de micrornas candidatos a influenciar a expressão do gene imunosupressor HLA-G(Universidade Federal de Goiás, 2014-02-19) Porto, Iane de Oliveira Pires; Georg , Raphaela de Castro; http://lattes.cnpq.br/3971276154067590; Castelli, Erick da Cruz; http://lattes.cnpq.br/0992559318175235MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional expression regulation by inducing mRNA degradation or translation inhibition. Some miRNAs are known to regulate HLA-G expression, an important immunemodulatory molecule that inhibits both Natural Killer and cytotoxic T cells through interaction with inhibitory receptors. The HLA-G is associated with maternal-fetal tolerance, tissue acceptance in transplants and the progression of tumors. The mechanisms underlying HLA-G expression control are not completely understood, however, its 3’untranslated region (3’UTR) is reported to play an important role on gene regulation influencing mRNA stability and interacting with miRNAs such as miR-148a-3p. In this study, we performed a systematic analysis of all miRNAs that are good candidates to act as HLA-G regulators. In order to determine the miRNAs with the highest potential to influence HLA-G expression, we compared the outputs of three distinct algorithms - miRanda, RNAhybrid and Pita. For this purpose, a method of miRNA inference was developed using Perl scripts to compare and filter results and a scoring system was created in order to evaluate both the binding stability of the miRNA/mRNA interaction and the miRNA specificity to its target sequence. Then, a panel of miRNAs with great potential of controlling HLA-G expression was generated.Item Avaliação da história evolutiva do gene HLA-G por meio de polimorfismos de base única e da inserção AluyHG(Universidade Federal de Goiás, 2013-11-25) Santos, Kaisson Ernane dos; Castelli, Erick da Cruz; http://lattes.cnpq.br/0992559318175235; Castelli, Erick da Cruz; Soares, Thannya Nascimento; Silva, Daniela Melo eThe Major Histocompatibility Complex is mainly composed by genes of the adaptive immune response. In humans, part of this complex is known as the Human Leukocyte Antigens (HLA), whose genes are responsible for specific antigen presentation to effector immune cells. The classical class I HLA genes (HLA-A, -B and -C) are responsible for antigen presentation to T CD8+ cells and they constitute the most polymorphic genes in the human genome. This variability is maintained by selection mediated by microorganisms. In contrast to their classical counterparts, the non classical class I genes (HLA-G, -E and -F) present low variability and are associated with immune tolerance due to the interaction with NK and T cells inhibitor receptors. HLA-G is the most studied non classical gene, which is associated with immune response modulation, mainly during pregnancy. Considering that natural selection is acting on the HLA-G regulatory regions maintaining high heterozigosity in this region, we evaluated a nearby Alu insertion (AluyHG) correlating this Alu element with coding and 3’UTR HLA-G polymorphisms. The AluyHG insertion was particularly associated with the HLA-G haplotype known as G*01:01:01:01/UTR-1, considered a high-expressing HLA-G haplotype. The G*01:01:01:01/UTR-1/AluyHG haplotype would be the most recent HLA-G haplotypes, in spite of its high frequency in worldwide populations.