Teses em Genética e Biologia Molecular (Doutorado) - PPGBM/ICB

URI Permanente para esta coleçãohttps://repositorio.ufpa.br/handle/2011/8840

O Doutorado Acadêmico pertence ao Programa de Pós-Graduação em Genética e Biologia Molecular (PPGBM) do Instituto de Ciências Biológicas (ICB) da Universidade Federal do Pará (UFPA).

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Biologia molecular aplicada à hanseníase: estudo de parâmetros genéticos e epigenéticos em uma amostra do estado do Pará
(Universidade Federal do Pará, 2016-09-02) PINTO, Pablo Diego do Carmo; SANTOS, Ândrea Kely Campos Ribeiro dos; http://lattes.cnpq.br/3899534338451625
Leprosy is caused by Mycobacterium leprae and patients can be grouped in Paucibacillary and Multibacillary. Alternatively, according by Ridley-Jopling (1966), using immune-hystogical criteria, grouped in two distinct pole: (i) Tuberculóide (TT); and (ii) lepromatous (LL), and your intermediaries. Independently these classification, the disease can be affected by molecules that modulates immune response, like genes that encode these molecules, and by small RNA (micro-RNA), wich regulated these genes, thus these study can improve the knowledge about the mechanism of response to infectious process, as well as enable the identification of new possibles biomarkers to assist diagnosis in leprosy. The objective of this study was to investigate eight INDEL polymorphisms on genes CYP19A1, NFKβ1, IL1α, CASP8, UGT1A1, PAR1, CYP2E1, and IL4, to identify possible susceptibility markers of leprosy and evaluate the influence of genetic ancestry on disease risk. Besides was performed the first genome wide miRNA profiling of Leprosy by next generation sequencing (NGS), assessing and describing the expression standard in leprosy. Our study shows that the NFKβ1, CASP8, PAR1, IL4 and CYP19A1 genes are possible markers for the susceptibility to development of leprosy and the severe clinical form MB. Moreover, after correcting for population structure within an admixture population, the results show that different levels of ethnic group composition can generate different OR rates for leprosy susceptibility. The differential expression profile from tissue samples reveal 67 miRNAs differentially expression, with 43 down and 24 upregulated and from blood sample were found a total of 10 miRNAs differentially expression with 9 down and one upregulated. Moreover was performed in silico target analysis and detect the genes (IL1β, IL6, IL8, IL12, TLR2, TLR4, IL17RB, IFNGR1, TGFBR1, NFκβ, família SMAD, STAT3, CASP8, CYP19A1, BCL-2, in others) involved on pathological of leprosy. Lastly, was showed for the first time the genome wide microRNA of leprosy.

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