Estudo comparativo do genoma de trypanosoma cruzi com ênfase nas regiões teloméricas e subteloméricas.

• Ano de defesa: 2018
• Autor(a) principal: Antonio, Cristiane Regina [UNIFESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Trypanosoma Cruzi; Polimorfismo Cromossômico; Acgh
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=6728658; https://repositorio.unifesp.br/handle/11600/52935

The protozoan parasite Trypanosoma cruzi is the etiologic agent of Chagas disease. T. cruzi subtelomeric regions are enriched in surface protein and retrotransposon hot spot protein genes suggesting they may have acted as a site for recombination and generation of new variants of surface proteins. Subtelomeric regions of clone CL Brener are highly polymorphic, mainly as a result of large changes in the abundance and organization of these genes. In this work, we analyzed the organization of subtelomeric regions in different T. cruzi lineages (TcIisolates Dm28 and G; TcIIEsmeraldo cl3; TcVICL Brener). We identified 28 telomerespecific markers that were hybridized to the chromosomal bands separated by PFGE. Interstitial markers of each chromosome were also hybridized as an internal control. Identical hybridization patterns were observed with the telomereand interstitial chromosomespecific markers in different isolates suggesting that synteny at chromosomal ends is conserved across T. cruzi lineages. We were able to identify two recombination events. It is possible that subtelomeric regions play a role in stabilizing replication and copy number of the chromosomes. Trypanosomes have large genomes, yet synteny seems highly conserved suggesting that there is a specific mechanism governing genome evolution within these organisms. We used comparative genomic hybridization (aCGH) to compare CL strain, CLB and CL14. The karyotypes of CL strain, CLB and CL14 were analyzed by hybridization of chromosomal bands with chromosome specificmarkers. This analysis revealed minor karyotypic differences between CL strain and its clones, most of chromosome length polymorphisms were of small amplitude. For instance, CL strain and CLB exhibited a large chromosomal band of 2.09 Mb which underwent a deletion resulting in a band of <2 Mb in CL14. We found 155 chromosomal abnormalities, 33 in CLB and 96 in CL14, plus 26 events common to both. We identified a 50,1 kb deletion in TcChr 39P and a 63,2 kb in TcChr 39S located on the band of <2 Mb in clone CL14. This deletion occured in an enriched region of hypothetical proteins and ribosomal proteins genes indicating a possible fragile site. Integration of aCGH data with those from hybridization of chromosomal bands provided significant information regarding the frequency and variety of chromosomal rearrangements observed in this protozoan parasite.