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Teixeira ARL, Hecht MM, Nitz N, Guimaro MC and Leonardecz E
Scientific Tracks Abstracts: Transl Med
The trypanosoma cruzi mitochondrial DNA (kDNA) minicircle sequences can transfer to the genome of rabbits, humans, and chickens. In order to eliminate a role played by the parasite in the pathogenesis of the disease, we used the chicken model refractory to T. cruzi infections. The inoculation of T. cruzi in fertile eggs generated parasite-free chicks, but the kDNA minicircle was retained in the genome. The kDNA mutations in the dystrophin gene were found in birds and progeny showing muscle weakness and cardiomyopathy. A tpTAIL-PCR with hostï¿½s primers combined with kDNA nested primers was used to disclose chimera kDNA minicircle-dystrophin sequences in a chicken family: F0 (2); F1 (4); F2 (4); F3 (4). Interestingly, kDNA-dystrophin mutations showed different minicircle sequence at the same base pair in locus NW_001471534.1. Chimera mosaics, resulting from a shear mass of kDNA minicircle integrations in the dystrophin gene, showed variegated profiles: 1) Different dystrophin- kDNA minicircle sequences in parental and progeny; 2) Chimeras showing truncated kDNA minicircle-host dystrophin; 3) Hitchhiking kDNA sequence-host retroelement insertion into the dystrophin locus. Southern blot hybridization bands showing migration differences indicated profiles change over time. The mosaics suggested a dynamic pattern of DNA mobilization in parental and progeny. The vertical transfer of T. cruzi kDNA minicircle sequences to dystrophin locus NW_001471534.1 is a semi-conservative non-Mendelian inheritance, for the kDNA variable region present in the parental is rarely documented in the progeny. Moreover, the kDNA mutation in the dystrophin locus can be associated with the pathogenesis of Chagas disease.
Antonio R. L. Teixeira received his MD degree from the Faculty of Medicine of the Federal University of Bahia, Brazil. From 1971 to 1974 he was a Research Fellow in Pathology at the New York Hospital, Cornell University Medical College. He trained at the L?Institut d?Imunog?n?tique et Cancerologie in Villejuif, France, and received his PhD Degree in Pathology from the Federal University of Minas Gerais, Brazil. He conducted Post-Doctoral studies at the National Institutes of Health, USA. His main research interest is epidemiology, clinics, and pathogenesis of the human Chagas disease. He is the founder of the genetically driven autoimmune theory in Chagas disease.