Heritable Integration of kDNA Minicircle Sequences from Trypanosoma cruzi into the Avian Genome: Insights into Human Chagas Disease

Nitz, Nadjar; Gomes, Clever; Rosa, Ana de Cássia; D’Souza-Ault, Marian R.; Moreno, F. Javier; Lauria-Pires, Liana; Nascimento, Rubens J.; Teixeira, Antônio R. L.

doi:10.1016/j.cell.2005.08.028

Cited by 30 publications

(72 citation statements)

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“…Up to 30% of the individuals in the indeterminate stage develop chronic Chagas disease. Pathologies observed in chronic chagasic patients include digestive tract anomalies (megacolon, megaesophagus) and cardiac enlargement and malfunction (Teixeira 1987), accompanied by integration of parasite minicircle DNA sequences into the host genome (Nitz et al 2004). Variations in disease have yet to be linked directly to host or parasite genetics; however, both of these factors are likely to play a role (Macedo and Pena 1998;Vago et al 2000;Macedo et al 2002Macedo et al , 2004Campbell et al 2004).…”

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confidence: 99%

Two Hybridization Events Define the Population Structure of Trypanosoma cruzi

et al. 2005

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Genetic variation in Trypanosoma cruzi is likely a key determinant in transmission and pathogenesis of Chagas disease. We have examined nine loci as markers for the extant T. cruzi strains. Four distinct alleles were found for each locus, corresponding to the sequence classes present in the homozygous discrete typing units (DTUs) I, IIa, IIb, and IIc. The alleles in DTUs IIa and IIc showed a spectrum of polymorphism ranging from DTU I-like to DTU IIb-like, in addition to DTU-specific sequence variation. DTUs IId and IIe were indistinguishable, showing DTU homozygosity at one locus and heterozygosity with DTU IIb and IIc allelic sequences at eight loci. Recombination between the DTU IIb and IIc alleles is evidenced from mosaic polymorphisms. These data imply that two discrete hybridization events resulted in the formation of the current DTUs. We propose a model in which a fusion between ancestral DTU I and IIb strains gave rise to a heterozygous hybrid that homogenized its genome to become the homozygous progenitor of DTUs IIa and IIc. The second hybridization between DTU IIb and IIc strains that generated DTUs IId and IIe resulted in extensive heterozygosity with subsequent recombination of parental genotypes.

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confidence: 99%

Two Hybridization Events Define the Population Structure of Trypanosoma cruzi

et al. 2005

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“…Se ha reportado que el ADN de los minicírculos del parásito puede insertarse en las células del huésped de forma que podría existir amplificación en ausencia del parásito vivo (35). Por lo anterior, se recomienda el uso de ambas pruebas de PCR, puesto que al estar amplificando blancos diferentes, productos del ADN del minicírculo y ADN nuclear, estas pruebas pueden evidenciar la presencia real de la infección.…”

Section: Días De Disección Despuésunclassified

Evaluación de las pruebas de PCR TcH2AF-R y S35-S36 para la detección de Trypanosoma cruzi en tejido cardiaco de ratón

Barrera¹,

Guevara²,

Pavía³

et al. 2008

biomedica

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Introducción. El trasplante es una opción terapéutica en la cardiomiopatía chagásica. Para la detección temprana de una posible reactivación de la infección, se propone el uso de pruebas de reacción en cadena de la polimerasa (PCR) a partir de biopsias endomiocárdicas; el modelo de ratón es una aproximación preliminar para evaluar la aplicación de éstas. Objetivo. Evaluar la aplicación de las pruebas de PCR basadas en los iniciadores TcH2AF-R y S35-S36 para la detección de T. cruzi en tejido cardiaco de ratones infectados con el parásito. Materiales y métodos. Se infectaron por vía intraperitoneal dos grupos de ratones ICR de 15 y 10 individuos con 0,3 ml de PBS que contenían 1x10 6 tripomastigotes de la cepa MHOM/CO/ 2001/D.A. (T. cruzi I) o 1x10 4 tripomastigotes de la cepa MHOM/BR/00/Y (T. cruzi II), respectivamente. El seguimiento de la parasitemia se realizó mediante microhematocrito y presencia de parásitos en el corazón a los 30, 60 (modelo agudo), 100 y 150 (modelo crónico) días por medio de histopatología y de las PCR TcH2AF-R y S35-S36. Resultados. La histopatología mostró alteraciones en el miocardio y presencia de amastigotes en los modelos agudo y crónico. En contraste al microhematocrito y al análisis histopatológico, la PCR S35-S36 permitió la detección de ambas cepas del parásito. La PCR TcH2AF-R detectó la cepa T. cruzi I con un desempeño superior al microhematocrito y al análisis histopatológico. Conclusiones. El uso de ambas pruebas de PCR puede ser útil en la confirmación de la reactivación de la infección postrasplante.Palabras clave: Trypanosoma cruzi, enfermedad de Chagas, cardiomiopatía chagásica, reacción en cadena de la polimerasa. Evaluation of TcH2AF-R and S35-S36 primers in PCR tests for the detection of Trypanosoma cruzi in mouse cardiac tissueIntroduction. Heart transplant is a therapeutic option in the treatment of chagasic cardiomyopathy. For early detection of Chagas reactivation cases, the use of PCR tests using endomyocardial biopsies has been proposed. Development of an animal model will be the first step in evaluating the applicability of this approach. Objective. PCR tests based on the TcH2AF-R and S35-S36 primers were evaluated for the detection of T. cruzi in heart tissue of mice experimentally infected with the parasite. Parasitemia and cardiac parasitic infection were determined at 30, 60 (acute model), 100 and 150 (chronic model) days by means of histopathological examination and by PCR, using the TcH2AF-R and S35-S36 primers. Results. The histopathological findings revealed alterations in the heart and the presence of intracellular amastigotes in acute and chronic models. In contrast to parasitemia levels and

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“…The revelation that minicircles are integrating into the host genome (Teixeira et al 1991, 1994a,b, Simões-Barbosa et al 1999) and correlated to the pathology of Chagas disease (Nitz et al 2004) has renewed interest in under- standing the composition of minicircles within the known sub-groups of T. cruzi. Minicircle kDNA integrations behave as mutagens in the host.…”

Section: Interlocking Networkmentioning

confidence: 99%

“…In addition, the Earth's development exerts an influence on biological evolution through subtle changes in climate and environment, or cataclysms such as tsunamis, necessitating adjustment of the clock to explain discontinuities beyond the Gondwanaland partition (Krause & Bonaparte 1993, Salgado-Laborieau 2001. However, chasms will remain wherever horizontal DNA transfer (HDT) among disparate species occurs (Nitz et al 20041 , Simonson et al 2005, Babushok 2006, complicating reconstruction of the universal tree of life. The expected shifts (e.g., mutations) are essentially normalized, and DNA accumulates substitutions at a stable pace.…”

Section: Eons and Interplaymentioning

confidence: 99%