Deletion in KARLN intron 5 and predictive relationship with bovine tuberculosis and brucellosis infection phenotype

Autores
Rossi, Ursula Amaranta; Caffaro, María Eugenia; Raschia, Maria Agustina; Hasenauer, Flavia Carolina; Poli, Mario Andres; Rossetti, Carlos Alberto
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Kalirin (gene: KALRN) is a Rho-GEF kinase linked to neurodegenerative diseases in humans. Unexpectedly, various polymorphisms in KALRN gene were previously associated with resistance to bacterial infections in ruminants. In this study, we evaluated the effect of the rs384223075 (RS-075) deletion in KALRN intron 5 on the occurrence of Mycobacterium bovis and Brucella abortus infections in cattle. We performed two separate case-control association analyses: one for bovine tuberculosis (bTB) using 308 Holstein and Jersey cows from three herds with prevalence between 5 and 15% for this infection; and another for brucellosis using 140 Holstein and beef crossbred cows from two herds with high prevalence for brucellosis (> 30%). In the bTB analysis, the RS-075 deletion frequency was higher among cases than controls (p = 0.0001), and the absence of the RS-075 deletion allele was associated with negative PPD-skin test results (p = 0.0009) at genotype level. On the contrary, RS-075 was not associated with Brucella spp. serological status (p = 0.72) but, unexpectedly, the deletion allele was more frequent among controls than cases in the beef crossbred herd (0.31 vs. 0.14, p = 0.02). In concordance with this observation, in vitro assays showed that the RS-075 deletion could be linked to an enhanced cellular response to bacterial antigens and unspecific stimulation in mononuclear cells derived from beef crossbred cows, specifically the reactive nitrogen species production (p = 0.008) and proliferation capacity (p = 0.018). This study is consistent with other reports that support an important role of the KALRN gene and its polymorphisms in the host response to intracellular pathogens.
Instituto de Patobiología
Fil: Rossi, Ursula. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; Argentina
Fil: Rossi, Ursula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Caffaro, Marí­a Eugenia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; Argentina
Fil: Raschia, Maria Agustina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; Argentina
Fil: Hasenauer, Flavia Carolina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; Argentina
Fil: Hasenauer, Flavia Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Poli, Mario Andres. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; Argentina
Fil: Rossetti, Carlos Alberto. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; Argentina
Fuente
Veterinary Research Communications 47 (2) : 779-789 (2023)
Materia
Ganado Bovino
Enfermedades de los Animales
Tuberculosis Bovina
Resistencia Genética
Brucelosis
Fenotipos
Cattle
Animal Diseases
Bovine Tuberculosis
Genetic Resistance
Brucellosis
Phenotypes
Nivel de accesibilidad
acceso restringido
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
INTA Digital (INTA)
Institución
Instituto Nacional de Tecnología Agropecuaria
OAI Identificador
oai:localhost:20.500.12123/14788
Acceder
id INTADig_9c4180cda6740ea0b5ddcc56b3a27e6e
oai_identifier_str oai:localhost:20.500.12123/14788
network_acronym_str INTADig
repository_id_str l
network_name_str INTA Digital (INTA)
spelling Deletion in KARLN intron 5 and predictive relationship with bovine tuberculosis and brucellosis infection phenotypeRossi, Ursula AmarantaCaffaro, María EugeniaRaschia, Maria AgustinaHasenauer, Flavia CarolinaPoli, Mario AndresRossetti, Carlos AlbertoGanado BovinoEnfermedades de los AnimalesTuberculosis BovinaResistencia GenéticaBrucelosisFenotiposCattleAnimal DiseasesBovine TuberculosisGenetic ResistanceBrucellosisPhenotypesKalirin (gene: KALRN) is a Rho-GEF kinase linked to neurodegenerative diseases in humans. Unexpectedly, various polymorphisms in KALRN gene were previously associated with resistance to bacterial infections in ruminants. In this study, we evaluated the effect of the rs384223075 (RS-075) deletion in KALRN intron 5 on the occurrence of Mycobacterium bovis and Brucella abortus infections in cattle. We performed two separate case-control association analyses: one for bovine tuberculosis (bTB) using 308 Holstein and Jersey cows from three herds with prevalence between 5 and 15% for this infection; and another for brucellosis using 140 Holstein and beef crossbred cows from two herds with high prevalence for brucellosis (> 30%). In the bTB analysis, the RS-075 deletion frequency was higher among cases than controls (p = 0.0001), and the absence of the RS-075 deletion allele was associated with negative PPD-skin test results (p = 0.0009) at genotype level. On the contrary, RS-075 was not associated with Brucella spp. serological status (p = 0.72) but, unexpectedly, the deletion allele was more frequent among controls than cases in the beef crossbred herd (0.31 vs. 0.14, p = 0.02). In concordance with this observation, in vitro assays showed that the RS-075 deletion could be linked to an enhanced cellular response to bacterial antigens and unspecific stimulation in mononuclear cells derived from beef crossbred cows, specifically the reactive nitrogen species production (p = 0.008) and proliferation capacity (p = 0.018). This study is consistent with other reports that support an important role of the KALRN gene and its polymorphisms in the host response to intracellular pathogens.Instituto de PatobiologíaFil: Rossi, Ursula. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; ArgentinaFil: Rossi, Ursula. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Caffaro, Marí­a Eugenia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; ArgentinaFil: Raschia, Maria Agustina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; ArgentinaFil: Hasenauer, Flavia Carolina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; ArgentinaFil: Hasenauer, Flavia Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Poli, Mario Andres. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; ArgentinaFil: Rossetti, Carlos Alberto. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; ArgentinaSpringer2023-07-20T15:06:03Z2023-07-20T15:06:03Z2023-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/14788https://link.springer.com/article/10.1007/s11259-022-10039-00165-73801573-7446https://doi.org/10.1007/s11259-022-10039-0Veterinary Research Communications 47 (2) : 779-789 (2023)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repograntAgreement/INTA/2019-PD-E5-I105-001/2019-PD-E5-I105-001, Patógenos animales: su interacción con el hospedador y el medio ambiente. Impacto en productividad, ecosistemas, sanidad animal y salud pública en el marco ?Una Salud?info:eu-repo/semantics/restrictedAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)2025-12-18T09:02:45Zoai:localhost:20.500.12123/14788instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2025-12-18 09:02:45.755INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv Deletion in KARLN intron 5 and predictive relationship with bovine tuberculosis and brucellosis infection phenotype
title Deletion in KARLN intron 5 and predictive relationship with bovine tuberculosis and brucellosis infection phenotype
spellingShingle Deletion in KARLN intron 5 and predictive relationship with bovine tuberculosis and brucellosis infection phenotype
Rossi, Ursula Amaranta
Ganado Bovino
Enfermedades de los Animales
Tuberculosis Bovina
Resistencia Genética
Brucelosis
Fenotipos
Cattle
Animal Diseases
Bovine Tuberculosis
Genetic Resistance
Brucellosis
Phenotypes
title_short Deletion in KARLN intron 5 and predictive relationship with bovine tuberculosis and brucellosis infection phenotype
title_full Deletion in KARLN intron 5 and predictive relationship with bovine tuberculosis and brucellosis infection phenotype
title_fullStr Deletion in KARLN intron 5 and predictive relationship with bovine tuberculosis and brucellosis infection phenotype
title_full_unstemmed Deletion in KARLN intron 5 and predictive relationship with bovine tuberculosis and brucellosis infection phenotype
title_sort Deletion in KARLN intron 5 and predictive relationship with bovine tuberculosis and brucellosis infection phenotype
dc.creator.none.fl_str_mv Rossi, Ursula Amaranta
Caffaro, María Eugenia
Raschia, Maria Agustina
Hasenauer, Flavia Carolina
Poli, Mario Andres
Rossetti, Carlos Alberto
author Rossi, Ursula Amaranta
author_facet Rossi, Ursula Amaranta
Caffaro, María Eugenia
Raschia, Maria Agustina
Hasenauer, Flavia Carolina
Poli, Mario Andres
Rossetti, Carlos Alberto
author_role author
author2 Caffaro, María Eugenia
Raschia, Maria Agustina
Hasenauer, Flavia Carolina
Poli, Mario Andres
Rossetti, Carlos Alberto
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Ganado Bovino
Enfermedades de los Animales
Tuberculosis Bovina
Resistencia Genética
Brucelosis
Fenotipos
Cattle
Animal Diseases
Bovine Tuberculosis
Genetic Resistance
Brucellosis
Phenotypes
topic Ganado Bovino
Enfermedades de los Animales
Tuberculosis Bovina
Resistencia Genética
Brucelosis
Fenotipos
Cattle
Animal Diseases
Bovine Tuberculosis
Genetic Resistance
Brucellosis
Phenotypes
dc.description.none.fl_txt_mv Kalirin (gene: KALRN) is a Rho-GEF kinase linked to neurodegenerative diseases in humans. Unexpectedly, various polymorphisms in KALRN gene were previously associated with resistance to bacterial infections in ruminants. In this study, we evaluated the effect of the rs384223075 (RS-075) deletion in KALRN intron 5 on the occurrence of Mycobacterium bovis and Brucella abortus infections in cattle. We performed two separate case-control association analyses: one for bovine tuberculosis (bTB) using 308 Holstein and Jersey cows from three herds with prevalence between 5 and 15% for this infection; and another for brucellosis using 140 Holstein and beef crossbred cows from two herds with high prevalence for brucellosis (> 30%). In the bTB analysis, the RS-075 deletion frequency was higher among cases than controls (p = 0.0001), and the absence of the RS-075 deletion allele was associated with negative PPD-skin test results (p = 0.0009) at genotype level. On the contrary, RS-075 was not associated with Brucella spp. serological status (p = 0.72) but, unexpectedly, the deletion allele was more frequent among controls than cases in the beef crossbred herd (0.31 vs. 0.14, p = 0.02). In concordance with this observation, in vitro assays showed that the RS-075 deletion could be linked to an enhanced cellular response to bacterial antigens and unspecific stimulation in mononuclear cells derived from beef crossbred cows, specifically the reactive nitrogen species production (p = 0.008) and proliferation capacity (p = 0.018). This study is consistent with other reports that support an important role of the KALRN gene and its polymorphisms in the host response to intracellular pathogens.
Instituto de Patobiología
Fil: Rossi, Ursula. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; Argentina
Fil: Rossi, Ursula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Caffaro, Marí­a Eugenia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; Argentina
Fil: Raschia, Maria Agustina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; Argentina
Fil: Hasenauer, Flavia Carolina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; Argentina
Fil: Hasenauer, Flavia Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Poli, Mario Andres. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; Argentina
Fil: Rossetti, Carlos Alberto. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; Argentina
description Kalirin (gene: KALRN) is a Rho-GEF kinase linked to neurodegenerative diseases in humans. Unexpectedly, various polymorphisms in KALRN gene were previously associated with resistance to bacterial infections in ruminants. In this study, we evaluated the effect of the rs384223075 (RS-075) deletion in KALRN intron 5 on the occurrence of Mycobacterium bovis and Brucella abortus infections in cattle. We performed two separate case-control association analyses: one for bovine tuberculosis (bTB) using 308 Holstein and Jersey cows from three herds with prevalence between 5 and 15% for this infection; and another for brucellosis using 140 Holstein and beef crossbred cows from two herds with high prevalence for brucellosis (> 30%). In the bTB analysis, the RS-075 deletion frequency was higher among cases than controls (p = 0.0001), and the absence of the RS-075 deletion allele was associated with negative PPD-skin test results (p = 0.0009) at genotype level. On the contrary, RS-075 was not associated with Brucella spp. serological status (p = 0.72) but, unexpectedly, the deletion allele was more frequent among controls than cases in the beef crossbred herd (0.31 vs. 0.14, p = 0.02). In concordance with this observation, in vitro assays showed that the RS-075 deletion could be linked to an enhanced cellular response to bacterial antigens and unspecific stimulation in mononuclear cells derived from beef crossbred cows, specifically the reactive nitrogen species production (p = 0.008) and proliferation capacity (p = 0.018). This study is consistent with other reports that support an important role of the KALRN gene and its polymorphisms in the host response to intracellular pathogens.
publishDate 2023
dc.date.none.fl_str_mv 2023-07-20T15:06:03Z
2023-07-20T15:06:03Z
2023-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12123/14788
https://link.springer.com/article/10.1007/s11259-022-10039-0
0165-7380
1573-7446
https://doi.org/10.1007/s11259-022-10039-0
url http://hdl.handle.net/20.500.12123/14788
https://link.springer.com/article/10.1007/s11259-022-10039-0
https://doi.org/10.1007/s11259-022-10039-0
identifier_str_mv 0165-7380
1573-7446
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repograntAgreement/INTA/2019-PD-E5-I105-001/2019-PD-E5-I105-001, Patógenos animales: su interacción con el hospedador y el medio ambiente. Impacto en productividad, ecosistemas, sanidad animal y salud pública en el marco ?Una Salud?
dc.rights.none.fl_str_mv info:eu-repo/semantics/restrictedAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv restrictedAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv Veterinary Research Communications 47 (2) : 779-789 (2023)
reponame:INTA Digital (INTA)
instname:Instituto Nacional de Tecnología Agropecuaria
reponame_str INTA Digital (INTA)
collection INTA Digital (INTA)
instname_str Instituto Nacional de Tecnología Agropecuaria
repository.name.fl_str_mv INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuaria
repository.mail.fl_str_mv tripaldi.nicolas@inta.gob.ar
_version_ 1851855663910617088
score 12.952241

Publicaciones similares