Deletion in KARLN intron 5 and predictive relationship with bovine tuberculosis and brucellosis infection phenotype
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...
| Main Authors: | , , , , , |
|---|---|
| Format: | info:ar-repo/semantics/artículo |
| Language: | Inglés |
| Published: |
Springer
2023
|
| Subjects: | |
| Online Access: | 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 |
| _version_ | 1855037181837443072 |
|---|---|
| author | Rossi, Ursula Amaranta Caffaro, María Eugenia Raschia, Maria Agustina Hasenauer, Flavia Carolina Poli, Mario Andres Rossetti, Carlos Alberto |
| author_browse | Caffaro, María Eugenia Hasenauer, Flavia Carolina Poli, Mario Andres Raschia, Maria Agustina Rossetti, Carlos Alberto Rossi, Ursula Amaranta |
| author_facet | Rossi, Ursula Amaranta Caffaro, María Eugenia Raschia, Maria Agustina Hasenauer, Flavia Carolina Poli, Mario Andres Rossetti, Carlos Alberto |
| author_sort | Rossi, Ursula Amaranta |
| collection | INTA Digital |
| 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. |
| format | info:ar-repo/semantics/artículo |
| id | INTA14788 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2023 |
| publishDateRange | 2023 |
| publishDateSort | 2023 |
| publisher | Springer |
| publisherStr | Springer |
| record_format | dspace |
| spelling | INTA147882023-07-20T15:10:56Z Deletion in KARLN intron 5 and predictive relationship with bovine tuberculosis and brucellosis infection phenotype Rossi, Ursula Amaranta Caffaro, María Eugenia Raschia, Maria Agustina Hasenauer, Flavia Carolina Poli, Mario Andres Rossetti, Carlos Alberto Ganado Bovino Enfermedades de los Animales Tuberculosis Bovina Resistencia Genética Brucelosis Fenotipos Cattle Animal Diseases Bovine Tuberculosis Genetic Resistance Brucellosis Phenotypes 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 2023-07-20T15:06:03Z 2023-07-20T15:06:03Z 2023-06 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 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 eng 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? 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) application/pdf Springer Veterinary Research Communications 47 (2) : 779-789 (2023) |
| spellingShingle | Ganado Bovino Enfermedades de los Animales Tuberculosis Bovina Resistencia Genética Brucelosis Fenotipos Cattle Animal Diseases Bovine Tuberculosis Genetic Resistance Brucellosis Phenotypes Rossi, Ursula Amaranta Caffaro, María Eugenia Raschia, Maria Agustina Hasenauer, Flavia Carolina Poli, Mario Andres Rossetti, Carlos Alberto 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 |
| 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_short | 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 |
| topic | Ganado Bovino Enfermedades de los Animales Tuberculosis Bovina Resistencia Genética Brucelosis Fenotipos Cattle Animal Diseases Bovine Tuberculosis Genetic Resistance Brucellosis Phenotypes |
| 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 |
| work_keys_str_mv | AT rossiursulaamaranta deletioninkarlnintron5andpredictiverelationshipwithbovinetuberculosisandbrucellosisinfectionphenotype AT caffaromariaeugenia deletioninkarlnintron5andpredictiverelationshipwithbovinetuberculosisandbrucellosisinfectionphenotype AT raschiamariaagustina deletioninkarlnintron5andpredictiverelationshipwithbovinetuberculosisandbrucellosisinfectionphenotype AT hasenauerflaviacarolina deletioninkarlnintron5andpredictiverelationshipwithbovinetuberculosisandbrucellosisinfectionphenotype AT polimarioandres deletioninkarlnintron5andpredictiverelationshipwithbovinetuberculosisandbrucellosisinfectionphenotype AT rossetticarlosalberto deletioninkarlnintron5andpredictiverelationshipwithbovinetuberculosisandbrucellosisinfectionphenotype |