Genome-Wide Scan for Visceral Leishmaniasis in Mixed-Breed Dogs Identifies Candidate Genes Involved in T Helper Cells and Macrophage Signaling
| Autor: | Cáris Maroni Nunes, Robert D. Schnabel, Tad S. Sonstegard, Valquiria R. Gazola, Jeremy F. Taylor, Amanda Pifano Neto Quintal, Henrique Borges de Paula, Yuri Tani Utsunomiya, Juliano R. Sangalli, Érica de Souza Ribeiro, Cristiana M. Trinconi, Silvia Helena Venturoli Perri, José Fernando Garcia, Valéria Marçal Felix de Lima |
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| Přispěvatelé: | Universidade Estadual Paulista (Unesp), University of Missouri, Agricultural Research Service-United States Department of Agriculture (ARS-USDA) |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
CD4-Positive T-Lymphocytes
Candidate gene Genotype Cellular differentiation Notch signaling pathway lcsh:Medicine Polymorphism Single Nucleotide 030308 mycology & parasitology 03 medical and health sciences Dogs Macrophage Animals Humans Leishmania infantum Enhancer lcsh:Science 030304 developmental biology 0303 health sciences Multidisciplinary biology Receptors Notch Receptors Interleukin-15 lcsh:R Interleukin-2 Receptor alpha Subunit Cell Differentiation T-Lymphocytes Helper-Inducer biology.organism_classification Leishmania Molecular biology 3. Good health Repressor Proteins Leishmaniasis Visceral lcsh:Q Signal transduction Co-Repressor Proteins Brazil Genome-Wide Association Study Signal Transduction Research Article |
| Zdroj: | PLoS ONE, Vol 10, Iss 9, p e0136749 (2015) PubMed Repositório Institucional da UNESP Universidade Estadual Paulista (UNESP) instacron:UNESP PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Made available in DSpace on 2015-12-07T15:33:41Z (GMT). No. of bitstreams: 0 Previous issue date: 2015. Added 1 bitstream(s) on 2015-12-07T15:52:43Z : No. of bitstreams: 1 PMC4562658.pdf: 1027127 bytes, checksum: d70e9ba0177f643e6abdf99c4143a192 (MD5) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) We conducted a genome-wide scan for visceral leishmaniasis in mixed-breed dogs from a highly endemic area in Brazil using 149,648 single nucleotide polymorphism (SNP) markers genotyped in 20 cases and 28 controls. Using a mixed model approach, we found two candidate loci on canine autosomes 1 and 2. The positional association on chromosome 2 mapped to a predicted DNAse sensitive site in CD14+ monocytes that serve as a cis-regulatory element for the expression of interleukin alpha receptors 2 (IL2RA) and 15 (IL15RA). Both interleukins were previously found to lead to protective T helper 1 cell (Th1) response against Leishmania spp. in humans and mice. The associated marker on chromosome 1 was located between two predicted transcription factor binding sites regulating the expression of the transducin-like enhancer of split 1 gene (TLE1), an important player in Notch signaling. This pathway is critical for macrophage activity and CD4+ T cell differentiation into Th1 and T helper 2. Together, these findings suggest that the human and mouse model for protective response against Leishmania spp., which involves Th1 and macrophage modulation by interleukins 2, 15, gamma interferon and Notch signaling, may also hold for the canine model. Departamento de Medicina Veterinária Preventiva e Reprodução Animal, Faculdade de Ciências Agrárias e Veterinárias, UNESP-Univ Estadual Paulista, Jaboticabal, São Paulo, Brazil. Departamento de Apoio, Saúde e Produção Animal, Faculdade de Medicina Veterinária de Araçatuba, UNESP-Univ Estadual Paulista, Araçatuba, São Paulo, Brazil. Division of Animal Sciences, University of Missouri, Columbia, 65211, United States of America. Animal Genomics and Improvement Laboratory, ARS-USDA-Agricultural Research Service-United States Department of Agriculture, Beltsville, Maryland, United States of America. Departamento de Medicina Veterinária Preventiva e Reprodução Animal, Faculdade de Ciências Agrárias e Veterinárias, UNESP-Univ Estadual Paulista, Jaboticabal, São Paulo, Brazil; Departamento de Apoio, Saúde e Produção Animal, Faculdade de Medicina Veterinária de Araçatuba, UNESP-Univ Estadual Paulista, Araçatuba, São Paulo, Brazil. Departamento de Medicina Veterinária Preventiva e Reprodução Animal, Faculdade de Ciências Agrárias e Veterinárias, UNESP-Univ Estadual Paulista, Jaboticabal, São Paulo, Brazil. Departamento de Apoio, Saúde e Produção Animal, Faculdade de Medicina Veterinária de Araçatuba, UNESP-Univ Estadual Paulista, Araçatuba, São Paulo, Brazil. Departamento de Medicina Veterinária Preventiva e Reprodução Animal, Faculdade de Ciências Agrárias e Veterinárias, UNESP-Univ Estadual Paulista, Jaboticabal, São Paulo, Brazil; Departamento de Apoio, Saúde e Produção Animal, Faculdade de Medicina Veterinária de Araçatuba, UNESP-Univ Estadual Paulista, Araçatuba, São Paulo, Brazil. FAPESP: 2014/01095-8 |
| Databáze: | OpenAIRE |
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