title: MYD88 and functionally related genes are associated with multiple infections in a model population of Kenyan village dogs.
abstract: The purpose of this study was to seek associations between immunity-related molecular markers and endemic infections in a model population of African village dogs from Northern Kenya with no veterinary care and no selective breeding. A population of village dogs from Northern Kenya composed of three sub-populations from three different areas (84, 50 and 55 dogs) was studied. Canine distemper virus (CDV), Hepatozoon canis, Microfilariae (Acantocheilonema dracunculoides, Acantocheilonema reconditum) and Neospora caninum were the pathogens studied. The presence of antibodies (CDV, Neospora), light microscopy (Hepatozoon) and diagnostic PCR (Microfilariae) were the methods used for diagnosing infection. Genes involved in innate immune mechanisms, NOS3, IL6, TLR1, TLR2, TLR4, TLR7, TLR9, LY96, MYD88, and three major histocompatibility genes class II genes were selected as candidates. Single nucleotide polymorphism (SNP) markers were detected by Sanger sequencing, next generation sequencing and PCR-RFLP. The Fisher´s exact test for additive and non-additive models was used for association analyses. Three SNPs within the MYD88 gene and one TLR4 SNP marker were associated with more than one infection. Combined genotypes and further markers identified by next generation sequencing confirmed associations observed for individual genes. The genes associated with infection and their combinations in specific genotypes match well our knowledge on their biological role and on the role of the relevant biological pathways, respectively. Associations with multiple infections observed between the MYD88 and TLR4 genes suggest their involvement in the mechanisms of anti-infectious defenses in dogs.
authors.affiliation: Department of Animal Genetics, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 61242, Brno, Czech Republic.
authors.forename: Michaela
authors.initials: M
authors.lastname: Necesankova
authors.affiliation: Department of Animal Genetics, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 61242, Brno, Czech Republic.
authors.forename: Leona
authors.initials: L
authors.lastname: Vychodilova
authors.affiliation: Department of Pathology and Parasitology, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 61242, Brno, Czech Republic.
authors.forename: Katerina
authors.initials: K
authors.lastname: Albrechtova
authors.affiliation: Centre for Integrated Genomic Medical Research, University of Manchester, Oxford Road, Manchester, M13 9PT, UK.
authors.forename: Lorna J
authors.initials: LJ
authors.lastname: Kennedy
authors.affiliation: Department of Pathology and Parasitology, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 61242, Brno, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Hlavac
authors.affiliation: State Veterinary Institute Prague, Sidlistni 136/24, 165 03, Praha, Czech Republic.
authors.forename: Kamil
authors.initials: K
authors.lastname: Sedlak
authors.affiliation: Ceitec VFU, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 61242, Brno, Czech Republic.|Department of Pathology and Parasitology, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 61242, Brno, Czech Republic.|Vétérinaires Sans Frontières Czech Republic, Palackeho 1, 61242, Brno, Czech Republic.|Biology Centre, Institute of Parasitology, Czech Academy of Sciences, Branisovska 31, 37005, Ceske Budejovice, Czech Republic.
authors.forename: David
authors.initials: D
authors.lastname: Modry
authors.affiliation: Department of Animal Genetics, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 61242, Brno, Czech Republic.|Ceitec VFU, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 61242, Brno, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Janova
authors.affiliation: Department of Animal Genetics, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 61242, Brno, Czech Republic.
authors.forename: Mirko
authors.initials: M
authors.lastname: Vyskocil
authors.affiliation: Department of Animal Genetics, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 61242, Brno, Czech Republic. horin@dior.ics.muni.cz.|Ceitec VFU, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 61242, Brno, Czech Republic. horin@dior.ics.muni.cz.
authors.forename: Petr
authors.initials: P
authors.lastname: Horin
mesh_terms: D000818:Animals; D004216:Distemper / Q000235:genetics*; D004285:Dogs; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D007630:Kenya; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011529:Protozoan Infections, Animal / Q000235:genetics*; D012424:Rural Population; D017422:Sequence Analysis, DNA; D051197:Toll-Like Receptor 4 / Q000235:genetics
chemical_list: D053594:Myeloid Differentiation Factor 88; D051197:Toll-Like Receptor 4
keywords: Associations; Immunity-related genes; Infectious diseases; Kenyan village dogs