title: Candidate gene approach for parasite resistance in sheep--variation in immune pathway genes and association with fecal egg count.
abstract: Sheep chromosome 3 (Oar3) has the largest number of QTLs reported to be significantly associated with resistance to gastro-intestinal nematodes. This study aimed to identify single nucleotide polymorphisms (SNPs) within candidate genes located in sheep chromosome 3 as well as genes involved in major immune pathways. A total of 41 SNPs were identified across 38 candidate genes in a panel of unrelated sheep and genotyped in 713 animals belonging to 22 breeds across Asia, Europe and South America. The variations and evolution of immune pathway genes were assessed in sheep populations across these macro-environmental regions that significantly differ in the diversity and load of pathogens. The mean minor allele frequency (MAF) did not vary between Asian and European sheep reflecting the absence of ascertainment bias. Phylogenetic analysis revealed two major clusters with most of South Asian, South East Asian and South West Asian breeds clustering together while European and South American sheep breeds clustered together distinctly. Analysis of molecular variance revealed strong phylogeographic structure at loci located in immune pathway genes, unlike microsatellite and genome wide SNP markers. To understand the influence of natural selection processes, SNP loci located in chromosome 3 were utilized to reconstruct haplotypes, the diversity of which showed significant deviations from selective neutrality. Reduced Median network of reconstructed haplotypes showed balancing selection in force at these loci. Preliminary association of SNP genotypes with phenotypes recorded 42 days post challenge revealed significant differences (P<0.05) in fecal egg count, body weight change and packed cell volume at two, four and six SNP loci respectively. In conclusion, the present study reports strong phylogeographic structure and balancing selection operating at SNP loci located within immune pathway genes. Further, SNP loci identified in the study were found to have potential for future large scale association studies in naturally exposed sheep populations.
authors.affiliation: Animal Production and Health Laboratory, Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture, International Atomic Energy Agency, Vienna, Austria.
authors.forename: Kathiravan
authors.initials: K
authors.lastname: Periasamy
authors.affiliation: Animal Production and Health Laboratory, Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture, International Atomic Energy Agency, Vienna, Austria.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Pichler
authors.affiliation: Instituto de Genética "Ewald A. Favret", Instituto Nacional de Tecnología Agropecuaria, Buenos Aires, Argentina.
authors.forename: Mario
authors.initials: M
authors.lastname: Poli
authors.affiliation: Anguil Experimental Station, Instituto Nacional de Tecnología Agropecuaria Santa Rosa, La Pampa, Argentina.
authors.forename: Silvina
authors.initials: S
authors.lastname: Cristel
authors.affiliation: Mercedes Experimental Station, Instituto Nacional de Tecnología Agropecuaria Mercedes, Corrientes, Argentina.
authors.forename: Bibiana
authors.initials: B
authors.lastname: Cetrá
authors.affiliation: Concepción del Uruguay Experimental Station, Instituto Nacional de Tecnología Agropecuaria Concepción del Uruguay, Entre Ríos, Argentina.
authors.forename: Daniel
authors.initials: D
authors.lastname: Medus
authors.affiliation: Department of Animal Sciences, Bogor Agricultural University, Bogor, Indonesia.
authors.forename: Muladno
authors.initials: M
authors.lastname: Basar
authors.affiliation: Veterinary College and Research Institute-Namakkal, Tamil Nadu Veterinary and Animal Sciences University, Chennai, India.
authors.forename: Thiruvenkadan
authors.initials: T
authors.lastname: A K
authors.affiliation: Veterinary College and Research Institute-Namakkal, Tamil Nadu Veterinary and Animal Sciences University, Chennai, India.
authors.forename: Saravanan
authors.initials: S
authors.lastname: Ramasamy
authors.affiliation: Department of Animal Genetics and Breeding, University of Veterinary and Animal Sciences, Lahore, Pakistan.
authors.forename: Masroor Babbar
authors.initials: MB
authors.lastname: Ellahi
authors.affiliation: Department of Animal Breeding and Genetics, Bangladesh Agricultural University, Mymensingh, Bangladesh.
authors.forename: Faruque
authors.initials: F
authors.lastname: Mohammed
authors.affiliation: University of Forestry, Sofia, Bulgaria.
authors.forename: Atanaska
authors.initials: A
authors.lastname: Teneva
authors.affiliation: Animal Production and Health Laboratory, Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture, International Atomic Energy Agency, Vienna, Austria.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Shamsuddin
authors.affiliation: Animal Production and Health Laboratory, Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture, International Atomic Energy Agency, Vienna, Austria.
authors.forename: Mario Garcia
authors.initials: MG
authors.lastname: Podesta
authors.affiliation: Animal Production and Health Laboratory, Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture, International Atomic Energy Agency, Vienna, Austria.
authors.forename: Adama
authors.initials: A
authors.lastname: Diallo
mesh_terms: D000818:Animals; D001499:Bayes Theorem; D016000:Cluster Analysis; D060467:Disease Resistance / Q000235:genetics*; D005243:Feces / Q000469:parasitology; D005787:Gene Frequency; D005838:Genotype; D005843:Geography; D006239:Haplotypes; D007107:Immune System; D018895:Microsatellite Repeats / Q000235:genetics; D009348:Nematoda; D010270:Parasite Egg Count; D010272:Parasitic Diseases / Q000235:genetics* / Q000635:transmission*; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D012756:Sheep; D013045:Species Specificity