Candidate gene approach for parasite resistance in sheep--variation in immune pathway genes and association with fecal egg count

PLoS One. 2014 Feb 12;9(2):e88337. doi: 10.1371/journal.pone.0088337. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bayes Theorem
  • Cluster Analysis
  • Disease Resistance / genetics*
  • Feces / parasitology
  • Gene Frequency
  • Genotype
  • Geography
  • Haplotypes
  • Immune System
  • Microsatellite Repeats / genetics
  • Nematoda
  • Parasite Egg Count
  • Parasitic Diseases / genetics*
  • Parasitic Diseases / transmission*
  • Polymorphism, Single Nucleotide
  • Sequence Analysis, DNA
  • Sheep
  • Species Specificity

Grants and funding

The study is funded by International Atomic Energy Agency through grant of Research Contracts to member state counterparts under the Coordinated Research Project D3.10.26 “Genetic Variation on the control of resistance to infectious diseases to improve productivity in small ruminants”. The Research Contracts Administration Section of IAEA (funder) had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.