Signatures of Selective Sweeps in Parasite Selection Flocks

Abstract

Gastrointestinal nematodes are the single most costly disease facing sheep production in New Zealand. Production loss due to parasitism is two-fold; the direct cost of anthelmintic treatment combines with production losses due to weight loss and death, costing New Zealand farmers an estimated $300 million per year. In the face of increasing drench resistance and the need to minimise drench residues in animal products, new strategies for control are called for. Breeding for host resistance is a viable method of nematode control, and the identification of genes or linked markers that have a significant association to host resistance against internal parasites would greatly accelerate genetic improvement. Recent advances in genomic technologies have provided new opportunities to understand the infection process of internal parasites in sheep at the genetic level. This project builds on prior studies to use whole genomic screens for selection to identify loci that affect individual resistance or susceptibility to nematode parasites. Divergent lines of Romney and Perendale sheep have been selectively bred for high and low faecal nematode egg count (FEC) by AgResearch since 1978 and 1986 respectively; animals wereselected as lambs solely on the basis of FEC following a mixed species nematode challenge. The Illumina® Ovine SNP50 BeadChip was used to genotype a selection of progeny from each of thelines, as well as selected sires and dams. The resulting genome-wide SNP data was analysed for selective sweeps on loci associated with resistance or susceptibility to nematode infection using the FST and Peddrift statistics. Nine regions were identified as showing the highest signals of selection in both Romney and Perendale lines and two regions, one on chromosome 1 (92,508,855-93,589,808bp) and another on chromosome 16 (18,182,900-19,903,458bp), were chosen for further analysis. This was achieved through fine-mapping with a denser set of SNPs, using Sequenom technology. The extended haplotype homozygosity (EHH) test and its derivatives, iHS and XP-EHH, were subsequently used to clarify the signals of selection observed in these regions. An undetermined variant in the region on chromosome one appears to confer susceptibility to gastrointestinal parasites in the Romney selection lines. This region contains the acidic mammalian chitinase gene CHIA, which has previously been implicated in helminth resistance. While sequencing of the CHIA exons did not identify any obvious candidate polymorphisms, the strongest signals are adjacent to CHIA, and the adjacent chitinase family member CHI3L2, indicating that the causal mutation may be within a regulatory region. The region on chromosome sixteen, containing BAG1, showed elevated XP-EHH in the Perendale lines, indicating that a variant in the region contributes to susceptibility to gastrointestinal parasites. Further work in both regions is required to track down the precise causal variants before they can be considered further for use in marker-assisted selection.