Genome-wide copy number variation in sheep : detection and utility as a genetic marker for quantitative traits, with reference to gastrointestinal nematodiasis : thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Animal Science at Massey University, Palmerston North, New Zealand

Abstract

Gastrointestinal nematodes are perhaps the most important parasites of domestic sheep world-wide. Genetic selection for nematode resistance in domestic sheep is being promoted in many countries including New Zealand. There are several strategies to identify genetic markers associated with quantitative traits. Single nucleotide polymorphism (SNP)-based strategies have been widely used in animal breeding. However, SNP cannot explain all the genetic variation for a particular trait. A new kind of variation, copy number variation (CNV) has been identified as contributing to genetic variation in production and disease traits. Compared with other domestic animals, CNV in sheep is poorly investigated. The primary objective of this thesis was to explore the utility of genome-wide CNV as a genetic marker for the analysis of quantitative traits in sheep. Five different studies were undertaken to fulfill the objective. The first two studies used 50 K SNP BeadChip genotype data and next generation sequencing (NGS) data to detect CNV. Extensive CNV differences were evident between breeds as well as detection algorithms. NGS-based detection resulted in better CNV resolution than that by SNP. Subsequently, a genome-wide association study (with a small sample size) using CNV detected from a high density (HD) SNP genotype data identified four CNV regions to be significantly associated with a couple of traits pertaining to gastrointestinal nematodiasis in Romney sheep, while no significant SNP associations were found. Somatic mosaicism of CNV, influenced by age (high in foetuses, compared to adults), individuals, detection algorithm and type of tissue analysed, was also evident in separate study. The final study detected CNV differences and SNP based selection signatures in two Romney lines selected for gastrointestinal nematode resistance or resilience. Several significant SNPs and line-specific CNV regions were identified. However, only one SNP overlapped to a CNV region, indicating that SNP-based selection signatures and CNV could represent different aspects of sheep immunogenetics. Overall, CNV could be a potential genetic marker, albeit with methods for detection and validation needing to be refined. The conclusions from this thesis expand our understanding of CNV in sheep and its potential application prospects for genetic breeding of sheep in the future.