Copy number variations in South African Nguni cattle : prevalence, characterization and genetic diversity

[摘要] ENGLISH ABSTRACT: Copy Number Variations (CNVs) comprise of deletions, duplications and insertions larger than 1kb thatoccur within genomes. The identification of CNVs within regions of the bovine genome important foradaptation renders them a potential role in breed formation and adaptation. South African Nguni cattle areadapted and demonstrate an enhanced ability to endure the harsh environmental conditions of SouthernAfrica. This study investigated the prevalence of CNVs in the genome of South African Nguni cattle. CNVoccurrence and distribution within Nguni subpopulations was assessed and comparisons with other SouthAfrican cattle breeds were performed. The dynamics between CNVs and haplotype blocks (HPBs),correlations amongst CNVs and the genic locality of CNVs were investigated with the objective ofdetermining CNV prevalence in adaptation. The Illumina BovineSNP50 beadchip was used in the firstexperiment to genotype 492 South African Nguni cattle sampled nationwide. PennCNV software identified334 CNV regions (CNVRs) of between 30kb and 1Mb in length. Population structure analyses wasperformed and HPBs identified using ADMIXTURE and PLINK software respectively. Five subpopulationswere evident with some degree of CNV segregation amongst populations. CNVRs covered or lay within10Mb of 289 genes of which 149, 28, 44, 2 and 14 genes exclusive to the five sub-populations wereidentified. Some degree of overlap between CNVRs and the 541 HPBs was evident. In the secondexperiment, 59 Nguni genotypes were analyzed using the Bovine 50K Beadchip in conjunction with sixother South African breeds. PennCNV software identified 356 unique CNVRs. One hundred and sixty threeCNVRs identified in more than 1 animal were utilized as genetic markers to assess within and between breedgenetic diversity (GD). Between breed group GD scores were 2.510, 6.115 and 4.233 for the Sanga, Taurineand composite breeds respectively. One hundred and two (Taurine) and seven (Sanga and composite) of theCNVRs demonstrated a significant (p≤0.05) association with one another. PANTHER overrepresentationanalyses demonstrated significant representation of a number of processes, functions, components andproteins by correlated CNVR genes. CNVR based phylogenetic clustered animals of the same breed grouptogether. In the third experiment 24 Nguni animals were sequenced at 7X coverage using illumina nextgeneration sequencing technologies. Reads were mapped to the UMD3.1 reference genome and RAPTR-SVsoftware was utilized to identify CNVs. CNVs identifed were filtered according to the number of reads thatsupport the event with low (F10), medium (F45) and high stringencies (F75). Adjacent and overlappingCNVs were merged to form 399, 55 and 23 unique CNVRs that covered or lay within 1Mb of 358, 51 and 23genes at F10, F45 and F75 stringencies respectively. NGS tools identified smaller CNVs compared to thosereported from SNP data. Despite discrepancies between array and NGS methods, CNVR genes representedthe same specific ontologies. The study demonstrated CNVRs to be prevalent in South African Nguni cattle,with potential role in breed formation and adaptation. CNVR GD scores, population structure, distributionand incidence dynamics were thus ascertained for the South African Nguni.

[发布机构] Stellenbosch University