Browsing by Author "Snell R"

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    Advantage of including Genomic Information to Predict Breeding Values for Lactation Yields of Milk, Fat, and Protein or Somatic Cell Score in a New Zealand Dairy Goat Herd
    (MDPI (Basel, Switzerland), 2021-01) Scholtens M; Lopez-Villalobos N; Lehnert K; Snell R; Garrick D; Blair HT
    Selection on genomic breeding values (GBVs) is now readily available for ranking candidates in improvement schemes. Our objective was to quantify benefits in terms of accuracy of prediction from including genomic information in the single-trait estimation of breeding values (BVs) for a New Zealand mixed breed dairy goat herd. The dataset comprised phenotypic and pedigree records of 839 does. The phenotypes comprised estimates of 305-day lactation yields of milk, fat, and protein and average somatic cell score from the 2016 production season. Only 388 of the goats were genotyped with a Caprine 50K SNP chip and 41,981 of the single nucleotide polymorphisms (SNPs) passed quality control. Pedigree-based best linear unbiased prediction (PBLUP) was used to obtain across-breed breeding values (EBVs), whereas a single-step BayesC model (ssBC) was used to estimate across-breed GBVs. The average prediction accuracies ranged from 0.20 to 0.22 for EBVs and 0.34 to 0.43 for GBVs. Accuracies of GBVs were up to 103% greater than EBVs. Breed effects were more reliably estimated in the ssBC model compared with the PBLUP model. The greatest benefit of genomic prediction was for individuals with no pedigree or phenotypic records. Including genomic information improved the prediction accuracy of BVs compared with the current pedigree-based BLUP method currently implemented in the New Zealand dairy goat population.
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    The genomes of precision edited cloned calves show no evidence for off-target events or increased de novo mutagenesis
    (BioMed Central Ltd, 2021-06-17) Jivanji S; Harland C; Cole S; Brophy B; Garrick D; Snell R; Littlejohn M; Laible G
    BACKGROUND: Animal health and welfare are at the forefront of public concern and the agricultural sector is responding by prioritising the selection of welfare-relevant traits in their breeding schemes. In some cases, welfare-enhancing traits such as horn-status (i.e., polled) or diluted coat colour, which could enhance heat tolerance, may not segregate in breeds of primary interest, highlighting gene-editing tools such as the CRISPR-Cas9 technology as an approach to rapidly introduce variation into these populations. A major limitation preventing the acceptance of CRISPR-Cas9 mediated gene-editing, however, is the potential for off-target mutagenesis, which has raised concerns about the safety and ultimate applicability of this technology. Here, we present a clone-based study design that has allowed a detailed investigation of off-target and de novo mutagenesis in a cattle line bearing edits in the PMEL gene for diluted coat-colour. RESULTS: No off-target events were detected from high depth whole genome sequencing performed in precursor cell-lines and resultant calves cloned from those edited and non-edited cell lines. Long molecule sequencing at the edited site and plasmid-specific PCRs did not reveal structural variations and/or plasmid integration events in edited samples. Furthermore, an in-depth analysis of de novo mutations across the edited and non-edited cloned calves revealed that the mutation frequency and spectra were unaffected by editing status. Cells in culture, however, appeared to have a distinct mutation signature where de novo mutations were predominantly C > A mutations, and in cloned calves they were predominantly T > G mutations, deviating from the expected excess of C > T mutations. CONCLUSIONS: We found no detectable CRISPR-Cas9 associated off-target mutations in the gene-edited cells or calves derived from the gene-edited cell line. Comparison of de novo mutation in two gene-edited calves and three non-edited control calves did not reveal a higher mutation load in any one group, gene-edited or control, beyond those anticipated from spontaneous mutagenesis. Cell culture and somatic cell nuclear transfer cloning processes contributed the major source of contrast in mutational profile between samples.