SNiP and cut: Quantifying the potential benefits of genomic selection tools for genetic fault elimination in sheep

ABSTRACT Whole genome single nucleotide polymorphism marker (SNP) technologies are rapidly being developed and could well play a role in the future selection of farmed animals. In sheep, work is being carried out to identify SNP's associated with economically important production traits and disease resistance. Stud sheep breeders routinely cull up to 30% of lambs born due to a variety of faults. Despite this culling pressure, the faults keep occurring, suggesting low heritability, recessive inheritance or incomplete penetration of fault causing genes. The objective of this paper was to identify the potential of SNP fault detection and elimination in sheep. Simulation was used to predict changes in gene frequencies and in an index of genetic merit of production traits over time when between two and 30 SNPs were used to aid selection. The SNPs are assumed to predict the presence of deleterious recessive genes. As selection pressure applied to individual or combination SNPs increased, the rate of increase in production trait genetic merit slowed down. Thus, a balance would be required between the emphasis on SNPs actively used to select against genetic faults, relative to emphasis on genetic merit. This work identified scope for substantial economic benefits from application of SNP technology for removal of faults to both stud breeders and commercial sheep farmers

Randomized clinical trial to assess the impact of the broadly neutralizing HIV-1 monoclonal antibody VRC01 on HIV-1 persistence in individuals on effective ART

Background. Broadly neutralizing monoclonal antibodies (bnMAbs) may promote clearance of HIV-1-expressing cells through antibody-dependent cell-mediated cytotoxicity. We evaluated the effect of the CD4-binding site bnMAb, VRC01, on measures of HIV-1 persistence in chronically infected individuals. Methods. A5342 was a phase 1, randomized, double-blind, placebo-controlled, parallel-arm study. Participants on effective antiretroviral therapy (ART) were randomized to receive 2 infusions of VRC01 (40 mg/kg) at entry and week 3, and 2 infusions of placebo (saline) at weeks 6 and 9; or 2 infusions of placebo at entry and week 3, and 2 infusions of VRC01 at weeks 6 and 9. Results. Infusion of VRC01 was safe and well tolerated. The median fold-change in the cell-associated HIV-1 RNA/DNA ratio from baseline to week 6 was 1.12 and 0.83 for the VRC01 and placebo arms, respectively, with no significant difference between arms (P = .16). There were no significant differences in the proportions with residual plasma viremia ≥1 copies/mL or in phorbol 12-myristate 13-acetate/ionomycin-induced virus production from CD4+ T cells between arms (both P > .05). Conclusions. In individuals with chronic HIV-1 infection on ART, VRC01 infusions were safe and well tolerated but did not affect plasma viremia, cellular HIV-1 RNA/DNA levels, or stimulated virus production from CD4+ T cells

Selection indices offer potential for New Zealand sheep farmers to reduce greenhouse gas emissions per unit of product

The New Zealand Government is a signatory of the Kyoto Protocol which provides incentive for it to reduce its total greenhouse gas emissions (GHG). The sheep industry is a significant contributor to the total GHG in New Zealand. It also has widespread use of selection index technology which could be a potential GHG mitigation tool. This paper provides an assessment of the potential for New Zealand sheep farmers to reduce GHG using selection indices. Trait weightings were altered in novel indices to facilitate greater reductions in GHG. These were compared to a conventional farm profit maximising index. Selection of sheep using the farm profit maximising index reduced GHG output in kilograms of carbon dioxide equivalent units (kg CO2e) per kilogram of lamb carcase weight (kg cwt) by 0.59% of total methane and nitrous oxide emissions per annum (pa). Novel ‘Dual Purpose Environment’ indices (DPE) were developed to provide greater GHG reductions in kg CO2e/kg cwt. A range of carbon prices were incorporated into the DPE. The study showed 96.6% of the potential farm profit (excluding emissions costs) and 69.8% of potential kg CO2e/kg cwt improvements could be obtained using a carbon price of NZ$100/tonne CO2e in the DPE. The corresponding figures for NZ$25/t CO2e were 99.8% and 56%. The carbon price used in the DPE therefore influenced the trade-off between progress in traits which reduce GHG in kg CO2e/kg cwt and those that improve farm profitability. Selection indices are an option for farmers to reduce GHG in kg CO2e/kg cwt in New Zealand sheep. However, farmers will need to consider the trade-off between improving traits which contribute to farm profit and those that reduce GHG