SNP associations and genetic-parameter estimation for nose and hoof pigmentation in Corriedale sheep

Published Online 7/6/23 OnlinePublContext. Quantity and quality of both meat and wool are important for selection programs of the dual-purpose Corriedale sheep. In Corriedales, black pigmentation of nose skin and hooves is preferred as part of the breed standard. However, within the breed, pigmentation can vary from none to complete pigmentation. Aims. The aim was to discover single-nucleotide polymorphisms (SNPs) and genes associated with nose and hoof pigmentation and to estimate genetic parameters of nose and hoof pigmentation, wool traits and meat traits. Methods. The phenotype and genotype data on Corriedale lambs (n = 764) produced from 44 sires (12 studs) and 300 ewes in 2017–2019 were used in this study. Lambs were slaughtered at 6–7 months of age. Nose pigmentation and hoof pigmentation were scored on a five-point scale, where no pigmentation was scored 0 and complete pigmentation was scored 5. Wool-and meat-quality traits were measured, including greasy fleece weight, fibre diameter, weaning weight, hot standard carcass weight and intramuscular fat percentage. The lambs were genotyped with the GGPOvine50K SNP chip. A genome-wide association study (GWAS) was conducted. Genetic parameters and bivariate analyses were estimated using ASReml-R. Results. The lambs had a mean nose-pigmentation score of 3.69 and hoof-pigmentation score of 4.12. The nose pigmentation (h2 = 0.58) and hoof pigmentation (h2 = 0.51) were highly heritable and highly correlated (rG = 0.73). The GWAS identified a genome-wide significant SNP (OAR19_33278780.1) associated with nose pigmentation (q-value = 0.04). This SNP is positioned in a known pigmentation gene, melanocyte-inducing transcription factor (MITF ). The same SNP was the sixth-most associated SNP for hoof pigmentation but did not reach significance level. OAR19_33278780.1 also had a significant effect on back conformation and weaning weight. Conclusions. The results of these analyses have provided information and an understanding of the genetics for pigmentation of nose and hooves in Corriedale sheep. Implications. Nose and hoof pigmentation are highly genetically correlated with each other, but with no negative effects on production traits.J. E. Aldersey, M. S. Khatkar, P. J. Blackwood, C. E. Blackwood, J. M. Pitchford, H. Gordon, S. C. Welsh and W. S. Pitchfor

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Obesity due to Melanocortin 4 Receptor (MC4R) Deficiency Is Associated with Increased Linear Growth and Final Height, Fasting Hyperinsulinemia, and Incompletely Suppressed Growth Hormone Secretion

Diabetes mellitus: pathophysiological changes and therap