Harnessing genetic potential of wheat germplasm banks through impact-oriented-prebreeding for future food and nutritional security

The value of exotic wheat genetic resources for accelerating grain yield gains is largely unproven and unrealized. We used next-generation sequencing, together with multi-environment phenotyping, to study the contribution of exotic genomes to 984 three-way-cross-derived (exotic/elite1//elite2) pre-breeding lines (PBLs). Genomic characterization of these lines with haplotype map-based and SNP marker approaches revealed exotic specific imprints of 16.1 to 25.1%, which compares to theoretical expectation of 25%. A rare and favorable haplotype (GT) with 0.4% frequency in gene bank identified on chromosome 6D minimized grain yield (GY) loss under heat stress without GY penalty under irrigated conditions. More specifically, the ‘T’ allele of the haplotype GT originated in Aegilops tauschii and was absent in all elite lines used in study. In silico analysis of the SNP showed hits with a candidate gene coding for isoflavone reductase IRL-like protein in Ae. tauschii. Rare haplotypes were also identified on chromosomes 1A, 6A and 2B effective against abiotic/biotic stresses. Results demonstrate positive contributions of exotic germplasm to PBLs derived from crosses of exotics with CIMMYT’s best elite lines. This is a major impact-oriented pre-breeding effort at CIMMYT, resulting in large-scale development of PBLs for deployment in breeding programs addressing food security under climate change scenarios

Genome-wide association studies identifies genetic loci related to fatty acid and branched-chain amino acid metabolism and histone modifications under varying nitrogen treatments in safflower (Carthamus tinctorius)

Effective identification and usage of genetic variation are prerequisites for developing nutrient-efficient cultivars. A collection of 94 safflower (Carthamus tinctorius ) genotypes (G) was investigated for important morphological and photosynthetic traits at four nitrogen (N) treatments. We found significant variation for all the studied traits except chlorophyll b (chl b ) among safflower genotypes, nitrogen treatments and G×N interaction. The examined traits showed a 2.82-50.00% increase in response to N application. Biological yield (BY) reflected a significantly positive correlation with fresh shoot weight (FSW), root length (RL), fresh root weight (FRW) and number of leaves (NOL), while a significantly positive correlation was also observed among carotenoids (C), chlorophyll a (chl a ), chl b and total chlorophyll content (CT) under all treatments. Superior genotypes with respect to plant height (PH), FSW, NOL, RL, FRW and BY were clustered into Group 3, while genotypes with better mean performance regarding chl a , chl b C and CT were clustered into Group 2 as observed in principal component analysis. The identified eight best-performing genotypes could be useful to develop improved nitrogen efficient cultivars. Genome-wide association analysis resulted in 32 marker-trait associations (MTAs) under four treatments. Markers namely DArT-45481731 , DArT-17812864 , DArT-15670279 and DArT-45482737 were found consistent. Protein-protein interaction networks of loci associated with MTAs were related to fatty acid and branched-chain amino acid metabolism and histone modifications

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease

Safety of Nonsteroidal Anti-inflammatory Drugs in Major Gastrointestinal Surgery: A Prospective, Multicenter Cohort Study

Background Significant safety concerns remain surrounding the use of nonsteroidal anti-inflammatory drugs (NSAIDs) following gastrointestinal surgery, leading to wide variation in their use. This study aimed to determine the safety profile of NSAIDs after major gastrointestinal surgery. Methods Consecutive patients undergoing elective or emergency abdominal surgery with a minimum one-night stay during a 3-month study period were eligible for inclusion. The administration of any NSAID within 3 days following surgery was the main independent variable. The primary outcome measure was the 30-day postoperative major complication rate, as defined by the Clavien–Dindo classification (Clavien–Dindo III–V). Propensity matching with multivariable logistic regression was used to produce odds ratios (OR) and 95 % confidence intervals. Results From 9264 patients, 23.9 % (n = 2212) received postoperative NSAIDs. The overall major complication rate was 11.5 % (n = 1067). Following propensity matching and adjustment, use of NSAIDs were not significantly associated with any increase in major complications (OR 0.90, 0.60–1.34, p = 0.560). Conclusions Early use of postoperative NSAIDs was not associated with an increase in major complications following gastrointestinal surgery

Critical care usage after major gastrointestinal and liver surgery: a prospective, multicentre observational study

Background Patient selection for critical care admission must balance patient safety with optimal resource allocation. This study aimed to determine the relationship between critical care admission, and postoperative mortality after abdominal surgery. Methods This prespecified secondary analysis of a multicentre, prospective, observational study included consecutive patients enrolled in the DISCOVER study from UK and Republic of Ireland undergoing major gastrointestinal and liver surgery between October and December 2014. The primary outcome was 30-day mortality. Multivariate logistic regression was used to explore associations between critical care admission (planned and unplanned) and mortality, and inter-centre variation in critical care admission after emergency laparotomy. Results Of 4529 patients included, 37.8% (n=1713) underwent planned critical care admissions from theatre. Some 3.1% (n=86/2816) admitted to ward-level care subsequently underwent unplanned critical care admission. Overall 30-day mortality was 2.9% (n=133/4519), and the risk-adjusted association between 30-day mortality and critical care admission was higher in unplanned [odds ratio (OR): 8.65, 95% confidence interval (CI): 3.51–19.97) than planned admissions (OR: 2.32, 95% CI: 1.43–3.85). Some 26.7% of patients (n=1210/4529) underwent emergency laparotomies. After adjustment, 49.3% (95% CI: 46.8–51.9%, P<0.001) were predicted to have planned critical care admissions, with 7% (n=10/145) of centres outside the 95% CI. Conclusions After risk adjustment, no 30-day survival benefit was identified for either planned or unplanned postoperative admissions to critical care within this cohort. This likely represents appropriate admission of the highest-risk patients. Planned admissions in selected, intermediate-risk patients may present a strategy to mitigate the risk of unplanned admission. Substantial inter-centre variation exists in planned critical care admissions after emergency laparotomies