Four Consistent Loci Confer Adult Plant Resistance to Leaf Rust in the Durum Wheat Lines Heller#1 and Dunkler.

The durum wheat lines Heller#1 and Dunkler from the International Maize and Wheat Improvement Center Global Wheat Program showed moderate and stable adult plant resistance to leaf rust under high disease pressure over field environments in northwestern Mexico. Leaf rust phenotyping was performed on two recombinant inbred line (RIL) populations derived from crosses of Heller#1 and Dunkler with the susceptible parent Atred#2, conducted under artificially induced Puccinia triticina epidemics in 2013, 2014, 2015, and 2016. The Atred#2 × Heller#1 and Atred#2 × Dunkler populations were genotyped by single nucleotide polymorphism (SNP) platforms and diversity arrays technology markers, respectively. Four leaf rust resistance quantitative trait loci were detected simultaneously in the two RIL populations: Lr46, QLr.cim-2BC, QLr.cim-5BL, and QLr.cim-6BL based on phenotypic data across all four crop seasons. They explained 11.7 to 46.8%, 7.2 to 26.1%, 8.4 to 24.1%, and 12.4 to 28.5%, respectively, of the phenotypic variation for leaf rust resistance in Atred#2 × Heller#1 and 16.3 to 56.6%, 6.7 to 15.7%, 4.1 to 10.1%, and 5.1 to 20.2% of the variation in the Atred#2 × Dunkler population. Only the resistance allele of QLr.cim-2BC was from the susceptible parent Atred#2, and resistance alleles at other loci came from the resistant parents Heller#1 and Dunkler. The SNP markers closely linked to Lr46 and QLr.cim-2BC were converted to kompetitive allele specific PCR markers for use in marker-assisted selection to improve leaf rust resistance through crosses with Heller#1 and Dunkler sources.

Genome-Wide Mapping of Adult Plant Resistance to Leaf Rust and Stripe Rust in CIMMYT Wheat Line Arableu#1.

Leaf (brown) rust (LR) and stripe (yellow) rust (YR), caused by Puccinia triticina and P. striiformis f. sp. tritici, respectively, significantly reduce wheat production worldwide. Disease-resistant wheat varieties offer farmers one of the most effective ways to manage these diseases. The common wheat (Triticum aestivum L.) Arableu#1, developed by the International Maize and Wheat Improvement Center and released as Deka in Ethiopia, shows susceptibility to both LR and YR at the seedling stage but a high level of adult plant resistance (APR) to the diseases in the field. We used 142 F5 recombinant inbred lines (RILs) derived from Apav#1 × Arableu#1 to identify quantitative trait loci (QTLs) for APR to LR and YR. A total of 4,298 genotyping-by-sequencing markers were used to construct a genetic linkage map. The study identified four LR resistance QTLs and six YR resistance QTLs in the population. Among these, QLr.cim-1BL.1/QYr.cim-1BL.1 was located in the same location as Lr46/Yr29, a known pleiotropic resistance gene. QLr.cim-1BL.2 and QYr.cim-1BL.2 were also located on wheat chromosome 1BL at 37 cM from Lr46/Yr29 and may represent a new segment for pleiotropic resistance to both rusts. QLr.cim-7BL is likely Lr68 given its association with the tightly linked molecular marker cs7BLNLRR. In addition, QLr.cim-3DS, QYr.cim-2AL, QYr.cim-4BL, QYr.cim-5AL, and QYr.cim-7DS are probably new resistance loci based on comparisons with published QTLs for resistance to LR and YR. Our results showed the diversity of minor resistance QTLs in Arableu#1 and their role in conferring near-immune levels of APR to both LR and YR, when combined with the pleiotropic APR gene Lr46/Yr29.

Two Main Stripe Rust Resistance Genes Identified in Synthetic-Derived Wheat Line Soru#1.

Stripe rust is a major disease constraint of wheat production worldwide. Resistance to stripe rust was analyzed using 131 F6 recombinant inbred lines (RILs) derived from a cross between synthetic derived wheat line Soru#1 and wheat cultivar Naxos. The phenotype was evaluated in Mexico and Norway at both seedling and adult plant stages. Linkage groups were constructed based on 90K single-nucleotide polymorphism (SNP), sequence-tagged site, and simple sequence repeat markers. Two major resistance loci conferred by Soru#1 were detected and located on chromosomes 1BL and 4DS. The 1BL quantitative trait loci explained 15.8 to 40.2 and 51.1% of the phenotypic variation at adult plant and seedling stages, respectively. This locus was identified as Yr24/Yr26 based on the flanking markers and infection types. Locus 4DS was flanked by molecular markers D_GB5Y7FA02JMPQ0_238 and BS00108770_51. It explained 8.4 to 27.8 and 5.5% of stripe rust variation at the adult plant and seedling stages, respectively. The 4DS locus may correspond to known resistance gene Yr28 based on the resistance source. All RILs that combine Yr24/Yr26 and Yr28 showed significantly reduced stripe rust severity in all four environments compared with the lines with only one of the genes. SNP marker BS00108770_51 was converted into a breeder-friendly kompetitive allele-specific polymerase chain reaction marker that will be useful to accelerate Yr28 deployment in wheat breeding programs.

Genetic analysis and mapping of adult plant resistance loci to leaf rust in durum wheat cultivar Bairds.

KEY MESSAGE: New leaf rust adult plant resistance (APR) QTL QLr.cim - 6BL was mapped and confirmed the known pleotropic APR gene Lr46 effect on leaf rust in durum wheat line Bairds. CIMMYT-derived durum wheat line Bairds displays an adequate level of adult plant resistance (APR) to leaf rust in Mexican field environments. A recombinant inbred line (RIL) population developed from a cross of Bairds with susceptible parent Atred#1 was phenotyped for leaf rust response at Ciudad Obregon, Mexico, during 2013, 2014, 2015 and 2016 under artificially created epidemics of Puccinia triticina (Pt) race BBG/BP. The RIL population and its parents were genotyped with the 50 K diversity arrays technology (DArT) sequence system and simple sequence repeat (SSR) markers. A genetic map comprising 1150 markers was used to map the resistance loci. Four significant quantitative trait loci (QTLs) were detected on chromosomes 1BL, 2BC (centromere region), 5BL and 6BL. These QTLs, named Lr46, QLr.cim-2BC, QLr.cim-5BL and QLr.cim-6BL, respectively, explained 13.5-60.8%, 9.0-14.3%, 2.8-13.9%, and 11.6-29.4%, respectively, of leaf rust severity variation by the inclusive composite interval mapping method. All of these resistance loci were contributed by the resistant parent Bairds, except for QLr.cim-2BC, which came from susceptible parent Atred#1. Among these, the QTL on chromosome 1BL was the known pleiotropic APR gene Lr46, whereas QLr.cim-6BL, a consistently detected locus, should be a new leaf rust resistance locus in durum wheat. The mean leaf rust severity of RILs carrying all four QTLs ranged from 8.0 to 17.5%, whereas it ranged from 10.9 to 38.5% for three QTLs (Lr46 + 5BL + 6BL) derived from the resistant parent Bairds. Two RILs with four QTLs combinations can be used as sources of complex APR in durum wheat breeding.

Stripe rust and leaf rust resistance in CIMMYT wheat line "Mucuy" is conferred by combinations of race-specific and adult-plant resistance loci.

Developing wheat varieties with durable resistance is a core objective of the International Maize and Wheat Improvement Center (CIMMYT) and many other breeding programs worldwide. The CIMMYT advanced wheat line "Mucuy" displayed high levels of resistance to stripe rust (YR) and leaf rust (LR) in field evaluations in Mexico and several other countries. To determine the genetic basis of YR and LR resistance, 138 F5 recombinant inbred lines (RILs) derived from the cross of Apav#1× Mucuy were phenotyped for YR responses from 2015 to 2020 at field sites in India, Kenya, and Mexico, and LR in Mexico. Seedling phenotyping for YR and LR responses was conducted in the greenhouse in Mexico using the same predominant races as in field trials. Using 12,681 polymorphic molecular markers from the DArT, SNP, and SSR genotyping platforms, we constructed genetic linkage maps and QTL analyses that detected seven YR and four LR resistance loci. Among these, a co-located YR/LR resistance loci was identified as Yr29/Lr46, and a seedling stripe rust resistance gene YrMu was mapped on the 2AS/2NS translocation. This fragment also conferred moderate adult plant resistance (APR) under all Mexican field environments and in one season in Kenya. Field trial phenotyping with Lr37-virulent Puccinia triticina races indicated the presence of an APR QTL accounting for 18.3-25.5% of the LR severity variation, in addition to a novel YR resistance QTL, QYr.cim-3DS, derived from Mucuy. We developed breeder-friendly KASP and indel molecular markers respectively for Yr29/Lr46 and YrMu. The current study validated the presence of known genes and identified new resistance loci, a QTL combination effect, and flanking markers to facilitate accelerated breeding for genetically complex, durable rust resistance.

Association Between Use of Warfarin for Atrial Fibrillation and Outcomes Among Patients With End-Stage Renal Disease: A Systematic Review and Meta-analysis.

Importance: Several studies have examined the role of warfarin in preventing strokes in patients with atrial fibrillation and end-stage renal disease; however, the results remain inconclusive. Objective: To assess recently published studies to examine the outcomes of the use of warfarin among patients with atrial fibrillation and end-stage renal disease. Data Sources: A literature search was performed using the terms warfarin and atrial fibrillation and end-stage renal disease and warfarin and atrial fibrillation and dialysis in the MEDLINE, Embase, and Google Scholar databases from January 1, 2008, to February 28, 2019. Study Selection: The studies included were those with patients with end-stage renal disease and atrial fibrillation who were receiving warfarin and with hazard ratios (HRs) of at least 1 primary outcome. The studies excluded were those with a lack of information on outcomes and unreliable 95% CIs of the results. Data Extraction and Synthesis: The Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed in selecting studies. Collected data were also scrutinized for reliable 95% CIs. Finally, studies were examined for perceived biases, their limitations, and the definitions of the outcomes. Main Outcomes and Measures: The HRs and 95% CIs were calculated for the incidence of ischemic stroke, hemorrhagic stroke, major bleeding, and mortality among patients receiving anticoagulants and those not receiving anticoagulants. Results: Study selection yielded 15 studies with a total of 47 480 patients with atrial fibrillation and end-stage renal disease. Of these patients, 10 445 (22.0%) were taking warfarin. With a mean (SD) follow-up period of 2.6 (1.4) years, warfarin use was associated with no significant change for the risk of ischemic stroke (HR, 0.96; 95% CI, 0.82-1.13), with a significantly higher risk of hemorrhagic stroke (HR, 1.49; 95% CI, 1.03-1.94), with no significant difference in the risk of major bleeding (HR, 1.20; 95% CI, 0.99-1.47), and with no change in overall mortality (HR, 0.95; 95% CI, 0.83-1.09). Conclusions and Relevance: In the studies reviewed, warfarin use appears to have been associated with no change in the incidence of ischemic stroke in patients with atrial fibrillation and end-stage renal disease. However, from the studies reviewed, it does appear to be associated with a significantly higher risk of hemorrhagic stroke, with no significant difference in the risk of major bleeding, and with no change in mortality.

Multiple-Race Stem Rust Resistance Loci Identified in Durum Wheat Using Genome-Wide Association Mapping.

Stem rust of wheat caused by Puccinia graminis Pers. f.sp. trtici Eriks and E. Henn., is the most damaging fungal disease of both common (Triticum aestivum L.) and durum (Triticum turgidum L., ssp. Durum) wheat. Continuously emerging races virulent to many of the commercially deployed qualitative resistance genes have caused remarkable loss worldwide and threaten global wheat production. The objectives of this study were to evaluate the response of a panel of 283 durum wheat lines assembled by the International Maize and Wheat Improvement Center (CIMMYT) to multiple races of stem rust in East Africa at the adult plant stage and map loci associated with field resistance. The lines were evaluated in Debre Zeit, Ethiopia and Njoro, Kenya from 2018 to 2019 in five environments (year × season). The panel was genotyped using genotyping-by-sequencing. After filtering, 26,439 Single Nucleotide Polymorphism (SNP) markers and 280 lines and three checks were retained for analysis. Population structure was assessed using principal component analysis. Genome-wide association analysis (GWAS) was conducted using Genomic Association and Prediction Integrated Tool (GAPIT). The broad-sense heritability of the phenotype data revealed that 64-83% of the variation in stem rust response explained by the genotypes and lines with multiple race resistance were identified. GWAS analysis detected a total of 160 significant marker trait associations representing 42 quantitative trait loci. Of those, 21 were potentially novel and 21 were mapped to the same regions as previously reported loci. Known stem rust resistance genes/alleles were postulated including Sr8a, Sr8155B1, SrWeb/Sr9h, Sr11, Sr12, Sr13/Sr13 alleles, Sr17, Sr28/Sr16, Sr22, and Sr49. Lines resistant to multiple races in East Africa can be utilized as parents in durum wheat breeding programs. Further studies are needed to determine if there are new alleles at the Sr13 locus and potential markers for the known Sr13 alleles.

Genome-wide mapping and allelic fingerprinting provide insights into the genetics of resistance to wheat stripe rust in India, Kenya and Mexico.

Stripe or yellow rust (YR) caused by Puccinia striiformis Westend. f. sp. tritici Erikss. is a persistent biotic-stress threatening global wheat production. To broaden our understanding of the shared genetic basis of YR resistance across multi-site and multi-year evaluations, we performed a large genome-wide association study using 43,706 YR observations on 23,346 wheat lines from the International Maize and Wheat Improvement Center evaluated between 2013 and 2019 at sites in India, Kenya and Mexico, against predominant races prevalent in the countries. We identified 114 repeatable markers tagging 20 quantitative trait loci (QTL) associated with YR on ten chromosomes including 1D, 2A, 2B, 2D, 3A, 4A, 4D, 5A, 5B and 6B, among which four QTL, QYr.cim-2DL.2, QYr.cim-2AS.1, QYr.cim-2BS.2 and QYr.cim-2BS.3 were significant in more than ten datasets. Furthermore, we report YR-associated allelic fingerprints for the largest panel of wheat breeding lines (52,067 lines) till date, creating substantial opportunities for YR favorable allele enrichment using molecular markers. Overall, the markers and fingerprints reported in this study provide excellent insights into the genetic architecture of YR resistance in different geographical regions, time-periods and wheat germplasm and are a huge resource to the global wheat breeding community for accelerating YR resistance breeding efforts.

Mapping and Validation of Stem Rust Resistance Loci in Spring Wheat Line CI 14275.

Stem rust caused by Puccinia graminis f. sp. tritici (Pgt) remains a constraint to wheat production in East Africa. In this study, we characterized the genetics of stem rust resistance, identified QTLs, and described markers associated with stem rust resistance in the spring wheat line CI 14275. The 113 recombinant inbred lines, together with their parents, were evaluated at the seedling stage against Pgt races TTKSK, TRTTF, TPMKC, TTTTF, and RTQQC. Screening for resistance to Pgt races in the field was undertaken in Kenya, Ethiopia, and the United States in 2016, 2017, and 2018. One gene conferred seedling resistance to race TTTTF, likely Sr7a. Three QTL were identified that conferred field resistance. QTL QSr.cdl-2BS.2, that conferred resistance in Kenya and Ethiopia, was validated, and the marker Excalibur_c7963_1722 was shown to have potential to select for this QTL in marker-assisted selection. The QTL QSr.cdl-3B.2 is likely Sr12, and QSr.cdl-6A appears to be a new QTL. This is the first study to both detect and validate an adult plant stem rust resistance QTL on chromosome arm 2BS. The combination of field QTL QSr.cdl-2BS.2, QSr.cdl-3B.2, and QSr.cdl-6A has the potential to be used in wheat breeding to improve stem rust resistance of wheat varieties.

Improving grain yield, stress resilience and quality of bread wheat using large-scale genomics.

Bread wheat improvement using genomic tools is essential for accelerating trait genetic gains. Here we report the genomic predictabilities of 35 key traits and demonstrate the potential of genomic selection for wheat end-use quality. We also performed a large genome-wide association study that identified several significant marker-trait associations for 50 traits evaluated in South Asia, Africa and the Americas. Furthermore, we built a reference wheat genotype-phenotype map, explored allele frequency dynamics over time and fingerprinted 44,624 wheat lines for trait-associated markers, generating over 7.6 million data points, which together will provide a valuable resource to the wheat community for enhancing productivity and stress resilience.

Identification and Validation of a Common Stem Rust Resistance Locus in Two Bi-parental Populations.

Races belonging to Ug99 lineage of stem rust fungus Puccinia graminis f. sp. tritici (Pgt) continue to pose a threat to wheat (Triticum aestivum L.) production in various African countries. Growing resistant varieties is the most economical and environmentally friendly control measure. Recombinant inbred line (RIL) populations from the crosses of susceptible parent 'Cacuke' with the resistant parents 'Huhwa' and 'Yaye' were phenotyped for resistance at the seedling stage to Pgt race TTKSK (Ug99) and in adult plants in field trials at Njoro, Kenya for two seasons in 2016. Using the Affymetrix Axiom breeders SNP array, two stem rust resistance genes, temporarily designated as SrH and SrY, were identified and mapped on chromosome arm 2BL through selective genotyping and bulked segregant analysis (BSA), respectively. Kompetitive allele specific polymorphism (KASP) markers and simple sequence repeat (SSR) markers were used to saturate chromosome arm 2BL in both RIL populations. SrH mapped between markers cim109 and cim114 at a distance of 0.9 cM proximal, and cim117 at 2.9 cM distal. SrY was flanked by markers cim109 and cim116 at 0.8 cM proximal, and IWB45932 at 1.9 cM distal. Two Ug99-effective stem rust resistance genes derived from bread wheat, Sr9h and Sr28, have been reported on chromosome arm 2BL. Infection types and map position in Huhwa and Yaye indicated that Sr28 was absent in both the parents. However, susceptible reactions produced by resistant lines from both populations against Sr9h-virulent race TTKSF+ confirmed the presence of a common resistance locus Sr9h in both lines. Test of allelism is required to establish genetic relationships between genes identified in present study and Sr9h. Marker cim117 linked to SrH was genotyped on set of wheat lines with Huhwa in the pedigree and is advised to be used for marker assisted selection for this gene, however, a combination of phenotypic and genotypic assays is desirable for both genes especially for selection of Sr9h in breeding programs.

Characterization and Mapping of Leaf Rust and Stripe Rust Resistance Loci in Hexaploid Wheat Lines UC1110 and PI610750 under Mexican Environments.

Growing resistant wheat varieties is a key method of minimizing the extent of yield losses caused by the globally important wheat leaf rust (LR) and stripe rust (YR) diseases. In this study, a population of 186 F8 recombinant inbred lines (RILs) derived from a cross between a synthetic wheat derivative (PI610750) and an adapted common wheat line (cv. "UC1110") were phenotyped for LR and YR response at both seedling and adult plant stages over multiple seasons. Using a genetic linkage map consisting of single sequence repeats and diversity arrays technology markers, in combination with inclusive composite interval mapping analysis, we detected a new LR adult plant resistance (APR) locus, QLr.cim-2DS, contributed by UC1110. One co-located resistance locus to both rusts, QLr.cim-3DC/QYr.cim-3DC, and the known seedling resistance gene Lr26 were also mapped. QLr.cim-2DS and QLr.cim-3DC showed a marginally significant interaction for LR resistance in the adult plant stage. In addition, two previously reported YR APR loci, QYr.ucw-3BS and Yr48, were found to exhibit stable performances in rust environments in both Mexico and the United States and showed a highly significant interaction in the field. Yr48 was also observed to confer intermediate seedling resistance against Mexican YR races, thus suggesting it should be re-classified as an all-stage resistance gene. We also identified 5 and 2 RILs that possessed all detected YR and LR resistance loci, respectively. With the closely linked molecular markers reported here, these RILs could be used as donors for multiple resistance loci to both rusts in wheat breeding programs.