Application of Genomic Approaches to Improve Yield and Bacterial Leaf Streak Resistance in Winter Wheat

Global wheat production is threatened by the change in climate thus leading lead to the increase in the biotic and abiotic stresses. We need to increase wheat productivity at a faster pace and manage these challenges to meet the growing demand. Development of cultivars with durable disease resistance and enhancing the rate of genetic gain in wheat are the major goals in wheat breeding programs. Bacterial Leaf Streak (BLS) is one of the most threatening bacterial diseases to wheat in the US Northern Great Plains. Unlike fungal diseases, bacterial diseases cannot be effectively managed using chemicals and thus developing disease resistant cultivars would be the most economical control for BLS. Identification and characterization of genomic regions in wheat that confer resistance to BLS can be an effective way to mobilize resistance genes in wheat breeding. Here we performed Genome – wide association mapping on a Hard Winter Wheat Association Panel (HWWMP) to identify genomic regions that confer resistance to BLS. The genotyped data for this panel of 300 winter wheat lines from the major breeding programs across the Midwestern region of the US was obtained from T3 Triticale Toolbox (under the GPL license). The responses of all these lines against Xanthomonas campestris pv. translucens in the greenhouse and field conditions were evaluated. Association Mapping (AM) was used to detect marker – trait associations using ECMLM, and we identified five QTL regions (Q.bls.sdsu.1AL, Q.bls.sdsu.1BS, Q.bls.sdsu.3AL, Q.bls.sdsu.4AL and Q.bls.sdsu.7AS) conferring BLS resistance. In total, these five QTLs explained 42% of the variation. Eleven genotypes were identified, which could be used as a source of resistance against BLS. Comparative analysis of three of the identified QTLs (Q.bls.sdsu.1AL, Q.bls.sdsu.3AL and Q.bls.sdsu.4AL) with rice showed BLS resistance genes in rice (qBLSr5d, qBLSr1, and qBLSr3d) located on syntenic regions in rice chromosomes 5R, 1R and 3R respectively. The 11 BLS resistant genotypes and SNP markers linked to QTLs identified in our study could facilitate breeding BLS resistance in wheat. For grain yield improvement, we assessed the robustness for genomic selection (GS) in the South Dakota State Winter Wheat Breeding program (SDSWWBP). We performed GS with a set of 434 advanced breeding lines (AYT and PYT nurseries) between the years 2014 – 2017. These lines were genotyped by sequencing GBS and the yield data from 34 years × location combinations were used as a phenotype. We developed training and validation datasets for testing the genomic prediction accuracies. Single and multiyear analysis were done using several GS models (rrBLUP, PLSR, ELNET and Random Forest). The average predictions accuracies within a single year across locations were 0.62. However, with the multi-year-location analysis, the average genomic prediction accuracies were 0.26 for two-year combination, 0.32 for three-year combination and 0.36 for the four-year combination. Our results suggested several years of data is required to develop better genome-wide selection models

Melanoma in a patient with DNMT3A overgrowth syndrome

Alterations in epigenetic regulators are increasingly recognized as early events in tumorigenesis; thus, patients with acquired or inherited variants in epigenetic regulators may be at increased risk for developing multiple types of cancer. DNMT3A overgrowth syndrome (DOS), caused by germline pathogenic variants in the DNA methyltransferase gen

Recurrent transcriptional responses in AML and MDS patients treated with decitabine

The molecular events responsible for decitabine responses in myelodysplastic syndrome and acute myeloid leukemia patients are poorly understood. Decitabine has a short serum half-life and limited stability in tissue culture. Therefore, theoretical pharmacologic differences may exist between patient molecular changes in vitro and the consequences of in vivo treatment. To systematically identify the global genomic and transcriptomic alterations induced by decitabine in vivo, we evaluated primary bone marrow samples that were collected during patient treatment and applied whole-genome bisulfite sequencing, RNA-sequencing, and single-cell RNA sequencing. Decitabine induced global, reversible hypomethylation after 10 days of therapy in all patients, which was associated with induction of interferon-induced pathways, the expression of endogenous retroviral elements, and inhibition of erythroid-related transcripts, recapitulating many effects seen previously in in vitro studies. However, at relapse after decitabine treatment, interferon-induced transcripts remained elevated relative to day 0, but erythroid-related transcripts now were more highly expressed than at day 0. Clinical responses were not correlated with epigenetic or transcriptional signatures, although sample size and interpatient variance restricted the statistical power required for capturing smaller effects. Collectively, these data define global hypomethylation by decitabine and find that erythroid-related pathways may be relevant because they are inhibited by therapy and reverse at relapse

Immunosuppression and outcomes in adult patients with de novo acute myeloid leukemia with normal karyotypes

Acute myeloid leukemia (AML) patients rarely have long first remissions (LFRs; \u3e5 y) after standard-of-care chemotherapy, unless classified as favorable risk at presentation. Identification of the mechanisms responsible for long vs. more typical, standard remissions may help to define prognostic determinants for chemotherapy responses. Using exome sequencing, RNA-sequencing, and functional immunologic studies, we characterized 28 normal karyotype (NK)-AML patients with \u3e5 y first remissions after chemotherapy (LFRs) and compared them to a well-matched group of 31 NK-AML patients who relapsed within 2 y (standard first remissions [SFRs]). Our combined analyses indicated that genetic-risk profiling at presentation (as defined by European LeukemiaNet [ELN] 2017 criteria) was not sufficient to explain the outcomes of many SFR cases. Single-cell RNA-sequencing studies of 15 AML samples showed that SFR AML cells differentially expressed many genes associated with immune suppression. The bone marrow of SFR cases had significantly fewer CD