scholarly journals Benchmarking of Whole Genome Sequencing (WGS) and Whole Transcriptome Sequencing (WTS) As Diagnostic Tools for the Genetic Characterization of Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL) in Adults

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 273-273
Author(s):  
Claudia Haferlach ◽  
Wencke Walter ◽  
Manja Meggendorfer ◽  
Anna Stengel ◽  
Constance Baer ◽  
...  
Keyword(s):  
Genetic Information ◽  
Normal Karyotype ◽  
Genetic Alterations ◽  
Error Rates ◽  
Diagnostic Tools ◽  
Fusion Transcripts ◽  
Molecular Abnormalities ◽  
Genome Wide ◽  
Disease Stratification

Abstract Background: In AML and ALL the application of WHO classification and ELN guidelines requires a combination of cytogenetics and targeted sequencing for specific mutations to determine the diagnostic and prognostic subgroup. WGS and WTS have emerged as comprehensive techniques that allow the simultaneous analysis and identification of all genetic alterations in a single approach with possible turnaround times of 1 week. Aim: Evaluate the accuracy of WGS and WTS in providing all relevant genetic information in a clinical setting. Patients and Methods: The cohort comprised 738 AML, 293 BCP-ALL and 124 T-ALL. The diagnosis was established following WHO guidelines. WGS (100x, 2x151bp) and WTS (50 Mio reads, 2x101bp) were performed on a NovaSeq instrument. Variants were called with Strelka2, Manta and GATK using a tumor w/o normal pipeline, fusions with Arriba, STAR-Fusion and Manta. Results: The combination of WGS and WTS detected all chromosomal and molecular abnormalities in the AML and ALL cohorts relevant for disease stratification and prognostication as identified by chromosome banding analysis (CBA) and targeted panel sequencing (TPS). A very high concordance between CBA and WGS was revealed for the detection of balanced structural variants (SV) with the added benefit of WGS to also detect cytogenetically cryptic rearrangements (i.e.: ETV6-MN1, NUP98-KDM5A), which all were confirmed either by FISH or RT-PCR. Fusion calling by WTS identified 96% of the WHO subtype defining rearrangements and detected 20 additional fusion transcripts relevant for disease stratification (e.g. EP300-ZNF384, TCF3-HLF) including 9 fusion transcripts that led to prognostic reassignment or could serve as a potential treatment target. Breakpoints of unbalanced SV can occur in repetitive sequences of the genome, hampering the detection by WGS. However, adding copy number alteration (CNA) calls to the analyses allows also reliable identification of unbalanced SV. WGS outperformed CBA in cases with insufficient in vitro proliferation due to suboptimal pre-analytics (i.e. longer transport time) and identified 36 chromosomal aberrations in 12 cases with CBA not evaluable. WGS's independence of in vitro cell proliferation was most impactful in ALL: 40 T-ALL cases showed a normal karyotype according to CBA. WGS detected SVs in 16 (40%) and CNAs in 20 (50%) of these cases, confirming the normal karyotype for only 9 samples. In the BCP-ALL cohort, CNV analysis identified 29 low hypodiploid and 16 high hyperdiploid karyotypes, 6 of which were missed by CBA. Due to the higher resolution and unrestricted, genome-wide assessment, WGS detected relevant gene deletions (RB1, ERG, PAX5, CDKN2A, IKZF1, ETV6, BTG1) in 59% of ALL cases, providing additional diagnostic and prognostic information. In the AML cohort CBA and WGS detected 795 CNA concordantly. In addition WGS called 54 CNA with size 1-5 MB (below the detection limit of CBA), i.e. 3 BCOR deletions in inv(3)(q21q26) cases and 67 CNA with size > 5 MB, which were missed by CBA. 35 CNA were missed by WGS due to small clone sizes (median 6% as determined by FISH). WGS detected copy neutral loss of heterozygosity (CN-LOH) in AML most frequently on 21q (n=17), 4q (n=15), 13q (n=15), 11q (n=13) and in T-ALL on 9p (n=19), mostly encompassing CDKN2A/B deletions. Expression profiling provided additional diagnostic information for 57 ALL cases (41 BCR-ABL1-like, 16 DUX4 rearranged) that can only insufficiently be obtained by WGS or CBA. WGS reliably detected all gene mutations with a VAF > 15% (n = 647) identified by TPS encompassing especially all mutations in genes relevant for WHO diagnosis and prognostication. 26/171 mutations with a VAF < 15% were missed by WGS. Evaluation of WGS data for 121 genes recurrently mutated in hematologic neoplasms revealed an additional 2 mutations per sample on average (range: 0-9) which might qualify as targets for therapy. Conclusions: WGS and WTS provide all necessary genetic information to accurately determine the diagnostic and prognostic subgroup according to WHO and ELN guidelines in AML and ALL. Compared to today's gold standards, these novel methods provide a comprehensive genome wide characterization with higher resolution that directly identifies genes of impact, offering the basis for targeted treatment selection and monitoring of residual disease. Both can be implemented with automated analysis pipelines, consequently reducing time and error rates. Figure 1 Figure 1. Disclosures Haferlach: MLL Munich Leukemia Laboratory: Other: Part ownership. Kern: MLL Munich Leukemia Laboratory: Other: Part ownership. Haferlach: MLL Munich Leukemia Laboratory: Other: Part ownership.

scholarly journals Significant Features of DNA Methylation at Bivalent Promotor and Repressed Polycomb Regions in Pediatric AML-the Jccg Study, JPLSG AML-05-

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2739-2739
Author(s):  
Genki Yamato ◽  
Tomoko Kawai ◽  
Norio Shiba ◽  
Yusuke Hara ◽  
Kentaro Ohki ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Hierarchical Clustering ◽  
Pediatric Patients ◽  
Normal Karyotype ◽  
Genetic Alterations ◽  
Promoter Regions ◽  
Cpg Sites ◽  
Genome Wide ◽  
Equity Ownership ◽  
Biallelic Mutations

Introduction Acute myeloid leukemia (AML) is a clinically and biologically heterogeneous hematologic malignancy characterized by various genetic alterations. Currently, DNA methylation patterns were reported to be associated with molecular subtypes, chromosomal abnormalities, gene fusion, and prognosis in AML. Furthermore, previous study reported that aberrant cancer-associated DNA hypermethylation targets CpG islands characterized by bivalent chromatin in human embryonic stem cells (hESCs), and the bivalent chromatin signature in hESCs was a key determinant of the instructive program for aberrant DNA methylation. Thus, we analyzed genome-wide DNA methylation in 64 pediatric patients with AML to reveal its association with clinical features, genetic alterations, and prognostic impact. Methods Between 2006 and 2010, 443 pediatric patients with de novo AML (0-17 years) participated in the Japanese AML-05 trial conducted by the Japanese Pediatric Leukemia/Lymphoma Study Group. Of these, 64 patients were enrolled in this study. The cytogenetic features of 64 patients were as follows: normal karyotype, 28; RUNX1-RUNX1T1, 8; KMT2A rearrangement, 15; complex karyotype, 6; and other cytogenetics, 7. This cohort included 15 patients with FLT3-internal tandem duplication (ITD), 8 with CEBPA biallelic mutations, 5 with high MECOM (EVI1) expression, and 17 with high PRDM16 (MEL1) expression. We performed genome-wide DNA methylation analysis using Infinium MethylationEPIC BeadChip (Illumina) in 64 pediatric patients. Results and Discussion 824,848 methylation sites per sample were analyzed in 64 pediatric patients with AML. To capture DNA methylation differences across samples, we selected 567 CpG sites which showed most variable methylation values between 64 individuals such as standard deviations across samples were more than 0.3. The unsupervised hierarchical clustering of DNA methylation data from 567 CpG sites generated 4 clusters (clusters 1-4) with distinct molecular and clinical characteristics. Cluster 1 or 2 was the lowest or highest methylation level, respectively. Clusters 3 and 4 showed intermediate methylation level. Cluster 1 was characterized by RUNX1-RUNX1T1 and KMT2A rearrangement with low MECOM expression, which are known as favorable prognostic factors. Clusters 2 and 4 were composed of patients with the molecular features showing adverse outcome such as FLT3-ITD, KMT2A-PTD and/or normal karyotype with high PRDM16 expression. Interestingly, KMT2A rearrangement with high MECOM expression, considered as the adverse prognostic factor, were included in clusters 2 or 4. As for KMT2A rearrangement, nine of 15 patients with KMT2A rearrangement harbored KMT2A-MLLT3. Of these, five of nine classified into the hypomethylation group, and all five patients had no event. On the other hand, remaining four patients with KMT2A-MLLT3 all relapsed. All patients with normal karyotype with CEBPA biallelic mutations considered as the favorable factor were found in cluster 3. When we focused on CpG sites with significant difference in their methylation values between patients with and without FLT3-ITD, 15 FLT3-ITD patients were divided into two clusters (clusters A and B) by the hierarchical clustering. Remarkably, 8 FLT3-ITD positive patients in cluster A showed significantly worse overall survival (OS) and event-free survival (EFS) when compared with those in cluster B (5-year OS, 13% vs. 100%, P = 0.002; 5-year EFS 0% vs. 86%, P < 0.001). Next, 244 CpG sites significantly associated with PRDM16 expression were extracted to investigate the relationship between PRDM16 expression and DNA methylation profiles. Interestingly, patients with high and low PRDM16 expression showed distinct methylation pattern, respectively. Furthermore, most of hypermethylated sites gene were PRDM16 gene body in patients with high PRDM16 expression and located at important regions which were the targets of repressed polycomb in reference cells. As for 567 CpG sites which were used for the unsupervised hierarchical clustering, 168 of 567 (30%) CpG sites colocalized at bivalent promoter regions in reference leukemic blast cells, and the hypermethylation of bivalent promoter regions tended to be related to worse outcome. These results indicate DNA methylation plays key role for leukemogenesis and is remarked as a novel biomarker to predict prognosis. Disclosures Ogawa: ChordiaTherapeutics, Inc.: Consultancy, Equity Ownership; RegCell Corporation: Equity Ownership; Kan Research Laboratory, Inc.: Consultancy; Asahi Genomics: Equity Ownership; Qiagen Corporation: Patents & Royalties; Dainippon-Sumitomo Pharmaceutical, Inc.: Research Funding.

JAK2 Gene Is Mutated in Patients with Myeloproliferative Disorders and Spontaneous Erythroid Colony Formation but Not in Patients with Spontaneous Megakaryocyte Growth Only.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3600-3600
Author(s):  
Satu Mustjoki ◽  
Ioana Borze ◽  
Riitta Alitalo ◽  
Sakari Knuutila ◽  
Eeva Juvonen
Keyword(s):  
Mutation Analysis ◽  
Colony Formation ◽  
Myeloproliferative Disorders ◽  
Colony Growth ◽  
Genetic Alterations ◽  
Diagnostic Tools ◽  
Diagnostic Laboratory ◽  
Jak2 Mutation ◽  
Specific Pcr

Abstract In the past two decades spontaneous erythroid (BFU-E) and megakaryocytic (CFU-Meg) colony formation have proved to be useful diagnostic tools in diagnosing myeloproliferative disorders (MPD). Recently a point mutation in the JAK2-gene was discovered to be a pathogenetic event in polycythemia vera (PV) and essential thrombocythemia (ET). JAK2 mutation analysis has been recommended to be used as a primary diagnostic method for these disorders. However, so far only a few studies comparing the in vitro growth pattern of hematopoietic progenitors and JAK2 mutation status have been published and, to the best of our knowledge, no studies describing the association between spontaneous CFU-Meg growth and the JAK2 status have been conducted. Therefore, the aim of this study was to compare the results obtained with these methods in PV and ET. 52 ET and 33 PV patients were studied. Allele-specific PCR based JAK2 mutation analysis and hematopoietic colony forming assays were done from bone marrow (BM) aspirate samples. Morphology of BM aspirates was analyzed in our routine diagnostic laboratory. 30/33 (91%) PV patients and 35/52 (67%) ET patients showed spontaneous BFU-E growth. Spontaneous CFU-Meg growth was found in 23/33 (70%) of PV patients and in 29/52 (56%) of ET patients. JAK2 mutation was seen in 26 (79%) PV patients and in 31 (60 %) ET patients. All JAK2 mutated PV and ET patients were found to have spontaneous BFU-E growth. In addition, 4 of 7 (57%) JAK2 mutation negative PV patients and 4 of 21 (19%) JAK2 mutation negative ET patients had spontaneous BFU-E colony formation. JAK2 mutated ET patients had spontaneous CFU-Meg growth more often than JAK2 mutation negative patients (71% vs. 33%), while in PV patients there was no clear difference between the two groups (JAK2 mutation positive 69% vs. negative 71%). Interestingly, 9 patients (6 with ET, 3 with PV) had only spontaneous CFU-Meg growth but no spontaneous BFU-E growth. They were all JAK2 mutation negative. In addition, 11/52 ET patients (21%) were JAK2 mutation negative and had neither spontaneous BFU-E nor spontaneous CFU-Meg growth. BM morphology was considered suggestive of ET or PV in 83% and 70% of the cases respectively. No significant differences in BM morphology were found between JAK2 mutation negative and positive patients. In conclusion, in this group of 88 MPD patients spontaneous BFU-E colony growth was the most sensitive diagnostic assay. All patients with JAK2 mutation also had spontaneous BFU-E growth and an additional 8 patients without the mutation also had spontaneous BFU-E growth. Although recently the JAK2 mutation has been described in megakaryocytes as well, none of the present patients with spontaneous CFU-Meg growth but without spontaneous BFU-E growth were JAK2 mutation positive. This suggests that JAK2 mutation may not be the only pathogenetic event causing spontaneous CFU-Meg growth and further studies are needed to define genetic alterations behind this phenomenon.

scholarly journals TMOD-05. GENOME-WIDE DNA METHYLATION PROFILE: A POWERFUL STRATEGY TO RECAPITULATE HETEROGENEITY OF PEDIATRIC BRAIN TUMORS IN PRIMARY CELL LINES

2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i36-i36
Author(s):  
Lucia Pedace ◽  
Simone Pizzi ◽  
Maria Vinci ◽  
Giulia Pericoli ◽  
Giuseppina Catanzaro ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cell Lines ◽  
Pediatric Brain Tumors ◽  
Genetic Alterations ◽  
In Vitro Models ◽  
Primary Cell ◽  
Genome Wide ◽  
Primary Cell Lines ◽  
Pediatric Brain

Abstract Background Development of in vitro models of pediatric brain tumors (pBT) is instrumental for both understanding the contributing oncogenic molecular mechanisms and identifying and testing new therapeutic strategies. Primary cell lines should be established and managed to prevent epigenetic and genetic alterations and thus recapitulating the original tumor. DNA methylation (DM) is a stable epigenetic modification, altered in cancer and recently used to classify tumors. We aim to apply DM and Copy Number Variation (CNV) profiling to characterize pBT primary cell lines and tumors. Methods We investigated 34 pBT tissues from different histology paired to 52 their derived primary cultures in both 2D and 3D conditions, as stem-cells or in serum-supplemented medium, and both short and long-terms in culture. We studied 18 additional pBT-derived cell-lines, 9 organoids, 5 commercial cell-lines, and 122 pBT tissues from the same histological categories, as controls, for a total of 240 genome-wide DM profiles. We analyzed DM and CNV profiles by using Illumina EPIC-arrays. By means of a bump hunting strategy, we identified differentially methylated regions in faithful vs unfaithful cell lines, and performed a functional characterization using over-representation analysis. Results The 69% (25/36) of cells at early passages retained genetic alteration and the same DM patterns of the original tumors, with no differences related to 2D/3D methods or the presence of serum in media. The 70% (24/34) of primary cell lines analyzed at later passages (&gt;5 or &gt;14 days in culture) diverged from the primary tumor, the totality of those cultured with serum. All divergent cells clustered together acquiring common deregulated epigenetic signature induced by serum culture media, 2D methods and longer time in culture. Conclusions We have shown that global DM profiles, along with CNV analysis are useful tools to detect the recapitulation of pBT-derived primary cell-lines from the original tumor. Whatever subgroups tested, our results suggest that in vitro models should be passaged as little as possible to retain the epigenetic and genetic alterations of the tumors and thus to be considered relevant for basic and translational biology.

scholarly journals Genome-Wide Mapping and Subtype Classification of Long Non-Coding RNA in Acute Myeloid Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2355-2355
Author(s):  
Rong Chen ◽  
Gabriel G Malouf ◽  
Jianping Zhang ◽  
Xuelin Huang ◽  
John N Weinstein ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Genetic Alterations ◽  
Cell Physiology ◽  
Fusion Transcripts ◽  
Subtype Classification ◽  
Genome Wide ◽  
Acute Myeloid

Abstract Background: Most efforts to characterize acute myeloid leukemia (AML) have focused so far on genetic and epigenetic aberrations, which can ultimately lead to altered protein-coding gene function. The roles of long non-coding RNAs (lncRNAs), which orchestrate cell physiology and act as key regulators of the AML oncogenic state, remain uncharacterized globally. Material and Methods: We performed a genomic analysis of GENCODE lncRNAs in 179 clinically annotated cases of de novo AML, using The Cancer Genome Atlas (TCGA) RNA-Seq data. In addition, we described global correlations between lncRNAs and the expression of cis- and trans-acting genes. We also established lncRNA-based subtype classification based on distinct signatures and then correlated that classification with fusion transcripts and genetic alterations. Results: Using stringent criteria (RPKM ≥1 in at least 10% of AML), we identified 2,913 expressed lncRNAs and used an integrative analysis to predict those that are potential regulators of AML oncogenic state. The expression of 1,935 (66.4%) lncRNAs showed positive correlations with the mRNA expression of their neighboring genes, while only 14 (0.4%) of the lncRNAs showed negative correlations. Gene ontology analysis using GREAT revealed enrichment of cis-neighboring genes in the PML body gene set (p=8.2x10-7). Unsupervised clustering of lncRNA-based expression showed five robust molecular clusters (C1 to C5), which were highly correlated with the mRNA-based classification. Of those, three clusters (C1, C2 and C5) were tightly associated with recurrent fusion transcripts; cluster C1 (n=16) was composed exclusively of promyelocytic leukemias, while cluster C5 (n=45) was enriched for MLL-rearranged cases (24.4%), and cluster C2 (n=31) was enriched for MYH11-CBFB or RUNX1-RUNX1T1 (55.2%) rearranged cases. Importantly, cluster C4 (n=30), which includes cytogenetically normal leukemias, was highly enriched for NPM1 (p=2.3x10-11) and FLT3 (p=1.6x10-4) mutations; conversely, cluster C3 (n=53) was highly enriched for recurrent copy-number alterations as well as RUNX1 (p=0.001) and TP53 somatic mutations (p=0.004). We further discovered a core of 37 lncRNAs significantly associated with a MLL-signature and 16 lncRNAs with a NPM1-mutated signature. Conclusion: This study describes the first genome-wide mapping and characterization of lncRNAs in AML and proposes a robust lncRNA-based classification. This classification may serve in defining core lncRNAs that orchestrate key oncogenic states in the different clinical subtypes. Disclosures No relevant conflicts of interest to declare.

New Molecular Abnormalities and Clonal Architecture in AML: From Reciprocal Translocations to Whole-Genome Sequencing

2014 ◽  
pp. e334-e340 ◽  
Author(s):  
Timothy A. Graubert ◽  
Andrew M. Brunner ◽  
Amir T. Fathi
Keyword(s):  
Clonal Evolution ◽  
Point Mutations ◽  
Normal Karyotype ◽  
Genetic Alterations ◽  
Epigenetic Alterations ◽  
Reciprocal Translocations ◽  
Molecular Alterations ◽  
Molecular Abnormalities ◽  
Improved Outcomes ◽  
History Of

Acute myeloid leukemia (AML) is characterized by recurrent genetic alterations, including amplifications, deletions, rearrangements, and point mutations. Clinically, these lesions can be used to stratify patients into categories of risk, which directs further clinical management and prognostication. Patient risk categories were first described based on recurrent karyotypic abnormalities; most patients with AML, however, fall into intermediate cytogenetic risk, the majority harboring a normal karyotype. Subsequently, identification of recurrently mutated genes, including FLT3, NPM1, and CEBPA, allowed further stratification of patients with a normal karyotype. More extensive genomic and epigenomic analysis of AML samples has expanded the number of known molecular alterations present in this disease. The further understanding of this mutational landscape has shed light into the pathogenesis of AML. AML arises in a founding clone that often gives rise to subclones. Clonal evolution is a feature of the natural history of the disease but may also be influenced by the selective pressure of chemotherapy. The complex network of genetic and epigenetic alterations in this disease has yielded numerous new targets for intervention. In the future, further understanding of this mutational framework, along with the development of novel therapeutic targets, may lead to improved outcomes for patients with AML.

Molecular genetic markers for thyroid FNAB

2015 ◽  
Vol 54 (03) ◽  
pp. 94-100 ◽  
Author(s):  
P. B. Musholt ◽  
T. J. Musholt
Keyword(s):  
Genetic Markers ◽  
Thyroid Nodules ◽  
Molecular Genetic ◽  
Genetic Alterations ◽  
Diagnostic Tools ◽  
Ultrasound Screening ◽  
Thyroid Malignancy ◽  
Thyroid Carcinomas ◽  
Molecular Genetic Markers ◽  
The Impact

SummaryAim: Thyroid nodules > 1 cm are observed in about 12% of unselected adult employees aged 18–65 years screened by ultrasound scan (40). While intensive ultrasound screening leads to early detection of thyroid diseases, the determination of benign or malignant behaviour remains uncertain and may trigger anxieties in many patients and their physicians. A considerable number of thyroid resections are consecutively performed due to suspicion of malignancy in the detected nodes. Fine needle aspiration biopsy (FNAB) has been recommended for the assessment of thyroid nodules to facilitate detection of thyroid carcinomas but also to rule out malignancy and thereby avoid unnecessary thyroid resections. However, cytology results are dependent on experience of the respective cytologist and unfortunately inconclusive in many cases. Methods: Molecular genetic markers are already used nowadays to enhance sensitivity and specificity of FNAB cytology in some centers in Germany. The most clinically relevant molecular genetic markers as pre-operative diagnostic tools and the clinical implications for the intraoperative and postoperative management were reviewed. Results: Molecular genetic markers predominantly focus on the preoperative detection of thyroid malignancies rather than the exclusion of thyroid carcinomas. While some centers routinely assess FNABs, other centers concentrate on FNABs with cytology results of follicular neoplasia or suspicion of thyroid carcinoma. Predominantly mutations of BRAF, RET/PTC, RAS, and PAX8/PPARγ or expression of miRNAs are analyzed. However, only the detection of BRAF mutations predicts the presence of (papillary) thyroid malignancy with almost 98% probability, indicating necessity of oncologic thyroid resections irrespective of the cytology result. Other genetic alterations are associated with thyroid malignancy with varying frequency and achieve less impact on the clinical management. Conclusion: Molecular genetic analysis of FNABs is increasingly performed in Germany. Standardization, quality controls, and validation of various methods need to be implemented in the near future to be able to compare the results. With increasing knowledge about the impact of genetic alterations on the prognosis of thyroid carcinomas, recommendations have to be defined that may lead to individually optimized treatment strategies.

scholarly journals Genome-Wide Transcriptomic Identification and Functional Insight of Lily WRKY Genes Responding to Botrytis Fungal Disease

Plants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 776
Author(s):  
Shipra Kumari ◽  
Bashistha Kumar Kanth ◽  
Ju young Ahn ◽  
Jong Hwa Kim ◽  
Geung-Joo Lee
Keyword(s):  
Abiotic Stress ◽  
Biotic Stress ◽  
Developmental Stages ◽  
Expression Patterns ◽  
Lilium Longiflorum ◽  
Biotic And Abiotic Stress ◽  
Biotic Stresses ◽  
Genome Wide

Genome-wide transcriptome analysis using RNA-Seq of Lilium longiflorum revealed valuable genes responding to biotic stresses. WRKY transcription factors are regulatory proteins playing essential roles in defense processes under environmental stresses, causing considerable losses in flower quality and production. Thirty-eight WRKY genes were identified from the transcriptomic profile from lily genotypes, exhibiting leaf blight caused by Botrytis elliptica. Lily WRKYs have a highly conserved motif, WRKYGQK, with a common variant, WRKYGKK. Phylogeny of LlWRKYs with homologous genes from other representative plant species classified them into three groups- I, II, and III consisting of seven, 22, and nine genes, respectively. Base on functional annotation, 22 LlWRKY genes were associated with biotic stress, nine with abiotic stress, and seven with others. Sixteen unique LlWRKY were studied to investigate responses to stress conditions using gene expression under biotic and abiotic stress treatments. Five genes—LlWRKY3, LlWRKY4, LlWRKY5, LlWRKY10, and LlWRKY12—were substantially upregulated, proving to be biotic stress-responsive genes in vivo and in vitro conditions. Moreover, the expression patterns of LlWRKY genes varied in response to drought, heat, cold, and different developmental stages or tissues. Overall, our study provides structural and molecular insights into LlWRKY genes for use in the genetic engineering in Lilium against Botrytis disease.

scholarly journals Analysing electrocardiographic traits and predicting cardiac risk in UK biobank

2021 ◽  
Vol 10 ◽  
pp. 204800402110236
Author(s):  
Julia Ramírez ◽  
Stefan van Duijvenboden ◽  
William J Young ◽  
Michele Orini ◽  
Aled R Jones ◽  
...  
Keyword(s):  
Genetic Information ◽  
Association Studies ◽  
Cardiac Risk ◽  
Genome Wide Association Studies ◽  
Uk Biobank ◽  
Biological Mechanisms ◽  
Clinical Tool ◽  
Genome Wide ◽  
Response To Exercise ◽  
Electrocardiogram Ecg

The electrocardiogram (ECG) is a commonly used clinical tool that reflects cardiac excitability and disease. Many parameters are can be measured and with the improvement of methodology can now be quantified in an automated fashion, with accuracy and at scale. Furthermore, these measurements can be heritable and thus genome wide association studies inform the underpinning biological mechanisms. In this review we describe how we have used the resources in UK Biobank to undertake such work. In particular, we focus on a substudy uniquely describing the response to exercise performed at scale with accompanying genetic information.

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