544 results match your criteria isogenic pairs

Identification of Candidate Genes for Root Traits Using Genotype-Phenotype Association Analysis of Near-Isogenic Lines in Hexaploid Wheat ( L.).

Int J Mol Sci 2021 Mar 30;22(7). Epub 2021 Mar 30.

UWA School of Agriculture and Environment, The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia.

Global wheat ( L.) production is constrained by different biotic and abiotic stresses, which are increasing with climate change. An improved root system is essential for adaptability and sustainable wheat production. Read More

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Genetic Cardiomyopathies: The Lesson Learned from hiPSCs.

J Clin Med 2021 Mar 9;10(5). Epub 2021 Mar 9.

Humanitas Clinical and Research Center-IRCCS, Rozzano, 20089 Milan, Italy.

Genetic cardiomyopathies represent a wide spectrum of inherited diseases and constitute an important cause of morbidity and mortality among young people, which can manifest with heart failure, arrhythmias, and/or sudden cardiac death. Multiple underlying genetic variants and molecular pathways have been discovered in recent years; however, assessing the pathogenicity of new variants often needs in-depth characterization in order to ascertain a causal role in the disease. The application of human induced pluripotent stem cells has greatly helped to advance our knowledge in this field and enabled to obtain numerous in vitro patient-specific cellular models useful to study the underlying molecular mechanisms and test new therapeutic strategies. Read More

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EML4-ALK induces cellular senescence in mortal normal human cells and promotes anchorage-independent growth in hTERT-transduced normal human cells.

BMC Cancer 2021 Mar 24;21(1):310. Epub 2021 Mar 24.

Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Room 3068A, Bethesda, MD, 20892, USA.

Background: Chromosomal inversions involving anaplastic lymphoma kinase (ALK) and echinoderm microtubule associated protein like 4 (EML4) generate a fusion protein EML4-ALK in non-small cell lung cancer (NSCLC). The understanding of EML4-ALK function can be improved by a functional study using normal human cells.

Methods: Here we for the first time conduct such study to examine the effects of EML4-ALK on cell proliferation, cellular senescence, DNA damage, gene expression profiles and transformed phenotypes. Read More

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CRISPR/Cas9-Mediated Introduction of Specific Heterozygous Mutations in Human Induced Pluripotent Stem Cells.

Methods Mol Biol 2021 Mar 24. Epub 2021 Mar 24.

Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.

Advances in genome editing and our ability to derive and differentiate human induced pluripotent stem cells (hiPSCs) into a wide variety of cell types present in the body is revolutionizing how we model human diseases in vitro. Central to this has been the development of the CRISPR/Cas9 system as an inexpensive and highly efficient tool for introducing or correcting disease-associated mutations. However, the ease with which CRISPR/Cas9 enables genetic modification is a double-edged sword, with the challenge now being to introduce changes precisely to just one allele without disrupting the other. Read More

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Resistance to BET inhibitors in lung adenocarcinoma is mediated by casein kinase phosphorylation of BRD4.

Oncogenesis 2021 Mar 12;10(3):27. Epub 2021 Mar 12.

Integrative Oncology, British Columbia Cancer, Vancouver, BC, V5Z 1L3, Canada.

Targeting the epigenome to modulate gene expression programs driving cancer development has emerged as an exciting avenue for therapeutic intervention. Pharmacological inhibition of the bromodomain and extraterminal (BET) family of chromatin adapter proteins has proven effective in this regard, suppressing growth of diverse cancer types mainly through downregulation of the c-MYC oncogene, and its downstream transcriptional program. While initially effective, resistance to BET inhibitors (BETi) typically occurs through mechanisms that reactivate MYC expression. Read More

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Abiotic Stress Response of Near-Isogenic Spring Durum Wheat Lines under Different Sowing Densities.

Int J Mol Sci 2021 Feb 19;22(4). Epub 2021 Feb 19.

Centre for Agricultural Research, Agricultural Institute, ELKH, 2462 Martonvásár, Hungary.

A detailed study was made of changes in the plant development, morphology, physiology and yield biology of near-isogenic lines of spring durum wheat sown in the field with different plant densities in two consecutive years (2013-2014). An analysis was made of the drought tolerance of isogenic lines selected for yield QTLs ( and ), and the presence of QTL effects was examined in spring sowings. Comparisons were made of the traits of the isogenic pairs and -- both within and between the pairs. Read More

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February 2021

Cooperative Blockade of CK2 and ATM Kinases Drives Apoptosis in VHL-Deficient Renal Carcinoma Cells through ROS Overproduction.

Cancers (Basel) 2021 Feb 2;13(3). Epub 2021 Feb 2.

Interdisciplinary Research Institute of Grenoble, IRIG-Biosanté, University Grenoble Alpes, CEA, UMR 1292, F-38000 Grenoble, France.

Kinase-targeted agents demonstrate antitumor activity in advanced metastatic clear cell renal cell carcinoma (ccRCC), which remains largely incurable. Integration of genomic approaches through small-molecules and genetically based high-throughput screening holds the promise of improved discovery of candidate targets for cancer therapy. The 786-O cell line represents a model for most ccRCC that have a loss of functional pVHL (von Hippel-Lindau). Read More

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February 2021

A chemical genetic screen identifies Aurora kinases as a therapeutic target in EGFR T790M negative, gefitinib-resistant head and neck squamous cell carcinoma (HNSCC).

EBioMedicine 2021 Feb 30;64:103220. Epub 2021 Jan 30.

Laboratory of Precision Oncology and Cancer Evolution, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Genome #02-01, Singapore 138672, Singapore. Electronic address:

Background: Overexpression of epidermal growth factor receptor (EGFR), and downstream pathway activation appears to be a common oncogenic driver in the majority of head and neck squamous cell cancers (HNSCCs); yet targeting EGFR for the treatment of HNSCC has met with limited success. Apart from the anti-EGFR antibody cetuximab, no small molecule EGFR/tyrosine kinase inhibitors (TKIs) have progressed to routine clinical use. The aim of this study was to determine factors contributing to the lack of response to TKIs and identify alternative therapeutic vulnerabilities. Read More

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February 2021

Transcriptomic profiling of wheat near-isogenic lines reveals candidate genes on chromosome 3A for pre-harvest sprouting resistance.

BMC Plant Biol 2021 Jan 21;21(1):53. Epub 2021 Jan 21.

UWA School of Agriculture and Environment, The University of Western Australia, Perth, WA, 6009, Australia.

Background: Pre-harvest sprouting (PHS) in wheat can cause severe damage to both grain yield and quality. Resistance to PHS is a quantitative trait controlled by many genes located across all 21 wheat chromosomes. The study targeted a large-effect quantitative trait locus (QTL) QPhs. Read More

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January 2021

The semi-dwarfing gene Rht-dp from dwarf polish wheat (Triticum polonicum L.) is the "Green Revolution" gene Rht-B1b.

BMC Genomics 2021 Jan 19;22(1):63. Epub 2021 Jan 19.

Triticeae Research Institute, Sichuan Agricultural University, Wenjiang, Chengdu, 611130, Sichuan, China.

Background: The wheat dwarfing gene increases lodging resistance, the grain number per spike and harvest index. Dwarf Polish wheat (Triticum polonicum L., 2n = 4x = 28, AABB, DPW), initially collected from Tulufan, Xinjiang, China, carries a semi-dwarfing gene Rht-dp on chromosome 4BS. Read More

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January 2021

/LKB1 Mutations in NSCLC Are Associated with KEAP1/NRF2-Dependent Radiotherapy Resistance Targetable by Glutaminase Inhibition.

Clin Cancer Res 2021 Mar 15;27(6):1720-1733. Epub 2020 Dec 15.

Departments of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Purpose: Radiotherapy with or without chemotherapy is a mainstay of treatment for locally advanced non-small cell lung cancer (NSCLC), but no predictive markers are currently available to select patients who will benefit from these therapies. In this study, we investigated the association between alterations in /LKB1, the second most common tumor suppressor in NSCLC, and response to radiotherapy as well as potential therapeutic approaches to improve outcomes.

Experimental Design: We conducted a retrospective analysis of 194 patients with stage I-III NSCLC, including 164 stage III patients bearing mutant or wild-type /LKB1 treated with radiotherapy, and assessed locoregional recurrence (LRR), distant metastasis rates, disease-free survival (DFS), and overall survival (OS), and we investigated the causal role of LKB1 in mediating radiotherapy resistance using isogenic pairs of NSCLC cell lines with LKB1 loss or gain. Read More

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Replaying the evolutionary tape to investigate subgenome dominance in allopolyploid Brassica napus.

New Phytol 2021 04 9;230(1):354-371. Epub 2021 Jan 9.

Department of Horticulture, Michigan State University, East Lansing, MI, 48824, USA.

Allopolyploidisation merges evolutionarily distinct parental genomes (subgenomes) into a single nucleus. A frequent observation is that one subgenome is 'dominant' over the other subgenome, often being more highly expressed. Here, we 'replayed the evolutionary tape' with six isogenic resynthesised Brassica napus allopolyploid lines and investigated subgenome dominance patterns over the first 10 generations postpolyploidisation. Read More

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Sweet Corn Sentinel Monitoring for Lepidopteran Field-Evolved Resistance to Bt Toxins.

J Econ Entomol 2021 Feb;114(1):307-319

Department of Entomology, University of Maryland, College Park, MD.

As part of an insect resistance management plan to preserve Bt transgenic technology, annual monitoring of target pests is mandated to detect susceptibility changes to Bt toxins. Currently Helicoverpa zea (Boddie) monitoring involves investigating unexpected injury in Bt crop fields and collecting larvae from non-Bt host plants for laboratory diet bioassays to determine mortality responses to diagnostic concentrations of Bt toxins. To date, this monitoring approach has not detected any significant change from the known range of baseline susceptibility to Bt toxins, yet practical field-evolved resistance in H. Read More

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February 2021

Induced pluripotent stem cells established from a female patient with Xq22 deletion confirm that BEX2 escapes from X-chromosome inactivation.

Congenit Anom (Kyoto) 2021 Mar 13;61(2):63-67. Epub 2020 Dec 13.

Institute of Medical Genetics, Tokyo Women's Medical genetics, Tokyo, Japan.

Large deletions in Xq22 are responsible for neurodevelopmental disorders, including severe intellectual disability and behavioral abnormalities. Although the deletion regions contain PLP1, the gene related to Pelizaeus-Merzbacher disease (PMD), patients with Xq22 deletions show no clinical features of PMD such as paraplegia and white matter abnormalities. This could be due to skewed X-chromosome inactivation (XCI) occurring predominantly in the affected allele. Read More

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TGFβ promotes YAP-dependent AXL induction in mesenchymal-type lung cancer cells.

Mol Oncol 2021 Feb 5;15(2):679-696. Epub 2020 Dec 5.

College of Pharmacy, Seoul National University, Korea.

The acquisition of chemoresistance remains a major cause of cancer mortality due to the limited accessibility of targeted or immune therapies. However, given that severe alterations of molecular features during epithelial-to-mesenchymal transition (EMT) lead to acquired chemoresistance, emerging studies have focused on identifying targetable drivers associated with acquired chemoresistance. Particularly, AXL, a key receptor tyrosine kinase that confers resistance against targets and chemotherapeutics, is highly expressed in mesenchymal cancer cells. Read More

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February 2021

Targeting Germline- and Tumor-Associated Nucleotide Excision Repair Defects in Cancer.

Clin Cancer Res 2021 Apr 16;27(7):1997-2010. Epub 2020 Nov 16.

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.

Purpose: Nucleotide excision repair (NER) gene alterations constitute potential cancer therapeutic targets. We explored the prevalence of NER gene alterations across cancers and putative therapeutic strategies targeting these vulnerabilities.

Experimental Design: We interrogated our institutional dataset with mutational data from more than 40,000 patients with cancer to assess the frequency of putative deleterious alterations in four key NER genes. Read More

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CRISPR-Mediated Isogenic Cell-SELEX Approach for Generating Highly Specific Aptamers Against Native Membrane Proteins.

Cell Mol Bioeng 2020 Oct 11;13(5):559-574. Epub 2020 Sep 11.

Department of Chemical and Biomolecular Engineering, Vanderbilt University, PMB 351604, 2301 Vanderbilt Place, Nashville, TN 37235-1604 USA.

Introduction: The generation of affinity reagents that bind native membrane proteins with high specificity remains challenging. Most selection paradigms utilize different cell types for positive and negative rounds of selection (where the positive selection is against a cell that expresses the desired membrane protein and the negative selection is against a cell that lacks the protein). However, this strategy can yield affinity reagents that bind unintended membrane proteins on the target cells. Read More

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October 2020

Transcripts of wheat at a target locus on chromosome 6B associated with increased yield, leaf mass and chlorophyll index under combined drought and heat stress.

PLoS One 2020 9;15(11):e0241966. Epub 2020 Nov 9.

School of Agriculture, Food and Wine, The University of Adelaide, Adelaide, South Australia, Australia.

Drought and heat stress constrain wheat (Triticum aestivum L.) yields globally. To identify putative mechanisms and candidate genes associated with combined drought and heat stress tolerance, we developed bread wheat near-isogenic lines (NILs) targeting a quantitative trait locus (QTL) on chromosome 6B which was previously associated with combined drought and heat stress tolerance in a diverse panel of wheats. Read More

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January 2021

New Insights Into the Nature of Interspecific Hybrid Sterility in Rice.

Front Plant Sci 2020 23;11:555572. Epub 2020 Sep 23.

Yunnan Key Laboratory for Rice Genetic Improvement, Food Crops Research Institute, Yunnan Academy of Agricultural Sciences (YAAS), Kunming, China.

Interspecific and intraspecific hybrid sterility is a typical and common phenomenon of postzygotic reproductive barrier in rice. This is an indicator of speciation involved in the formation of new species or subspecies, and it significantly hampers the utilization of favorable genes from distant parents for rice improvement. The genus includes eight species with the same AA genome and is a model plant for studying the nature of hybrid sterility and its relationship with speciation. Read More

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September 2020

CD44-Associated Tn Antigen as a New Biomarker of Tumor Cells with Aberrant Glycosylation.

Biochemistry (Mosc) 2020 Sep;85(9):1064-1081

Institute of Immunology National Research Center, Federal Medical and Biological Agency of Russia, Moscow, 115522, Russia.

Tn antigen is a tumor-associated antigen that appears on cancer cells as a result of aberrant O-glycosylation. The most studied form of Tn antigen is found in mucins, in particular, in mucin 1 (MUC1). Antibodies against this form of Tn antigen are used to diagnose tumors, as well as to generate T-killers with a chimeric receptor. Read More

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September 2020

Development and Characterization of Near-Isogenic Lines Revealing Candidate Genes for a Major 7AL QTL Responsible for Heat Tolerance in Wheat.

Front Plant Sci 2020 28;11:1316. Epub 2020 Aug 28.

Faculty of Science, UWA School of Agriculture and Environment, The University of Western Australia, Perth, WA, Australia.

Wheat is one of the most important food crops in the world, but as a cool-season crop, it is more prone to heat stress, which severely affects crop production and grain quality. Heat tolerance in wheat is a quantitative trait, and the genes underlying reported quantitative trait loci (QTL) have rarely been identified. Near-isogenic lines (NILs) with a common genetic background but differing at a particular locus could turn quantitative traits into a Mendelian factor; therefore, they are suitable material for identifying candidate genes for targeted locus/loci. Read More

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Virulence phenotypes result from interactions between pathogen ploidy and genetic background.

Ecol Evol 2020 Sep 7;10(17):9326-9338. Epub 2020 Aug 7.

Department of Biology Emory University Atlanta GA USA.

Studying fungal virulence is often challenging and frequently depends on many contexts, including host immune status and pathogen genetic background. However, the role of ploidy has often been overlooked when studying virulence in eukaryotic pathogens. Since fungal pathogens, including the human opportunistic pathogen , can display extensive ploidy variation, assessing how ploidy impacts virulence has important clinical relevance. Read More

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September 2020

Physiological, ultrastructural, biochemical, and molecular responses of glandless cotton to hexavalent chromium (Cr) exposure.

Environ Pollut 2020 Nov 13;266(Pt 1):115394. Epub 2020 Aug 13.

College of Agriculture and Biotechnology, Zhejiang University, Hangzhou, Zhejiang, 310058, China. Electronic address:

Glandless cotton can be grown to obtain cotton seeds free of toxic gossypol for use as both food and feed. However, they are not grown normally due to their lesser productivity and higher susceptibility to biotic stress. Great attention has been paid to biotic stresses rather than abiotic stresses on glandless cotton. Read More

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November 2020

Identification of Genomewide Alternative Splicing Events in Sequential, Isogenic Clinical Isolates of Candida albicans Reveals a Novel Mechanism of Drug Resistance and Tolerance to Cellular Stresses.

mSphere 2020 08 12;5(4). Epub 2020 Aug 12.

Amity Institute of Integrative Sciences and Health, Amity University Gurgaon, Gurgaon, India

Alternative splicing (AS)-a process by which a single gene gives rise to different protein isoforms in eukaryotes-has been implicated in many basic cellular processes, but little is known about its role in drug resistance and fungal pathogenesis. The most common human fungal pathogen, , has introns in 4 to 6% of its genes, the functions of which remain largely unknown. Here, we report AS regulating drug resistance in Comparative RNA-sequencing of two different sets of sequential, isogenic azole-sensitive and -resistant isolates of revealed differential expression of splice isoforms of 14 genes. Read More

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Identification of Genetic Alterations Associated with Acquired Colistin Resistance in Isogenic Strains by Whole-Genome Sequencing.

Antibiotics (Basel) 2020 Jul 2;9(7). Epub 2020 Jul 2.

Department of Microbiology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea.

The present study was undertaken to find novel genes associated with colistin resistance in . Five colistin-resistant mutants were derived from four colistin-susceptible parental strains belonging to different clones. Whole-genome sequencing was performed for the nine strains to screen altered candidate genes. Read More

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Loss of STAT6 leads to anchorage-independent growth and trastuzumab resistance in HER2+ breast cancer cells.

PLoS One 2020 11;15(6):e0234146. Epub 2020 Jun 11.

Division of Hematology, Oncology, and Cell Therapy, Department of Medicine, Rush University Medical Center, Chicago, Illinois, United States of America.

Approximately 20% of breast cancers are HER2-positive. Trastuzumab has improved patient outcomes significantly for these cancers. However, acquired resistance remains a major hurdle in the clinical management of these patients. Read More

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Identification of lncRNAs involved in wheat tillering development in two pairs of near-isogenic lines.

Funct Integr Genomics 2020 Sep 1;20(5):669-679. Epub 2020 Jun 1.

Triticeae Research Institute, Sichuan Agricultural University, Wenjiang, Chengdu, 611130, China.

Emerging evidence demonstrates that lncRNAs participate in various developmental processes in plants via post-transcription regulation. However, few lncRNAs have been identified as regulators of tiller development in wheat (Triticum aestivum L.). Read More

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September 2020

Dissection and validation of a QTL cluster linked to Rht-B1 locus controlling grain weight in common wheat (Triticum aestivum L.) using near-isogenic lines.

Theor Appl Genet 2020 Sep 2;133(9):2639-2653. Epub 2020 Jun 2.

State Key Laboratory for Agrobiotechnology/Key Laboratory of Crop Heterosis and Utilization, Ministry of Education/Beijing Key Laboratory of Crop Genetic Improvement/College of Agronomy and Biotechnology, China Agricultural University, Beijing, 100193, China.

Key Message: This study dissected and validated a QTL cluster associated with thousand grain weight on chromosome 4B using multiple near-isogenic lines in common wheat. Grain size and weight are crucial components of wheat yield. Previously, we identified a QTL cluster for thousand grain weight (TGW) on chromosome 4B using the Nongda3338 (ND3338)/Jingdong6 (JD6) doubled haploid population. Read More

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September 2020

Generation and genetic repair of 2 iPSC clones from a patient bearing a heterozygous c.1120del18 mutation in the ACVRL1 gene leading to Hereditary Hemorrhagic Telangiectasia (HHT) type 2.

Stem Cell Res 2020 07 28;46:101786. Epub 2020 May 28.

LUMC hiPSC Hotel, Leiden University Medical Center, Leiden, 2333 ZC, The Netherlands; Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, 2333 ZC, The Netherlands.

Fibroblasts from a patient carrying a heterozygous 18bp deletion in exon 8 of the ACVRL1 gene (c.1120del18) were reprogrammed using episomal vectors. The in-frame deletion in ACVRL1 causes the loss of 6 amino acids of the protein, which is associated with Hereditary Hemorrhagic Telangiectasia (HHT) type 2 (Letteboer et al. Read More

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Phenotypic and Genotypic Comparison of a Live-Attenuated Genotype I Japanese Encephalitis Virus SD12-F120 Strain with Its Virulent Parental SD12 Strain.

Viruses 2020 05 16;12(5). Epub 2020 May 16.

Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.

The phenotypic and genotypic characteristics of a live-attenuated genotype I (GI) strain (SD12-F120) of Japanese encephalitis virus (JEV) were compared with its virulent parental SD12 strain to gain an insight into the genetic changes acquired during the attenuation process. SD12-F120 formed smaller plaque on BHK-21 cells and showed reduced replication in mouse brains compared with SD12. Mice inoculated with SD12-F120 via either intraperitoneal or intracerebral route showed no clinical symptoms, indicating a highly attenuated phenotype in terms of both neuroinvasiveness and neurovirulence. Read More

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