Journal articles: 'CRITICAL GENES'

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Epstein, Charles J. "Critical genes in a critical region." Nature 441, no. 7093 (May 31, 2006): 582–83. http://dx.doi.org/10.1038/441582a.

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Foster, Russell G., and Robert J. Lucas. "Clocks, criteria and critical genes." Nature Genetics 22, no. 3 (July 1999): 217–19. http://dx.doi.org/10.1038/10270.

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Kobayashi, Yohei, Zhanlei Ye, and Takao K. Hensch. "Clock Genes Control Cortical Critical Period Timing." Neuron 86, no. 1 (April 2015): 264–75. http://dx.doi.org/10.1016/j.neuron.2015.02.036.

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Mteyrek, Ali, Elisabeth Filipski, Catherine Guettier, Malgorzata Oklejewicz, Gijsbertus T. J. van der Horst, Alper Okyar, and Francis Lévi. "Critical cholangiocarcinogenesis control by cryptochrome clock genes." International Journal of Cancer 140, no. 11 (March 16, 2017): 2473–83. http://dx.doi.org/10.1002/ijc.30663.

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Evans, Kathryn L. "Minibrain genes and critical loci for down syndrome." Molecular Medicine Today 2, no. 12 (December 1996): 495. http://dx.doi.org/10.1016/s1357-4310(97)81450-5.

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Buchinsky, Farrel J., Craig S. Derkay, Suzanne M. Leal, Joseph Donfack, Garth D. Ehrlich, and J. Christopher Post. "Multicenter Initiative Seeking Critical Genes in Respiratory Papillomatosis." Laryngoscope 114, no. 2 (February 2004): 349–57. http://dx.doi.org/10.1097/00005537-200402000-00032.

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Dickson, David. "European patent directive in critical test over genes." Nature 372, no. 6504 (November 1994): 310. http://dx.doi.org/10.1038/372310a0.

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Galeev, Roman, Aurelie Baudet, Anders Kvist, Therese Törngren, and Jonas Larsson. "Cohesin genes are critical regulators of HSC renewal." Experimental Hematology 43, no. 9 (September 2015): S48. http://dx.doi.org/10.1016/j.exphem.2015.06.062.

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Hampton, Tracy. "Scientists Identify Genes Critical to Development of Leukemia." JAMA 315, no. 9 (March 1, 2016): 860. http://dx.doi.org/10.1001/jama.2016.1486.

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Roots, Kimberly. "Critical Mass: Inner space/genes/origins/environment/outer space." Science & Spirit 16, no. 4 (July 1, 2005): 15–24. http://dx.doi.org/10.3200/sspt.16.4.15-24.

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Song, Jane Y., Kyriel M. Pineault, Jesús M. Dones, Ronald T. Raines, and Deneen M. Wellik. "Hox genes maintain critical roles in the adult skeleton." Proceedings of the National Academy of Sciences 117, no. 13 (March 13, 2020): 7296–304. http://dx.doi.org/10.1073/pnas.1920860117.

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Hox genes are indispensable for the proper patterning of the skeletal morphology of the axial and appendicular skeleton during embryonic development. Recently, it has been demonstrated that Hox expression continues from embryonic stages through postnatal and adult stages exclusively in a skeletal stem cell population. However, whether Hox genes continue to function after development has not been rigorously investigated. We generated a Hoxd11 conditional allele and induced genetic deletion at adult stages to show that Hox11 genes play critical roles in skeletal homeostasis of the forelimb zeugopod (radius and ulna). Conditional loss of Hox11 function at adult stages leads to replacement of normal lamellar bone with an abnormal woven bone-like matrix of highly disorganized collagen fibers. Examining the lineage from the Hox-expressing mutant cells demonstrates no loss of stem cell population. Differentiation in the osteoblast lineage initiates with Runx2 expression, which is observed similarly in mutants and controls. With loss of Hox11 function, however, osteoblasts fail to mature, with no progression to osteopontin or osteocalcin expression. Osteocyte-like cells become embedded within the abnormal bony matrix, but they completely lack dendrites, as well as the characteristic lacuno-canalicular network, and do not express SOST. Together, our studies show that Hox11 genes continuously function in the adult skeleton in a region-specific manner by regulating differentiation of Hox-expressing skeletal stem cells into the osteolineage.

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Lin-Shiao, Enrique, Yemin Lan, Julia Welzenbach, Katherine A. Alexander, Zhen Zhang, Michael Knapp, Elisabeth Mangold, Morgan Sammons, Kerstin U. Ludwig, and Shelley L. Berger. "p63 establishes epithelial enhancers at critical craniofacial development genes." Science Advances 5, no. 5 (May 2019): eaaw0946. http://dx.doi.org/10.1126/sciadv.aaw0946.

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The transcription factor p63 is a key mediator of epidermal development. Point mutations in p63 in patients lead to developmental defects, including orofacial clefting. To date, knowledge on how pivotal the role of p63 is in human craniofacial development is limited. Using an inducible transdifferentiation model, combined with epigenomic sequencing and multicohort meta-analysis of genome-wide association studies data, we show that p63 establishes enhancers at craniofacial development genes to modulate their transcription. Disease-specific substitution mutation in the DNA binding domain or sterile alpha motif protein interaction domain of p63, respectively, eliminates or reduces establishment of these enhancers. We show that enhancers established by p63 are highly enriched for single-nucleotide polymorphisms associated with nonsyndromic cleft lip ± cleft palate (CL/P). These orthogonal approaches indicate a strong molecular link between p63 enhancer function and CL/P, illuminating molecular mechanisms underlying this developmental defect and revealing vital regulatory elements and new candidate causative genes.

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Pichiorri, F., S. S. Suh, M. Ladetto, M. Kuehl, T. Palumbo, D. Drandi, C. Taccioli, et al. "MicroRNAs regulate critical genes associated with multiple myeloma pathogenesis." Proceedings of the National Academy of Sciences 105, no. 35 (August 26, 2008): 12885–90. http://dx.doi.org/10.1073/pnas.0806202105.

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Hrycaj, Steven M., and Deneen M. Wellik. "Hox genes and evolution." F1000Research 5 (May 10, 2016): 859. http://dx.doi.org/10.12688/f1000research.7663.1.

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Hox proteins are a deeply conserved group of transcription factors originally defined for their critical roles in governing segmental identity along the antero-posterior (AP) axis in Drosophila. Over the last 30 years, numerous data generated in evolutionarily diverse taxa have clearly shown that changes in the expression patterns of these genes are closely associated with the regionalization of the AP axis, suggesting that Hox genes have played a critical role in the evolution of novel body plans within Bilateria. Despite this deep functional conservation and the importance of these genes in AP patterning, key questions remain regarding many aspects of Hox biology. In this commentary, we highlight recent reports that have provided novel insight into the origins of the mammalian Hox cluster, the role of Hox genes in the generation of a limbless body plan, and a novel putative mechanism in which Hox genes may encode specificity along the AP axis. Although the data discussed here offer a fresh perspective, it is clear that there is still much to learn about Hox biology and the roles it has played in the evolution of the Bilaterian body plan.

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Sakashita, Midori, and Masaomi Nangaku. "Multi-omics studies reveal genes critical for AKI and ferroptosis." Kidney International 101, no. 4 (April 2022): 665–67. http://dx.doi.org/10.1016/j.kint.2021.10.032.

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Bordon, Yvonne. "A new set of genes linked to critical COVID-19." Nature Reviews Immunology 22, no. 4 (March 14, 2022): 208. http://dx.doi.org/10.1038/s41577-022-00709-0.

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Li, Xiu-Min, Hui Wang, Li-Li Zhu, Run-Zhen Zhao, and Hong-Long Ji. "Genes Regulating Epithelial Polarity Are Critical Suppressors of Esophageal Oncogenesis." Journal of Cancer 6, no. 8 (2015): 694–700. http://dx.doi.org/10.7150/jca.11709.

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Burcham, Zachary M., Carl J. Schmidt, Jennifer L. Pechal, Christopher P. Brooks, Jason W. Rosch, M. Eric Benbow, and Heather R. Jordan. "Detection of critical antibiotic resistance genes through routine microbiome surveillance." PLOS ONE 14, no. 3 (March 14, 2019): e0213280. http://dx.doi.org/10.1371/journal.pone.0213280.

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Xu, Yonggang, Jie Wang, Yanbin Xu, Hong Xiao, Jianhua Li, and Zhi Wang. "Screening critical genes associated with malignant glioma using bioinformatics analysis." Molecular Medicine Reports 16, no. 5 (May 2017): 6580–89. http://dx.doi.org/10.3892/mmr.2017.7471.

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Chumachenko, A. G., A. E. Myazin, A. N. Kuzovlev, A. M. Gaponov, A. V. Tutelyan, L. N. Porokhovnik, A. M. Golubev, and V. M. Pisarev. "Allelic Variants of NRF2 and TLR9 Genes in Critical Illness." General Reanimatology 12, no. 4 (January 1, 2016): 8–23. http://dx.doi.org/10.15360/1813-9779-2016-4-8-23.

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Marion, Marie-Jeanne. "Critical genes as early warning signs: example of vinyl chloride." Toxicology Letters 102-103 (December 1998): 603–7. http://dx.doi.org/10.1016/s0378-4274(98)00255-0.

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Pallante, Pierlorenzo, Romina Sepe, Antonella Federico, Floriana Forzati, Mimma Bianco, and Alfredo Fusco. "CBX7 Modulates the Expression of Genes Critical for Cancer Progression." PLoS ONE 9, no. 5 (May 27, 2014): e98295. http://dx.doi.org/10.1371/journal.pone.0098295.

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Sommers, Marilyn Sawyer, and Juanita Schackmann. "Designer genes and critical care nursing: The future is now." Heart & Lung 24, no. 3 (May 1995): 228–37. http://dx.doi.org/10.1016/s0147-9563(05)80041-x.

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Zhu, Yong-Guan, Michael Gillings, Pascal Simonet, Dov Stekel, Steven Banwart, and Josep Penuelas. "Human dissemination of genes and microorganisms in Earth's Critical Zone." Global Change Biology 24, no. 4 (December 20, 2017): 1488–99. http://dx.doi.org/10.1111/gcb.14003.

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Yoshimura, Akihiko, Hitomi Nishinakamura, and Hiromi Takaki. "SOCS genes: Critical regulators of cytokine signaling and immune responses." International Congress Series 1285 (November 2005): 121–29. http://dx.doi.org/10.1016/j.ics.2005.07.028.

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Hu, Xuyun, Xiaoli Chen, Bingbing Wu, Irene Mademont Soler, Shaoke Chen, and Yiping Shen. "Further defining the critical genes for the 4q21 microdeletion disorder." American Journal of Medical Genetics Part A 173, no. 1 (September 8, 2016): 120–25. http://dx.doi.org/10.1002/ajmg.a.37965.

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Airey, David C., and Richard C. Shelton. "Praise for a critical perspective." Behavioral and Brain Sciences 29, no. 4 (August 2006): 405. http://dx.doi.org/10.1017/s0140525x06229091.

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The target article skillfully evaluates data on mental disorders in relation to predictions from evolutionary genetic theories of neutral evolution, balancing selection, and polygenic mutation-selection balance, resulting in a negative outlook for the likelihood of success finding genes for mental disorders. Nevertheless, new conceptualizations, methods, and continued interactions across disciplines provide hope.

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Wu, Jun, Xiao-Jun Liu, Jia-Nan Hu, Xu-Hui Liao, and Fei-Fei Lin. "Transcriptomics and Prognosis Analysis to Identify Critical Biomarkers in Invasive Breast Carcinoma." Technology in Cancer Research & Treatment 19 (January 1, 2020): 153303382095701. http://dx.doi.org/10.1177/1533033820957011.

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Objective: Invasive breast cancer (BRCA) is one of the prevalent types of invasive tumors with high mortality worldwide. Due to the lack of effective treatment to control the recurrence of distant metastases, the prognosis of BRCA is still very unsatisfactory. We aimed to find some biomarkers by bioinformatics analysis for survival prediction. Methods: Differentially expressed genes (DEGs) were screened out based on tumor group and normal group. Then, the weighted gene correlation network analysis (WGCNA) was employed to identify the clinically associated gene sets. Meanwhile, the enrichment analyses were performed for the functional annotation of the critical genes. The Kaplan Meier analysis calculated the essential genes’ prognostic value. Results: After threshold screening, 1655 DEGs were obtained for subsequent analysis. 51 out of 1655 DEGs were significantly associated with BRCA patients’ estrogen receptor status via WGCNA. Three genes (FABP7, CXCL3, and LOC284578) out of the 51 genes were associated with overall survival, and 3 genes were relapse-free survival associated. Finally, we obtained 5 essential prognostic associated genes (FABP7, CXCL3, LOC284578, CAPN6, and NRG2), which could be used as prognostic factors for BRCA. Conclusion: Our findings obtained a gene module associated with BRCA clinical trait and several key genes that acted as essential components in the prognostic of cancer, which may improve its treatment.

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Jing, Hekun, Xiaorui Chen, and Daoxin Wang. "Identification of biomarkers associated with diagnosis of acute lung injury based on bioinformatics and machine learning." Medicine 102, no. 33 (August 18, 2023): e34840. http://dx.doi.org/10.1097/md.0000000000034840.

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Background: Acute lung injury (ALI) is an acute inflammatory disease characterized by excess production of inflammatory factors in lung tissue and has a high mortality. This research was designed for the identification of novel diagnostic biomarkers for ALI and analyzing the possible association between critical genes and infiltrated immune cells. Methods: The study used 2 datasets (GSE2411 and GSE18341) to identify differentially expressed genes (DEGs) between 2 groups. Then we performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses to identify the functions of these DEGs. The study also used SVM-recursive feature elimination analysis and least absolute shrinkage and selection operator regression model to screen possible markers. The study further analyzed immune cell infiltration via CIBERSORT. Gene Set Enrichment Analysis was used to explore the molecular mechanism of the critical genes. Results: DEGs were identified between 2 groups. In total, 690 DEGs were obtained: 527 genes were upregulated and 163 genes were downregulated. We identified PDZK1IP1, CCKAR, and CXCL2 as critical genes. And we then found that these critical genes correlated with Mast Cells, Neutrophil Cells, M1 Macrophage, dendritic cell Actived, Eosinophil Cells, B Cells Naive, Mast Cells, and dendritic cell Immature. Furthermore, we investigated the specific signaling pathways involved in key genes and derived some potential molecular mechanisms by which key genes affect disease progression by use of Gene Set Enrichment Analysis. Moreover, we predict transcription factors. Also, we obtained critical gene-related microRNAs through the targetscan database, and visualized the microRNA network of the genes. Conclusion: Our findings might provide some novel clue for the exploration of novel markers for ALI diagnosis. The critical genes and their associations with immune infiltration may offer new insight into understanding ALI developments.

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Motelow, Joshua E., Natalie C. Lippa, Joseph Hostyk, Evin Feldman, Matthew Nelligan, Zhong Ren, Anna Alkelai, et al. "Risk Variants in the Exomes of Children With Critical Illness." JAMA Network Open 5, no. 10 (October 28, 2022): e2239122. http://dx.doi.org/10.1001/jamanetworkopen.2022.39122.

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ImportanceDiagnostic genetic testing can lead to changes in management in the pediatric intensive care unit. Genetic risk in children with critical illness but nondiagnostic exome sequencing (ES) has not been explored.ObjectiveTo assess the association between loss-of-function (LOF) variants and pediatric critical illness.Design, Setting, and ParticipantsThis genetic association study examined ES first screened for causative variants among 267 children at the Morgan Stanley Children’s Hospital of NewYork-Presbyterian, of whom 22 were otherwise healthy with viral respiratory failure; 18 deceased children with bronchiolitis from the Office of the Chief Medical Examiner of New York City, of whom 14 were previously healthy; and 9990 controls from the Institute for Genomic Medicine at Columbia University Irving Medical Center. The ES data were generated between January 1, 2015, and December 31, 2020, and analyzed between January 1, 2017, and September 2, 2022.ExposureCritical illness.Main Outcomes and MeasuresOdds ratios and P values for genes and gene-sets enriched for rare LOF variants and the loss-of-function observed/expected upper bound fraction (LOEUF) score at which cases have a significant enrichment.ResultsThis study included 285 children with critical illness (median [range] age, 4.1 [0-18.9] years; 148 [52%] male) and 9990 controls. A total of 228 children (80%) did not receive a genetic diagnosis. After quality control (QC), 231 children harbored excess rare LOF variants in genes with a LOEUF score of 0.680 or less (intolerant genes) (P = 1.0 × 10−5). After QC, 176 children without a diagnosis harbored excess ultrarare LOF variants in intolerant genes but only in those without a known disease association (odds ratio, 1.8; 95% CI, 1.3-2.5). After QC, 25 children with viral respiratory failure harbored excess ultrarare LOF variants in intolerant genes but only in those without a known disease association (odds ratio, 2.8; 95% CI, 1.1-6.6). A total of 114 undiagnosed children were enriched for de novo LOF variants in genes without a known disease association (observed, 14; expected, 6.8; enrichment, 2.05).Conclusions and RelevanceIn this genetic association study, excess LOF variants were observed among critically ill children despite nondiagnostic ES. Variants lay in genes without a known disease association, suggesting future investigation may connect phenotypes to causative genes.

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Humbert, Patrick O., Raluca Verona, Jeffrey M. Trimarchi, Catherine Rogers, Savita Dandapani, and Jacqueline A. Lees. "E2f3 is critical for normal cellular proliferation." Genes & Development 14, no. 6 (March 15, 2000): 690–703. http://dx.doi.org/10.1101/gad.14.6.690.

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E2F is a family of transcription factors that regulate both cellular proliferation and differentiation. To establish the role of E2F3 in vivo, we generated an E2f3 mutant mouse strain. E2F3-deficient mice arise at one-quarter of the expected frequency, demonstrating that E2F3 is important for normal development. To determine the molecular consequences of E2F3 deficiency, we analyzed the properties of embryonic fibroblasts derived from E2f3 mutant mice. Mutation of E2f3 dramatically impairs the mitogen-induced, transcriptional activation of numerous E2F-responsive genes. We have been able to identify a number of genes, including B-myb,cyclin A, cdc2, cdc6, and DHFR, whose expression is dependent on the presence of E2F3 but not E2F1. We further show that a critical threshold level of one or more of the E2F3-regulated genes determines the timing of the G1/S transition, the rate of DNA synthesis, and thereby the rate of cellular proliferation. Finally, we show that E2F3 is not required for cellular immortalization but is rate limiting for the proliferation of the resulting tumor cell lines. We conclude that E2F3 is critical for the transcriptional activation of genes that control the rate of proliferation of both primary and tumor cells.

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Keerthivasan, Ganesan, Jing Yang, Piu Wong, John Doench, David E. Root, and Peng Ji. "Targeted ShRNA Screening Identified Critical Role of Pleckstrin-2 in Erythropoiesis." Blood 120, no. 21 (November 16, 2012): 3199. http://dx.doi.org/10.1182/blood.v120.21.3199.3199.

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Abstract Abstract 3199 Mammalian erythropoiesis is globally regulated by erythropoietin (Epo). Epo binds to its receptor on the cell surface of erythroid precursor; induces a series of downstream pathways that promote cell differentiation and inhibit apoptosis. Recent genome wide transcriptional profile study demonstrated that over 500 genes are up-regulated during erythropoiesis. Many of these genes encode erythroid specific proteins that play well-known functions in red cells. However, the functions of the most other genes in the erythroid cells are still unknown. To identify novel genes in erythropoiesis, we infected mouse fetal liver erythroblasts with lentiviruses containing mammalian shRNA knockdown library that selectively includes the most highly upregulated 100 genes with unknown functions in erythroid cells. The infected cells were cultured in two different conditions for the characterization of early and late stage erythropoiesis using a high throughput flow cytometry based analysis. With these methods, we identified 33 novel genes that regulate cell differentiation or apoptosis in early stage erythropoisis; 20 genes play important roles in late stage erythropoiesis including enucleation. Significantly, there is an overlap of 16 genes that function in both early and late stage erythropoiesis. We focused on pleckstrin-2, which is specifically and abundantly expressed in erythroid cells, to further characterize its detailed functions in red cell development. We found that knockdown of pleckstrin-2 leads to dramatic apoptosis in early stage erythropoiesis. Knockdown of pleckstrin-2 in late stage erythropoiesis blocks enucleation with no apparent effects on cell differentiation, proliferation or apoptosis. We further discovered that pleckstrin-2 deficiency in early and late erythroblasts disrupts normal actin cytoskeleton as evidenced by super-resolution immunofluorescence microscope. To elucidate the detailed mechanisms of the functions of pleckstrin-2 in different stages of erythropoiesis, we performed proteomic studies and identified candidate proteins that interact with pleckstrin-2 that may contribute to the phenotypes of apoptosis and enucleation defects. In summary, our study identified pleckstrin-2 as a critical regulator of mammalian erythropoiesis and proved the significance of large-scale shRNA screening in the discovery of novel genes in development. Disclosures: No relevant conflicts of interest to declare.

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Mendha, Aishwarya. "The genetic etiology of critical congenital heart disease." Annals of Circulation 7, no. 1 (December 31, 2022): 008–14. http://dx.doi.org/10.17352/ac.000020.

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Congenital Heart Disease (CHD) is the most common kind of birth defect. Congenital heart disease is the most common birth defect and the leading cause of death in newborns. The causes of CHD are complicated and involve both genes and the environment. Congenital heart disease includes problems with the septum, the valves, and the outflow tract. Correctional heart surgery and new strategies for managing CHD have massively enhanced life expectancy. 490 percent of CHD newborns who live through their first year will become adults. Studies of the molecular genetics of humans and animal models of development are enhancing our understanding of normal heart development and cardiac diseases. A recent study demonstrates that microRNAs are implicated in congenital heart diseases. Epigenetic variables were eventually revealed to influence heart development. Several genes are responsible for congenital cardiac abnormalities as well as genetic disorders. This paper describes the categorization, environmental, and genetic causes of Coronary Heart Disease (CHD), the role of key CHD-causing genes, and potential options for preventing CHD.

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Agrawal, Piyush, Navami Jain, Vishaka Gopalan, and Sridhar Hannenhalli. "Abstract A36: Network-based approach elucidates critical genes in BRCA subtypes." Cancer Immunology Research 10, no. 12_Supplement (December 1, 2022): A36. http://dx.doi.org/10.1158/2326-6074.tumimm22-a36.

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Abstract Intratumor heterogeneity is a common characteristic across cancer types and poses a major therapeutic challenge. Breast cancer is no exception. In 2020 alone, more than 2.3 million women were diagnosed with breast cancer, resulting in 685,000 deaths globally. Breast cancer is broadly classified into four subtypes, viz. Basal, Her2, Luminal-A & Luminal-B and substantial transcriptional heterogeneity has been observed, both across subtypes, as well as within each subtype. However, the observed heterogeneity could be partly due to stochastic expression variability and the extent to which the transcriptional heterogeneity reflects phenotypic variability is unclear. A key insight exploited by our recent network-based approach, PathExt (and others), is that the global transcriptional changes in a disease context is mediated by a small number of key genes and identifying such functional mediators of the global transcription is more likely to provide functional insights into the disease process and better reflect functional heterogeneity. Here we apply PathExt to 1059 BRCA tumors and 112 healthy control samples across 4 subtypes to identify frequent key mediator genes in each subtype. Relative to conventional differential expression approach, PathExt-identified genes exhibit greater commonality across tumors, revealing key biological processes such as cell cycle, response to hormone, regulation of apoptotic processes, etc. Subtype specific biological processes were also observed, for instance, regulation of DNA binding in Basal, positive regulation of inflammatory response in Her2, positive regulation of protein phosphorylation in Luminal-A and second messenger-mediated signaling in Luminal B. Importantly, PathExt-identified genes exhibit much greater dependency scores in subtype-specific cancer cell lines. Compared to the differential expression approach as well as a previous systems approach, PathExt better recapitulates potential driver genes in multiple benchmarks. For instance, PathExt recapitulates many of the significantly mutated protein interaction modules from the NEST database, such as Cell Cycle, Immune systems, Ribonucleo-protein complexes, and Regulation of Transcription. PathExt-identified genes also show a significant overlap with BRCA driver genes in DriverDBv3 and IndoGen databases. Furthermore, PathExt recapitulates the gene sets previously associated with BRCA treatment response, such as immune response, proliferation, and DNA repair deficiency. Lastly, analysis of subtype-specific BRCA scRNA-seq data reveals that while a majority of PathExt-identified genes are highly expressed in malignant cells, many other genes are predominantly expressed in immune and stromal cells, and the distribution of key genes across cell types varies substantially across the four BRCA subtypes. Overall, application of PathExt to BRCA cohort tempers and refines previous view of inter-tumor heterogeneity, and identifies potential functional mediators of BRCA subtypes, paving way for further research. Citation Format: Piyush Agrawal, Navami Jain, Vishaka Gopalan, Sridhar Hannenhalli. Network-based approach elucidates critical genes in BRCA subtypes [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy; 2022 Oct 21-24; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(12 Suppl):Abstract nr A36.

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Yu, Jianfeng, Jie Li, Sai He, Lu Xu, Yanping Zhang, Honglin Jiang, Daoqing Gong, and Zhiliang Gu. "Sirt1 regulates the expression of critical metabolic genes in chicken hepatocytes." Animal Production Science 60, no. 11 (2020): 1381. http://dx.doi.org/10.1071/an18606.

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Context Studies in mammals show that SIRT1 plays an important role in many biological processes including liver metabolism through histone and non-histone deacetylation. Little is known about the function of Sirt1 in the chicken. Aims The current study investigated the expression pattern of Sirt1 mRNA in the chicken and its functions in the chicken liver. Methods In this work, we used real-time quantitative polymerase chain reaction to quantify the expression levels of Sirt1 mRNA in major chicken organs and tissue types, siRNA to knock down Sirt1 expression in primary chicken hepatocytes, RNA sequencing to identify gene-expression changes induced by Sirt1 knockdown, and analysed the function of the differentially expressed genes (DEGs) through gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes ontology analysis. Key results In total, 86 DEGs were found between Sirt1 knockdown and control chicken hepatocytes, of which 63 genes were downregulated and 23 genes were upregulated by Sirt1 knockdown. The Kyoto Encyclopedia of Genes and Genomes analysis showed that 24 DEGs were involved in metabolism. Seven DEGs were involved in carbohydrate and lipid metabolism. Conclusions The present study showed that Sirt1 regulates the expression of genes involved in carbohydrate and lipid metabolism and many other biological processes in the chicken liver. Implications The results of the present study imply that Sirt1 has various functions in the chicken liver and that Sirt1 plays a potentially important role in hepatic carbohydrate and lipid metabolism in the chicken.

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Zhang, Kai, Kuikui Jiang, Ruoxi Hong, Fei Xu, Wen Xia, Ge Qin, Kaping Lee, et al. "Identification and characterization of critical genes associated with tamoxifen resistance in breast cancer." PeerJ 8 (December 4, 2020): e10468. http://dx.doi.org/10.7717/peerj.10468.

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Background Tamoxifen resistance in breast cancer is an unsolved problem in clinical practice. The aim of this study was to determine the potential mechanisms of tamoxifen resistance through bioinformatics analysis. Methods Gene expression profiles of tamoxifen-resistant MCF-7/TR and MCF-7 cells were acquired from the Gene Expression Omnibus dataset GSE26459, and differentially expressed genes (DEGs) were detected with R software. We conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses using Database for Annotation, Visualization and Integrated Discovery. A protein–protein interaction (PPI) network was generated, and we analyzed hub genes in the network with the Search Tool for the Retrieval of Interacting Genes database. Finally, we used siRNAs to silence the target genes and conducted the MTS assay. Results We identified 865 DEGs, 399 of which were upregulated. GO analysis indicated that most genes are related to telomere organization, extracellular exosomes, and binding-related items for protein heterodimerization. PPI network construction revealed that the top 10 hub genes—ACLY, HSPD1, PFAS, GART, TXN, HSPH1, HSPE1, IRAS, TRAP1, and ATIC—might be associated with tamoxifen resistance. Consistently, RT-qPCR analysis indicated that the expression of these 10 genes was increased in MCF-7/TR cells comparing with MCF-7 cells. Four hub genes (TXN, HSPD1, HSPH1 and ATIC) were related to overall survival in patients who accepted tamoxifen. In addition, knockdown of HSPH1 by siRNA may lead to reduced growth of MCF-7/TR cell with a trend close to significance (P = 0.07), indicating that upregulation of HSPH1 may play a role in tamoxifen resistance. Conclusion This study revealed a number of critical hub genes that might serve as therapeutic targets in breast cancer resistant to tamoxifen and provided potential directions for uncovering the mechanisms of tamoxifen resistance.

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Williams, BD, and RH Waterston. "Genes critical for muscle development and function in Caenorhabditis elegans identified through lethal mutations." Journal of Cell Biology 124, no. 4 (February 15, 1994): 475–90. http://dx.doi.org/10.1083/jcb.124.4.475.

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By taking advantage of a lethal phenotype characteristic of Caenorhabditis elegans embryos that fail to move, we have identified 13 genes required for muscle assembly and function and discovered a new lethal class of alleles for three previously known muscle-affecting genes. By staining mutant embryos for myosin and actin we have recognized five distinct classes of genes: mutations in four genes disrupt the assembly of thick and thin filaments into the myofilament lattice as well as the polarized location of these components to the sarcolemma. Mutations in another three genes also disrupt thick and thin filament assembly, but allow proper polarization of lattice components based on the myosin heavy chain isoform that we analyzed. Another two classes of genes are defined by mutations with principal effects on thick or thin filament assembly into the lattice, but not both. The final class includes three genes in which mutations cause relatively minor defects in lattice assembly. Failure of certain mutants to stain with antibodies to specific muscle cell antigens suggest that two genes associated with severe disruptions of myofilament lattice assembly may code for components of the basement membrane and the sarcolemma that are concentrated where dense bodies (Z-line analogs) and M-lines attach to the cell membrane. Similar evidence suggests that one of the genes associated with mild effects on lattice assembly may code for tropomyosin. Many of the newly identified genes are likely to play critical roles in muscle development and function.

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Rao, Chinthalapally V., Chao Xu, Mudassir Farooqui, Yuting Zhang, Adam S. Asch, and Hiroshi Y. Yamada. "Survival-Critical Genes Associated with Copy Number Alterations in Lung Adenocarcinoma." Cancers 13, no. 11 (May 25, 2021): 2586. http://dx.doi.org/10.3390/cancers13112586.

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Chromosome Instability (CIN) in tumors affects carcinogenesis, drug resistance, and recurrence/prognosis. Thus, it has a high impact on outcomes in clinic. However, how CIN occurs in human tumors remains elusive. Although cells with CIN (i.e., pre/early cancer cells) are proposed to be removed by apoptosis and/or a surveillance mechanism, this surveillance mechanism is poorly understood. Here we employed a novel data-mining strategy (Gene Expression to Copy Number Alterations [CNA]; “GE-CNA”) to comprehensively identify 1578 genes that associate with CIN, indicated by genomic CNA as its surrogate marker, in human lung adenocarcinoma. We found that (a) amplification/insertion CNA is facilitated by over-expressions of DNA replication stressor and suppressed by a broad range of immune cells (T-, B-, NK-cells, leukocytes), and (b) deletion CNA is facilitated by over-expressions of mitotic regulator genes and suppressed predominantly by leukocytes guided by leukocyte extravasation signaling. Among the 39 CNA- and survival-associated genes, the purine metabolism (PPAT, PAICS), immune-regulating CD4-LCK-MEC2C and CCL14-CCR1 axes, and ALOX5 emerged as survival-critical pathways. These findings revealed a broad role of the immune system in suppressing CIN/CNA and cancer development in lung, and identified components representing potential targets for future chemotherapy, chemoprevention, and immunomodulation approaches for lung adenocarcinoma.

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Laurant, Darrell. "Critical Mass: Inner space/outer space/genes/gender/origins Engineering Solutions." Science & Spirit 16, no. 2 (March 1, 2005): 15–24. http://dx.doi.org/10.3200/sspt.16.2.15-24.

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Oliveira, Graziele, Rodrigo Rodrigues, Maurício Lima, Betânia Drumond, and Jônatas Abrahão. "Poxvirus Host Range Genes and Virus–Host Spectrum: A Critical Review." Viruses 9, no. 11 (November 7, 2017): 331. http://dx.doi.org/10.3390/v9110331.

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Von Ohlen, Tonia, Alison Luce-Fedrow, M. Teresa Ortega, Roman R. Ganta, and Stephen K. Chapes. "Identification of Critical Host Mitochondrion-Associated Genes during Ehrlichia chaffeensis Infections." Infection and Immunity 80, no. 10 (July 30, 2012): 3576–86. http://dx.doi.org/10.1128/iai.00670-12.

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ABSTRACTEhrlichia chaffeensisis an obligate intracellular bacterium that causes human monocytic ehrlichiosis (HME). To determine what host components are important for bacterial replication, we performed microarray analysis onDrosophila melanogasterS2 cells by comparing host gene transcript levels between permissive and nonpermissive conditions forE. chaffeensisgrowth. Five-hundred twenty-seven genes had increased transcript levels unique to permissive growth conditions 24 h postinfection. We screened adult flies that were mutants for several of the “permissive” genes for the ability to supportEhrlichiareplication. Three additionalD. melanogasterfly lines with putative mutations in pyrimidine metabolism were also tested. Ten fly lines carrying mutations in the genesCG6479,separation anxiety,chitinase 11,CG6364(Uck2),CG6543(Echs1),withered(whd),CG15881(Ccdc58),CG14806(Apop1),CG11875(Nup37), anddumpy(dp) had increased resistance to infection withEhrlichia. Analysis of RNA by quantitative real-time reverse transcription-PCR (qRT-PCR) confirmed that the bacterial load was decreased in these mutant flies compared to wild-type infected control flies. Seven of these genes (san,Cht11,Uck2,Echs1,whd, Ccdc58, andApop1) encoded proteins that had mitochondrial functions or could be associated with proteins with mitochondrial functions. Treatment of THP-1 cells with double-stranded RNA to silence the humanUCK2gene indicates that the disruption of the uridine-cytidine kinase affectsE. chaffeensisreplication in human macrophages. Experiments with cyclopentenyl cytosine (CPEC), a CTP synthetase inhibitor and cytosine, suggest that the nucleotide salvage pathway is essential forE. chaffeensisreplication and that it may be important for the provision of CTP, uridine, and cytidine nucleotides.

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Turer, Emre E., Kuan-wen Wang, William McAlpine, and Bruce Beutler. "Tu1793 - Rapid and Automated Mapping of Genes Critical for Intestinal Homeostasis." Gastroenterology 154, no. 6 (May 2018): S—1021. http://dx.doi.org/10.1016/s0016-5085(18)33419-x.

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Koh, Dong-In, Dohyun Han, Hoon Ryu, Won-Il Choi, Bu-Nam Jeon, Min-Kyeong Kim, Youngsoo Kim, et al. "KAISO, a critical regulator of p53-mediated transcription ofCDKN1Aand apoptotic genes." Proceedings of the National Academy of Sciences 111, no. 42 (October 6, 2014): 15078–83. http://dx.doi.org/10.1073/pnas.1318780111.

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Mahaffey, Victor J., Jack L. Spurbeck, Richard O. Carlson, and Gordon W. Dewald. "Hematologic malignancies, critical genes and representative pictures for 166 chromosome anomalies." Leukemia Research 28, no. 12 (December 2004): 1351–56. http://dx.doi.org/10.1016/j.leukres.2004.04.006.

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Breuskin, Ingrid, Morgan Bodson, Nicolas Thelen, Marc Thiry, Laurent Nguyen, Shibeshih Belachew, Philippe P. Lefebvre, and Brigitte Malgrange. "Strategies to regenerate hair cells: Identification of progenitors and critical genes." Hearing Research 236, no. 1-2 (February 2008): 1–10. http://dx.doi.org/10.1016/j.heares.2007.08.007.

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Cohen, Carla J., Wynne M. Lock, and Dixie L. Mager. "Endogenous retroviral LTRs as promoters for human genes: A critical assessment." Gene 448, no. 2 (December 2009): 105–14. http://dx.doi.org/10.1016/j.gene.2009.06.020.

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O'Bryan, Moira K., Claire Borg, Stefan White, David M. de Kretser, H. W. Gordon Baker, Robert I. McLachlan, and Andrew H. Sinclair. "The Identification of Critical Male Meiosis Genes in Mice and Men." Biology of Reproduction 78, Suppl_1 (May 1, 2008): 281–82. http://dx.doi.org/10.1093/biolreprod/78.s1.281c.

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Bahassi, El Mustapha, Saikumar Karyala, Craig R. Tomlinson, Maureen A. Sartor, Mario Medvedovic, and Robert F. Hennigan. "Critical regulation of genes for tumor cell migration by AP-1." Clinical & Experimental Metastasis 21, no. 4 (2004): 293–304. http://dx.doi.org/10.1023/b:clin.0000046132.46946.dd.

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Darlington, Gretchen J., Naidy Wang, and Richard W. Hanson. "C/EBPα: a critical regulator of genes governing integrative metabolic processes." Current Opinion in Genetics & Development 5, no. 5 (October 1995): 565–70. http://dx.doi.org/10.1016/0959-437x(95)80024-7.

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Boultwood, Jacqueline, Carrie Fidler, Pascal Soularue, Amanda J. Strickson, Markus Kostrzewa, Rina J. Jaju, Finbarr E. Cotter, et al. "Novel Genes Mapping to the Critical Region of the 5q− Syndrome." Genomics 45, no. 1 (October 1997): 88–96. http://dx.doi.org/10.1006/geno.1997.4899.

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Journal articles on the topic 'CRITICAL GENES'

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