کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8456714 | 1548750 | 2015 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Functional genomic screening approaches in mechanistic toxicology and potential future applications of CRISPR-Cas9
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کلمات کلیدی
protospacer-adjacent motifPAMNHEJshRNACMLIPSCBFACRISPR-Cas9ORFMct1ERADMOAdsRNANGSHDRPLP2PDAAOPsingle-guide RNAOTEHTSShort-interfering RNAlncRNADSB3-BrPAHSC1,2,4-benzenetriol - 1،2،4-بنزنتریولlong non-coding RNA - RNA بدون رمزگذاری طولانیRNA interference - RNA تداخل کنندهdouble-stranded RNA - RNA دو رشته ایRNAi - RNA سرکوبگر،RNA مداخلهگر، RNA خاموش کنندهshort hairpin RNA - RNA موی سر کوتاهsgRNA - scRNAsiRNA - siRNAOff-target effects - اثرات غیر هدفHomology-directed repair - اصلاح شده با همسانیbrefeldin A - برفلدین AToxicity testing - تست سمیتNext-generation sequencing - تعیین توالی نسل بعدیMode of action - حالت عملESC - خروجTranscription activator-like effector nuclease - رونویسی مانند actuator nucleaseTALEN - زبان هاelectron transport chain - زنجیره انتقال الکترونHematopoietic stem cell - سلول بنیادی هماتوپوئیتEmbryonic stem cell - سلول های بنیادی جنینیInduced pluripotent stem cell - سلول های بنیادی پلوروپتوژن منجر شده استendoplasmic reticulum - شبکه آندوپلاسمی double-strand break - شکست دو ردیفhigh-throughput screening - غربالگری بالاopen reading frame - قاب خواندن بازChronic myeloid leukemia - لوسمی میلوئید مزمنMHC - مجموعه سازگاری بافتی اصلیYeast - مخمرadverse outcome pathway - مسیر ناخوشایندGenome-wide association studies - مطالعات مرتبط با ژنومGWAS - مطالعهٔ همخوانی سراسر ژنومmonocarboxylate transporter 1 - مونوکربوکیلات 1Hydroquinone - هیدروکینونETc - و غیرهpolymerase chain reaction - واکنش زنجیره ای پلیمرازPCR - واکنش زنجیرهٔ پلیمرازFunctional genomics - ژنومیک عملکردیCosmid - کاسیمیدGecko - گوکو
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Functional genomic screening approaches in mechanistic toxicology and potential future applications of CRISPR-Cas9 Functional genomic screening approaches in mechanistic toxicology and potential future applications of CRISPR-Cas9](/preview/png/8456714.png)
چکیده انگلیسی
Characterizing variability in the extent and nature of responses to environmental exposures is a critical aspect of human health risk assessment. Chemical toxicants act by many different mechanisms, however, and the genes involved in adverse outcome pathways (AOPs) and AOP networks are not yet characterized. Functional genomic approaches can reveal both toxicity pathways and susceptibility genes, through knockdown or knockout of all non-essential genes in a cell of interest, and identification of genes associated with a toxicity phenotype following toxicant exposure. Screening approaches in yeast and human near-haploid leukemic KBM7 cells have identified roles for genes and pathways involved in response to many toxicants but are limited by partial homology among yeast and human genes and limited relevance to normal diploid cells. RNA interference (RNAi) suppresses mRNA expression level but is limited by off-target effects (OTEs) and incomplete knockdown. The recently developed gene editing approach called clustered regularly interspaced short palindrome repeats-associated nuclease (CRISPR)-Cas9, can precisely knock-out most regions of the genome at the DNA level with fewer OTEs than RNAi, in multiple human cell types, thus overcoming the limitations of the other approaches. It has been used to identify genes involved in the response to chemical and microbial toxicants in several human cell types and could readily be extended to the systematic screening of large numbers of environmental chemicals. CRISPR-Cas9 can also repress and activate gene expression, including that of non-coding RNA, with near-saturation, thus offering the potential to more fully characterize AOPs and AOP networks. Finally, CRISPR-Cas9 can generate complex animal models in which to conduct preclinical toxicity testing at the level of individual genotypes or haplotypes. Therefore, CRISPR-Cas9 is a powerful and flexible functional genomic screening approach that can be harnessed to provide unprecedented mechanistic insight in the field of modern toxicology.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Mutation Research/Reviews in Mutation Research - Volume 764, AprilâJune 2015, Pages 31-42
Journal: Mutation Research/Reviews in Mutation Research - Volume 764, AprilâJune 2015, Pages 31-42
نویسندگان
Hua Shen, Cliona M. McHale, Martyn T. Smith, Luoping Zhang,