目的从基因水平探讨湖北地区汉族人食管癌 HEN-DQB1等位基因的遗传易感性.方法运用序列特异性引物聚合酶链反应技术,检测无亲缘关系湖北汉族健康人136例、食管癌组42例患者的 HLA-DQB1等位基因.SAS system 统计软件数据处理.结果湖北汉...目的从基因水平探讨湖北地区汉族人食管癌 HEN-DQB1等位基因的遗传易感性.方法运用序列特异性引物聚合酶链反应技术,检测无亲缘关系湖北汉族健康人136例、食管癌组42例患者的 HLA-DQB1等位基因.SAS system 统计软件数据处理.结果湖北汉族人食管癌患者与正常人比较,HEN-DQB1*0301基因频率显著增高(0.2976 vs 0.1875),P=0.046,OR=1.835,病因分数=0.1354);两组间 HLA-DQB1其余各等位基因分布频率的比较,HLA-DQB1*0201(0.0833 vs 0.1016),*0301(0.2976 vs 0.1875),*0302(0.0595 vs 0859),*0303(0.2381 vs 0.1875),*0304(0.0000 vs 0.0039),*0401(0.0714 vs 0.0469),*0402(0.0119 vs 0.0156),*0501(0.0357 vs 0.0703),*0502(0.0595 vs 0.0664),*0503(0.0119 vs 0.0195),*0504(0.0000 vs 0.0039),*0601(0.0595 vs 0.0781),*0602(0.0476 vs 0.0742),*0603(0.0000 vs 0.0078),*0604(0.0238 vs 0.0508),差异均无显著性.结论 HLA-DQB1*0301等位基因与湖北汉族人食管癌正关联,为其易感基因.展开更多
RNA quality control of endogenous RNAs is an integral part of eukaryotic gene expression and often relies on exonucleolytic degradation to eliminate dysfunctional transcripts. In parallel, exogenous and selected endog...RNA quality control of endogenous RNAs is an integral part of eukaryotic gene expression and often relies on exonucleolytic degradation to eliminate dysfunctional transcripts. In parallel, exogenous and selected endogenous RNAs are degraded through RNA silencing, which is a genome defense mechanism used by many eukaryotes. In plants, RNA silencing is triggered by the production of double-stranded RNAs （dsRNAs） by RNA-DEPENDENT RNA POLYMERASEs （RDRs） and proceeds through small interfering （si） RNA-directed, ARGONAUTE （AGO）-mediated cleavage of homologous transcripts. Many studies revealed that plants avert inappropriate posttranscriptional gene silencing of endogenous coding genes by using RNA surveillance mechanisms as a safeguard to protect their transcriptome profiles. The tug of war between RNA surveillance and RNA silencing ensures the appropriate partitioning of endogenous RNA substrates among these degradation pathways. Here we review recent advances on RNA quality control and its role in the suppression of RNA silencing at endogenous genes and discuss the mechanisms underlying the crosstalk among these pathways.展开更多
Murine monoclonal antibodies(mAbs)are widely used but have limitations if administered in humans.The use of chimeric or humanized mAbs can reduce immunogenicity.The first step in producing such mAbs is to clone murine...Murine monoclonal antibodies(mAbs)are widely used but have limitations if administered in humans.The use of chimeric or humanized mAbs can reduce immunogenicity.The first step in producing such mAbs is to clone murine variable genes from a hybridoma,but it is possible to amplify both functional and aberrant variable genes,as they coexist in the hybridoma.During the development of a murine–human chimeric antibody,we have cloned from a hybridoma the functional heavy chain variable region(VH)and light chain variable region(VL)genes of a mAb that blocks the binding of anthrax lethal factor to protective antigen.In this study,we report the detection of two aberrant transcripts from a hybridoma produced using myeloma cell line OUR-1,the development of a method to distinguish between the functional and abundant aberrant VL transcripts,and the origins of these aberrant genes.The aberrant VL gene is derived from OUR-1 cells,while the aberrant VH gene might derive from antibody repertoires in B cells or from gene rearrangement in the hybridoma cells.The aberrant VH and VL genes in this study may facilitate discrimination between the functional and aberrant variable genes from hybridoma cells.展开更多
Although whole-exome sequencing and whole-genome sequencing has tremendously improved our understanding of the genetic etiology of human disorders,about half of the patients still do not receive a molecular diagnosis....Although whole-exome sequencing and whole-genome sequencing has tremendously improved our understanding of the genetic etiology of human disorders,about half of the patients still do not receive a molecular diagnosis.The high fraction of variants with uncertain significance and the challenges of interpretation of noncoding variants have urged scientists to implement RNA sequencing(RNA-seq)in the diagnostic approach as a high throughput assay to complement genomic data with functional evidence.RNA-seq data can be used to identify aberrantly spliced genes,detect allele-specific expression,and identify gene expression outliers.Amongst eight studies utilizing RNA-seq,a mean diagnostic uplift of 15%has been reported.Here,we provide an overview of how RNA-seq has been implemented to aid in identifying the causal variants of Mendelian disorders.展开更多
The hepatotoxic effect of potassium bromide(KBr)on rat liver tissues were determined,as well as the potential protective effect of Tegillaraca granosa(T.granosa)flesh body extract.Twenty adult male albino rats were eq...The hepatotoxic effect of potassium bromide(KBr)on rat liver tissues were determined,as well as the potential protective effect of Tegillaraca granosa(T.granosa)flesh body extract.Twenty adult male albino rats were equally distributed into four groups;Group(I)treated with physiological saline(control group),Group(II)was orally gavaged by 200 mg/kg of T.granosa body extract day after day,Group(III)was intoxicated by KBr(150 mg/kg bwt day after day orally)and finally,Group(IV)was given a combination of T.granosa flesh body extract plus KBr with similar doses in the second and third groups.At the end of one month,blood,liver tissue and bone marrow samples were collected to be used for the required laboratory examinations.In response to KBr toxicity,there was a significant increase in serum antioxidant biomarkers,which was accompanied by a significant change in hepatocyte ultrastructure and a significant change in carbohydrate and protein levels within the liver organ.In addition,KBr intoxication resulted in a substantial increase in the incidence of chromosomal aberrations such as holes,splits,deletions,fragments,ploidy,and ring chromosomes,as well as significant upregulation of TGF-1,VEGF,and COX-2 gene expression.The hepatotoxic effect of KBr was counteracted by treatment with T.granosa flesh body extract.T.granosa flesh body extract has a curative antioxidant and numerous protective effects against KBr hepatotoxicity.展开更多
文摘目的从基因水平探讨湖北地区汉族人食管癌 HEN-DQB1等位基因的遗传易感性.方法运用序列特异性引物聚合酶链反应技术,检测无亲缘关系湖北汉族健康人136例、食管癌组42例患者的 HLA-DQB1等位基因.SAS system 统计软件数据处理.结果湖北汉族人食管癌患者与正常人比较,HEN-DQB1*0301基因频率显著增高(0.2976 vs 0.1875),P=0.046,OR=1.835,病因分数=0.1354);两组间 HLA-DQB1其余各等位基因分布频率的比较,HLA-DQB1*0201(0.0833 vs 0.1016),*0301(0.2976 vs 0.1875),*0302(0.0595 vs 0859),*0303(0.2381 vs 0.1875),*0304(0.0000 vs 0.0039),*0401(0.0714 vs 0.0469),*0402(0.0119 vs 0.0156),*0501(0.0357 vs 0.0703),*0502(0.0595 vs 0.0664),*0503(0.0119 vs 0.0195),*0504(0.0000 vs 0.0039),*0601(0.0595 vs 0.0781),*0602(0.0476 vs 0.0742),*0603(0.0000 vs 0.0078),*0604(0.0238 vs 0.0508),差异均无显著性.结论 HLA-DQB1*0301等位基因与湖北汉族人食管癌正关联,为其易感基因.
文摘RNA quality control of endogenous RNAs is an integral part of eukaryotic gene expression and often relies on exonucleolytic degradation to eliminate dysfunctional transcripts. In parallel, exogenous and selected endogenous RNAs are degraded through RNA silencing, which is a genome defense mechanism used by many eukaryotes. In plants, RNA silencing is triggered by the production of double-stranded RNAs （dsRNAs） by RNA-DEPENDENT RNA POLYMERASEs （RDRs） and proceeds through small interfering （si） RNA-directed, ARGONAUTE （AGO）-mediated cleavage of homologous transcripts. Many studies revealed that plants avert inappropriate posttranscriptional gene silencing of endogenous coding genes by using RNA surveillance mechanisms as a safeguard to protect their transcriptome profiles. The tug of war between RNA surveillance and RNA silencing ensures the appropriate partitioning of endogenous RNA substrates among these degradation pathways. Here we review recent advances on RNA quality control and its role in the suppression of RNA silencing at endogenous genes and discuss the mechanisms underlying the crosstalk among these pathways.
文摘Murine monoclonal antibodies(mAbs)are widely used but have limitations if administered in humans.The use of chimeric or humanized mAbs can reduce immunogenicity.The first step in producing such mAbs is to clone murine variable genes from a hybridoma,but it is possible to amplify both functional and aberrant variable genes,as they coexist in the hybridoma.During the development of a murine–human chimeric antibody,we have cloned from a hybridoma the functional heavy chain variable region(VH)and light chain variable region(VL)genes of a mAb that blocks the binding of anthrax lethal factor to protective antigen.In this study,we report the detection of two aberrant transcripts from a hybridoma produced using myeloma cell line OUR-1,the development of a method to distinguish between the functional and abundant aberrant VL transcripts,and the origins of these aberrant genes.The aberrant VL gene is derived from OUR-1 cells,while the aberrant VH gene might derive from antibody repertoires in B cells or from gene rearrangement in the hybridoma cells.The aberrant VH and VL genes in this study may facilitate discrimination between the functional and aberrant variable genes from hybridoma cells.
基金Bavarian State Ministry of Health and Care,Grant/Award Number:DMB-1805-0002。
文摘Although whole-exome sequencing and whole-genome sequencing has tremendously improved our understanding of the genetic etiology of human disorders,about half of the patients still do not receive a molecular diagnosis.The high fraction of variants with uncertain significance and the challenges of interpretation of noncoding variants have urged scientists to implement RNA sequencing(RNA-seq)in the diagnostic approach as a high throughput assay to complement genomic data with functional evidence.RNA-seq data can be used to identify aberrantly spliced genes,detect allele-specific expression,and identify gene expression outliers.Amongst eight studies utilizing RNA-seq,a mean diagnostic uplift of 15%has been reported.Here,we provide an overview of how RNA-seq has been implemented to aid in identifying the causal variants of Mendelian disorders.
基金This study was funded by Taif University Researchers Supporting Project No.(TURSP-2020/222),Taif University,Taif,Saudi Arabia.
文摘The hepatotoxic effect of potassium bromide(KBr)on rat liver tissues were determined,as well as the potential protective effect of Tegillaraca granosa(T.granosa)flesh body extract.Twenty adult male albino rats were equally distributed into four groups;Group(I)treated with physiological saline(control group),Group(II)was orally gavaged by 200 mg/kg of T.granosa body extract day after day,Group(III)was intoxicated by KBr(150 mg/kg bwt day after day orally)and finally,Group(IV)was given a combination of T.granosa flesh body extract plus KBr with similar doses in the second and third groups.At the end of one month,blood,liver tissue and bone marrow samples were collected to be used for the required laboratory examinations.In response to KBr toxicity,there was a significant increase in serum antioxidant biomarkers,which was accompanied by a significant change in hepatocyte ultrastructure and a significant change in carbohydrate and protein levels within the liver organ.In addition,KBr intoxication resulted in a substantial increase in the incidence of chromosomal aberrations such as holes,splits,deletions,fragments,ploidy,and ring chromosomes,as well as significant upregulation of TGF-1,VEGF,and COX-2 gene expression.The hepatotoxic effect of KBr was counteracted by treatment with T.granosa flesh body extract.T.granosa flesh body extract has a curative antioxidant and numerous protective effects against KBr hepatotoxicity.
