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2003-2022 全部
为您找到包含“gene copy”的内容共4

杨正伟,张娟

2020-08-18

【目的】寻找对胃癌的发生发展有驱动作用的基因和信号通路,为胃癌的靶向治疗提供可能的靶点。【方法】从TCGA下载胃癌的RNA-Seq和DNA拷贝数变异数据,利用Perl脚本和R语言中的edgR包筛选出既差异表达且拷贝数发生变异的基因。将筛选出的基因进行基因功能富集分析和通路分析。再将富集过后的基因上传String数据库,生成蛋白质相互作用网络(PPI),进而从PPI网络中分离出结合度高的稠密子网络,最后结合MalaCards疾病数据库构建胃癌的核心网络,进而寻找因差异表达与基因拷贝数呈正相关的基因。【结果】本文一共筛选出26个胃癌驱动基,以及PI3K-Akt信号通路、ECM-受体相互作用、Wnt信号通路和胃酸分泌等可能与胃癌的发生发展相关的信号通路,为胃癌的诊断和治疗提供潜在的靶点。

华北电力大学数理学院,北京,102200,华北电力大学数理学院,北京,102200

#数学#

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Zhen Ai,Ming Li,Wenting Liu,Jia-Nee Foo,Omniah Mansouri,Peiran Yin,Qian Zhou,Xueqing Tang,Xiuqing Dong,Shaozhen Feng,Ricong Xu,Zhong Zhong,Jian Chen,Jianxin Wan,Tanqi Lou,Jianwen Yu,Qin Zhou,Jinjin Fan,Haiping Mao,Daniel GalUCL,Jonathan Barratt,John AL Armour,Jianjun Liu,Xueqing Yu

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Although being a major source of genetic variation, copy number variations (CNVs) are poorly studied for their involvement in disease development. Here we performed association analysis of DEFA1A3 CNV locus in two independent IgAN cohorts of Southern Chinese Han (total 1189 cases and 1187 healthy controls). We discovered three independent copy number associations within the locus: DEFA1A3 (P=3.99×10-9, OR=0.88), DEFA3 (P=6.55×10-5, OR=0.82) and a noncoding deletion variant (211bp) (P=3.50×10-16, OR=0.75) (OR per copy, fixed-effects meta-analysis). While showing strong association with increased risk for IgAN (P=9.56×10-20), low total copy numbers of the three variants also showed significant association with poor long-term renal survival of IgAN (P=0.03, HR=3.69, after controlling the effects of known prognostic factors) as well as the high serum IgA1 level (P=0.02) and high proportion of galactose-deficient IgA1 (P=0.03). As replication, we confirmed the associations of DEFA1A3 (P=4.42×10-4, OR=0.82) and DEFA3 copy numbers (P=4.30×10-3, OR=0.74) with IgAN in a Caucasian cohort (531 cases and 198controls) and found 211bp variant to be extremely rare in Caucasians. Interestingly, we also observed an association of 211bp copy number with membranous nephropathy (P=1.11×10-7, OR=0.74 in 493 Chinese cases and 500 matched controls), but not with diabetic kidney disease (in 806 Chinese cases and 786 matched controls). By explaining 4.96% of risk variance (the strongest genetic susceptibility locus so far) and influencing the renal progression of IgAN, the DEFA1A3 CNV locus is a potential candidate of novel therapeutic target and prognostic biomarker.

2017-05-03

grant from the BBSRC (BB/1006370/1) to JALA(

and the Agency for Science & Technology and Research (A*STAR) of Sing(20120171120087

Yong Scholars Fund for the Doctoral Program of Higher Education of China(2011A080300002

Guangdong Department of Science & Technology Translational Medicine Center grant (2012J5100031

Guangzhou Committee of Science and Technology(S4674

China(81200489

OM is supported by the Division of Higher Education(2013B051000019

Kingdom of Saudi Arabia(20130171130008

Young Scientists Fund of National Natural Science Foundation of China(0

the Science and Technology Planning Project of Guangdong Province(0

China(0

the Specialized Research Fund for the Doctoral Program of Higher Education of China(0

Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China,Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China,Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China,Human Genetics, Genome Institute of Singapore, Singapore 138672, Singapore. 4School of Life Sciences, University Jia-Nee Foo Human Genetics, Genome Institute of Singapore, Singapore 138672, Singapore, School of Life Sciences, University of Nottingham, Queen’s Medical Centre, Nottingham NG7 2UH, UK,Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China,Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China,Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China,Department of Nephrology,

#Clinical Medicine#

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林同,李立娜

2006-05-19

昆虫乙酰胆碱酯酶是有机磷杀虫剂和氨基甲酸酯类杀虫剂的作用靶标,乙酰胆碱酯酶基因突变可导致乙酰胆碱酯酶对杀虫剂不敏感而是昆虫产生抗药性。黑腹果蝇和家蝇等昆虫只有一个乙酰胆碱酯酶基因,但冈比亚按蚊等昆虫乙酰胆碱酯酶基因有两个或多个拷贝。本文还综述了昆虫乙酰胆碱酯酶基因的结构和表达调控等。

华南农业大学林学院,华南农业大学林学院

#林学#

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张宁

2017-03-20

基因的拷贝数变异(CNV)作为DNA突变的一种变异形式已经被报道和人类肿瘤有密切的关系。为了更好地理解人类不同肿瘤与CNV之间的关系,本文采用一种理论计算方法基于CNV变异水平值来对6种人类肿瘤进行分类。将每种基因的CNV变异水平值作为一种分类特征,采用mRMR(最小冗余和最大相关性)算法对24,175个基因的CNV变异程度进行重要性排序,筛选出与不同肿瘤的关系最为密切的前1,000个特征。然后使用IFS(增量特征选择)的方法来从这1000个特征中筛选出最能准确分类6种肿瘤的最优特征集。基于SMO(支持向量机)的分类算法对特征进行分类、采用10折交叉验证对分类结果进行误差评估。得出的结果是当使用mRMR排序后的前479个基因的CNV变异水平创建的分类器可达到最高分类准确率80.86%。对这479个基因中的一些重要基因的生物学分析表明,大部分基因与肿瘤有密切关系。本文结果印证了CNV与不同人类肿瘤之间的关系,对进一步了解基因与肿瘤发病之间的关系,以及发现新的肿瘤致病基因都将具有很重要的意义。

高等学校博士学科点专项科研基金(新教师类

天津大学精密仪器与光电子工程学院

#生物学#

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