Analysis of Alternative Splicing Patterns in the Cystic Fibrosis Transmembrane Conductance Regulator Gene Using mRNA Derived from Lymphoblastoid Cells of Cystic Fibrosis Patients
Analysis of Alternative Splicing Patterns in the Cystic Fibrosis Transmembrane Conductance Regulator Gene Using mRNA Derived from Lymphoblastoid Cells of Cystic Fibrosis Patients
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使用来自囊性纤维化患者的淋巴母细胞的 mRNA 分析囊性纤维化跨膜电导调节基因的选择性剪接模式
DOI：
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发表时间：
1996
影响因子：
5.2
通讯作者：
J. Kaplan
中科院分区：
文献类型：
--
作者：
T. Bienvenu;C. Beldjord;J. Chelly;N. Fonknechten;D. Hubert;D. Dusser;J. Kaplan
利用聚合酶链反应体外扩增的cDNA，我们分析了囊性纤维化跨膜传导调节基因在淋巴母细胞的选择性剪接事件。10个选择性剪接的转录本被确定使用的6个重叠片段的扩增的cDNA，其中4个以前没有被描述的分析。这些包括缺乏外显子16、17 b、22的转录物和使用隐蔽受体和供体剪接位点产生的转录物。此外，在2例携带无义突变E60 X或W1282 X的囊性纤维化（CF）患者中，我们观察到无义突变与体内剪接位点选择的改变相关，导致组成性外显子的外显子跳跃或使用隐蔽剪接位点。此外，尽管淋巴母细胞样细胞不是解决临床呼吸表型和基因型之间关系的相关组织，但我们关于成人CF患者（ΔF508/ΔF508）的结果表明，个体特异性RNA剪接模式可能影响CF肺病的严重程度。如果这种选择性剪接现象在CF中被证明是重要的，并且是疾病基因的共同特征，那么RNA剪接的研究可能成为分析许多遗传性疾病中基因型-表型关系的重要工具。
Using in vitro amplification of cDNA by the polymerase chain reaction, we analyzed alternatively spliced events of cystic fibrosis transmembrane conductance regulator gene in lymphoblastoid cells. Ten alternatively spliced transcripts were identified using analysis of 6 overlapping segments of amplified cDNA, 4 of which have not been described previously. These include transcripts lacking exon 16, 17b, 22 and a transcript resulting from the use of a cryptic acceptor and donor splice sites. Moreover, in 2 cystic fibrosis (CF) patients bearing nonsense mutations E60X or W1282X, we observed that nonsense mutations are associated with an alteration of splice site selection in vivo resulting in exon skipping of constitutive exons or in the use of cryptic splice sites. In addition, even though lymphoblastoid cells are not the relevant tissue to address the question of the relationship between clinical respiratory phenotype and genotype, our results concerning adult CF patients (ΔF508/ΔF508) suggest that individual-specific RNA splicing patterns could influence the severity of the CF pulmonary disease. If this phenomenon of alternative splicing events proves to be significant in CF and to be a common feature of disease genes, the study of RNA splicing could become an important tool for the analysis of the genotype-phenotype relationship in many inherited disorders.
人淋巴细胞转录囊性纤维化跨膜电导调节基因并表现出 CF 缺陷的 cAMP 调节的氯电流。
DOI：
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发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
McDonald,TV;Nghiem,PT;Gardner,P;Martens,CL
通讯作者：
Martens,CL
以色列德鲁兹和穆斯林阿拉伯患者 Hurler 综合征的分子分析：IDUA 基因在小地理区域内的多个等位基因突变。
影响因子：
9.8
作者：
Bach,G;Moskowitz,SM;Tieu,PT;Matynia,A;Neufeld,EF
通讯作者：
Neufeld,EF
对具有 621 个 1G-->T 和 711 个 1G-->T 突变的囊性纤维化患者的鼻上皮细胞和淋巴母细胞中的 CFTR 转录本进行分析。
影响因子：
3.5
作者：
Zielenski,J;Bozon,D;Markiewicz,D;Aubin,G;Simard,F;Rommens,JM;Tsui,LC
通讯作者：
Tsui,LC