Screening of the TAP1 gene by denaturing gradient gel electrophoresis in insulin-dependent diabetes mellitus: detection and comparison of new polymorphisms between patients and controls.
Screening of the TAP1 gene by denaturing gradient gel electrophoresis in insulin-dependent diabetes mellitus: detection and comparison of new polymorphisms between patients and controls.
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通过变性梯度凝胶电泳筛选胰岛素依赖性糖尿病中的 TAP1 基因：患者和对照之间新多态性的检测和比较。
DOI：
10.1111/j.1399-0039.1997.tb02915.x
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Faustman,DL
中科院分区：
文献类型：
--
作者：
Yan,G;Shi,L;Fu,Y;Wang,X;Schoenfeld,D;Ma,L;Penfornis,A;Gebel,H;Faustman,DL
采用变性梯度凝胶电泳（DGGE）筛选基因组DNA，在胰岛素依赖型糖尿病（IDDM）患者中寻找新的保护性或疾病相关的TAP 1基因多态性。TAP 1基因位于人类白细胞抗原（HLA）II类基因组区域，编码HLA I类分子抗原呈递所必需的肽转运蛋白组分。PCR扩增TAP 1基因5′端启动子、11个外显子（含部分内含子区）和3′端侧翼区的片段，DGGE分析。TAP1DNA片段产生的DGGE谱带在IDDM患者和对照组中的频率不同。特异性DGGE条带模式与相应的启动子，外显子或内含子3，6，7，8，9或10的TAP 1的片段检测仅在患者或对照组。对包含外显子7的TAP 1片段进行测序，结果显示仅在1例IDDM患者中观察到DGGE带型，测序结果显示在密码子518（GTCATC，ValIle）处存在以前未鉴定的多态性。DGGE发现的另一个独特的多态性是通过对糖尿病患者内含子2的多态性进行测序发现的。另外的HLA II类匹配的患者和对照组的基因型进行了测定，关于5个外显子和1个内含子TAP1多态性。内含子9中的10个碱基对内含子插入仅在对照组中确定，而在患者中缺失（P= 0.017）。进一步的大规模人群研究可能会揭示这些新发现的风险或保护性TAP 1变体是否在不同人群中赋予统计学风险标志物。
New protective or disease‐associated polymorphisms in theTAP1gene were sought in insulin‐dependent diabetes mellitus (IDDM) patients with the use of denaturing gradient gel electrophoresis (DGGE) screening of genomic DNA. TheTAP1gene is located in the human leukocyte antigen (HLA) class II region of the genome and encodes components of a peptide transporter essential for antigen presentation by HLA class I molecules. Fragments ofTAP1corresponding to the 5′ promoter, each of the 11 exons (with portions of adjacent intronic regions) and the 3′ flanking region were amplified by the polymerase chain reaction and then subjected to DGGE. DNA fragments ofTAP1yielded DGGE bands with patterns whose frequencies differed between IDDM patients and controls. Specific DGGE band patterns with fragments corresponding to the promoter, exons or introns 3, 6, 7, 8, 9 or 10 ofTAP1were detected exclusively in either patients or controls. Sequencing ofTAP1fragments encompassing exon 7 gave rise to a DGGE band pattern exclusively observed in an IDDM patient and sequencing revealed a previously unidentified polymorphisms at codon 518 (GTCATC, ValIle). Another unique polymorphism uncovered by DGGE revealed by sequencing a polymorphism in intron 2 in a diabetic patient. The genotypes of additional HLA class II matched patients and controls were determined with regard to five exonic and one intronicTAP1polymorphism. A 10 base pair intronic insertion in intron 9 was exclusively identified in controls and missing from patients (P= 0.017). Further large population‐based studies may reveal whether these newly identified at risk or protectiveTAP1variants confer markers of statistical risk in diverse population groups.
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影响因子：
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作者：
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影响因子：
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