Tissue-specific alternative splicing of TCF7L2.
Tissue-specific alternative splicing of TCF7L2.
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TCF7L2的组织特异性替代剪接。
DOI：
10.1093/hmg/ddp321
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发表时间：
2009-10-15
影响因子：
3.5
通讯作者：
Hall, Jennifer L.
中科院分区：
文献类型：
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作者：
Prokunina-Olsson, Ludmila;Welch, Cullan;Hansson, Ola;Adhikari, Neeta;Scott, Laura J.;Usher, Nicolle;Tong, Maurine;Sprau, Andrew;Swift, Amy;Bonnycastle, Lori L.;Erdos, Michael R.;He, Zhi;Saxena, Richa;Harmon, Brennan;Kotova, Olga;Hoffman, Eric P.;Altshuler, David;Groop, Leif;Boehnke, Michael;Collins, Francis S.;Hall, Jennifer L.
转录因子7样2（TCF 7 L2）基因的常见变异已被确定为2型糖尿病（T2 D）最强的遗传风险因素。然而，这些非编码变异增加T2 D风险的机制尚未明确。我们使用了13种表达检测方法来调查来自8种人体组织（胰腺、胰岛、结肠、肝脏、单核细胞、骨骼肌、皮下脂肪组织和淋巴母细胞系）的多达380个样本中多种TCF 7 L2剪接形式的mRNA表达，并观察到组织特异性的选择性剪接模式。我们检测了TCF 7 L2剪接形式的表达是否与单核苷酸多态性（SNP）rs7903146和rs 12255372相关，这些SNP位于基因的内含子3和4内，与T2 D相关性最强。随着SNP的T2 D相关等位基因计数的增加，胰岛中两种剪接形式的表达降低：一种普遍存在的剪接形式（对于rs7903146 P = 0.018，对于rs 12255372 P = 0.020）和在胰岛中发现的剪接形式，胰腺和结肠，但在此处测试的其他组织中没有（对于rs 12255372，P = 0.009;对于rs7903146，P = 0.053）。在葡萄糖刺激的胰岛中，这种形式的表达与胰岛素原的表达相关（r2 = 0.84-0.90，P < 0.00063）。总之，我们确定了TCF 7 L2选择性剪接的组织特异性模式。经过多次测试调整后，8种人体组织样本中TCF 7 L2的表达与T2 D相关遗传变异之间没有显著关联。TCF 7 L2在胰岛中的选择性剪接值得进一步研究。GenBank登录号：FJ 010164-FJ 010174。
Common variants in the transcription factor 7-like 2 (TCF7L2) gene have been identified as the strongest genetic risk factors for type 2 diabetes (T2D). However, the mechanisms by which these non-coding variants increase risk for T2D are not well-established. We used 13 expression assays to survey mRNA expression of multiple TCF7L2 splicing forms in up to 380 samples from eight types of human tissue (pancreas, pancreatic islets, colon, liver, monocytes, skeletal muscle, subcutaneous adipose tissue and lymphoblastoid cell lines) and observed a tissue-specific pattern of alternative splicing. We tested whether the expression of TCF7L2 splicing forms was associated with single nucleotide polymorphisms (SNPs), rs7903146 and rs12255372, located within introns 3 and 4 of the gene and most strongly associated with T2D. Expression of two splicing forms was lower in pancreatic islets with increasing counts of T2D-associated alleles of the SNPs: a ubiquitous splicing form (P = 0.018 for rs7903146 and P = 0.020 for rs12255372) and a splicing form found in pancreatic islets, pancreas and colon but not in other tissues tested here (P = 0.009 for rs12255372 and P = 0.053 for rs7903146). Expression of this form in glucose-stimulated pancreatic islets correlated with expression of proinsulin (r2 = 0.84–0.90, P < 0.00063). In summary, we identified a tissue-specific pattern of alternative splicing of TCF7L2. After adjustment for multiple tests, no association between expression of TCF7L2 in eight types of human tissue samples and T2D-associated genetic variants remained significant. Alternative splicing of TCF7L2 in pancreatic islets warrants future studies. GenBank Accession Numbers: FJ010164–FJ010174.
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影响因子：
4.7
作者：
Humphries, Steve E.;Gable, David;Talmud, Philippa J.
通讯作者：
Talmud, Philippa J.
影响因子：
5.3
作者：
Atcha, Fawzia A.;Syed, Adeela;Waterman, Marian L.
通讯作者：
Waterman, Marian L.
影响因子：
14.9
作者：
Brantjes, H;Roose, J;Clevers, H
通讯作者：
Clevers, H
影响因子：
8.2
作者：
Chandak, G. R.;Janipalli, C. S.;Yajnik, C. S.
通讯作者：
Yajnik, C. S.
DOI：
10.1159/000015534
发表时间：
2000-01-01
期刊：
CYTOGENETICS AND CELL GENETICS
影响因子：
--
作者：
Duval, A;Busson-Leconiat, M;Hamelin, R
通讯作者：
Hamelin, R