Genomic imprinting and instability in IDDM

IDDM 中的基因组印记和不稳定性

• 批准号: 08671183
• 负责人: SASAKI Takashi
• 金额: $ 1.22万
• 依托单位: Jikei University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671183/
• 关键词: Genomic Imprinting; Genetic Instability; Family Analysis; Transmission; Linkage Diseguilibrium; TDT; Haplotype; HLA; インスリノーマ; RNA; データベース; RT-PCR; 膵島; 遺伝子; IDDM; ゲノムの不安定性; 抗GAD抗体

Association studies in Caucasian in Caucasian populations have revealed that excess of compound DQB1^<**>0302/^<**>0201 in type 1 diabetes, orIDDM,is consistently observed compared to the ratio in Hardy-Weinberg's equilibrium. This genetic complixity strongly suggests that epigenetic and postzygotic events could be involved in the pathogenesis of this multifactorial disorder.In order to elucidate of genomic imprinting might be involved at IDDM1, in this project, test for ^<**>transmission linkage disequilibrium (TDT) of haplotypes according to the parent-of-origin among twenty-seven informative families of the autoimmune-mediated type 1 diabetic offspring were performed. We found that the highly susceptible allele DQA1^<**>0301-DQB1^<**>0302 is associated with autoimmune-mediated type 1 diabetes also in Japanese population in stead of ethnic variations of haplotypes. We also found that the susceptible allele would be preferentially transmitted from mothers but not from fathers to the a … More ffected offspring. This finding supports the hypothesis that the IDDM1 is involved in the pathogenesis of type 1 diabetes by an epigenetic mechanism.We next attempted to isolate genes that are expressed in B cells of pancreatic islets differentially between IDDM and healthy controls. For this purpose, we extracted total cellular RNA from human inslinoma and its surrounding pancreatic tissues from the same individuals. Insulin cDNA could be amplified from the RNA samples by RT-PCR using its specific primers as a control. We then reverse-transcribed the RNA with 3'anchor primer, and performed RT-PCR by 3'anchor primer and labeled 5'arbitrary primer. The patterns of identified bands in electrophoresis investigated several ESTs that expressed in the pancreatic B cells and could be detected what ESTs were B-cell specific when compared to that of normal pancreatic tissue. These results should represent an important database for the identification of differential expression of genes in B cells in according to the pathogenesis of IDDM. Less

在高加索人群中进行的相关性研究表明，与Hardy-Weinberg平衡中的比例相比，在1型糖尿病或IDDM中始终观察到过量的化合物DQB 1 ^** 0302/^** 0201。为了阐明IDDM 1基因组印记可能参与了IDDM 1的遗传过程，本研究对27个自身免疫介导的1型糖尿病家系进行了单倍型传递连锁不平衡（TDT）检测。我们发现高度易感等位基因DQA 1 ^**>0301-DQB 1 ^**>0302也与日本人群中自身免疫介导的1型糖尿病相关，而不是单倍型的种族差异。我们还发现，易感等位基因将优先从母亲而不是从父亲传递给a ...更多信息 受影响的后代这一发现支持了IDDM 1通过表观遗传机制参与1型糖尿病发病机制的假设。我们接下来试图分离在IDDM和健康对照之间胰岛B细胞中差异表达的基因。为此，我们从同一个体的人胰岛素瘤及其周围胰腺组织中提取总细胞RNA。以胰岛素特异性引物为对照，通过RT-PCR方法从RNA样品中扩增出胰岛素cDNA。用3 '端锚定引物反转录，用3'端锚定引物和5 '端标记引物进行RT-PCR。电泳中鉴定的条带的模式研究了在胰腺B细胞中表达的几种EST，并且当与正常胰腺组织相比时，可以检测到哪些EST是B细胞特异性的。这些结果为进一步研究B细胞基因的差异表达提供了重要的数据。少