Genomic imprinting and instability in IDDM

高加索人群中高加索人群的关联研究表明，与Hardy-Weinberg平衡中的比率相比，在1型糖尿病或IDDM中持续观察到化合物DQB1^&lt；**&gt；0302/^&lt；**&gt；0201的过量。这一遗传顺应性强烈表明表观遗传和合子后事件可能参与了这种多基因紊乱的发病机制。为了阐明IDDM1可能涉及的基因组印记，在本项目中，对27个自身免疫介导的1型糖尿病后代的信息家系进行了单倍型传递连锁不平衡(TDT)的检测。我们发现，在日本人群中，高危等位基因DQA1^&lt；**&gt；0301-DQB1^&lt；**&gt；0302也与自身免疫介导的1型糖尿病有关，而不是与单倍型的种族变异有关。我们还发现，易感等位基因会优先从母亲那里传播到a…，而不是从父亲那里传播。受影响的后代更多。这一发现支持IDDM1通过表观遗传机制参与1型糖尿病发病机制的假设。接下来，我们试图分离在IDDM和健康对照组之间差异表达的胰岛B细胞基因。为此，我们从人的胰岛素瘤及其周围的胰腺组织中提取了总的细胞RNA。以胰岛素的特异性引物为对照，用RT-PCR方法从RNA样品中扩增出胰岛素基因。然后用3‘端锚定引物对RNA进行逆转录，用3’端锚定引物和5‘端任意标记引物进行RT-PCR。电泳鉴定的条带模式研究了几个在胰腺B细胞中表达的EST，并可以检测到与正常胰腺组织相比，哪些EST是B细胞特有的。这些结果为根据IDDM的发病机制鉴定B细胞基因的差异表达提供了重要的数据库。较少

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