公开(公告)号：US5541060A

公开(公告)日：1996-07-30

申请号：US872678

申请日：1992-04-22

申请人： Graeme I. Bell ,  Markus Stoffel ,  Jun Takeda ,  Nathalie Vionnet ,  Kazuki Yasuda ,  Simon J. Pilkis ,  Habib Zouali ,  Gilberto Velho ,  Daniel Cohen ,  Philippe Froguel

发明人： Graeme I. Bell ,  Markus Stoffel ,  Jun Takeda ,  Nathalie Vionnet ,  Kazuki Yasuda ,  Simon J. Pilkis ,  Habib Zouali ,  Gilberto Velho ,  Daniel Cohen ,  Philippe Froguel

IPC分类号： C12N9/12 ,  C12Q1/68 ,  C12P19/34

CPC分类号： C12N9/12 ,  C12Q1/6883 ,  C12Q2600/156

摘要： The invention relates to the observed tight linkage between DNA polymorphisms in the glucokinase gene (GCK) on the short arm of chromosome 7, and NIDDM in a cohort of sixteen French families having MODY. It further relates to identification of mutations in GCK and their linkage with diabetes in particular families are disclosed. This invention provides the first evidence implicating specific mutations in a gene involved in glucose metabolism in the pathogenesis of NIDDM. The invention further discloses the isolation and characterization of human pancreatic .beta.-cell GCK and a method for searching for mutations that cause early-onset NIDDM. To assess the effect of these mutations on glucokinase activity, a method is disclosed for generating an .alpha.-carbon backbone model for human glucokinase based on the crystal structure of the structurally-related yeast hexokinase B. Thus, in its most general sense, the invention relates to a method for detecting a propensity to develop early-onset, non-insulin-dependent diabetes mellitus.

摘要翻译： 本发明涉及在染色体7的短臂上的葡萄糖激酶基因（GCK）中的DNA多态性与具有MODY的16个法国家族的NIDDM中观察到的紧密连锁。 其进一步涉及GCK突变的鉴定及其与特定家族中糖尿病的联系。 本发明提供了涉及NIDDM发病机理中涉及葡萄糖代谢的基因中的特定突变的第一个证据。 本发明进一步公开了人胰腺β细胞GCK的分离和表征，以及用于搜索引起早发型NIDDM的突变的方法。 为了评估这些突变对葡糖激酶活性的影响，公开了一种基于结构相关的酵母己糖激酶B的晶体结构产生人类葡萄糖激酶的α-碳骨架模型的方法。因此，在其最普遍的意义上，本发明 涉及用于检测发展早发型非胰岛素依赖性糖尿病倾向的方法。