Arch Development Corporation

Daniel Cohen

Graeme I Bell

Kazuki Yasuda

Philippe Froguel

Gilberto Velho

Simon J Pilkis

Habib Zouali

Nathalie Vionnet

Markus Stoffel

Jun Takeda

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.

Detection of glucokinase-linked early-onset non-insulin-dependent

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Sauigny/Orge, France

Daniel Cohen