Biomedical subjects

J T Cook

Publications and source records attributed to J T Cook.

30 records · Page 2Linked to original sources

PubMed1992

Linkage analysis of glucokinase gene with NIDDM in Caucasian pedigrees.

NIDDM has a strong genetic component, as evidenced by the high level of concordance between identical twins. The nature of the genetic predisposition has remained largely unknown. Recently, the glucokinase gene locus on chromosome 7p has been shown to be linked to a subtype of NIDDM known as MODY in French and British pedigrees, and glucokinase mutations have been identified. To study the relationship between the glucokinase gene and NIDDM, we performed a linkage analysis in 12 Caucasian pedigrees ascertained through a proband with classical NIDDM. The LINKAGE program was used under four models, including autosomal dominant and recessive, with individuals with glucose intolerance counted as either affected or of unknown status. Linkage was significantly rejected with the dominant models (LOD scores -4.65, -4.25), and was unlikely with the recessive model when glucose intolerance was considered as affected (LOD score -1.38). These findings suggest that mutations in or near the glucokinase gene are unlikely to be the major cause of the inherited predisposition to NIDDM in Caucasian pedigrees, but do not exclude a role for this locus with a polygenic model, or a major role in some pedigrees.

Adult↗

PubMed1991

Multiple restriction fragment length polymorphisms at the GLUT2 locus: GLUT2 haplotypes for genetic analysis of type 2 (non-insulin-dependent) diabetes mellitus.

The liver/islet glucose transporter (GLUT2) is expressed in the liver and in the Beta cells of pancreatic islets and is a candidate gene for the inherited defect in Type 2 (non-insulin-dependent) diabetes mellitus. A series of restriction fragment length polymorphisms have been identified using a GLUT2 cDNA probe with five restriction enzymes in a British white Caucasian population. Five independent restriction fragment length polymorphisms detected by restriction enzymes EcoRI (two restriction fragment length polymorphisms termed EcoRI-1, EcoRI-2), TaqI (two restriction fragment length polymorphisms termed TaqI-1, TaqI-2), and BclI (BclI-2) were used to construct GLUT2 haplotypes. Significant linkage disequilibrium was observed between four polymorphic sites EcoRI-2, TaqI-1, TaqI-2 and BclI-2 but linkage disequilibrium was not observed with EcoRI-1 polymorphic site and the other four sites. The frequencies of GLUT2 restriction fragment length polymorphisms and haplotypes in 50 Type 2 diabetic subjects and 50 non-diabetic control subjects show no significant differences suggesting that it is unlikely that there is a single major defect of this gene contributing to the inherited susceptibility to Type 2 diabetes in a Caucasian population.

Alleles↗

PubMed1991

Non-linkage of the islet amyloid polypeptide gene with type 2 (non-insulin-dependent) diabetes mellitus.

Type 2 (non-insulin-dependent) diabetes is associated with the deposition of islet amyloid. The major formative peptide, islet amyloid polypeptide, has recently been characterised and an abnormality of the structure or expression of this gene is a possible candidate for the inherited component of Type 2 diabetes. A restriction fragment length polymorphism of the gene has been identified with Pvu II. To study the relationship between the islet amyloid polypeptide gene and Type 2 diabetes, two distinct genetic approaches have been undertaken. Firstly, non-linkage has been demonstrated in four pedigrees, with four normoglycaemic first degree relatives having an allele associated with diabetes in other family members, and one affected relative not having the putatively associated allele. The LOD score taking age-related penetrance into account was -1.68, making linkage unlikely (p = 0.02). Secondly, in a population-based restriction fragment length polymorphism survey, no linkage disequilibrium of the alleles was found between a population of unrelated Caucasian subjects with Type 2 diabetes and a normal population. A mutation in or near the islet amyloid polypeptide gene is thus unlikely to be a common cause of Type 2 diabetes.

Amyloid↗

PubMed1991