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  • 1
    ISSN: 1432-0428
    Keywords: Glucokinase ; polymerase chain reaction ; micro satellite DNA polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The glucose phosphorylating enzyme glucokinase plays an important role in the regulation of glucose homeostasis. Studies in rodents indicate that pancreatic Beta cells and hepatocytes express different isoforms of this protein as a consequence of the presence of tissue-specific promoters and exon 1 sequences which are spliced to a shared group of nine exons which encode most of the mRNA and protein. Here, we report the isolation and characterization of cDNA clones encoding human Beta-cell glucokinase. The sequence of human Beta-cell glucokinase shows 97% amino acid identity with that of the cognate rat protein. We also mapped the human glucokinase gene to the short arm of chromosome 7 by analysing its segregation in a panel of reduced human mouse somatic cell hybrids. In situ hybridization to metaphase chromosomes confirmed the localization of the human glucokinase gene to chromosome 7 and indicated that it was in band p 13. A microsatellite DNA polymorphism that can be typed using the polymerase chain reaction was identified upstream of exon 1 a, the Beta-cell specific first exon. The glucokinase cDNA clone and highly informative DNA polymorphism will be useful for examining the role of this gene in the pathogenesis of diabetes mellitus.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Keywords Diabetes mellitus ; insulin resistance ; genetics ; linkage analysis.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The expansion of trinucleotide repeats has been associated with late-onset neurodegenerative disorders. Although the genes harbouring the triplet expansions may be widely expressed, the pathological expression of these diseases is restricted to specific tissues. Non-insulin-dependent diabetes mellitus (NIDDM) shares several features with diseases resulting from such dynamic mutations including late-onset and specific but limited sites of tissue pathology – muscle, fat, liver and insulin-secreting pancreatic beta cells. In order to examine the contribution of genes containing polymorphic CAG/CTG repeats to the development of NIDDM, we screened an adult human skeletal muscle cDNA library for expressed sequences containing tandem repeats of CAG and/or CTG. Ten different loci with polymorphic CAG/CTG repeats were identified, of which seven had a heterozygosity greater than 0.20. There was no evidence for linkage between these seven loci and NIDDM in a group of affected Mexican-American sib pairs. Nor was there a significant difference in the distribution of alleles between Caucasian patients with NIDDM and normal healthy control subjects or evidence for repeat expansion in diabetic subjects. Thus, muscle genes with polymorphic CAG/CTG repeats do not appear to play a significant role in the development of NIDDM. [Diabetologia (1996) 39: 725–730]
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Diabetes mellitus ; insulin resistance ; genetics ; linkage analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The expansion of trinucleotide repeats has been associated with late-onset neurodegenerative disorders. Although the genes harbouring the triplet expansions may be widely expressed, the pathological expression of these diseases is restricted to specific tissues. Non-insulin-dependent diabetes mellitus (NIDDM) shares several features with diseases resulting from such dynamic mutations including late-onset and specific but limited sites of tissue pathology — muscle, fat, liver and insulin-secreting pancreatic beta cells. In order to examine the contribution of genes containing polymorphic CAG/CTG repeats to the development of NIDDM, we screened an adult human skeletal muscle cDNA library for expressed sequences containing tandem repeats of CAG and/or CTG. Ten different loci with polymorphic CAG/CTG repeats were identified, of which seven had a heterozygosity greater than 0.20. There was no evidence for linkage between these seven loci and NIDDM in a group of affected Mexican-American sib pairs. Nor was there a significant difference in the distribution of alleles between Caucasian patients with NIDDM and normal healthy control subjects or evidence for repeat expansion in diabetic subjects. Thus, muscle genes with polymorphic CAG/CTG repeats do not appear to play a significant role in the development of NIDDM.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
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