Isolation of the human LIM/homeodomain gene islet-1 and identification of a simple sequence repeat polymorphism [corrected]

• Published in: Diabetes (New York, N.Y.) Vol. 43; no. 7; pp. 935 - 941
• Main Authors: Tanizawa, Y., Riggs, A. C., Dagogo-Jack, S., Vaxillaire, M., Froguel, P., Liu, L., Donis-Keller, H., Permutt, M. A.
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.07.1994
• Subjects: Alleles; Asian People - genetics; Base Sequence; Black or African American; Black People - genetics; Chromosome Mapping; Chromosomes, Human, Pair 5; Consensus Sequence; Diabetes Mellitus, Type 2 - genetics; DNA - genetics; DNA Primers; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; Enhancer Elements, Genetic; Gene Frequency; Genes, Homeobox; Genetic Linkage; Genetic Markers; Genetics; Glucokinase - genetics; Homeodomain Proteins; Human genetics; Humans; Insulin - biosynthesis; Japan; Life Sciences; LIM-Homeodomain Proteins; Lod Score; Missouri; Molecular Sequence Data; Mutation; Nerve Tissue Proteins; Nigeria; Pedigree; Polymerase Chain Reaction - methods; Polymorphism, Genetic; Recombination, Genetic; Repetitive Sequences, Nucleic Acid; Restriction Mapping; Transcription Factors - biosynthesis; Transcription Factors - genetics; White People - genetics; Nigeria; Japan; Missouri
• ISSN: 0012-1797; 1939-327X; 0012-1797
• DOI: 10.2337/diabetes.43.7.935

Isolation of the human LIM/homeodomain gene islet-1 and identification of a simple sequence repeat polymorphism [corrected] Y Tanizawa , A C Riggs , S Dagogo-Jack , M Vaxillaire , P Froguel , L Liu , H Donis-Keller and M A Permutt Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110. Abstract The islet-1 (Isl-1) gene encodes a protein that binds to the enhancer region of the insulin gene. Isl-1 is a member of the LIM/homeodomain family of transcription factors. Because insulin deficiency, either relative or absolute, is a cardinal feature of non-insulin-dependent diabetes mellitus (NIDDM), this study addressed the question of whether mutations in genes that regulate insulin production could be involved. Rat Isl-1 was the first insulin enhancer binding protein to be isolated, and, in this study, the rat gene was used to isolate a partial human islet Isl-1 cDNA and subsequently to isolate genomic clones. A simple sequence repeat was found in the Isl-1 gene, and polymerase chain reaction amplification of this region of genomic DNA revealed 12 alleles in St. Louis African-Americans (het = 0.87), 14 alleles in black Nigerians (het = 0.89), 8 alleles in Japanese (het = 0.69), and 8 alleles in Caucasians (het = 0.81). Genetic linkage analysis uniquely placed Isl-1 on chromosome 5q (D5S395[12.8 cM]Isl-1 [11.6 cM]D5S407). The simple sequence repeat polymorphism at the Isl-1 locus was used to evaluate mutations in this gene as a possible contributor to the pathogenesis of NIDDM. Allelic frequencies did not differ between patients with NIDDM (n = 165) and nondiabetic control subjects (n = 163) in two black populations (St. Louis African-Americans and Nigerians). Linkage analyses in 15 nonglucokinase maturity-onset diabetes of the young pedigrees indicated that linkage could be rejected (LOD score < -3.0) over a distance of 15 cM.