Isolation of the Human LIM/Homeodomain Gene Islet-1 and Identification of a Simple Sequence Repeat 1

• Published in: Diabetes (New York, N.Y.) Vol. 43; no. 7; pp. 935 - 941
• Main Authors: Tanizawa, Yukio, Riggs, Andrew C, Dagogo-Jack, Samuel, Vaxillaire, Martine, Froguel, Philippe, Liu, Li, Donis-Keller, Helen, Permutt, M Alan
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.07.1994
• Subjects: Biological and medical sciences; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Genetic aspects; Insulin; Medical sciences; Pancreatic beta cells; Physiological aspects; Type 2 diabetes; Endocrinopathy; Genetic mapping; Human; Maturity onset diabetes young; Insulation; Pancreatic hormone; B5-Chromosome; Insulin; Protein hormone; Gene; Transcription factor; Genome; Homeobox sequence
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diab.43.7.935

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.