Isolation of the human LIM/homeodomain gene islet-1 and identification of a simple sequence repeat polymorphism [corrected].
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.(ABSTRACT TRUNCATED AT 250 WORDS)
Tanizawa
Y
Y
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Riggs
A C
AC
Dagogo-Jack
S
S
Vaxillaire
M
M
Froguel
P
P
Liu
L
L
Donis-Keller
H
H
Permutt
M A
MA
D000483:Alleles; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D044383:Black People / Q000235:genetics; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5; D016384:Consensus Sequence; D004247:DNA / Q000235:genetics; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D005787:Gene Frequency; D005801:Genes, Homeobox; D008040:Genetic Linkage; D005819:Genetic Markers; D005941:Glucokinase / Q000235:genetics; D018398:Homeodomain Proteins; D006801:Humans; D007328:Insulin / Q000096:biosynthesis*; D007564:Japan; D060850:LIM-Homeodomain Proteins; D008126:Lod Score; D008923:Missouri; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins; D009549:Nigeria; D010375:Pedigree; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D044465:White People / Q000235:genetics; D001741:Black or African American
D017931:DNA Primers; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D018398:Homeodomain Proteins; D007328:Insulin; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1; D004247:DNA; D005941:Glucokinase