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

Yukio Tanizawa, Andrew C. Riggs, Samuel Dagogo-Jack, Martine Vaxillaire, Philippe Froguel, Li Liu, Helen Donis-Keller, M. Alan Permutt

Research output: Contribution to journalArticle

29 Citations (Scopus)

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. This marker for Isl- 1 will prove valuable in assessing the role of mutations in this gene in other populations and families with NIDDM.

Original languageEnglish (US)
Pages (from-to)935-941
Number of pages7
JournalDiabetes
Volume43
Issue number7
DOIs
StatePublished - Jan 1 1994
Externally publishedYes

Fingerprint

Microsatellite Repeats
Type 2 Diabetes Mellitus
Genes
Alleles
Insulin
African Americans
Mutation
Genetic Linkage
Chromosomes, Human, Pair 1
Pedigree
Population
Carrier Proteins
Transcription Factors
Complementary DNA
Clone Cells
Polymerase Chain Reaction
DNA
Proteins

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Tanizawa, Y., Riggs, A. C., Dagogo-Jack, S., Vaxillaire, M., Froguel, P., Liu, L., ... Permutt, M. A. (1994). Isolation of the human LIM/homeodomain gene islet-1 and identification of a simple sequence repeat 1. Diabetes, 43(7), 935-941. https://doi.org/10.2337/diab.43.7.935

Isolation of the human LIM/homeodomain gene islet-1 and identification of a simple sequence repeat 1. / Tanizawa, Yukio; Riggs, Andrew C.; Dagogo-Jack, Samuel; Vaxillaire, Martine; Froguel, Philippe; Liu, Li; Donis-Keller, Helen; Permutt, M. Alan.

In: Diabetes, Vol. 43, No. 7, 01.01.1994, p. 935-941.

Research output: Contribution to journalArticle

Tanizawa, Y, Riggs, AC, Dagogo-Jack, S, Vaxillaire, M, Froguel, P, Liu, L, Donis-Keller, H & Permutt, MA 1994, 'Isolation of the human LIM/homeodomain gene islet-1 and identification of a simple sequence repeat 1', Diabetes, vol. 43, no. 7, pp. 935-941. https://doi.org/10.2337/diab.43.7.935
Tanizawa, Yukio ; Riggs, Andrew C. ; Dagogo-Jack, Samuel ; Vaxillaire, Martine ; Froguel, Philippe ; Liu, Li ; Donis-Keller, Helen ; Permutt, M. Alan. / Isolation of the human LIM/homeodomain gene islet-1 and identification of a simple sequence repeat 1. In: Diabetes. 1994 ; Vol. 43, No. 7. pp. 935-941.
@article{a13eebbb80ba4e95bfc1b2fd166a2868,
title = "Isolation of the human LIM/homeodomain gene islet-1 and identification of a simple sequence repeat 1",
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. This marker for Isl- 1 will prove valuable in assessing the role of mutations in this gene in other populations and families with NIDDM.",
author = "Yukio Tanizawa and Riggs, {Andrew C.} and Samuel Dagogo-Jack and Martine Vaxillaire and Philippe Froguel and Li Liu and Helen Donis-Keller and Permutt, {M. Alan}",
year = "1994",
month = "1",
day = "1",
doi = "10.2337/diab.43.7.935",
language = "English (US)",
volume = "43",
pages = "935--941",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "7",

}

TY - JOUR

T1 - Isolation of the human LIM/homeodomain gene islet-1 and identification of a simple sequence repeat 1

AU - Tanizawa, Yukio

AU - Riggs, Andrew C.

AU - Dagogo-Jack, Samuel

AU - Vaxillaire, Martine

AU - Froguel, Philippe

AU - Liu, Li

AU - Donis-Keller, Helen

AU - Permutt, M. Alan

PY - 1994/1/1

Y1 - 1994/1/1

N2 - 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. This marker for Isl- 1 will prove valuable in assessing the role of mutations in this gene in other populations and families with NIDDM.

AB - 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. This marker for Isl- 1 will prove valuable in assessing the role of mutations in this gene in other populations and families with NIDDM.

UR - http://www.scopus.com/inward/record.url?scp=0028277885&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028277885&partnerID=8YFLogxK

U2 - 10.2337/diab.43.7.935

DO - 10.2337/diab.43.7.935

M3 - Article

VL - 43

SP - 935

EP - 941

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 7

ER -