Paternally transmitted IDDM2 influences diabetes susceptibility despite biallelic expression of the insulin gene in human pancreas

Marilyn M. Bui, De Fang Luo, Jan Y. She, Noel K. Maclaren, Andrew Muir, Glenys Thomson, Jin-Xiong She

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Whereas it is well known that the insulin gene (INS) region at 11p15.5 (IDDM2) confers susceptibility to insulin-dependent diabetes mellitus (IDDM), it is still controversial whether the parental origin of IDDM2 influences IDDM susceptibility. We have analysed the PstI+1127 polymorphism in 123 USA multiplex families and detected linkage only in male meioses using the affected sibpair analysis (P = 0.009). Application of the transmission/disequilibrium test (TDT) found significantly increased transmission of the IDDM-associated INS allele from fathers heterozygous for INS to their diabetic offspring (P = 0.00002), but the transmission from heterozygous mothers was not significantly different from expectation. In non-diabetic families, the transmission from heterozygous for INS was not significantly different from random expectation in either paternal or maternal meioses. Maternal imprinting of the INS gene in pancreatic islets was originally considered the most favorable explanation for the observed gender-related difference. However, our study has demonstrated biallelic expression of INS in pancreatic tissues from human fetuses and thus suggests that INS is probably not imprinted in the pancreatic islets.

Original languageEnglish (US)
Pages (from-to)97-103
Number of pages7
JournalJournal of Autoimmunity
Volume9
Issue number1
DOIs
StatePublished - Jan 1 1996
Externally publishedYes

Fingerprint

Pancreas
Insulin
Gene Expression
Genes
Type 1 Diabetes Mellitus
Mothers
Meiosis
Islets of Langerhans
Fathers
Fetus
Alleles

Keywords

  • Gene expression
  • Genomic imprinting
  • Insulin gene
  • Linkage analysis
  • Transmission bias

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Paternally transmitted IDDM2 influences diabetes susceptibility despite biallelic expression of the insulin gene in human pancreas. / Bui, Marilyn M.; Luo, De Fang; She, Jan Y.; Maclaren, Noel K.; Muir, Andrew; Thomson, Glenys; She, Jin-Xiong.

In: Journal of Autoimmunity, Vol. 9, No. 1, 01.01.1996, p. 97-103.

Research output: Contribution to journalArticle

Bui, Marilyn M. ; Luo, De Fang ; She, Jan Y. ; Maclaren, Noel K. ; Muir, Andrew ; Thomson, Glenys ; She, Jin-Xiong. / Paternally transmitted IDDM2 influences diabetes susceptibility despite biallelic expression of the insulin gene in human pancreas. In: Journal of Autoimmunity. 1996 ; Vol. 9, No. 1. pp. 97-103.
@article{efdf74f2f57446f18cd634af102c6229,
title = "Paternally transmitted IDDM2 influences diabetes susceptibility despite biallelic expression of the insulin gene in human pancreas",
abstract = "Whereas it is well known that the insulin gene (INS) region at 11p15.5 (IDDM2) confers susceptibility to insulin-dependent diabetes mellitus (IDDM), it is still controversial whether the parental origin of IDDM2 influences IDDM susceptibility. We have analysed the PstI+1127 polymorphism in 123 USA multiplex families and detected linkage only in male meioses using the affected sibpair analysis (P = 0.009). Application of the transmission/disequilibrium test (TDT) found significantly increased transmission of the IDDM-associated INS allele from fathers heterozygous for INS to their diabetic offspring (P = 0.00002), but the transmission from heterozygous mothers was not significantly different from expectation. In non-diabetic families, the transmission from heterozygous for INS was not significantly different from random expectation in either paternal or maternal meioses. Maternal imprinting of the INS gene in pancreatic islets was originally considered the most favorable explanation for the observed gender-related difference. However, our study has demonstrated biallelic expression of INS in pancreatic tissues from human fetuses and thus suggests that INS is probably not imprinted in the pancreatic islets.",
keywords = "Gene expression, Genomic imprinting, Insulin gene, Linkage analysis, Transmission bias",
author = "Bui, {Marilyn M.} and Luo, {De Fang} and She, {Jan Y.} and Maclaren, {Noel K.} and Andrew Muir and Glenys Thomson and Jin-Xiong She",
year = "1996",
month = "1",
day = "1",
doi = "10.1006/jaut.1996.0012",
language = "English (US)",
volume = "9",
pages = "97--103",
journal = "Journal of Autoimmunity",
issn = "0896-8411",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Paternally transmitted IDDM2 influences diabetes susceptibility despite biallelic expression of the insulin gene in human pancreas

AU - Bui, Marilyn M.

AU - Luo, De Fang

AU - She, Jan Y.

AU - Maclaren, Noel K.

AU - Muir, Andrew

AU - Thomson, Glenys

AU - She, Jin-Xiong

PY - 1996/1/1

Y1 - 1996/1/1

N2 - Whereas it is well known that the insulin gene (INS) region at 11p15.5 (IDDM2) confers susceptibility to insulin-dependent diabetes mellitus (IDDM), it is still controversial whether the parental origin of IDDM2 influences IDDM susceptibility. We have analysed the PstI+1127 polymorphism in 123 USA multiplex families and detected linkage only in male meioses using the affected sibpair analysis (P = 0.009). Application of the transmission/disequilibrium test (TDT) found significantly increased transmission of the IDDM-associated INS allele from fathers heterozygous for INS to their diabetic offspring (P = 0.00002), but the transmission from heterozygous mothers was not significantly different from expectation. In non-diabetic families, the transmission from heterozygous for INS was not significantly different from random expectation in either paternal or maternal meioses. Maternal imprinting of the INS gene in pancreatic islets was originally considered the most favorable explanation for the observed gender-related difference. However, our study has demonstrated biallelic expression of INS in pancreatic tissues from human fetuses and thus suggests that INS is probably not imprinted in the pancreatic islets.

AB - Whereas it is well known that the insulin gene (INS) region at 11p15.5 (IDDM2) confers susceptibility to insulin-dependent diabetes mellitus (IDDM), it is still controversial whether the parental origin of IDDM2 influences IDDM susceptibility. We have analysed the PstI+1127 polymorphism in 123 USA multiplex families and detected linkage only in male meioses using the affected sibpair analysis (P = 0.009). Application of the transmission/disequilibrium test (TDT) found significantly increased transmission of the IDDM-associated INS allele from fathers heterozygous for INS to their diabetic offspring (P = 0.00002), but the transmission from heterozygous mothers was not significantly different from expectation. In non-diabetic families, the transmission from heterozygous for INS was not significantly different from random expectation in either paternal or maternal meioses. Maternal imprinting of the INS gene in pancreatic islets was originally considered the most favorable explanation for the observed gender-related difference. However, our study has demonstrated biallelic expression of INS in pancreatic tissues from human fetuses and thus suggests that INS is probably not imprinted in the pancreatic islets.

KW - Gene expression

KW - Genomic imprinting

KW - Insulin gene

KW - Linkage analysis

KW - Transmission bias

UR - http://www.scopus.com/inward/record.url?scp=0029880861&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029880861&partnerID=8YFLogxK

U2 - 10.1006/jaut.1996.0012

DO - 10.1006/jaut.1996.0012

M3 - Article

C2 - 8845059

AN - SCOPUS:0029880861

VL - 9

SP - 97

EP - 103

JO - Journal of Autoimmunity

JF - Journal of Autoimmunity

SN - 0896-8411

IS - 1

ER -