Genetic susceptibility factors in type 1 diabetes: Linkage, disequilibrium and functional analyses

Jin-Xiong She, Michele P. Marron

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Continuing progress has been made in elucidating the genetic factors involved in type 1 diabetes (insulin-dependent diabetes mellitus [IDDM]) in the past year. Two genome scans suggested additional susceptibility intervals and provided supporting evidence for several previously reported linkages. Other studies focused on the confirmation of linkage using multipoint sibpair analyses with densely spaced markers and multiethnic collections of families. Although significant and consistent linkage evidence was reported for the susceptibility intervals IDDM8 (on human chromosome 6q27), IDDM4 (on 11q) and IDDM5 (on 6q25), evidence for most other intervals varies in different data sets - probably due to a weak effect of the disease genes, genetic heterogeneity or random variation. Linkage disequilibrium mapping has become an increasingly important tool for both the confirmation and line-mapping of susceptibility intervals, as well as identification of etiological mutations. Functional studies indicate, firstly, that the susceptible and protective HLA class II molecules HLA-DR and -DQ bind and present nonoverlapping peptides and, secondly, that the variable number of tandem repeats at the 5' end of the insulin gene (susceptibility interval IDDM2) regulates insulin expression in the thymus.

Original languageEnglish (US)
Pages (from-to)682-689
Number of pages8
JournalCurrent Opinion in Immunology
Volume10
Issue number6
DOIs
StatePublished - Jan 1 1998
Externally publishedYes

Fingerprint

Linkage Disequilibrium
Genetic Predisposition to Disease
Type 1 Diabetes Mellitus
Insulin
HLA-DQ Antigens
Minisatellite Repeats
Genetic Heterogeneity
Chromosome Mapping
Human Chromosomes
HLA-DR Antigens
Thymus Gland
Genes
Genome
Peptides
Mutation
Datasets
Insulin-Dependent Diabetes Mellitus 4
Insulin-Dependent Diabetes Mellitus 8
Insulin-Dependent Diabetes Mellitus 5

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Genetic susceptibility factors in type 1 diabetes : Linkage, disequilibrium and functional analyses. / She, Jin-Xiong; Marron, Michele P.

In: Current Opinion in Immunology, Vol. 10, No. 6, 01.01.1998, p. 682-689.

Research output: Contribution to journalArticle

@article{36777e7107ef476faa8784f403ece935,
title = "Genetic susceptibility factors in type 1 diabetes: Linkage, disequilibrium and functional analyses",
abstract = "Continuing progress has been made in elucidating the genetic factors involved in type 1 diabetes (insulin-dependent diabetes mellitus [IDDM]) in the past year. Two genome scans suggested additional susceptibility intervals and provided supporting evidence for several previously reported linkages. Other studies focused on the confirmation of linkage using multipoint sibpair analyses with densely spaced markers and multiethnic collections of families. Although significant and consistent linkage evidence was reported for the susceptibility intervals IDDM8 (on human chromosome 6q27), IDDM4 (on 11q) and IDDM5 (on 6q25), evidence for most other intervals varies in different data sets - probably due to a weak effect of the disease genes, genetic heterogeneity or random variation. Linkage disequilibrium mapping has become an increasingly important tool for both the confirmation and line-mapping of susceptibility intervals, as well as identification of etiological mutations. Functional studies indicate, firstly, that the susceptible and protective HLA class II molecules HLA-DR and -DQ bind and present nonoverlapping peptides and, secondly, that the variable number of tandem repeats at the 5' end of the insulin gene (susceptibility interval IDDM2) regulates insulin expression in the thymus.",
author = "Jin-Xiong She and Marron, {Michele P.}",
year = "1998",
month = "1",
day = "1",
doi = "10.1016/S0952-7915(98)80089-7",
language = "English (US)",
volume = "10",
pages = "682--689",
journal = "Current Opinion in Immunology",
issn = "0952-7915",
publisher = "Elsevier Limited",
number = "6",

}

TY - JOUR

T1 - Genetic susceptibility factors in type 1 diabetes

T2 - Linkage, disequilibrium and functional analyses

AU - She, Jin-Xiong

AU - Marron, Michele P.

PY - 1998/1/1

Y1 - 1998/1/1

N2 - Continuing progress has been made in elucidating the genetic factors involved in type 1 diabetes (insulin-dependent diabetes mellitus [IDDM]) in the past year. Two genome scans suggested additional susceptibility intervals and provided supporting evidence for several previously reported linkages. Other studies focused on the confirmation of linkage using multipoint sibpair analyses with densely spaced markers and multiethnic collections of families. Although significant and consistent linkage evidence was reported for the susceptibility intervals IDDM8 (on human chromosome 6q27), IDDM4 (on 11q) and IDDM5 (on 6q25), evidence for most other intervals varies in different data sets - probably due to a weak effect of the disease genes, genetic heterogeneity or random variation. Linkage disequilibrium mapping has become an increasingly important tool for both the confirmation and line-mapping of susceptibility intervals, as well as identification of etiological mutations. Functional studies indicate, firstly, that the susceptible and protective HLA class II molecules HLA-DR and -DQ bind and present nonoverlapping peptides and, secondly, that the variable number of tandem repeats at the 5' end of the insulin gene (susceptibility interval IDDM2) regulates insulin expression in the thymus.

AB - Continuing progress has been made in elucidating the genetic factors involved in type 1 diabetes (insulin-dependent diabetes mellitus [IDDM]) in the past year. Two genome scans suggested additional susceptibility intervals and provided supporting evidence for several previously reported linkages. Other studies focused on the confirmation of linkage using multipoint sibpair analyses with densely spaced markers and multiethnic collections of families. Although significant and consistent linkage evidence was reported for the susceptibility intervals IDDM8 (on human chromosome 6q27), IDDM4 (on 11q) and IDDM5 (on 6q25), evidence for most other intervals varies in different data sets - probably due to a weak effect of the disease genes, genetic heterogeneity or random variation. Linkage disequilibrium mapping has become an increasingly important tool for both the confirmation and line-mapping of susceptibility intervals, as well as identification of etiological mutations. Functional studies indicate, firstly, that the susceptible and protective HLA class II molecules HLA-DR and -DQ bind and present nonoverlapping peptides and, secondly, that the variable number of tandem repeats at the 5' end of the insulin gene (susceptibility interval IDDM2) regulates insulin expression in the thymus.

UR - http://www.scopus.com/inward/record.url?scp=0032404079&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032404079&partnerID=8YFLogxK

U2 - 10.1016/S0952-7915(98)80089-7

DO - 10.1016/S0952-7915(98)80089-7

M3 - Article

C2 - 9914216

AN - SCOPUS:0032404079

VL - 10

SP - 682

EP - 689

JO - Current Opinion in Immunology

JF - Current Opinion in Immunology

SN - 0952-7915

IS - 6

ER -