title: Commonality in the genetic control of Type 1 diabetes in humans and NOD mice: variants of genes in the IL-2 pathway are associated with autoimmune diabetes in both species.
abstract: Variants within the IL-2 (interleukin 2) and CD25 genes are associated with T1DM (Type 1 diabetes mellitus) in mice and humans respectively. Both gene products are essential for optimal immune tolerance and a partial failure to tolerize is linked to the autoimmune responses to insulin and other beta-cell proteins that precede T1DM onset. Gene variants that contribute to common disease susceptibility often alter gene expression only modestly. Small expression changes can be technically challenging to measure robustly, especially since biological variation usually contributes negatively to this goal. The present review focuses on allele-specific expression assays that can be used to quantify genotype-determined expression differences such as those observed for IL-2, where the susceptibility allele is transcribed 2-fold less than the resistance allele.
authors.affiliation: Juvenile Diabetes Research Foundation/Wellcome Trust (JDRF/WT) Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke's Hospital, UK.
authors.forename: Dan B
authors.initials: DB
authors.lastname: Rainbow
authors.forename: Laura
authors.initials: L
authors.lastname: Esposito
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Howlett
authors.forename: Kara M
authors.initials: KM
authors.lastname: Hunter
authors.forename: John A
authors.initials: JA
authors.lastname: Todd
authors.forename: Laurence B
authors.initials: LB
authors.lastname: Peterson
authors.forename: Linda S
authors.initials: LS
authors.lastname: Wicker
mesh_terms: D000483:Alleles; D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics*; D051379:Mice; D016688:Mice, Inbred NOD; D013045:Species Specificity
chemical_list: D007376:Interleukin-2