Natural genetic variants influencing type 1 diabetes in humans and in the NOD mouse.
The understanding of the genetic basis of type 1 diabetes and other autoimmune diseases and the application of that knowledge to their treatment, cure and eventual prevention has been a difficult goal to reach. Cumulative progress in both mouse and human are finally giving way to some successes and significant insights have been made in the last few years. Investigators have identified key immune tolerance-associated phenotypes in convincingly reliable ways that are regulated by specific diabetes-associated chromosomal intervals. The combination of positional genetics and functional studies is a powerful approach to the identification of downstream molecular events that are causal in disease aetiology. In the case of type 1 diabetes, the availability of several animal models, especially the NOD mouse, has complemented the efforts to localize human genes causing diabetes and has shown that some of the same genes and pathways are associated with autoimmunity in both species. There is also growing evidence that the initiation or progression of many autoimmune diseases is likely to be influenced by some of the same genes.
Wicker
Linda S
LS
Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes & Inflammation Laboratory, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 2XY, UK.
Moule
Carolyn L
CL
Fraser
Heather
H
Penha-Goncalves
Carlos
C
Rainbow
Dan
D
Garner
Valerie E S
VE
Chamberlain
Giselle
G
Hunter
Kara
K
Howlett
Sarah
S
Clark
Jan
J
Gonzalez-Munoz
Andrea
A
Cumiskey
Anne Marie
AM
Tiffen
Paul
P
Howson
Joanna
J
Healy
Barry
B
Smink
Luc J
LJ
Kingsnorth
Amanda
A
Lyons
Paul A
PA
Gregory
Simon
S
Rogers
Jane
J
Todd
John A
JA
Peterson
Laurence B
LB
D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics; D001483:Base Sequence; D060908:CTLA-4 Antigen; D004247:DNA; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein; D051379:Mice; D016688:Mice, Inbred NOD; D020641:Polymorphism, Single Nucleotide; D012689:Sequence Homology, Nucleic Acid
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; C556692:ICOS protein, human; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; D004247:DNA