Polymorphism discovery and association analyses of the interferon genes in type 1 diabetes.
BACKGROUND
The aetiology of the autoimmune disease type 1 diabetes (T1D) involves many genetic and environmental factors. Evidence suggests that innate immune responses, including the action of interferons, may also play a role in the initiation and/or pathogenic process of autoimmunity. In the present report, we have adopted a linkage disequilibrium (LD) mapping approach to test for an association between T1D and three regions encompassing 13 interferon alpha (IFNA) genes, interferon omega-1 (IFNW1), interferon beta-1 (IFNB1), interferon gamma (IFNG) and the interferon consensus-sequence binding protein 1 (ICSBP1).


RESULTS
We identified 238 variants, most, single nucleotide polymorphisms (SNPs), by sequencing IFNA, IFNB1, IFNW1 and ICSBP1, 98 of which where novel when compared to dbSNP build 124. We used polymorphisms identified in the SeattleSNP database for INFG. A set of tag SNPs was selected for each of the interferon and interferon-related genes to test for an association between T1D and this complex gene family. A total of 45 tag SNPs were selected and genotyped in a collection of 472 multiplex families.


CONCLUSIONS
We have developed informative sets of SNPs for the interferon and interferon related genes. No statistical evidence of a major association between T1D and any of the interferon and interferon related genes tested was found.
Morris
Gerard A J
GA
Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Institute for Medical Research, University of Cambridge, Addenbrooke's Hospital, Cambridge, CB2 2XY, UK. gmorris@hsph.harvard.edu
Lowe
Christopher E
CE
Cooper
Jason D
JD
Payne
Felicity
F
Vella
Adrian
A
Godfrey
Lisa
L
Hulme
John S
JS
Walker
Neil M
NM
Healy
Barry C
BC
Lam
Alex C
AC
Lyons
Paul A
PA
Todd
John A
JA
D001327:Autoimmune Diseases / Q000235:genetics; D030541:Databases, Genetic; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005091:Exons; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D007370:Interferon Type I / Q000235:genetics; D016898:Interferon-alpha / Q000235:genetics; D016899:Interferon-beta / Q000235:genetics; D007371:Interferon-gamma / Q000235:genetics; D007372:Interferons / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D015233:Models, Statistical; D005810:Multigene Family; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
D007370:Interferon Type I; D016898:Interferon-alpha; C063743:interferon omega 1; D016899:Interferon-beta; D007371:Interferon-gamma; D007372:Interferons