No linkage or association of telomeric and centromeric T-cell receptor beta-chain markers with susceptibility to type 1 insulin-dependent diabetes in HLA-DR4 multiplex families.
The T-cell receptor beta locus (TCRB) on chromosome 7q35 was studied as a candidate region for genetic susceptibility to type 1 insulin-dependent diabetes (IDDM). A highly polymorphic microsatellite marker mapping to the TCRBV6.7 gene and a TCRB C-region RFLP were used to genotype the members of a total of 21 multiplex IDDM families from two different geographical areas. There was no evidence to support linkage to either of these markers with IDDM, and conventional two-point analysis excluded linkage to the telomeric end of the TCRB complex, in the region of the highly informative TCRBV6.7 marker. There was significant linkage of IDDM to the class II HLA-D locus with significant lod scores > 3.0 obtained for the HLA-DRB1 and HLA-DQB1 genes. Affected sib-pair (ASP) and transmission disequilibrium (TDT) association tests confirmed these findings.
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD, USA.
M F
MF
McDermott
G
G
Schmidt-Wolf
A A
AA
Sinha
M
M
Koo
M A
MA
Porter
L
L
Briant
A
A
Cambon-Thomsen
N K
NK
Maclaren
D
D
Fiske
S
S
Bertera
M
M
Trucco
C I
CI
Amos
H O
HO
McDevitt
D L
DL
Kastner
D000293:Adolescent; D002503:Centromere; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D015804:HLA-DR4 Antigen / Q000235:genetics*; D006801:Humans; D019169:Jurkat Cells; D015810:Linkage Disequilibrium; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D016615:Telomere
D015804:HLA-DR4 Antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta