Genetic linkage and transmission disequilibrium of marker haplotypes at chromosome 1q41 in human systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies to a wide range of self-antigens. Recent genome screens have implicated numerous chromosomal regions as potential SLE susceptibility loci. Among these, the 1q41 locus is of particular interest, because evidence for linkage has been found in several independent SLE family collections. Additionally, the 1q41 locus appears to be syntenic with a susceptibility interval identified in the NZM2410 mouse model for SLE. Here, we report the results of genotyping of 11 microsatellite markers within the 1q41 region in 210 SLE sibpair and 122 SLE trio families. These data confirm the modest evidence for linkage at 1q41 in our family collection (LOD = 1.21 at marker D1S2616). Evidence for significant linkage disequilibrium in this interval was also found. Multiple markers in the region exhibit transmission disequilibrium, with the peak single marker multiallelic linkage disequilibrium noted at D1S490 (pedigree disequilibrium test [PDT] global P value = 0.0091). Two- and three-marker haplotypes from the 1q41 region similarly showed strong transmission distortion in the collection of 332 SLE families. The finding of linkage together with significant transmission disequilibrium provides strong evidence for a susceptibility locus at 1q41 in human SLE.
Graham
R R
RR
Department of Medicine, Center for Immunology, University of Minnesota Medical School, 312 Church Street SE, Minneapolis, MN 55455, USA.
Langefeld
C D
CD
Gaffney
P M
PM
Ortmann
W A
WA
Selby
S A
SA
Baechler
E C
EC
Shark
K B
KB
Ockenden
T C
TC
Rohlf
K E
KE
Moser
K L
KL
Brown
W M
WM
Gabriel
S E
SE
Messner
R P
RP
King
R A
RA
Horak
P
P
Elder
J T
JT
Stuart
P E
PE
Rich
S S
SS
Behrens
T W
TW
D002878:Chromosomes, Human, Pair 1; D004247:DNA / Q000032:analysis; D005192:Family Health; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D010375:Pedigree; D020161:Physical Chromosome Mapping
D005819:Genetic Markers; D004247:DNA