A genome-wide search for susceptibility genes in human systemic lupus erythematosus sib-pair families.
Systemic lupus erythematosus (SLE) is an autoimmune multisystem inflammatory disease characterized by the production of pathogenic autoantibodies. Previous genetic studies have suggested associations with HLA Class II alleles, complement gene deficiencies, and Fc receptor polymorphisms; however, it is likely that other genes contribute to SLE susceptibility and pathogenesis. Here, we report the results of a genome-wide microsatellite marker screen in 105 SLE sib-pair families. By using multipoint nonparametric methods, the strongest evidence for linkage was found near the HLA locus (6p11-p21) [D6S257, logarithm of odds (lod) = 3.90, P = 0.000011] and at three additional regions: 16q13 (D16S415, lod = 3.64, P = 0.000022), 14q21-23 (D14S276, lod = 2.81, P = 0.00016), and 20p12 (D20S186, lod = 2.62, P = 0.00025). Another nine regions (1p36, 1p13, 1q42, 2p15, 2q21-33, 3cent-q11, 4q28, 11p15, and 15q26) were identified with lod scores >/=1.00. These data support the hypothesis that multiple genes, including one in the HLA region, influence susceptibility to human SLE.
Gaffney
P M
PM
University of Minnesota Medical School, 312 Church Street SE, Minneapolis, MN 55455, USA.
Kearns
G M
GM
Shark
K B
KB
Ortmann
W A
WA
Selby
S A
SA
Malmgren
M L
ML
Rohlf
K E
KE
Ockenden
T C
TC
Messner
R P
RP
King
R A
RA
Rich
S S
SS
Behrens
T W
TW
D000328:Adult; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism
D006680:HLA Antigens; D009687:Nuclear Proteins