Visualizing human leukocyte antigen class II risk haplotypes in human systemic lupus erythematosus.
Human leukocyte antigen (HLA) class I and class II alleles are implicated as genetic risk factors for many autoimmune diseases. However, the role of the HLA loci in human systemic lupus erythematosus (SLE) remains unclear. Using a dense map of polymorphic microsatellites across the HLA region in a large collection of families with SLE, we identified three distinct haplotypes that encompassed the class II region and exhibited transmission distortion. DRB1 and DQB1 typing of founders showed that the three haplotypes contained DRB1*1501/ DQB1*0602, DRB1*0801/ DQB1*0402, and DRB1*0301/DQB1*0201 alleles, respectively. By visualizing ancestral recombinants, we narrowed the disease-associated haplotypes containing DRB1*1501 and DRB1*0801 to an approximately 500-kb region. We conclude that HLA class II haplotypes containing DRB1 and DQB1 alleles are strong risk factors for human SLE.
Graham
Robert R
RR
Department of Medicine, Division of Rheumatic and Autoimmune Diseases, University of Minnesota Medical School, Minneapolis, MN, 55455, USA.
Ortmann
Ward A
WA
Langefeld
Carl D
CD
Jawaheer
Damini
D
Selby
Scott A
SA
Rodine
Peter R
PR
Baechler
Emily C
EC
Rohlf
Kristine E
KE
Shark
Katherine B
KB
Espe
Karl J
KJ
Green
Linda E
LE
Nair
Rajan P
RP
Stuart
Philip E
PE
Elder
James T
JT
King
Richard A
RA
Moser
Kathy L
KL
Gaffney
Patrick M
PM
Bugawan
Teodorica L
TL
Erlich
Henry A
HA
Rich
Stephen S
SS
Gregersen
Peter K
PK
Behrens
Timothy W
TW
D000483:Alleles; D016022:Case-Control Studies; D018703:Founder Effect; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008126:Lod Score; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D011995:Recombination, Genetic
D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen