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Am J Hum Genet ; 71(3): 543-53, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12145745

ABSTRACT

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.


Subject(s)
Genetic Predisposition to Disease , HLA-DQ Antigens/genetics , HLA-DR Antigens/genetics , Haplotypes/genetics , Lupus Erythematosus, Systemic/genetics , Alleles , Case-Control Studies , Founder Effect , Genotype , HLA-DQ beta-Chains , HLA-DRB1 Chains , Humans , Linkage Disequilibrium , Lod Score , Recombination, Genetic
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