Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by diverse and variable clinical manifestations. The etiology of SLE is still unknown, but both environmental and genetic factors are involved. Recent genome-wide scans and candidate genes studies in different ethnic groups have already suggested susceptibility loci for SLE, but most of the genetic component remains unexplained. We have previously conducted a genome-wide scan in 35 Finnish families multiply affected with SLE. With 417 microsatellite markers, we detected suggestive linkage in regions on chromosomes 6q and 14q as well as HLA on 6p. The 14q locus has also been implicated in three previous genome scans on SLE, whereas a partially overlapping region on 6q was implicated in one previous study. In an effort to obtain additional evidence for susceptibility loci on 6q and 14q and in order to refine their positions, we performed fine mapping at 1 cM density across the suggestive regions of linkage. Our results show evidence for excess sharing of a haplotype on 14q and excess transmission of a haplotype on 6q. Our results are compatible with the idea of a founder effect for susceptibility genes in SLE in central eastern Finland and suggest a path to the isolation of the putative susceptibility genes.
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Acknowledgements
We thank all the patients and their family members who participated in this study and the many physicians who referred families and verified the diagnosis. We thank Riitta Lehtinen, Sinikka Lindh, Sirkka Ruohomäki, Sirkku Ekström, Päivi Malinen and Teija Baas for expert help in the laboratory and sample collection, Anne Lehto for invaluable help with data management and Päivi Tikka and Päivi Lahermo for help with characterizing markers and genotyping. This study was supported by the Stockmann Foundation, Sigrid Jusélius Foundation, Helsinki UniversityCentral Hospital research funds, and Academy of Finland.
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Koskenmies, S., Widén, E., Onkamo, P. et al. Haplotype associations define target regions for susceptibility loci in systemic lupus erythematosus. Eur J Hum Genet 12, 489–494 (2004). https://doi.org/10.1038/sj.ejhg.5201125
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DOI: https://doi.org/10.1038/sj.ejhg.5201125