The scientists began their comprehensive sequence analysis using the DNA samples of 1,349 American Europeans (773 with SLE disease and 576 without) from sample collections at UT Southwestern, the University of Southern California, UCLA, Oklahoma Medical Research Foundation, and the Université Catholique de Louvain in Belgium.

They then determined the precise DNA sequences at SLE-associated genetic regions scattered throughout the genome. They found that SLE risk is associated with specific clusters of DNA variations, commonly called haplotypes, and that some haplotypes increased the risk for SLE while others provided protection from SLE.


After identifying the sets of DNA variants that increased SLE susceptibility in Caucasians, they used multiple public databases, including the international 1000 Genomes Project (2,504 genomic samples from the global human population) to determine whether these haplotypes also were found in South American, South Asian, African, and East Asian populations.

They discovered that the variants and haplotypes were distributed across subpopulations worldwide. Their findings indicate that many common haplotypes in the immune system are shared at different frequencies throughout the global population, suggesting that these variations in the immune system have ancient origins and persist in populations for long periods, Dr. Wakeland said.

"We thank the many SLE patients and control participants whose sample contributions were essential for these studies," the researchers wrote.

Dr. Wakeland and colleagues plan to continue the research by obtaining more DNA samples and expanding their analysis to additional SLE risk genes with the goal of obtaining a data set that can be used to predict an individual's unique risk of SLE, as well as the likelihood of benefiting from specific treatments.

"It is feasible that this same type of genetic analysis will allow the clustering of SLE patients into specific groups, based on their genetic predispositions, which would improve clinical management and potentially allow the development of more targeted therapies," Dr. Wakeland said.

Earlier this month, UT Southwestern announced that Dr. Wakeland, whose laboratory has long served as the institution's Genomics and Microarray Core Facility, will be leading a large DNA-sequencing initiative to address important clinical challenges. The new clinical sequencing facility, in collaboration with the Department of Pathology, will provide panel sequencing for cancer and other diagnoses, and eventually expand to whole-exome and whole-genome sequence analysis for a variety of patients. The laboratory will be established in the BioCenter on the East Campus. To commit full effort to this initiative, Dr. Wakeland will step down as Chair of Immunology, but will remain in this role until his successor is named.

Medical Research Homepage