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NIH to Fund Genomics Studies Linking HLA and KIR Regions with Diseases

NEW YORK (GenomeWeb) – The National Institute of Health will award up to $3.4 million next year to fund genomics research programs and projects aimed at better understanding how two complex human genomic regions are involved in a range of immune system diseases.

The grants will support research programs focused on the HLA (human leukocyte antigen) and the KIR (natural killer cell immunoglobin-like receptor) genomic regions, which are involved in human susceptibility and resistance to immune-related diseases.

The investigators and institutions that receive these funds will participate in the HLA and KIR Region Genomics in Immune-Mediated Diseases Consortium (HLAGC), a cooperative research group that was created to discover and characterize associations between polymorphisms in these regions and immune-related diseases. These diseases and conditions may include autoimmune diseases, primary immunodeficiencies, and the outcomes of cell, tissue, and organ transplantations, such as rejection, tolerance, and graft-versus host disease.

Earlier studies by the HLAGC members has shown how common sequence variations in these regions may be linked to multiple diseases, such as multiple sclerosis, rheumatoid arthritis, Crohn's disease, systemic sclerosis, systemic lupus erythematosus, and others.

But the HLA region is the most polymorphic and gene-dense region in the human genome, based on past genome-wide association studies, and it has a high degree of linkage disequilibrium, making it a complicated region to study, NIH said. The four-megabase region has at least 150 coding genes, and has three classes of gene families that encode molecules that are involved in immune functions. However, NIH said that conventional GWAS techniques are not adequate to fully investigate this cluster of genes.

The research programs supported under these grants will seek to further identify, map, and characterize how genetic variants in these regions may influence disease phenotype, progression, and severity, predict health outcomes, and guide treatment strategies. These investigators also will make the genomic and phenotype data from their studies of the HLA and KIR regions publicly available through databases.

Potential research projects include, but are not limited to, studies of the association of HLA and/or KIR regions with disease susceptibility, resistance, progression, phenotype, or therapeutic response; associations between transplantation outcomes, such as graft rejection or tolerance, with mismatches between donors and recipients at the HLA and/or KIR region; association studies of immune-mediated diseases that disproportionately affect specific racial, ethnic, or gender groups; and a range of association and mechanistic studies in these areas.