Genomic organization of classical human low-affinity Fcγ receptor genes

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Abstract
The classical low-affinity Fcγ receptor genes (FcγRIIA, B, C and FcγRIIIA, B) are located on chromosome 1q23, a region that shows strong linkage with human systemic lupus erythematosus (SLE) in several genome-wide scans, and family-based association between FcγRIIIA and SLE is now established. High homology among the Fcγ receptor genes, however, has hampered further study of this region. We have used a human bacterial artificial chromosome (BAC) library to determine the order and orientation of these Fcγ receptor genes and have sequenced the very highly homologous 5´ region (including 3.4 kb of the promoter and the 8 kb from exon 1 to exon 3) of the FcγRIIB and FcγRIIC genes to enable study of their unique single nucleotide polymorphisms (SNP). We have utilized these data to characterize a linked set of three coding region SNPs in the FcγRIIC exon 3 (EC1) that includes the stop codon SNP, which provides an important insight into natural killer cell function. Together, these data provide the basis for the study of additional SNPs in FcγR genes in SLE disease susceptibility.