Genomic organization of classical human low-affinity Fcγ receptor genes

The classical low-affinity Fay receptor genes (FcgammaRIIA, B, C and FcgammaRIIA, B) are located on chromosome 1q23, a region that shows strong linkage with human systemic lupus etythematosus (SLE) in several genome-wide scans, and family-based association between FcgammaRIIA and SLE is now established. High homology among the Fcgamma 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 Fcy receptor genes and have sequenced the very highly homologous 6 region (including 3.4 kb of the promoter and the 8 kb from exon 1 to exon 3) of the FcgammaRIIB and FcgammaRIIC 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 FcgammaRIIC 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 FcgammaR genes in SLE disease susceptibility.