Linkage of the NKG2 and CD94 receptor genes to D12S77 in the human natural killer gene complex

The human natural killer (NK) gene complex is located on the short arm of chromosome 12 and contains a number of genes encoding C-type lectin receptors important for natural killer cell function. Among these are CD94 and the five NKG2 genes. The CD94 protein associates with different NKG2 isoforms to heterodimeric receptors which function to inhibit or trigger cytotoxicity of NK cells depending on the NKG2 isoform. We selected two yeast artificial chromosome clones comprising approximately 1.5 Mb of the NK gene complex and established a contig of underlying P1-derived artificial chromosome clones containing all NKG2 and the CD94 genes. A detailed analysis shows that all six genes are found within a region of 100 to 200 kilobases proximal of the marker D12S77. The gene order established is D12S77 - CD84 - NKG2D - NKG2F - NKG2E - NKG2C - NKG2A. The NKG2 genes are of identical transcriptional orientation, whereas the CD94 gene is placed in opposite orientation. The tight genomic linkage of these genes and the identical orientation of the NKG2 genes suggest coordinate regulation of expression during the differentiation of natural killer cells.