Extensive gene duplications and a large inversion characterize the human leukocyte receptor cluster

The chromosomal region 19q13.4 harbors the human leukocyte receptor cluster (LRC) which has been demonstrated to contain 19 genes encoding leukocyte-e xpressed receptors of the immunoglobulin (Ig) superfamily. A spotted PAC li brary was used to construct a contig of 65 overlapping clones spanning the complete LRC. Within the 900 kb covered by the contig, we identified one cl uster containing killer cell inhibitory receptor genes and two clusters con taining Ig-like transcript (ILT) genes. Of these, the second ILT cluster, l ocated at the centromeric end of the LRC, was previously unknown. Detailed analysis of the ILT receptor genes in this cluster revealed one novel (ILT1 1) and six already known ILT genes. The two ILT clusters are transcribed in opposite directions and are separated by about 200 kb, which contains two leukocyte-associated inhibitory receptor (LAIR) genes. The data suggest tha t the two ILT clusters, each including one LAIR locus, arose from a single ancestral ILT/LAIR cluster by inverse duplication of a large genomic fragme nt. Furthermore, the NK cell-expressed NKp46 gene was localized 20 kb telom eric of FCAR; and 14 novel genes mapping within the LRC were identified by cDNA selection. Together with the gene for the ribosomal protein 89 (RPS9), which had previously been assigned to 19q13.4, the total number of LRC gen es is now 44. Of these, 29 belong to the Ig superfamily.