Arrangement of the ILT gene cluster: a common null allele of the ILT6 gene results from a 6.7-kbp deletion.

Abstract

The leukocyte receptor cluster (LRC) is a highly polymorphic region of human chromosome 19q13.4 that encompasses at least 24 members of the immunoglobulin superfamily (Ig-SF). The centromeric end of the LRC contains eight Ig-SF loci, namely LAIR1 and seven ILT genes. All ILT genes conform to prototypic ILT gene structures. ILT6 is the only member of the ILT family that lacks a transmembrane and cytoplasmic domain. Close examination of the ILT6 genomic sequence reveals high similarity of this locus with the organization of activating ILT genes. However, the ILT6 transcript runs through the putative splice site of exon 8 that encodes for an extracellular stalk region, leading to a premature in-frame stop codon. Downstream of exon 8 are three pseudo exons that are not included in any of the known ILT6 transcripts, but share high homology to the equivalent region in activating ILT loci, suggesting that these genes have evolved from a common ancestral sequence. Comparison of two haplotypes over this region revealed a remarkable polymorphism with respect to the ILT6 gene which lacks exons 1-7 in one allele, reminiscent of the presence/absence variation displayed by the closely related and genetically linked KIR loci. Detailed sequence analysis of the two LAIR/ILT clusters suggests that the two complexes may have evolved from an inverted duplication.