Abstract
Killer cell immunoglobulin-like receptors (KIRs), expressed on natural killer cells and T cells, have considerable biomedical relevance playing significant roles in immunity, pregnancy and transplantation. The KIR locus is one of the most complex and polymorphic regions of the human genome. Extensive sequence homology and copy number variation makes KIRs technically laborious and expensive to type. To aid the investigation of KIRs in human disease we developed a high-throughput, multiplex real-time polymerase chain reaction method to determine gene copy number for each KIR locus. We used reference DNA samples to validate the accuracy and a cohort of 1698 individuals to evaluate capability for precise copy number discrimination. The method provides improved information and identifies KIR haplotype alterations that were not previously visible using other approaches.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-016-0358-0) contains supplementary material, which is available to authorized users.
Highlights
Complex and multi-allelic copy number variation is abundant in the human genome and is a potential source of genetic diversity in relation to disease [1]
We extend the approach to leukocyte immunoglobulin-like receptor (LILR) loci, demonstrating that the underlying strategy of Quantitative Killer cell immunoglobulin-like receptors (KIRs) semi-automated typing (qKAT) offers a model for analysing and visualizing other highly variable multi-allelic copy number variation (mCNV) regions
Assay validation We tested 16 UCLA KIR exchange samples with KIR presence/absence data and three Centre d’Etude du Polymorphisme Humain (CEPH)/UTAH families previously studied for KIR haplotypes
Summary
Complex and multi-allelic copy number variation (mCNV) is abundant in the human genome and is a potential source of genetic diversity in relation to disease [1]. Human leukocyte antigen (HLA) DRB, complement component 4 (C4) loci in the MHC and leukocyte immunoglobulin-like receptor (LILR) loci are recognised examples of multicopy gene families with mCNV linked to disease susceptibility [3,4,5,6,7]. Another genomic region of interest in this regard encompasses the killer cell immunoglobulin-like receptor (KIR) genes [8, 9]. KIR were discovered nearly 20 years ago by serological methods [10, 11].
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