qKAT: a high-throughput qPCR method for KIR gene copy number and haplotype determination

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 $\textit{KIR }$ locus is one of the most complex and polymorphic regions of the human genome. Extensive sequence homology and copy number variation makes $\textit{KIR }$s technically laborious and expensive to type. To aid the investigation of $\textit{KIR }$s in human disease we developed a high-throughput, multiplex real-time polymerase chain reaction method to determine gene copy number for each $\textit{KIR }$ 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 $\textit{KIR }$ haplotype alterations that were not previously visible using other approaches.