KIR Haplotype Assigment By Next Generation Sequencing

The Killer immunoglobulin-like receptor (KIR) genetic system is polygenic and highly polymorphic. Several studies confirmed the KIR haplotype association with hematopoietic stem cell transplant (HSCT) outcome, however, KIR haplotype assignment using KIR genotypes, is still a challenge even with family information available, because KIR haplotypes may vary in gene copy-number, gene content and allelic diversity. The goal of the present study is to assign KIR haplotypes in related HSCT patient-donor pairs using next generation sequencing (NGS) method. We selected 10 families (n=38 in total): 6 with both parents available. All of them were previously typed with SSP-Multiplex for KIR genotyping and Sequencing for 3DL1/2/3 alleles. Scisco KIR NGS method can distinguish KIR genotypes, calculate gene copy number, estimate gene-content haplotypes and assign KIR alleles. KIR genotypes obtained with two methods:SSP and NGS were identical. We are able to distinguish KIR haplotype distribution within families. KIR gene copy number is essential in this regard. However, if a sibling pair are both KIR AA genotype, it is difficult to distinguish KIR haplotype matching, without KIR allele information. KIR allele assignments are in progress.