Revealing complete complex KIR haplotypes phased by long-read sequencing technology

Genes Immun. 2017 Sep;18(3):127-134. doi: 10.1038/gene.2017.10. Epub 2017 Jun 1.

Abstract

The killer cell immunoglobulin-like receptor (KIR) region of human chromosome 19 contains up to 16 genes for natural killer (NK) cell receptors that recognize human leukocyte antigen (HLA)/peptide complexes and other ligands. The KIR proteins fulfill functional roles in infections, pregnancy, autoimmune diseases and transplantation. However, their characterization remains a constant challenge. Not only are the genes highly homologous due to their recent evolution by tandem duplications, but the region is structurally dynamic due to frequent transposon-mediated recombination. A sequencing approach that precisely captures the complexity of KIR haplotypes for functional annotation is desirable. We present a unique approach to haplotype the KIR loci using single-molecule, real-time (SMRT) sequencing. Using this method, we have-for the first time-comprehensively sequenced and phased sixteen KIR haplotypes from eight individuals without imputation. The information revealed four novel haplotype structures, a novel gene-fusion allele, novel and confirmed insertion/deletion events, a homozygous individual, and overall diversity for the structural haplotypes and their alleles. These KIR haplotypes augment our existing knowledge by providing high-quality references, evolutionary informers, and source material for imputation. The haplotype sequences and gene annotations provide alternative loci for the KIR region in the human genome reference GrCh38.p8.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Chromosomes, Human, Pair 19 / genetics
  • Haplotypes*
  • Humans
  • Receptors, KIR / genetics*
  • Whole Genome Sequencing / methods*

Substances

  • Receptors, KIR