title: Novel insights in the genomic organization and hotspots of recombination in the human KIR locus through analysis of intergenic regions.
abstract: The Killer Immunoglobulin-like Receptor (KIR) proteins constitute a family of highly homologous surface receptors involved in the regulation of the innate cytotoxicity of natural killer (NK) cells. Within the human genome, 17 KIR genes are present, many of which show large variation across the population owing to the high number of allelic variants and copy number variation (CNV). KIR genotyping and CNV determination were used to map the KIR locus in a large cohort of >400 Caucasian individuals. Gene order and structure was determined by sequence-specific polymerase chain reaction of the intergenic regions. In this way, we could show that KIR3DL1 and KIR2DS4 gene variants are linked and that--contrary to current views--the gene KIR2DS5 is only present in the telomeric half of the KIR locus. Our study revealed novel insights in the highly organized distribution of KIR genes. Novel recombination hotspots were identified that contribute to the diversity of KIR gene distribution in the Caucasian population. Next-generation sequencing of the KIR intergenic regions allowed for a detailed single-nucleotide polymorphism analysis, which demonstrated several gene-specific as well as haplotype-specific nucleotides for a more accurate genotyping of this notoriously complex gene cluster.
authors.affiliation: Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Vendelbosch
authors.affiliation: Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: de Boer
authors.affiliation: Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: van Leeuwen
authors.affiliation: Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Pourfarzad
authors.affiliation: Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Geissler
authors.affiliation: Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands.
authors.forename: T K
authors.initials: TK
authors.lastname: van den Berg
authors.affiliation: 1] Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands [2] Emma Children's Hospital, Department of Pediatric Hematology, Immunology and Infectious diseases, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: T W
authors.initials: TW
authors.lastname: Kuijpers
mesh_terms: D056915:DNA Copy Number Variations; D021901:DNA, Intergenic; D023061:Gene Order; D015894:Genome, Human; D006239:Haplotypes; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D011401:Promoter Regions, Genetic; D054340:Receptors, KIR / Q000235:genetics*; D054341:Receptors, KIR3DL1 / Q000235:genetics*; D011995:Recombination, Genetic
chemical_list: D021901:DNA, Intergenic; C473953:KIR2DS4 protein, human; C531595:KIR2DS5 protein, human; C515083:KIR3DL1 protein, human; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1