Haplotype-Based Analysis of KIR-Gene Profiles in a South European Population—Distribution of Standard and Variant Haplotypes, and Identification of Novel Recombinant Structures
Inhibitory Killer-cell Immunoglobulin-like Receptors (KIR) specific for HLA class I molecules enable human natural killer cells to monitor altered antigen presentation in pathogen-infected and tumor cells. KIR genes display extensive copy-number variation and allelic polymorphism. They organize in a...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-03-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00440/full |
| _version_ | 1818863805886627840 |
|---|---|
| author | Elisa Cisneros Manuela Moraru Natalia Gómez-Lozano Aura Muntasell Miguel López-Botet Miguel López-Botet Carlos Vilches |
| author_facet | Elisa Cisneros Manuela Moraru Natalia Gómez-Lozano Aura Muntasell Miguel López-Botet Miguel López-Botet Carlos Vilches |
| author_sort | Elisa Cisneros |
| collection | DOAJ |
| description | Inhibitory Killer-cell Immunoglobulin-like Receptors (KIR) specific for HLA class I molecules enable human natural killer cells to monitor altered antigen presentation in pathogen-infected and tumor cells. KIR genes display extensive copy-number variation and allelic polymorphism. They organize in a series of variable arrangements, designated KIR haplotypes, which derive from duplications of ancestral genes and sequence diversification through point mutation and unequal crossing-over events. Genomic studies have established the organization of multiple KIR haplotypes—many of them are fixed in most human populations, whereas variants of those have less certain distributions. Whilst KIR-gene diversity of many populations and ethnicities has been explored superficially (frequencies of individual genes and presence/absence profiles), less abundant are in-depth analyses of how such diversity emerges from KIR-haplotype structures. We characterize here the genetic diversity of KIR in a sample of 414 Spanish individuals. Using a parsimonious approach, we manage to explain all 38 observed KIR-gene profiles by homo- or heterozygous combinations of six fixed centromeric and telomeric motifs; of six variant gene arrangements characterized previously by us and others; and of two novel haplotypes never detected before in Caucasoids. Associated to the latter haplotypes, we also identified the novel transcribed KIR2DL5B*0020202 allele, and a chimeric KIR2DS2/KIR2DL3 gene (designated KIR2DL3*033) that challenges current criteria for classification and nomenclature of KIR genes and haplotypes. |
| first_indexed | 2024-12-19T10:21:36Z |
| format | Article |
| id | doaj.art-e06a7268799144a7917e31e06f5d233c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-19T10:21:36Z |
| publishDate | 2020-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-e06a7268799144a7917e31e06f5d233c2022-12-21T20:26:03ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-03-011110.3389/fimmu.2020.00440528207Haplotype-Based Analysis of KIR-Gene Profiles in a South European Population—Distribution of Standard and Variant Haplotypes, and Identification of Novel Recombinant StructuresElisa Cisneros0Manuela Moraru1Natalia Gómez-Lozano2Aura Muntasell3Miguel López-Botet4Miguel López-Botet5Carlos Vilches6Immunogenetics and Histocompatibility, Instituto de Investigación Sanitaria Puerta de Hierro Segovia de Arana, Madrid, SpainImmunogenetics and Histocompatibility, Instituto de Investigación Sanitaria Puerta de Hierro Segovia de Arana, Madrid, SpainImmunogenetics and Histocompatibility, Instituto de Investigación Sanitaria Puerta de Hierro Segovia de Arana, Madrid, SpainHospital del Mar Medical Research Institute (IMIM), Barcelona, SpainHospital del Mar Medical Research Institute (IMIM), Barcelona, SpainDepartment of Experimental and Health Sciences, University Pompeu Fabra, Barcelona, SpainImmunogenetics and Histocompatibility, Instituto de Investigación Sanitaria Puerta de Hierro Segovia de Arana, Madrid, SpainInhibitory Killer-cell Immunoglobulin-like Receptors (KIR) specific for HLA class I molecules enable human natural killer cells to monitor altered antigen presentation in pathogen-infected and tumor cells. KIR genes display extensive copy-number variation and allelic polymorphism. They organize in a series of variable arrangements, designated KIR haplotypes, which derive from duplications of ancestral genes and sequence diversification through point mutation and unequal crossing-over events. Genomic studies have established the organization of multiple KIR haplotypes—many of them are fixed in most human populations, whereas variants of those have less certain distributions. Whilst KIR-gene diversity of many populations and ethnicities has been explored superficially (frequencies of individual genes and presence/absence profiles), less abundant are in-depth analyses of how such diversity emerges from KIR-haplotype structures. We characterize here the genetic diversity of KIR in a sample of 414 Spanish individuals. Using a parsimonious approach, we manage to explain all 38 observed KIR-gene profiles by homo- or heterozygous combinations of six fixed centromeric and telomeric motifs; of six variant gene arrangements characterized previously by us and others; and of two novel haplotypes never detected before in Caucasoids. Associated to the latter haplotypes, we also identified the novel transcribed KIR2DL5B*0020202 allele, and a chimeric KIR2DS2/KIR2DL3 gene (designated KIR2DL3*033) that challenges current criteria for classification and nomenclature of KIR genes and haplotypes.https://www.frontiersin.org/article/10.3389/fimmu.2020.00440/fullcopy-number variationgeneshaplotypesKIRNK cellspolymorphism |
| spellingShingle | Elisa Cisneros Manuela Moraru Natalia Gómez-Lozano Aura Muntasell Miguel López-Botet Miguel López-Botet Carlos Vilches Haplotype-Based Analysis of KIR-Gene Profiles in a South European Population—Distribution of Standard and Variant Haplotypes, and Identification of Novel Recombinant Structures Frontiers in Immunology copy-number variation genes haplotypes KIR NK cells polymorphism |
| title | Haplotype-Based Analysis of KIR-Gene Profiles in a South European Population—Distribution of Standard and Variant Haplotypes, and Identification of Novel Recombinant Structures |
| title_full | Haplotype-Based Analysis of KIR-Gene Profiles in a South European Population—Distribution of Standard and Variant Haplotypes, and Identification of Novel Recombinant Structures |
| title_fullStr | Haplotype-Based Analysis of KIR-Gene Profiles in a South European Population—Distribution of Standard and Variant Haplotypes, and Identification of Novel Recombinant Structures |
| title_full_unstemmed | Haplotype-Based Analysis of KIR-Gene Profiles in a South European Population—Distribution of Standard and Variant Haplotypes, and Identification of Novel Recombinant Structures |
| title_short | Haplotype-Based Analysis of KIR-Gene Profiles in a South European Population—Distribution of Standard and Variant Haplotypes, and Identification of Novel Recombinant Structures |
| title_sort | haplotype based analysis of kir gene profiles in a south european population distribution of standard and variant haplotypes and identification of novel recombinant structures |
| topic | copy-number variation genes haplotypes KIR NK cells polymorphism |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.00440/full |
| work_keys_str_mv | AT elisacisneros haplotypebasedanalysisofkirgeneprofilesinasoutheuropeanpopulationdistributionofstandardandvarianthaplotypesandidentificationofnovelrecombinantstructures AT manuelamoraru haplotypebasedanalysisofkirgeneprofilesinasoutheuropeanpopulationdistributionofstandardandvarianthaplotypesandidentificationofnovelrecombinantstructures AT nataliagomezlozano haplotypebasedanalysisofkirgeneprofilesinasoutheuropeanpopulationdistributionofstandardandvarianthaplotypesandidentificationofnovelrecombinantstructures AT auramuntasell haplotypebasedanalysisofkirgeneprofilesinasoutheuropeanpopulationdistributionofstandardandvarianthaplotypesandidentificationofnovelrecombinantstructures AT miguellopezbotet haplotypebasedanalysisofkirgeneprofilesinasoutheuropeanpopulationdistributionofstandardandvarianthaplotypesandidentificationofnovelrecombinantstructures AT miguellopezbotet haplotypebasedanalysisofkirgeneprofilesinasoutheuropeanpopulationdistributionofstandardandvarianthaplotypesandidentificationofnovelrecombinantstructures AT carlosvilches haplotypebasedanalysisofkirgeneprofilesinasoutheuropeanpopulationdistributionofstandardandvarianthaplotypesandidentificationofnovelrecombinantstructures |