KIR genotype and haplotype frequencies in the multi-ethnic population of Malaysia

Kevin-Tey, Wen Fei; Wang, Wen; Bee, Ping Chong; Eng, Hooi Sian; Ho, Kim Wah; Tan, Sen Mui; Anuar, Nur Adila; Pung, Yuh Fen; Zain, Sharifuddin M.

doi:10.1016/j.humimm.2022.11.006

Cited by 3 publications

(1 citation statement)

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“…The absence of correct phasing information complicates the investigation of structural variations among KIR genes, including crossover events, gene deletions, and gene duplications. These challenges are compounded by the ongoing expansion and evolution of KIR genes in all populations (Alicata et al 2020;NurWaliyuddin et al 2022;Kevin-Tey et al 2023).…”

Section: Introductionmentioning

confidence: 99%

Genetic Diversity and Structural Complexity of the Killer-Cell Immunoglobulin-Like Receptor Gene Complex: A Comprehensive Analysis Using Human Pangenome Assemblies

Hung,

Liu,

Lai

et al. 2023

Preprint

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The killer-cell immunoglobulin-like receptor (KIR) gene complex, a highly polymorphic region of the human genome that encodes proteins involved in immune responses, poses strong challenges in genotyping due to its remarkable genetic diversity and structural intricacy. Accurate analysis of KIR alleles, including their structural variations, is crucial for understanding their roles in various immune responses. Leveraging the high-quality genome assemblies from the Human Pangenome Reference Consortium (HPRC), we present a novel bioinformatic tool, the Structural KIR annoTator (SKIRT), to investigate gene diversity and facilitate precise KIR allele analysis. We applied SKIRT on 47 HPRC-phased assemblies and identified a recurrent novelKIR2DS4/3DL1fusion gene in the paternal haplotype of HG02630 and maternal haplotype of NA19240. Additionally, SKIRT accurately identifies eight structural variants and 17 novel nonsynonymous alleles, all of which were independently validated using short-read data or quantitative polymerase chain reaction. Our study has discovered a total of 570 novel alleles, among which eight haplotypes harbor at least one KIR gene duplication, six haplotypes have lost at least one framework gene, and 75 out of 94 haplotypes (79.8%) carry at least five novel alleles, thus confirming KIR genetic diversity. These findings are pivotal in providing insights into KIR gene diversity and serve as a solid foundation for understanding the functional consequences of KIR structural variations. High-resolution genome assemblies offer unprecedented opportunities to explore polymorphic regions that are challenging to investigate using short-read sequencing methods. The SKIRT pipeline emerges as a highly efficient tool, enabling the comprehensive detection of the complete spectrum of KIR alleles within human genome assemblies.

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Section: Introductionmentioning

confidence: 99%

Genetic Diversity and Structural Complexity of the Killer-Cell Immunoglobulin-Like Receptor Gene Complex: A Comprehensive Analysis Using Human Pangenome Assemblies

Hung,

Liu,

Lai

et al. 2023

Preprint

View full text Add to dashboard Cite

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Genetic complexity of killer-cell immunoglobulin-like receptor genes in human pangenome assemblies

Hung,

Liu,

Lai

et al. 2024

Genome Res.

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The killer-cell immunoglobulin-like receptor (KIR) gene complex, a highly polymorphic region of the human genome that encodes proteins involved in immune responses, poses strong challenges in genotyping owing to its remarkable genetic diversity and structural intricacy. Accurate analysis of KIR alleles, including their structural variations, is crucial for understanding their roles in various immune responses. Leveraging the high-quality genome assemblies from the Human Pangenome Reference Consortium (HPRC), we present a novel bioinformatic tool, the structural KIR annoTator (SKIRT), to investigate gene diversity and facilitate precise KIR allele analysis. In 47 HPRC-phased assemblies, SKIRT identifies a recurrent novelKIR2DS4/3DL1fusion gene in the paternal haplotype of HG02630 and maternal haplotype of NA19240. Additionally, SKIRT accurately identifies eight structural variants and 15 novel nonsynonymous alleles, all of which are independently validated using short-read data or quantitative polymerase chain reaction. Our study has discovered a total of 570 novel alleles, among which eight haplotypes harbor at least one KIR gene duplication, six haplotypes have lost at least one framework gene, and 75 out of 94 haplotypes (79.8%) carry at least five novel alleles, thus confirming KIR genetic diversity. These findings are pivotal in providing insights into KIR gene diversity and serve as a solid foundation for understanding the functional consequences of KIR structural variations. High-resolution genome assemblies offer unprecedented opportunities to explore polymorphic regions that are challenging to investigate using short-read sequencing methods. The SKIRT pipeline emerges as a highly efficient tool, enabling the comprehensive detection of the complete spectrum of KIR alleles within human genome assemblies.

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Unveiling the Significance of HLA and KIR Diversity in Underrepresented Populations

Santiago-Lamelas,

Castro-Santos,

Carracedo

et al. 2024

Biomedicines

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Human leukocyte antigen (HLA) molecules and their relationships with natural killer (NK) cells, specifically through their interaction with killer-cell immunoglobulin-like receptors (KIRs), exhibit robust associations with the outcomes of diverse diseases. Moreover, genetic variations in HLA and KIR immune system genes offer limitless depths of complexity. In recent years, a surge of high-powered genome-wide association studies (GWASs) utilizing single nucleotide polymorphism (SNP) arrays has occurred, significantly advancing our understanding of disease pathogenesis. Additionally, advances in HLA reference panels have enabled higher resolution and more reliable imputation, allowing for finer-grained evaluation of the association between sequence variations and disease risk. However, it is essential to note that the majority of these GWASs have focused primarily on populations of Caucasian and Asian origins, neglecting underrepresented populations in Latin America and Africa. This omission not only leads to disparities in health care access but also restricts our knowledge of novel genetic variants involved in disease pathogenesis within these overlooked populations. Since the KIR and HLA haplotypes prevalent in each population are clearly modelled by the specific environment, the aim of this review is to encourage studies investigating HLA/KIR involvement in infection and autoimmune diseases, reproduction, and transplantation in underrepresented populations.

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KIR genotype and haplotype frequencies in the multi-ethnic population of Malaysia

Cited by 3 publications

References 69 publications

Genetic Diversity and Structural Complexity of the Killer-Cell Immunoglobulin-Like Receptor Gene Complex: A Comprehensive Analysis Using Human Pangenome Assemblies

Genetic Diversity and Structural Complexity of the Killer-Cell Immunoglobulin-Like Receptor Gene Complex: A Comprehensive Analysis Using Human Pangenome Assemblies

Genetic complexity of killer-cell immunoglobulin-like receptor genes in human pangenome assemblies

Unveiling the Significance of HLA and KIR Diversity in Underrepresented Populations

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