Distribution of KIR genes in the Czech population

Killer cells immunoglobulin-like receptors (KIRs) are a family of inhibitory and activating receptors expressed mainly by natural killer (NK) cells and few subsets of T lymphocytes. KIRs regulate NK cells' activity through interactions with specific HLA class I molecules and other yet unknown ligands presented on target cells. At present, 17 KIR genes and pseudogenes have been identified. As the number of KIR genes in different haplotypes varies, a wide range of genotypes in different ethnic populations may be observed. In our study, 125 healthy non-related Czech individuals were KIR typed both by sequence-specific primers and by sequence-specific oligonucleotide KIR genotyping methods. Thirty-eight different genotypes were observed in the Czech population and all 16 KIR genes known to date were found. Framework genes KIR 3DL3, KIR 2DL4, KIR 3DL2 and the pseudogene KIR 3DP1 were present in all individuals. The most frequent non-framework KIR genes detected in the Czech population were: KIR 2DL1 (95%), KIR 3DL1 (94%), KIR 2DS4 (92%) and the pseudogene 2DP1 (94%). Human leucocyte antigen (HLA)-C typing demonstrated prevalence of the C1/C2 heterozygosity (43%) and C1 homozygosity (41%) over the C2 heterozygosity. One hundred and twenty individuals from our panel carried at least one inhibitory KIR for the corresponding HLA-C group found in the genotype. Gene frequencies and found genotypes demonstrated similarity of the Czech population's KIR repertoire with the KIR repertoires of other Caucasian populations studied before.     

Distribution of KIR genes in the Iranian population

Killer-cell immunoglobulin-like receptors (KIR) are a family of inhibitory and activating receptors that are expressed mainly by natural killer cells. The KIR gene family is highly polymorphic, and its genomic diversity is achieved through differences in gene content as well as allelic polymorphism. The number of KIR loci has been reported to be various among individuals and therefore resulting in different KIR haplotypes. This study represents the first report on the distribution of 17 presently defined KIR genes and pseudogenes in the Iranian population. In our study, 200 unrelated healthy individuals were KIR typed by a novel polymerase chain reaction–sequence-specific primers genotyping assay, and Iranian KIR genes distribution was compared with other ethnic groups. Over all, twenty-six different genotype profiles were found in our population and all KIR genes were observed. The most frequent non-framework KIR genes detected in our population were KIR2DL1 (96.5%), KIR3DL1 (91.5%), KIR2DS4 (91.5%) and the pseudogene KIR2DP1 (96.5%). The most commonly observed KIR genotype in Iranian population with a frequency of 27.5% consisted of KIR2DL1 , KIR2DL3 , KIR2DL4 , KIR3DL1 , KIR3DL2 , KIR3DL3 and KIR2DS4 genes and the pseudogenes KIR2DP1 and KIR3DP1 , which was compatible with a homozygote group-A haplotype. In addition, we found a new genotype ( KIR2DL2 , KIR2DL4 , KIR2DL5 , KIR3DL2 , KIR3DL3 , KIR2DS2 , KIR2DS3 , KIR2DS5 , KIR3DS1 and KIR3DP1 ) in our samples. The results show that distribution of KIR genes in the Iranian population has common general features with the Caucasian populations studied before but still with unique, decreased or increased frequencies of several loci.     

Distribution of KIR genes in the Croatian population

The KIR locus with genes involved in immune processes is among the most polymorphic and structurally diverse human loci. KIR genes encode activating and inhibitory receptors that differ in specificity for HLA class I ligands and signaling potential. These receptors are expressed principally by natural killer (NK) cells and subpopulations of T cells. This study represents the first report of the distribution of KIR genes, KIR genotypes and KIR/HLA pairs in 121 unrelated healthy Croatian individuals. Twenty-three different genotypes were observed in the Croatian population and all 16 KIR genes known to date were found. The most frequent KIR genotype was the AA genotype. All individuals had at least one inhibitory KIR/HLA pair with the majority of individuals with three inhibitory KIR/HLA pairs. The most frequent KIR/HLA pair was the KIR2DL3/C1 group. Our results demonstrated the similarity of the Croatian population’s KIR repertoire with other Caucasian populations reported so far.     

Allelic diversity of KIR3DL1/3DS1 in a southern Chinese population

The inhibitory KIR3DL1 and the activating KIR3DS1 segregate as alleles of the same locus. KIR3DL1 is highly diversified at the allele level and KIR3DL1 alleles exhibit varied levels of expression and ligand binding affinity resulting in varied degrees of NK cell inhibition. Previous studies have shown that the KIR3DL1/3DS1 polymorphism associated with viral infection, cancer and transplantation. However, little is known about the population distribution of KIR3DL1/3DS1 alleles in Chinese. The present study examined allelic diversity of KIR3DL1/3DS1 in a southern Chinese population (N = 306) using PCR-SSP and sequencing based typing. The presence of KIR3DL1 and KIR3DS1 were detected in 97.1% and 34.0% of the tested individuals respectively. A total of 10 KIR3DL1 alleles (including 2 novel ones) and 6 KIR3DS1 alleles (including 5 novel ones) were identified. Common KIR3DL1 alleles (>10%) were KIR3DL1*01502 (74.8%), KIR3DL1*00501 (23.9%) and KIR3DL1*00701 (15.7%). KIR3DS1*01301 was the predominant KIR3DS1 allele with other KIR3DS1 alleles only sporadically observed. The knowledge of the allelic polymorphism of KIR3DL1/3DS1 may help to better understand the role played by KIR3DL1/3DS1 in associated diseases and clinical transplantation in southern Chinese.     

Human KIR repertoires: shaped by genetic diversity and evolution

Killer cell immunoglobulin-like receptors (KIRs) on natural killer (NK) cells are crucially involved in the control of cancer development and virus infection by probing cells for proper expression of HLA class I. The clonally distributed expression of KIRs leads to great combinatorial diversity that develops in the presence of the evolutionary older CD94/NKG2A receptor to create highly stochastic but tolerant repertoires of NK cells. These repertoires are present at birth and are subsequently shaped by an individuals’ immunological history toward recognition of self. The single most important factor that shapes functional NK cell repertoires is the genetic diversity of KIR, which is characterized by the presence of group A and B haplotypes with complementary gene content that are present in all human populations. Group A haplotypes constitute the minimal genetic entity that provides high affinity recognition of all major human leukocyte antigen class I-encoded ligands, whereas group B haplotypes contribute to the diversification of NK cell repertoires by providing sets of stimulatory KIR genes that modify NK cell responses. We suggest a cooperative model for the balancing selection of A and B haplotypes, which is driven by the need to provide a suitable corridor of repertoire complexity in which A/A individuals with only 16 different KIR combinations coexist with A/B and B/B donors expressing up to 2048 different clone types.     

Investigation of killer cell immunoglobulin-like receptor KIR2DL4 diversity by sequence-based typing in Chinese population

Human killer cell immunoglobulin-like receptors (KIRs) play an important role in controlling natural killer (NK) cell function. Here, polymerase chain reaction sequence-based typing (PCR-SBT) procedures identifying alleles of the KIR2DL4 gene have been established. The method was designed around the specific amplification of exon 3 to exon 5 and exon 7 to exon 9 of the KIR2DL4 gene and produce discrimination of KIR2DL4 alleles. Genomic DNAs from 83 healthy unrelated Chinese Han individuals were typed for KIR2DL4 alleles by this method. Each sample was assigned to the putative KIR2DL4 allele combination according to the nucleotide polymorphism profiles of all KIR2DL4 alleles. Twenty-one different genotypes and seven KIR2DL4 alleles were observed in the population, with KIR2DL4*00102 having the highest frequency, 0.5. Five individuals bear a recombinant allele KIR3DP*004 that associated with three putative KIR2DL4 alleles. Our data demonstrated that the established PCR-SBT method for KIR2DL4 allele typing was reliable, and Chinese Han population is distinct in KIR2DL4 allele frequencies in comparison to some other populations.     

Investigation of killer cell immunoglobulin-like receptors gene KIR3DL2 diversity and confirmation of KIR3DL2*015 in a Chinese population

Human killer cell immunoglobulin-like receptors (KIRs) are a subfamily of the immunoglobulin superfamily. Here, we established polymerase chain reaction-sequence-based typing (PCR-SBT) procedure to identify alleles of KIR3DL2 gene. The method was designed around the specific amplification of exon 3 to exon 4 and exon 8 to exon 9 of the KIR3DL2 gene. Genomic DNA from 104 healthy, unrelated Chinese Han individuals was typed for KIR3DL2 alleles. Each sample was assigned to the putative allele combination according to the sequences of all KIR3DL2 alleles. We observed 18 different genotypes and eight KIR3DL2 alleles in the population, with KIR3DL2*002 having the highest frequency of 0.558, and confirmed the new KIR3DL2*015 allele. Our data showed that the established PCR-SBT methods for KIR3DL2 allele typing were reliable, and Chinese Han population is distinct in KIR3DL2 allele frequencies.     

The extensive polymorphism of KIR genes

The functions of human natural killer (NK) cells are controlled by diverse families of antigen receptors. Prominent among these are the killer cell immunoglobulin‐like receptors (KIR), a family of genes clustered in one of the most variable regions of the human genome. Within this review we discuss the vast polymorphism of the KIR gene complex which rivals that of the human leucocyte antigen (HLA) complex. There are several aspects to this polymorphism. Initially there is presence/absence of individual KIR genes, with four of these genes, termed framework genes, being present in all individuals tested to date, except on those very occasional instances when the gene has been deleted. Within each gene, alleles are present at different frequencies. We provide details of a new website that enables convenient searching for data on KIR gene, allele and genotype frequencies in different populations and show how these frequencies vary in different worldwide populations and the high probability of individuals differing in their KIR repertoire when both gene and allele polymorphism is considered. The KIR genes present in an individual may be classified into A and/or B haplotypes, which respectively have a more inhibitory role or a more activating role on the function of the NK cell. Family studies have been used to ascertain the make‐up of these haplotypes, inclusion of allele typing enabling determination of whether one or two copies of a particular gene is present. In addition to genetic diversification the KIR gene complex shows differences at the functional level with different alleles having different protein expression levels and different avidity with their HLA ligand.     

中国北方汉族人群FUT5基因编码区序列特征

目的 揭示中国北方汉族人群岩藻糖基转移酶基因V(fucosyltransferase 5 gene,FUT5)编码区序列特征.方法 对160名健康中国北方汉族人群血液样品进行研究,DNA测序分析其中30例FUT5基因编码区序列;突变基因亚克隆后测序鉴定其单倍型;聚合酶链反应-限制性片段长度法分析130名C560T(rs778970)和C484A位点的遗传多态性.结果 DNA测序共鉴定出7个单核苷酸多态性(single nucleotide polymorphism,SNPs)及2个新突变点C484A(Leu162Met)和T684C;9种碱基替换共鉴定出7种单倍型;160名样本的rs778970位点遗传多态性分析结果显示等位基因频率C为0.3031,T为0.6969;而C484A未发现其具有多态性.结论 中国北方汉族人群FUT5基因编码区序列呈现出高度的变异性;rs778970位点等位基因分布具有较好多态性.     

中国汉族群体KIR基因多样性的研究进展

人杀伤细胞免疫球蛋白样受体分子(killer cell immnoglobulin-like receptor,KIR)主要表达于NK细胞和部分T细胞表面.KIR分子的配体是表达于靶细胞上的某些HLA Ⅰ类分子,两者可形成配体/受体复合物.HLA-Ⅰ/KIR分子相互识别,通过传导活化或抑制信号调节NK细胞的杀伤功能,这是NK细胞参与适应性免疫应答的重要机制之一.在免疫应答过程中,HLA-Ⅰ/KIR分子的相互作用,可保护机体抵御各种各样病原体的侵袭.本文就我国汉族群体KIR基因多样性的研究进展作一综述.     

Association between KIR genes and dust mite sensitization in a Brazilian population

Background

Killer cell immunoglobulin-like receptors (KIRs), found on the surface of natural killer (NK) cells, play a key role in controlling the innate response. Such response depends on a series of cellular interactions between these receptors and HLA activating/inhibiting ligands. Atopic diseases have been associated with genes that regulate cytokine production and HLA genes, which may either protect or predispose to hypersensitivity.

KIR3DL2: diversity in a hematopoietic stem cell transplant population

Exons 2 through 9 of KIR3DL2 were amplified from genomic DNA from 79 bone marrow transplantation patients and their unrelated donors. Sequencing of heterozygotes and isolated alleles identified 9 of the 17 known alleles. The alleles provide confirmation of previously submitted sequences and are carried by transformed B-cell lines that can be used as references for assay development. Alleles 3DL2*001, *002, *007 and *009 accounted for 111 of the total 144 possible alleles and were the only ones found in a homozygous state. New alleles (3DL2*017, *018, *019, *020, and *021) were found in seven transplant samples and one workshop cell. This study describes the development of reagents and protocols for sequencing of KIR3DL2 alleles from genomic DNA.     

Genetic profile of KIR and HLA in southern Chinese Han population

KIR and their HLA ligands are encoded by two of the most diverse gene families in the human genome. The function of KIR on the NK cell is highly dependent on the normal expression of class I HLA on the target cell. Previous population studies in southern Chinese have been focused on the KIR framework genes and genotypes but little is known about the compound profiles of KIR/HLA. The present study examined 503 unrelated individuals from southern Chinese Han population for the polymorphism of KIR and class I HLA genes. All 16 KIR genes were detected in the study population and the four framework genes KIR3DL2, 3DL3, 3DP1, and 2DL4 were present in all individuals. Thirty unique KIR gene profiles were found reflecting a rather limited number of KIR haplotypes in this population. KIRAA1 was the most common profile observed in 54.7% of the samples. Among the AA1 individuals, 15.6% were homozygous for the deleted KIR2DS4. Haplotype A (74.8%) was more common than haplotype B (25.2%). HLA-C1 was a much more common ligand for 2D KIRs than C2. Bw4-80I, Bw4-80T, and the Bw4-bearing HLA-A alleles were detected at similar frequencies. The matched KIR+HLA pairs 2DL2/3+C1 (98.1%), 3DL1+Bw4 (73.3%), 3DL2+A3/11 (60.0%) were the most common ones whereas 3DS1+Bw4-80I was the least common (9.4%). A total of 193 unique compound profiles of KIR–HLA were identified in 480 informative individuals, 130 of the profiles being detected only once. The study provided a comprehensive analysis of the KIR/HLA profiles in southern Chinese in regards of the presence/absence of KIR genes, HLA ligands, matched KIR+HLA pairs, and KIR/HLA compound profiles. The results could help to better understand the role played by KIR/HLA interaction in associated diseases and clinical transplantation in southern Chinese.     

Diversity of killer cell immunoglobulin like receptor genes in the Mongolian population

Killer cell immunoglobulin like receptor (KIR) is highly polymorphic in genotype, haplotype and allele levels. This study was done to investigate KIR genes frequencies, genotypes and inheritance in Mongolian. Gene-specific PCR amplification was used to identify the presence or absence of 16 KIR loci.KIR genotypes were obtained by a KIR genotypes website. The KIR genes frequencies of Mongolian were compared to 24 different populations around the world. The distribution of haplotype B in Mongolian was higher than that in Mongoloid and less than that in Caucasian. Thirty discovered genotypes and five novel genotypes were identified from 1 to 34 individuals. 37.8% of Mongolian carried KIR haplotype AA.Mongolian was exhibited between North Mongoloid and Caucasus by principal component and genetic tree analysis.     

Investigation of killer cell immunoglobulin-like receptor gene diversity in KIR3DL1 and KIR3DS1 in a transplant population

Several overlapping amplicons were used to obtain the sequence of genomic DNA covering most of the coding regions of KIR3DL1 and KIR3DS1 from a family and 77 bone marrow transplant patients and their unrelated donors. Alleles 3DL1*00101 and *002 were most frequently observed in addition to 12 other known 3DL1 alleles. A single 3DS1 allele, 3DS1*01301, was identified in the 31 of 32 individuals carrying this gene. Two new alleles, 3DL1*01702 and 3DS1*058, were characterized. Three samples appeared to carry the duplicated killer cell immunoglobulin-like receptor (KIR) haplotype observed in other studies based on the presence of 3DS1 and two 3DL1 alleles. Additionally, one sample appeared to carry a novel KIR haplotype containing one 3DL1 and two 3DS1 alleles.     

The geographical vector in distribution of genetic diversity for Clonorchis sinensis

Parasitology Research - Clonorchis sinensis, the causative agent of clonorchiasis, is one of the most important parasites that inhabit countries of East and Southeast Asia. In this study, we...     

Association of KIR2DS4 and its variant KIR1D with syphilis in a Chinese Han population

Syphilis is a sexually transmitted infection caused by the Treponema pallidum subspecies pallidum spirochaete bacterium. The killer immunoglobulin-like receptor (KIR) gene family encodes cell surface receptors that are found on natural killer (NK) cells and certain T-cell subsets. NK cells are fast-acting effector lymphocytes of innate immunity that respond to infection. The activity of NK cells depends on the dynamic balance of activating and inhibitory signals that are transmitted through respective receptors including KIRs. KIR2DS4 is the only activating KIR gene in KIR haplotype A. KIR1D is a partial deletion KIR2DS4 variant encoding protein devoid of transmembrane region. Up to now, there is no knowledge of association of KIR2DS4 and its variant KIR1D with syphilis in a population that belongs to KIR gene haplotype A. Polymerase chain reaction with sequence-specific primers (PCR-SSP) method was used to genotype KIR genes in 190 patients with syphilis and 192 healthy controls. The gene frequencies of KIR2DS4 and KIR1D were analysed for the association with syphilis in patients and healthy controls who belong to KIR gene haplotype A. The gene frequency of KIR1D/KIR1D in patients with syphilis classified as haplotype A was 16.85% and was significantly higher than that in the control group (6.59%) (P = 0.032). However, there was no significant difference for the gene frequencies of KIR2DS4/KIR2DS4 and KIR2DS4/KIR1D between the two groups (P > 0.05). KIR1D/KIR1D was found in association with susceptibility to syphilis in the Chinese Han population that belongs to KIR gene haplotype A.     

内蒙古蒙古族人群杀伤细胞免疫球蛋白样受体基因簇多态性研究

目的 研究中国蒙古族人群杀伤细胞免疫球蛋白样受体(killer cell immunoglobulin-like receptors,KIR)基因的携带频率、KIR基因型及其遗传规律.方法 采集90名内蒙古农牧区蒙古族个体的血样,应用序列特异性引物聚合酶链反应(polymerase chain reaction-sequence specific primer,PCR-SSP)方法分别扩增KIR基因簇16个基因,依据实验结果计算各基因的携带频率并查询样本的基因型,和已报道的24个其他人群的相关数据进行主成分分析、计算Nei氏遗传距离并绘制遗传树.结果 (1)蒙古族人群KIR 2DL2、2DS2携带率高于蒙古利亚人,低于高加索人.(2)蒙古族KIR基因单倍型AA为37.78%,高于高加索人,低于蒙古利亚人.(3)系统进化树显示蒙古利亚人和高加索人分别聚类,蒙古族人群则介于两者之间.结论 蒙古族其成因似与受到高加索人和蒙古利亚人的双重影响有关,表现为介于高加索人和蒙古利亚人之间的中间形式.

Abstract：

Objective To investigate the killer cell immunoglobulin-like receptor (KIR) gene frequencies and genotypes distributions in the Inner Mongolian population. Methods Ninety genomic DNA samples were extracted from blood samples of randomly chosen Mongolian individuals. Gene-specific PCR amplification was used to identify genes present or absent for 16 KIR loci. KIR genotype distributions were obtained and compared to that of 24 populations published in literatures using principal component analysis by SAS8.0 software. Genetic tree was constructed by the calculate Nei's genetic distance. Results (1) The frequency of KIR 2DL2,2DS2 in Mongolian individual is higher than that in north Mongoloid and less than that in Caucasian. (2) Haplotype AA was identified in 37.78% of individuals, which is higher than that in north Mongoloid and lower than that in Caucasian. (3) Mongolian was considered between north Mongoloid and Caucasian by principal component and genetic tree analysis. Conclusion Mongolian might be affected by the north Mongoloid and Caucasian, and showed intermediate between the two populations.     

Study of genetic diversity of KIR and TLR in the Rabhas,an endogamous primitive tribe of India

The Rabha tribe is a little known small endogamous population belonging to Indo-mongoloid group of north-eastern India. We have analyzed 16 KIR and 5 TLR gene polymorphisms in the Rabha population of northern West Bengal, India for the first time. The observed frequencies of the KIR genes (except framework and pseudogene loci) ranged between 0.26 (KIR2DS3) and 0.96 (KIR2DL1). Comparisons based on KIR polymorphism have revealed that although the Rabhas are of Indian origin the presence of mongoloid component in their gene pool cannot be denied. The frequencies of the 5 TLR genes ranged between 0.90 (TLR4) and 0.46 (TLR5). TLR variations found in the Rabhas may play a synergistic role in fighting against the bacterial invasions. Our results may contribute to the understanding of (1) genetic background and extent of genetic admixture in the Rabhas, (2) population migration events and (3) KIR-disease-TLR interactions.