The distribution of genetic diversity of KIR genes in the Chinese Mongolian population

Killer cell immunoglobulin-like receptors (KIRs) are expressed on natural killer cells and as such regulate their response against infection and malignancy. KIR genes are variable in gene content and type, which results in different KIR haplotypes, and can be used to discriminate individuals and populations from different regions or ethnic groups. In the present study, we represent the first report on the KIR gene frequency and content diversities of 14 KIR genes (KIR2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 3DL1, 3DL2, 3DL3, 3DS1) and 2 pseudogenes (KIR3DP1 and 2DP1) in the Chinese Mongolian population. The 16 detected KIR genes were all observed. All the individuals were typed positive for the four framework genes KIR3DL3, 3DL2, 2DL4 and the pseudogene KIR3DP1, as well as for the pseudogene KIR2DP1. The observed carrier gene frequencies (OF) of the other KIR genes ranged from 16% at the KIR2DL2 locus to 93% at the KIR3DL1 locus. Over all, 48 different gene profiles were found in the study population and the most commonly observed KIR gene profile with a frequency of 14% consisted of KIR2DL4, 3DL2, 3DL3, 2DP1, 3DP1, 2DL1, 2DL3 and 3DL1 which belongs to the AA genotype. Principal component analysis (PCA) and the dendrogram illustrated the genetic distances between our study population and previously published populations from other ethnic groups or regions. The results of the present study show that the KIR gene family is highly polymorphic and can be a valuable tool for enriching the Chinese ethnical gene information resources, for anthropological studies, as well as for KIR gene related disease research.     

Distribution of killer-cell immunoglobulin-like receptor (KIR) in Comoros and Southeast France

Killer-cell immunoglobulin-like receptors (KIRs) expressed by natural killer cells are cell surface molecules able to recognize groups of HLA class I alleles. The number and distribution of KIR genes vary among individuals and populations. The aim of this study is to analyse the KIR gene content in a Comorian population in order to investigate genetic relationships with other populations and to reconstruct past migration events. The Comorian population consisted of 54 unrelated immigrants living in France and a control population consisted of 38 individuals from Southeast France. We investigated the presence or absence of 15 KIR genes, two pseudogenes expressed and non-expressed forms of KIR2DL5 and the two major subtype full-length and deleted forms of KIR2DS4. All individuals were typed positive for the framework genes, i.e. KIR2DL4, KIR3DL2 and KIR3DL3, and the two pseudogenes KIR3DP1 and KIR2DP1. The frequencies of full-length KIR2DS4 (*00101/00102/002) were lower in the French population (F = 29%) than in the Comorian population (F = 72%) (P(c) < 0.05). No significant differences were found for other KIR genes. A total of 11 genotypes were identified in the Southeast French population and 22 genotypes in the Comorian population. The most common genotype (2DL1, 2DL3, 2DL4, 3DL1, 3DL2, 3DL3 and 2DS4) accounted for 41% in the Comorian population and 34% in the Southeast French population. Principal component analysis using KIR gene data from 20 populations was performed to determine genetic differences and relations between populations. The Comorian population exhibited closest kinship with Africans and Asians. As KIR gene content is heterogeneous among ethnic groups, it can probably be used to assess the genetic relationships among populations from different geographic areas.     

Diversity of killer cell immunoglobulin-like receptor genes in the Bai ethnic minority of Yunnan, China

Killer cell immunoglobulin-like receptors (KIRs), expressed in both natural killer (NK) cells and a subset of T cells, represent a family of both inhibitory and activating receptors that can regulate NK and T cells upon interacting with human leucocyte antigen (HLA) class I molecules on target cells. The number and distribution of KIR genes vary between individuals and populations from different geographical regions and ethnic origins. In this study, we investigated KIR gene frequencies and genotype diversities of 13 KIR genes, 2 pseudogenes, expressed and non-expressed forms of KIR2DL5 and the two subtypes, full-length and deleted forms, of KIR2DS4 in 100 unrelated healthy individuals of the Bai population, living in the Dali Bai autonomous prefecture in the Yunnan province. All individuals were typed positive for the three framework loci KIR3DL3, 2DL4 and 3DL2, as well as for three non-framework genes KIR2DL1, 2DL3 and the pseudogene KIR2DP1. The gene frequencies of the other KIR genes ranged from 7%-95%. The results of tested linkage disequilibrium (LD) among KIR genes demonstrated that they display a wide range of LD. χ2 analysis among non-ubiquitous genes, using the KIR gene frequency data from our study population, as well as from previously published population data, was conducted and revealed significant differences in the KIR2DL1, 2DL2, 3DL1 and KIR2DS1 genes. The results of the present study can be valuable for enriching the Chinese ethnic gene information resources of the KIR gene pool, for anthropological studies, as well as for KIR-related disease research.     

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.     

Diversity of Killer Cell Immunoglobulin‐Like Receptor Genes in the Bengali Population of Northern West Bengal,India

The Indian Subcontinent exhibits extensive diversity in its culture, religion, ethnicity and linguistic heritage, which symbolizes extensive genetic variations within the populations. The highly polymorphic Killer cell Immunoglobulin‐like Receptor (KIR) family plays an important role in tracing genetic differentiation in human population. In this study, we aimed to analyse the KIR gene polymorphism in the Bengali population of northern West Bengal, India. To our knowledge, this is the first report on the KIR gene polymorphism in the Bengalis of West Bengal, India. Herein, we have studied the distribution of 14 KIR genes (KIR3DL1‐3DL3, KIR2DL1‐2DL5, KIR2DS1‐2DS5 AND KIR3DS1) and two pseudogenes (KIR3DP1 and 2DP1) in the Bengalis. Apart from the framework genes (KIR2DL4, 3DL2, 3DL3 and 3DP1), which are present in all the individuals, the gene frequencies of other KIR genes varied between 0.34 and 0.88. Moreover, upon comparing the KIR polymorphism of the Bengalis with the available published data of other world populations, it has been found that the Indo‐European‐speaking Bengalis from the region share both Dravidian and Indo‐Aryan gene pool with considerable influences of mongoloid and European descents. Furthermore, evidences from previously published data on human leucocyte antigen and Y‐chromosome haplogroup diversity support the view. Our results will help to understand the genetic background of the Bengali population, in illustrating the population migration events in the eastern and north‐eastern part of India, in explaining the extensive genetic admixture amongst the different linguistic groups of the region and also in KIR‐related disease researches.     

上海地区汉族人群杀伤细胞免疫球蛋白样受体基因多样性及单倍型组合研究

目的 分析上海地区汉族人群杀伤细胞免疫球蛋白样受体(killer Ig-like receptors，KIR)基因多态性及单倍型，为进一步研究不同人群KIRs与某些疾病的相关性提供线索。方法 采用序列特异性引物PCR法对87名无关汉族健康志愿者进行KIR基因低分辨率检测和单倍型分析。结果 (1)共检出Xv、KIRlD在内的18个KIRs基因。3DL3、2DL4、3DL2和3DLl存在于所有个体；较常见为2DL3、Z、2DLl、X；其次为2DS4、1D、2DL5、2DSl、3DSl、2DS5；2DS2、2DL2、2DS3、Xv频率较低。(2)共检出13种单倍型，最常见的是单倍型2。(3)共检出18种基因型．以AJ(2．2)、AF(1．2)型最常见，其次为AH(5，2)、AI(1，5)和AG(1，1)。另外有5种基因型FZl(2，9或6，16)、FZ2(1，16或2，15)、FZ3(6，17)、FZ4(4，13)和FZ5(2，6)，目前在白人中尚未发现。结论 上海地区汉族人群有其独特的KIRs基因频率、单倍型频率和基因型频率分布。     

Real-time PCR分型法检测苏南地区汉族人群KIR基因多态性

目的利用SYBR Green I Real-time PCR分型方法检测杀伤细胞免疫球蛋白样受体(killer cell immunoglobulin-likereceptor,KIR)基因,探讨苏南地区汉族人群KIR基因的分布特点。方法应用SYBR Green I Real-time PCR法对191名苏南地区汉族非亲缘健康人群进行KIR基因分型。结果 SYBR Green I Real-time PCR法有效地进行了KIR基因分型。已知的16种KIR基因在苏南地区汉族人群均被检出。框架基因2DL4、3DL2、3DL3和假基因3DP1存在于所有受检个体中。最常见的非框架基因为2DL1、2DL3、3DL1、2DS4以及假基因2DP1。共检出33种KIR基因型,最常见的为AA1(39.27%),其次为BX2、BX4和BX8。发现仅在新加坡华人报道的罕见基因型BX331和BX337,及仅在墨西哥人群罕见的基因型BX427。结论苏南汉族人群中检测出已知的16种KIR基因,共发现33种基因型,最常见的为AA1,并见到3个罕见基因型BX331、BX337和BX427。     

Haplotype analysis of killer cell immunoglobulin-like receptor genes in 77 Korean families

Killer cell immunoglobulin-like receptor (KIR) genes constitute a multigene family whose genomic diversity is achieved through variation in gene content and allelic polymorphism within individual KIR genes. To date, 16 KIR genes and pseudogenes have been identified, and group A and group B haplotypes are characterized by a dominance of genes encoding inhibitory and activating receptors, respectively. In the present study, we have investigated the presence or absence of 16 KIR genes and pseudogenes and subtypes of four genes (3DP1, 3DP1 variant; 2DL1, 2DL1 variant; expressed and nonexpressed variant of 2DL5; full length and deleted form of 2DS4) in 352 members of 77 unrelated Korean families using a PCR-based sequence-specific priming method. KIR haplotypes were determined by segregation analysis. A total of 29 different KIR genotypes and 19 (two group A and 17 group B) haplotypes were identified in 154 parents. The distribution of genotypes, in terms of combination of haplotypes, was AA 55.2%, AB 36.4%, and BB 8.4%. Different from Caucasians, full-length 2DS4 (80.5%) was the predominant subtype of 2DS4 and group A (73.4%) outnumbered group B haplotypes (26.6%). The KIR gene frequencies and the predominance of A haplotypes in Koreans are similar to those in the Japanese.     

KIR genes polymorphism in Argentinean Caucasoid and Amerindian populations

In natural killer cells, killer immunoglobulin-like receptors (KIRs) loci code for either inhibitory or activating receptors, and according to the number of genes present in each individual, it is possible to identify a high rate of polymorphism in the populations. We performed KIR typing by polymerase chain reaction-sequence-specific oligonucleotide probing in 402 Argentinean Caucasoid and in two Amerindian populations (101 Wichis and 54 Chiriguanos) from the North of Argentina. KIR2DL4, KIR3DL2, KIR3DL3 and KIR3DP1 were always present, whereas the frequencies of KIR2DL1, KIR2DL3, KIR2DS4, KIR3DL1 and KIR2DP1 ranged between 84% and 96%. The frequencies of KIR2DS2, KIR2DL2, KIR2DL5, KIR2DS5, KIR2DS1 and KIR3DS1 ranged between 41% and 62%. The KIR2DS3 with a frequency of 29% in Argentinean Caucasoid population was present at a very low frequency in Amerindian populations. Haplotype segregation studies performed in 10 Wichi families showed the presence of only three haplotypes: A, B5 and B1. The Amerindian populations showed several similarities to Asian but not to Caucasoid populations with regard to the frequency of KIR2DS3, full-length KIR2DS4 gene and KIR2DL4 alleles.     

Distribution of killer cell immunoglobulin-like receptor genes in Roma from Republic of Macedonia

The aim of this study was to analyze Killer Ig-Like Receptor (KIR) gene polymorphisms in Roma people from Republic of Macedonia. The studied sample consists of 103 healthy unrelated individuals, aged 20-45 years. All individuals are of Roma origin, residents of different geographical regions (Gostivar, Skopje, and Kochani). The population genetics analysis package, Arlequin, was used for analysis of the data. We found that all 16 KIR genes were observed in the Roma individuals and framework genes (KIR3DL3, KIR3DP1, KIR- 2DL4, and KIR3DL2) were present in all individuals. The frequencies of other KIR genes were: KIR2DP1 (1), KIR2DL1 (0.961), KIR2DL2 (0.544), KIR2DL3 (0.874), KIR2DL5 (0.311), KIR3DL1 (0.990), KIR- 2DS1 (0.330), KIR2DS2 (0.553), KIR2DS3 (0.359), KIR2DS4 (0.981), KIR2DS5 (0.291), and KIR3DS1 (0.379). The results of tested linkage disequilibrium (LD) among KIR genes demonstrated that KIR genes present a wide range of linkage disequilibrium. The obtained results for KIR genes and genotype frequencies in Macedonian Roma individuals can be used for anthropological comparisons.     

中国北方人群系统性红斑狼疮患者KIR基因多态性的研究

目的:检测和分析系统性红斑狼疮患者的杀伤细胞免疫球蛋白样受体(KIR)基因的多态性, 探讨系统性红斑狼疮(SLE)从基因到临床表达的发病机制.方法:应用PCR-SSP技术检测北方62例确诊SLE患者和61例同一区域同一民族正常对照者的KIR基因位点多态性.结果:SLE 患者KIR基因表型分布较常见的为KIR3DP1、 2DL1、 2DP1、 3DL1、 2DL3及1D, 其次为2DS4、 2DL5、 3DS1、 2DS2、 2DS5和2DL2, 较低者为2DS1、 2DS3及3DP1V, SLE病例组KIR3DS1, 2DL2、 2DL5和2DL3基因型频率比对照组显著降低(P<0.01).结论:中国北方人群的SLE的发生可能与多个KIR基因等位基因有相关性.     

Distribution of killer cell immunoglobulin-like receptors in the Greek population

The interaction between killer cell immunoglobulin-like receptors (KIR) expressed on natural killer (NK) cells, and human leukocyt antigen (HLA) molecules expressed on target cells is known to regulate the cytolytic activity. A wide range of KIR genotypes is observed in the population, as the number of KIR loci can vary. In the present study we have determined the frequencies and combinations of 13 KIR genes and two CD94:NKG2 receptor genes and their distribution in the two haplotype groups in a panel of 233 unrelated healthy Greek Caucasians. We have typed genomic DNA for the presence of the putative KIR loci KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4, KIR3DL1, KIR3DL2, KIR3DL3, KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS4, KIR2DS5, and KIR3DS1 using modified polymerase chain reaction sequence-specific primers. The frequency of KIR loci combined with the linkage disequilibrium values suggest that the Greek population shares several general features with other Caucasoid populations studied before, but still distinguishes itself by the increased or decreased frequency of several alleles. The majority of the 45 different KIR genotypes seen in Greeks have been observed in Caucasoid populations studied before. Nevertheless, two of these genotypes, although met in other populations, have not been found in Caucasians before. One individual possesses a novel profile with no KIR inhibitory gene. The A haplotypes remain the most prevalent, with AA1 being the most common genotype, and the number of inhibitory KIRs being more variable than the number of noninhibitory KIRs in most haplotypes.     

Study of genetic diversity of killer cell immunoglobulin-like receptor loci in the Tujia ethnic minority

The aim of this study was to analyze the genetic profiles of 14 killer cell immunoglobulin-like receptor (KIR) genes and 2 pseudogenes of 124 individuals from Tujia ethnic minority residing in Enshi Tujia and Miao autonomous prefecture of Hubei province of China and investigate the genetic relationships between the Tujia ethnic minority and other reported groups for the first time. Sequence specific primer amplification (PCR-SSP) methods were used to genotype the 14 KIR genes and 2 pseudogenes. The observed carrier frequencies (OF) and the gene frequencies (GF) of the KIR genes were measured. Neighbor-joining (N-J) tree and the principal component analysis (PCA) plot were constructed. All individuals were typed positive for the three framework loci KIR3DL3, 2DL4 and 3DL2, as well as for pseudogene KIR3DP1. The gene frequencies of the other KIR genes ranged from 9% in KIR2DS2 to 98% in KIR2DP1 and KIR3DL1. The present study of the KIR genes may be a powerful tool for enriching the Chinese ethnical gene information resources of the KIR gene pool, as well as for the anthropological research.     

中国新疆地区维吾尔族人群杀伤细胞免疫球蛋白样受体基因多态性研究

背景：研究发现,杀伤细胞免疫球蛋白样受体基因具有遗传多态性,不同个体和NK细胞克隆表达不同的杀伤细胞免疫球蛋白样受体库。 目的：分析新疆维吾尔族人群杀伤细胞免疫球蛋白样受体基因多态性及基因型和单倍型特点。 方法：采用序列特异性引物PCR方法检测84名新疆维吾尔族志愿者杀伤细胞免疫球蛋白样受体基因频率,采用Hsu等的标准进行基因型和单倍型分析。 结果与结论：①共检测已知的16个杀伤细胞免疫球蛋白样受体基因,其中3DL3、2DL4、3DL2基因存在于所有个体;2DL1、3DP1、2DP1、2DL3基因较为常见;其次为2DS4、3DL1、2DL5、2DS2、2DL2、2DS1、 2DS5、3DS1;而2DS3基因频率最低。②共检测19种基因型,其中以 AJ(2,2)、AH(5,2) 和M(2,8)型较常见,频率分别为25.00%,10.71%和10.71%,其次为P(2,17)、AI(1,5)、H(2,4)和C(5,3),频率为9.52%,5.95%。5.95%和4.76%;比对发现U(17,21)、T(8,8)基因型共4例在国内文献汉族人群中未见报道。③共检出11种单倍型,最常见单倍型2占48.7%,其次是单倍型5,占15.8%;另外,发现有3种新基因型,且无法根据现有相关文献标准进行单倍型分析。表明新疆维吾尔族人群具有其独特的杀伤细胞免疫球蛋白样受体基因频率、基因型频率和单倍型频率分布,并有可能存在新的基因型和单倍型。     

Study of the KIR gene profiles and analysis of the phylogenetic relationships of Rajbanshi population of West Bengal,India

The natural killer (NK) cells have distinct receptors called killer cell immunoglobulin-like receptors (KIR) which are responsible for regulating NK cell responses to infections and malignancy. The extensive variations in the number and type of KIR genes can be used as a tool to understand the differentiation of populations and also for tracing genetic background. In this study, we have aimed to analyze the KIR gene polymorphism in the Rajbanshi population of West Bengal, India. To our knowledge this is the first report on the KIR gene polymorphism in the Rajbanshis, a population widely distributed in the Terai and Dooars region of West Bengal, India. Herein, we have studied the gene distribution of 14 KIR genes (KIR3DL1–3DL3, KIR 2DL1–2DL5, 2DS1–2DS5 and 3DS1) and two pseudogenes (KIR3DP1 and 2DP1). The gene frequencies and genotypic frequencies were calculated, based on which statistical analyses were performed. The presence of a considerable number of genotypic profiles suggests substantial diversity in the KIR gene pool of the Rajbanshis in the region studied. Apart from the framework genes (KIR2DL4, 3DL2, 3DL3 and 3DP1) present in all the individuals, the gene frequencies of other KIR genes varied between 0.84 and 0.15. Moreover the KIR polymorphisms of the Rajbanshis were also compared with that of available published data of the populations of other ethnicities. Though the Rajbanshi population showed a tendency to cluster with other Indian population based on KIR gene frequencies, the influence of Tibeto–Burman Lineage on their KIR genotypic profiles cannot be overlooked. Furthermore, evidences from previously published data on Y chromosome haplogroup diversity study on Rajbanshis support the view. Our results will not only help to understand the genetic background of the Rajbanshi population, but also in tracing the population migration events in the North–Eastern part of India and in illustrating the extensive genetic admixture amongst the different linguistic groups of the country and also in KIR-related disease researches.     

Killer cell immunoglobulin-like receptor (KIR) genes in 4 distinct populations and 51 families in mainland China

In this study, we investigated the killer cell immunoglobulin-like receptor (KIR) genes and HLA-C1/C2 dimorphism in 819 healthy, unrelated individuals composed of two southern Chinese Han populations (Hunan Han and Guangdong Han) and two northern Chinese populations (Inner Mongolia Han and Inner Mongolia Mongol), using polymerase chain reaction-sequence-specific priming (PCR-SSP) method. Fifty-one Chinese families were used to determine KIR haplotypic configuration. Our data showed that KIR2DL4, KIR3DL2, KIR3DL3, and KIR3DP1 genes were present in all of the 819 individuals. However, KIR2DL4 and KIR3DP1 genes were not detected in two members of a northern Chinese family. None of the KIR genes showed significant difference between the four populations. Thirty-five different KIR gene profiles were identified, one of which has not been previously reported in the Allele Frequencies KIR database. Eleven distinct KIR haplotypic configurations were determined through family analysis. Individuals with KIR2DLl and KIR2DL3 genes but lacking KIR2DSl and KIR2DS2 genes, coupled with HLA-C1 (Asn(80)) homozygosity, predominated in each population. At least one known inhibitory KIR-HLA pair was detected in each individual. The findings shown here are valuable for future studies of the potential role of KIR genes as well as KIR-HLA interaction in disease susceptibility in related ethnic groups.     

KIR及HLA-A、B基因多态性与急性淋巴细胞白血病的相关性

目的探讨急性淋巴细胞白血病患者的杀伤细胞免疫球蛋白样受体（killer cell immunoglobulin-like receptors,KIR）和人类白细胞抗原（human leukocyte antigen,HLA）HLA-A、B等位基因多态性。方法采用Luminex流式技术-序列特异性寡核苷酸探针反向杂交（flow cytometry-sequence specific oligonucleotide probe,FLOW-SSOP）方法对内蒙地区48例急性淋巴细胞白血病患者HLA-A、B等位基因多态性进行分析,PCR-SSP技术进行KIR抑制基因的低分辨率检测。以北方地区健康群体资料作为正常对照。结果 （1）在急性淋巴细胞白血病中HLA-A＊31XX,A＊6901等位基因频率高于对照组（1.955%,0.071%）,差异有统计学意义（P〈0.05）;A＊33XX等位基因频率低于对照组（5.825%）,差异有统计意义（P〈0.05）;（2）在HLA-B等位基因中,急性淋巴细胞白血病B＊07XX,＊27XX,＊38XX,＊41XX,＊49XX,＊59XX等位基因频率高于对照组（2.069%,0.968%,0.702%,0.091%,0.051%,0.061%）,差异有统计学意义（P〈0.05）;其中HLA-B＊59XX的相对危险度高（RR=35.156）,其它等位基因频率在两组之间无显著性差异。在急性白血病患者中,高频率KIR基因有KIR3DP1,2DP1,2DL1,2DL3,3DL1、2DL5,2DS4及3DS1。急性白血病组3DL1基因型频率比对照组的显著降低。结论 HLA-A＊31XX,A＊6901;B＊07XX,B＊27XX,B＊38XX,B＊41XX,B＊49XX,B＊59XX;等位基因与ALL相关联,有遗传易感作用。HLA-B＊59XX等位基因携带者,可能患ALL的危险度增高（RR=35.156）KIR3DL1和2DS4均与ALL呈关联。     

Development of a PCR-SSOP approach capable of defining the natural killer cell inhibitory receptor (KIR) gene sequence repertoires

A molecular typing method based on polymerase chain reaction (PCR) amplification of three different target domains (immunoglobulin domains 1 and 3, and the transmembrane-cytoplasmic domain), followed by hybridisation with 26 digoxigenin-labelled sequence-specific oligonucleotide probes (SSOP) has been established for the polymorphic killer inhibitory receptor (KIR) genes. In addition to identifying the 12 KIR subfamilies, our PCR-SSOP typing approach could also distinguish the putative alleles, NKB1 and NKAT3, that comprise the KIR3DL1 subfamily. Ninety unrelated blood donors and 13 families (52 individuals), including both parents, were subjected to our KIR PCR-SSOP typing approach. All 12 KIR subfamilies, including a 2DS5 variant sequence, were present in the 90 individuals and displayed varied phenotype frequencies: 2DL1 (0.96), 2DL2 (0.31), 2DL3 (0.95), 2DS1 (0.56) 2DS2 (0.51), 2DS3 (0.27), 2DS4 (0.96), 2DS5v (0.35), 3DS1 (0.47), 3DL1 (0.96), 3DL2 (1.0) and 2DL4 (1.0). A total of 23 different KIR phenotypes were defined in this study, and 10 of these were only found on one occasion in one individual, indicating considerable diversity in the KIR phenotype profiles within the Irish population. Most individuals (93%) possessed the complement of inhibitory KIR specificities for the three well-defined HLA-B and -C ligands. An unusual probe pattern for 3DS1 was observed in 3 individuals indicating a variant 3DS1 gene sequence with changes at nucleotide positions 1185-1186, within the cytoplasmic domain. Sequencing analysis revealed a new single nucleotide polymorphism in exon 3 of 3DL1 NKB1(195, G-A) and a 22-bp deletion polymorphism in exon 5 of 2DS4 (nucleotides 777-798 deleted). A number of strong KIR associations were observed, namely 2DL1 with 2DL3, 2DS4 with 3DL1, 2DL2 with 2DS1/2DS2/2DS3, 2DS1 with 2DS3/2DS5v/3DS1, 2DS2 with 2DS3 and 2DS5v with 3DS1. Analysis of the KIR segregation observed in the 13 families confirmed these strong associations and permitted the definition of a number of partial KIR haplotypes, e.g. 2DL2-2DS1-2DS2-2DS3-3DL1. The segregation analysis concluded that at least 3 distinct gene loci encode 2DL1-4 and at least 4 gene loci encode the non-inhibitory KIR2DS1-2DS5. In the case of 3DL1-2 and 3DS1, our data suggests 3 gene loci, one for each subfamily.     

Diversity distributions of killer cell immunoglobulin-like receptor genes and their ligands in the Chinese Shaanxi Han population

In the present study, 17 killer cell immunoglobulin-like receptors (KIR) genes and KIR ligands (human leukocyte antigen [HLA] -A and -B) were detected by using a polymerase chain reaction-sequence-specific primer (PCR-SSP) method in 104 unrelated healthy Han individuals living in Shaanxi province, China. The observed carrier frequencies of the 12 KIR genes ranged from 0.14 to 0.96. KIR2DL4, 3DL2, 3DL3, 2DP1 and 3DP1 were found to be present in every individual. A total of 51 different KIR gene profiles were identified, in which 11 gene profiles exclusively belonged to the study population. Neighbor-joining phylogenetic tree between the studing population and its neighboring ethnic groups was constructed using the observed carrier frequencies of 13 KIR loci. The phylogenetic tree shows that the Shaanxi Han population, Han populations in different regions, Yi, Japanese, and Koreans were in the same cluster. KIR/HLA relationships show that KIR3DS1(-)/3DL1(+)/Bw4(+) was the most common association in the population. In conclusion, the present study findings reveal the high polymorphism of KIRs in the Shaanxi Han population, demonstrate the KIR/HLA association in the study population, and enrich the KIR and HLA gene resources. The obtained KIR data will further the understanding of genetic relationships among populations in different geographic areas, and assist in answering questions regarding KIR/HLA relationships.     

Killer cell immunoglobulin-like receptor genes in four human West Nile virus infections reported 2011 in the Republic of Macedonia

West Nile virus (WNV) is a neurotropic, arthropod-borne flavivirus that is maintained in an enzootic cycle between mosquitoes and birds, but can also infect and cause disease in horses and humans. The aim of this study was to examine KIR gene polymorphisms by determining the frequencies of 16 KIR genes and pseudogenes and KIR genotypes in Macedonian patients with West Nile virus infection, and to compare with healthy Macedonians. The studied sample consists Republic of Macedonia, hospitalized at the University Clinic of Infective Diseases between September 2011 and October 2011, and reported through WHO. For KIR genotyping, commercially available PEL-FREEZ KIR genotyping SSP kit (Dynal Biotech, Brown Deer, WI) was used. The population genetics analysis package, Arlequin, was used for analysis of the data. We found that all 16 KIR genes were observed in the studied individuals and framework genes (KIR3DL3, KIR3DP1, KIR2DL4, and KIR3DL2) were present in all individuals. Comparison of KIR frequencies between Macedonian patients with West Nile virus infection and healthy Macedonian population reveals several significant differences in the inhibitory group (KIR2DL2), and in the non inhibitory group (KIR2DS1, KIR2DS2, KIR2DS5, and KIR3DS1). The single most frequent genotypes in the Bx group were genotypes ID71 and ID89 with statistically significant difference compared to healthy Macedonians. Our results suggest that specific KIR genotypes could be connected with West Nile virus infection.