KIR and HLA haplotype analysis in a family lacking the KIR 2DL1-2DP1 genes.

The killer cell immunoglobulin-like receptor (KIR) gene cluster exhibits extensive allelic and haplotypic diversity that is observed as presence/absence of genes, resulting in expansion and contraction of KIR haplotypes and by allelic variation of individual KIR genes. We report a case of KIR pseudogene 2DP1 and 2DL1 gene absence in members of one family with the children suffering from acute myelogenous leukemia (AML). Killer cell immunoglobulin-like receptor low resolution genotyping was performed by the polymerase chain reaction (PCR)-sequence-specific primers (SSP)/sequence-specific oligonucleotide (SSO) method and haplotype assignment was done by gene content analysis. Both parents and the maternal grandfather, shared the same Cen-B2 KIR haplotype, containing KIR 3DL3, -2DS2, -2DL2 and -3DP1 genes. The second haplotype in the KIR genotype of the mother and grandfather was Tel-A1 with KIR 2DL4 (normal and deleted variant), -3DL1, -22 bp deletion variant of the 2DS4 gene and -3DL2, while the second haplotype in the KIR genotype of the father was Tel-B1 with 2DL4 (normal variant), -3DS1, -2DL5, -2DS5, -2DS1 and 3DL2 genes. Haplotype analysis in all three offsprings revealed that the children inherited the Cen-B2 haplotype with the same gene content but two of the children inherited a deleted variant of the 2DL4 gene, while the third child inherited a normal one. The second haplotype of all three offspring contained KIR 2DL4, -2DL5, -2DS1, -2DS4 (del 22bp variant), -2DS5, -3DL1 and -3DL2 genes, which was the basis of the assumption that there is a hybrid haplotype and that the present 3DL1 gene is a variant of the 3DS1 gene. Due to consanguinity among the ancestors, the results of KIR segregation analysis showed the existence of a very rare KIR genotype in the offspring. The family who is the subject of this case is even more interesting because the father was 10/10 human leukocyte antigen (HLA)-matched to his daughter, all members of the family have the "best" donor KIR-B content and the presence of a rare KIR genotype with KIR 2DP1-2DL1 genes absence.

Distribution of HLA-DRB1 and HLA-DQB1 families of alleles and haplotypes in Vojvodina population.

Major histocompatibility complex encoding human leucocyte antigens (HLA) is a highly polymorphic gene cluster that makes it a valuable tool in the population genetic studies. The aim of our study was to compare HLA class II gene frequencies with other populations from Europe and to determine the relationship between the investigated populations. In this study, one hundred and twenty healthy individuals from Vojvodina, northern Serbia, were studied for 18 of the HLA-DRB1 and HLA-DQB1 loci. The HLA families of alleles were analysed by using sequence-specific primers for polymerase chain reaction (PCR-SSP). The results showed the increased frequency of HLA-DRB1*11(0.333), -DRB1*04(0.300), -DRB1*07(0.250), -DQB1*03(0.730) and -DQB1* 05(0.391), among the tested families of alleles. The two-locus haplotype analysis revealed significant positive linkage disequilibrium for DRB1*11DQB1*03 (Δ = 0.0788, χ(2) = 12.61) and DRB1*04DQB1*03 (Δ = 0.0583, χ(2) = 8.04). A phylogenetic tree constructed on the basis of the DRB1* gene frequencies derived from other populations revealed the clustering among the Vojvodina population together with other populations in Europe (Croats, Austrians and Hungarians). Close relationship of the Vojvodina population with the populations of Hungarians and Austrians can be the result of their historical influence on the region of Vojvodina.

Human leukocyte antigen-b27 and disease susceptibility in vojvodina, serbia.

There are numerous studies showing the role of human leukocyte antigens (HLAs) related with susceptibility or resistance to certain diseases. The aim of this study was to determine the association of HLA-B27 with ankylosing spondylitis (AS), polyarthralgia, lumboishialgia, acute anterior uveitis (AAU), psoriatic arthritis (PA), synovitis coxae and rheumatoid arthritis (RA) in patients from Vojvodina, Serbia. An HLA I class typing was performed by the serological immunomagnetic two-color fluorescence method using peripheral blood T lymphocytes in 97 patients and 224 healthy controls from the population of Vojvodina, Serbia. We calculated HLA-B27 frequencies, relative risk (RR), ethiologic fraction (EF), e.g., population attributive risk, when RR was greater than 1, while, preventive fraction (PF) was calculated when RR was lower than 1. This study revealed the strongest association of AS with HLAB27 antigen: RR = 25.0, while the EF was greater than 0.15, respectively. The χ(2) test showed the significant difference (p <0.05) in HLA-B27 in patients with AS in comparison to controls (χ(2) = 52.5). It was concluded that there is a positive association of HLA-B27 with AS and that HLA-B27 can serve as a marker for predisposition to diseases.

Study of the HLA class II allele polymorphism and phylogenetic analysis in Vojvodina population.

The polymorphism at the HLA DRB1 and DQB1 loci in the population of Vojvodina was studied by PCR-SSP method. A total of 13 DRB1 and 5 DQB1 specificities displaying population-specific frequency distribution pattern were described. The most frequent HLA Class II alleles in Vojvodina population were: HLA-DRB1*11 (af = 0.30), -DRB1*04 (af = 0.28), -DRB1*07(af = 0.21), -DRB1*13 and -DRB1*16 (af = 0.18), -DQB1*03 (af = 0.64), -DQB1*05 (af = 0.39) and -DQB1*02 (af = 0.35). The haplotypes with high frequencies (> or = 0.02) included HLA DRB1*11 DQB1*03 (0.0825), DRB1*04DQB1*03 (0.0725), DRB1*07DQB1*02 (0.0475). The allele DRB1*07 showed the strongest association with DQB1*02 (delta = 0.0261, chi2 = 4.437) and DRB1*13 allele with DQB1*06 (delta = 0.0222, chi2 = 4.247). The allelic frequencies and populations distance dendrogram revealed the closest relationship of Vojvodina population with Hungarians, Croat, and Greeks which can be the result of turbulent migration within this region and admixture with neighbour populations during the history.