Next-generation sequencing (NGS) is increasingly used in transplantation settings, but also as a method of choice for in-depth analysis of population-specific HLA genetic architecture and its linkage to various diseases. With respect to complex ethnic admixture characteristic for East Croatian population, we aimed to investigate class-I (HLA-A, -B, -C) and class-II (HLA-DRB1, -DQA1, -DQB1) HLA diversity at the highest, 4-field resolution level in 120 healthy, unrelated, blood donor volunteers. Genomic DNA was extracted and HLA genotypes of class I and DQA1 genes were defined in full-length, -DQB1 from intron 1 to 3' UTR, and -DRB1 from intron 1 to intron 4 (Illumina MiSeq platform, Omixon Twin algorithms, IMGT/HLA release 3.30.0_5). Linkage disequilibrium statistics, Hardy-Weinberg departures, and haplotype frequencies were inferred by exact tests and iterative Expectation-Maximization algorithm using PyPop 0.7.0 and Arlequin v3.5.2.2 software. Our data provide first description of 4-field allele and haplotype frequencies in Croatian population, revealing 192 class-I and class-II alleles and extended haplotypic combinations not apparent from the existing 2-field HLA reports from Croatia. This established reference database complements current knowledge of HLA diversity and should prove useful in future population studies, transplantation settings, and disease-associated HLA screening.

• MeSH
• běloši genetika   MeSH
• dárci krve MeSH
• dospělí MeSH
• frekvence genu MeSH
• haplotypy MeSH
• HLA-A antigeny genetika   MeSH
• HLA-B antigeny genetika   MeSH
• HLA-C antigeny genetika   MeSH
• HLA-DQ alfa řetězec genetika   MeSH
• HLA-DQ beta řetězec genetika   MeSH
• HLA-DRB1 řetězec genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• sekvenční analýza DNA MeSH
• vazebná nerovnováha MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• zdraví dobrovolníci pro lékařské studie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Chorvatsko MeSH
• Názvy látek
• HLA-A antigeny MeSH
• HLA-B antigeny MeSH
• HLA-C antigeny MeSH
• HLA-DQ alfa řetězec MeSH
• HLA-DQ beta řetězec MeSH
• HLA-DQA1 antigen MeSH Prohlížeč
• HLA-DQB1 antigen MeSH Prohlížeč
• HLA-DRB1 řetězec MeSH

We detected a somatic mutation in the HLA-B gene in a Czech hematooncological patient. We followed the development of this somatic mutation during the transition from severe aplastic anaemia through to myelodysplastic syndrome to acute myeloid leukaemia until haploidentical related transplantation. The somatic mutation differs from HLA-B*14:02 in exon 3 resulting in an exchange from cysteine to serine at position 101 of the mature protein. Homology modelling of mutated S101 in HLA-B*14 indicated possible conformational changes, which might also result in an aberrant expression. The assumption is that somatic mutation arose as a possible result of a selection mediated by a protective immune response against leukaemia.

• MeSH
• akutní myeloidní leukemie genetika   patologie   MeSH
• aplastická anemie genetika   patologie   MeSH
• dospělí MeSH
• HLA-B antigeny genetika   MeSH
• lidé MeSH
• mutace * MeSH
• myelodysplastické syndromy genetika   patologie   MeSH
• nádorová transformace buněk genetika   MeSH
• progrese nemoci MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• HLA-B antigeny MeSH

Human leukocyte antigen (HLA) genes play a key role in the immune response to infectious diseases, some of which are highly prevalent in specific environments, like malaria in sub-Saharan Africa. Former case-control studies showed that one particular HLA-B allele, B*53, was associated with malaria protection in Gambia, but this hypothesis was not tested so far within a population genetics framework. In this study, our objective was to assess whether pathogen-driven selection associated with malaria contributed to shape the HLA-B genetic landscape of Africa. To that aim, we first typed the HLA-A and -B loci in 484 individuals from 11 populations living in different environments across the Sahel, and we analysed these data together with those available for 29 other populations using several approaches including linear modelling on various genetic, geographic and environmental parameters. In addition to relevant signatures of populations' demography and migrations history in the genetic differentiation patterns of both HLA-A and -B loci, we found that the frequencies of three HLA alleles, B*53, B*78 and A*74, were significantly associated with Plasmodium falciparum malaria prevalence, suggesting their increase through pathogen-driven selection in malaria-endemic environments. The two HLA-B alleles were further identified, by high-throughput sequencing, as B*53:01:01 (in putative linkage disequilibrium with one HLA-C allele, C*04:01:01:01) and B*78:01 in all but one individuals tested, making them appropriate candidates to malaria protection. These results highlight the role of environmental factors in the evolution of the HLA polymorphism and open key perspectives for functional studies focusing on HLA peptide-binding properties.

• Klíčová slova
• African populations, HLA polymorphism and disease associations, geographic patterns, human population genetics, malaria protection, pathogen-driven selection,
• MeSH
• alely MeSH
• HLA-B antigeny genetika   MeSH
• lidé MeSH
• odolnost vůči nemocem genetika   MeSH
• populační genetika * MeSH
• tropická malárie genetika   MeSH
• vazebná nerovnováha MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• subsaharská Afrika MeSH
• Názvy látek
• HLA-B antigeny MeSH

The identification of a novel HLA-B*35:279 allele in a Czech patient is described. This allele is identical to the B*35:03:01 variant except the G/A nucleotide exchange at position 652 of the HLA-B gene that corresponds to the amino acid substitution from valine to isoleucine in alpha 3 domain of the HLA-B antigen.

• MeSH
• alely * MeSH
• HLA-B antigeny genetika   imunologie   izolace a purifikace   MeSH
• lidé MeSH
• sekvence nukleotidů MeSH
• substituce aminokyselin MeSH
• testování histokompatibility MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• HLA-B antigeny MeSH

Human leucocyte antigen (HLA) modifications observed in blast cells in haematologic malignancies can play an important role in disease progression and its therapy. Here we describe an insertion/deletion mutation in the second exon of HLA-B*39:01 that occurred in the blast cells of a patient with B-ALL. This mutation was not present in the nonleukemic cells, in which HLA-B*39:01 was normally expressed.

• MeSH
• exony MeSH
• HLA-B antigeny genetika   MeSH
• krevní buňky patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace genetika   MeSH
• pre-B-buněčná leukemie genetika   patologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• HLA-B antigeny MeSH

A novel HLA-B (human leukocyte antigen-B) allele, HLA-B*4442, was identified both in a Czech patient with leukaemia and in his mother. The presence of a novel allele was initially suspected because conflicting results were obtained by serological and DNA typing techniques. The HLA typing using the polymerase chain reaction-sequence-specific primers (PCR-SSP) at the two-digit level indicated an allele belonging to the HLA-B*44 group, whereas serological typing indicated HLA-B21. Typing with PCR-sequence-specific oligonucleotides (PCR-SSO) resulted in a unique reaction pattern that could not be assigned to a known allele, PCR-SSP typing at the four-digit level did not match any known B*44 allele, either. The sequencing-based typing of the HLA-B locus then revealed the novel B*4442 allele that is identical with B*4405 except a single C-->G nucleotide exchange at position 572. This exchange results in an amino acid substitution from serine to tryptophan at position 167 of the expressed HLA-B protein. The B21 serological reactivity of the novel B*4442 allele product was confirmed by employing an additional serological panel of typing sera. Our findings support previous reports claiming that serine at the position 167 in the alpha-2 domain of the HLA-B protein is a major determinant of the HLA-B44(12) serological epitope.

• MeSH
• alely * MeSH
• bodová mutace * imunologie   MeSH
• HLA-B antigeny genetika   imunologie   MeSH
• HLA-B44 antigen MeSH
• leukemie genetika   imunologie   MeSH
• lidé MeSH
• molekulární sekvence - údaje MeSH
• regulace genové exprese u leukemie genetika   imunologie   MeSH
• rodokmen MeSH
• sekvence nukleotidů MeSH
• substituce aminokyselin * imunologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• HLA-B antigeny MeSH
• HLA-B*44:42 antigen MeSH Prohlížeč
• HLA-B21 antigen MeSH Prohlížeč
• HLA-B44 antigen MeSH

A novel human leukocyte antigen-B (HLA-B) allele, B*420502, was identified in a patient with leukemia (Caucasoid, Czech ancestry) and his mother during intrafamily search for the hematopoietic stem cell donor. The novel allele was initially detected by HLA typing at low resolution using both sequence specific primers and sequence specific oligonucleotides techniques that resulted in unique reaction patterns. The alleles of the HLA-B locus were separated by the haplotype-specific extraction technique. Sequencing of those alleles revealed a novel allele, B*420502, that is identical with B*420501 except a T-->G exchange (synonymous mutation) at position 618.

• MeSH
• alely * MeSH
• běloši genetika   MeSH
• bodová mutace MeSH
• HLA-B antigeny genetika   MeSH
• leukemie genetika   MeSH
• lidé MeSH
• molekulární sekvence - údaje MeSH
• polymerázová řetězová reakce MeSH
• sekvence nukleotidů MeSH
• sekvenční analýza DNA MeSH
• testování histokompatibility MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• HLA-B antigeny MeSH
• HLA-B*42:05:02 antigen MeSH Prohlížeč

The HLA allelic frequency was determined in three groups of autoimmune endocrinopathies: A) 30 patients with autoimmune thyroiditis, B) 20 patients with polyglandular activation of autoimmunity, and C) 10 patients with the autoimmune polyglandular syndrome type II. The groups were defined by the clinical state and serological parameters. Healthy blood donors of Caucasian population from the US database of HLA frequencies served as the controls. In group A, a higher occurrence of HLA-A24 (21.7 %) was found as compared to group B (5.0 %) and to the controls (8.5 %), of HLA-B27 (15.0 %) and of HLA-DR-11 (20 %) as compared to the controls (4.2 % and 8.5 %). In group B, a higher occurrence of HLA-A3 (25.0 %) was found as compared to group A (10 %) and to the controls (11.8 %), and of HLA-B8 (22.5 %) as compared to group A (8.3 %) and to the controls (8.6 %). In this group the occurrence of HLA-DR3 (30.0 %) was higher as compared to group A (10.0 %) and to the controls (9.8 %) and of HLA-B8 (30.0 %) as compared to group A (8.3 %) and to the controls (8.6 %). Genetic markers indicate a similarity of groups B and C. Patients in these groups could be at different stages of the same disease, however, some distinctions between them lead us to consider the possibility whether different epigenetic factors could extend the difference between these groups in the course of clinical development.

• MeSH
• autoimunitní polyglandulární syndromy genetika   imunologie   MeSH
• autoimunitní tyreoiditida genetika   imunologie   MeSH
• autoprotilátky krev   MeSH
• DNA genetika   izolace a purifikace   MeSH
• dospělí MeSH
• frekvence genu MeSH
• glutamát dekarboxyláza imunologie   MeSH
• HLA antigeny genetika   MeSH
• HLA-A antigeny genetika   MeSH
• HLA-B antigeny genetika   MeSH
• HLA-DR antigeny genetika   MeSH
• Langerhansovy ostrůvky imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nadledviny imunologie   MeSH
• ovarium imunologie   MeSH
• steroid-21-hydroxylasa imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• autoprotilátky MeSH
• DNA MeSH
• glutamát dekarboxyláza MeSH
• HLA antigeny MeSH
• HLA-A antigeny MeSH
• HLA-B antigeny MeSH
• HLA-DR antigeny MeSH
• ICA512 autoantibody MeSH Prohlížeč
• steroid-21-hydroxylasa MeSH

The occurrence rate of HLA class I and class II alleles was established in 24 patients suffering from dermatological disorders associated with the Helicobacter pylori infection. The increased frequency of HLA-C*0602, 4 was found to be 0.1875 compared to 0.0733 in the control group (odds ratio: 2.913; two-sided P value: P = 0.0251). Our data suggest that the HLA-Cw6 molecule play a role in the susceptibility to the Helicobacter pylori infection.

• MeSH
• alely MeSH
• bakteriální nemoci kůže genetika   imunologie   MeSH
• DNA krev   MeSH
• frekvence genu MeSH
• gastritida mikrobiologie   MeSH
• genetická predispozice k nemoci genetika   MeSH
• Helicobacter pylori * MeSH
• HLA-A antigeny genetika   MeSH
• HLA-B antigeny genetika   MeSH
• HLA-C antigeny genetika   MeSH
• infekce vyvolané Helicobacter pylori genetika   imunologie   MeSH
• lidé MeSH
• odds ratio MeSH
• polymerázová řetězová reakce MeSH
• referenční hodnoty MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DNA MeSH
• HLA-A antigeny MeSH
• HLA-B antigeny MeSH
• HLA-C antigeny MeSH
• HLA-C*06 antigen MeSH Prohlížeč

The occurrence rates of class I HLA alleles were investigated in a sample of the Slovak population by a PCR-SSP method. The frequencies of HLA-A alleles ranged from 0.00 for A*4301 to 0.2798 for A*0201-22; the frequencies of HLA-B alleles ranged from 0.00 for B 4601,B* 4801-3, B*5901,B* 7301, and B* 8101 to 0.1101 for B* 4402-10, and those of HLA-C alleles from 0.00 for Cw*1301 and Cw* 1402-3 to 0.2661 for Cw 0701-10. The occurrence rates of class I HLA alleles established in our study were compared with those in the Czech population. No significant differences were found.

• MeSH
• alely MeSH
• DNA krev   MeSH
• elektroforéza v agarovém gelu MeSH
• frekvence genu * MeSH
• geny MHC třídy I * MeSH
• HLA-A antigeny genetika   MeSH
• HLA-B antigeny genetika   MeSH
• HLA-C antigeny genetika   MeSH
• lidé MeSH
• polymerázová řetězová reakce metody   MeSH
• polymorfismus genetický * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Slovenská republika MeSH
• Názvy látek
• DNA MeSH
• HLA-A antigeny MeSH
• HLA-B antigeny MeSH
• HLA-C antigeny MeSH