RESUMO
Here we correct the nucleotide sequence of a single known variant of the HLA-DRA gene. We show that the coding regions of the HLA-DRA*0101 and HLA-DRA*0102 alleles do not differ at two codons as reported previously, but only in codon 217. Using nucleotide sequencing and DNA samples from individuals homozygous in the major histocompatibility complex, we found that the variant, leucine 217-encoding HLA-DRA*0102 allele was present on the haplotypes HLA-B*0801, DRB1*03011, DQB1*0201 (ancestral haplotype AH8.1), HLA-B*07021, DRB1*15011, DQB1*0602 (AH7.1), HLA-B*1501, DRB1*15011, DQB1*0602, HLA-B*1501, DRB1*1402, DQB1*03011 and HLA-A3, B*07021, DRB1*1301, DQB1*0603. The HLA-DRA*0101 allele coding for valine 217 was observed on the haplotypes HLA-B*5701, DRB1*0701, DQB1*03032 (AH57.1), HLA-DRB1*04011, DQB1*0302, HLA-DRB1*0701, DQB1*0202, and HLA-DRB1*0101, DQB1*05011.
Assuntos
Alelos , Antígenos HLA-DR/genética , Haplótipos , Humanos , Desequilíbrio de Ligação , Dados de Sequência Molecular , Polimorfismo GenéticoRESUMO
A 77G allele of the gene encoding CD45, also known as the protein tyrosine phosphatase receptor-type C gene (PTPRC), has been associated with multiple sclerosis (MS). Here we determine allele frequencies in large numbers of MS patients, primary immunodeficiencies linked to major histocompatibility complex (MHC) locus and over 1,000 controls to assess whether aberrant splicing of PTPRC caused by the 77C-->G polymorphism results in increased susceptibility to these diseases. Our results show no difference in the frequency of the 77G allele in patients and controls and thus do not support a causative role for the polymorphism in the development of disorders with a strong autoimmune component in etiology.
Assuntos
Doenças Autoimunes/genética , Antígenos Comuns de Leucócito/genética , Complexo Principal de Histocompatibilidade/genética , Mutação Puntual , Animais , Cromossomos Humanos Par 1 , Genótipo , Humanos , Splicing de RNARESUMO
We present a dense STR/linkage disequilibrium(LD)/gene map between the RING3 and HLA-B loci, reference allelic sizes on the most prevalent HLA haplotypes and their allelic frequencies in pedigree founders. This resource will facilitate LD, evolution and gene mapping studies, including comparisons of HLA and STR haplotypes and identification of HLA recombinants. The map was constructed by testing novel and previously reported STRs using a panel of 885 individuals in 211 families and 60 DNA samples from cell lines and bone marrow donors homozygous in the HLA-A, -B and -DR loci selected from over 15 000 entries into the registry of Swedish bone marrow donors. We have also analysed the variability of STR alleles/haplotypes on the most prevalent HLA haplotypes to identify STRs useful for fine mapping of disease genes in the region previously implicated in susceptibility to many disorders. The analysis of 40 HLA-A*01, B*0801, DRB1*03011, DQB1*0201 haplotypes in homozygous donors showed a surprising stability in 23 STRs between the class II recombination hot spot and HLA-B, with the average of 1.9% (16/838) variant alleles. However, 40% variant alleles were found at the D6S2670 locus in intron 19 of the tenascin-X gene both in the families and homozygous donors. The nucleotide sequence analysis of this STR showed a complex polymorphism consisting of tetra- (CTTT)(8-18) and penta-nucleotide (CTTTT)(1-2) repeats, separated by an intervening non-polymorphic sequence of 42 bp. The HLA-A1, B*0801, DRB1*03011, DQB1*0201 haplotypes had five (CTTT)(14-18)/(CTTTT)(2) variants with a predominant (CTTT)(16) allele, implicating the tetranucleotide component as the source of this ancestral haplotype diversification, which may be due to the location of D6S2670 in the region of the highest GC content in the human MHC.
Assuntos
Mapeamento Cromossômico/métodos , Haplótipos/genética , Desequilíbrio de Ligação/genética , Complexo Principal de Histocompatibilidade/genética , Proteínas Serina-Treonina Quinases/genética , Sequências de Repetição em Tandem/genética , Centrômero/genética , Ordem dos Genes/genética , Marcadores Genéticos/genética , Variação Genética/genética , Antígeno HLA-A1/genética , Antígeno HLA-B8/genética , Antígenos HLA-DQ/genética , Cadeias beta de HLA-DQ , Antígenos HLA-DR/genética , Antígeno HLA-DR3/genética , Cadeias HLA-DRB1 , Humanos , Fatores de TranscriçãoRESUMO
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.
Assuntos
Predisposição Genética para Doença/genética , Antígenos HLA-C/genética , Infecções por Helicobacter/imunologia , Helicobacter pylori , Dermatopatias Bacterianas/imunologia , Alelos , DNA/sangue , Gastrite/microbiologia , Frequência do Gene , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Infecções por Helicobacter/genética , Humanos , Razão de Chances , Reação em Cadeia da Polimerase , Valores de Referência , Dermatopatias Bacterianas/genéticaRESUMO
A comparison of the HLA class I typing in 50 unrelated individuals by means of serological and molecular genetic (PCR-SSP) methods was carried out. DNA-typing is more fast and reliable method in comparison with serology. It is necessary to introduce molecular genetic methods for the detection of HLA class I alleles. On the other hand there are alleles, which are not expressed on cell surface. In our laboratory both methods are established and the results of both were compared. It may be useful for determining the selection strategy of HLA-identical donor-recipient pair suitable for bone marrow transplantation. The results demonstrated 9% misassignments of HLA-A antigens by serology, 11% of HLA-B and 39% of HLA-C. The serological discrepancies found were of three categories: false negatives, false positives, and an incomplete typing. The vast majority of the discrepancies were due to a combination of relatively low expression of HLA antigens, lack of serological reagents and misclassification of antigens within cross-reactive groups. These results indicate that nowadays the serological typing is insufficient for clinical histocompatibility testing. (Tab. 3, Ref. 16.)
Assuntos
Antígenos HLA/análise , Teste de Histocompatibilidade/métodos , Reação em Cadeia da Polimerase , Alelos , Testes Imunológicos de Citotoxicidade , Primers do DNA , Antígenos HLA/genética , Humanos , EslováquiaRESUMO
In the years 1985-1999 452 were families investigated with the aim to find up an HLA-identical sibling for a patient suffering from a disease, the treatment of which requires bone marrow transplantation. Total number of investigated siblings (including patients) was 1334. HLA typing was done by serological methods, mixed lymphocyte culture test (MLC), and in the last three years also by DNA-typing (PCR-SSP). 188 HLA identical donor-recipient sib-pairs were found. At the same time the number shows that a potential donor could be found in 41.5% of investigated families.
Assuntos
Transplante de Medula Óssea/imunologia , Família , Antígenos HLA/análise , Doadores Vivos , Haplótipos , Teste de Histocompatibilidade , Humanos , Teste de Cultura Mista de Linfócitos , Reação em Cadeia da PolimeraseRESUMO
Results on HLA-A, -B and -Cw antigen frequencies in the Slovak population are presented. HLA-A, -B, -Cw antigens were determined in 654 healthy unrelated individuals. The highest frequency was observed for the antigens HLA-A2, -A1; HLA-B12, -B35, and HLA-Cw8. The least frequent antigens were HLA-A34, -A36, HLA-B58, -B67, -B70, -B77, and HLA-Cw8. The results were compared with those of the previous study and with those of Czech, Austrian and Hungarian populations. No statistically significant differences were observed. (Tab. 5, Fig. 2, Ref. 9.)