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4.
Front Med (Lausanne) ; 11: 1356646, 2024.
Article in English | MEDLINE | ID: mdl-39257885

ABSTRACT

Environment and lifestyle can affect the epigenome passed down from generation to generation. A mother's nutrition can impact the methylation levels of her offspring's epigenome, but it's unclear which genes may be affected by malnutrition during gestation or early development. In this study, we examined the levels of methylated GC in the promoter region of HLA-C in mothers and infants from the Kichwa community in Ecuador. To do this, we analyzed saliva samples using bisulfite DNA sequencing. While we did not observe any significant differences in the mean methylation percentages in exon 1 of HLA-C between mothers and their infants after the first two years of lactation and life, respectively, we did find that infants tended to increase their methylation level during the first two years of life, while mothers tended to decrease it after the first two years of breastfeeding. When we compared methylation levels between mothers and infants using an ANOVA/posthoc Tukey test, we found that the average methylation for the entire population was less than 3% at T1 and T2. Although there was a tendency for infants to have higher methylation levels during their first two years of life and for mothers to have lower methylation levels after the first two years of breastfeeding, the mean values were not significantly different. However, we found a significant difference when we contrasted the data using a Kruskal-Wallis test at 0.05 for T1 AND T2 (p-value: 0.0148). Specifically, mothers had an average of X̅ = 2.06% and sons had X̅ = 1.57% at T2 (p-value: 0.7227), while the average for mothers was X̅ = 1.83% and for sons X̅ =1.77%. Finally, we identified three CpG motif nucleotide positions (32-33, 43-44, and 96-97) along the 122 bp analysis of HLA-C exon one, which was found to retain methylation patterns over time and is inherited from mother to offspring. Finally, our small pilot study did not reveal significant correlations between maternal and offspring nutritional status and DNA methylation levels of HLA-C exon one.

6.
HLA ; 104(3): e15692, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39291365

ABSTRACT

Six novel HLA-C variants with nucleotide changes in non-coding regions: HLA-C*04:32:01:02, -C*07:01:01:142, -C*08:04:01:05, -C*12:03:01:68, -C*12:03:01:69 and -C*16:01:01:41.


Subject(s)
Alleles , HLA-C Antigens , Humans , HLA-C Antigens/genetics , Exons , Histocompatibility Testing , Sequence Analysis, DNA/methods , Base Sequence , Polymorphism, Single Nucleotide , Sequence Alignment
7.
Int J Mol Sci ; 25(17)2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39273630

ABSTRACT

Efforts towards an effective HIV-1 vaccine have remained mainly unsuccessful. There is increasing evidence for a potential role of HLA-C-restricted CD8+ T cell responses in HIV-1 control, including our recent report of HLA-C*03:02 among African children. However, there are no documented optimal HIV-1 CD8+ T cell epitopes restricted by HLA-C*03:02; additionally, the structural influence of HLA-C*03:02 on epitope binding is undetermined. Immunoinformatics approaches provide a fast and inexpensive method to discover HLA-restricted epitopes. Here, we employed immunopeptidomics to identify HLA-C*03:02 CD8+ T cell epitopes. We identified a clade-specific Gag-derived GY9 (GTEELRSLY) HIV-1 p17 matrix epitope potentially restricted to HLA-C*03:02. Residues E62, T142, and E151 in the HLA-C*03:02 binding groove and positions p3, p6, and p9 on the GY9 epitope are crucial in shaping and stabilizing the epitope binding. Our findings support the growing evidence of the contribution of HLA-C molecules to HIV-1 control and provide a prospect for vaccine strategies.


Subject(s)
Epitopes, T-Lymphocyte , HIV-1 , HLA-C Antigens , gag Gene Products, Human Immunodeficiency Virus , gag Gene Products, Human Immunodeficiency Virus/immunology , gag Gene Products, Human Immunodeficiency Virus/chemistry , gag Gene Products, Human Immunodeficiency Virus/genetics , Humans , Epitopes, T-Lymphocyte/immunology , Epitopes, T-Lymphocyte/chemistry , HLA-C Antigens/immunology , HLA-C Antigens/metabolism , HLA-C Antigens/genetics , HIV-1/immunology , HIV-1/genetics , T-Lymphocytes, Cytotoxic/immunology , Amino Acid Sequence , Protein Binding , HIV Infections/immunology , HIV Infections/virology , HIV Antigens
8.
HLA ; 104(3): e15672, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39234798

ABSTRACT

HLA-C*07:02:81 differs from HLA-C*07:02:01:01 by one nucleotide substitution at position 465 (C→A) in exon 3.


Subject(s)
Alleles , Base Sequence , Exons , HLA-C Antigens , Histocompatibility Testing , Humans , HLA-C Antigens/genetics , Sequence Analysis, DNA , Silent Mutation , Sequence Alignment , Codon
10.
HLA ; 104(3): e15701, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39307952

ABSTRACT

Two novel HLA alleles HLA-B*15:699 and HLA-C*03:677 were detected during routine HLA typing by next generation sequencing.


Subject(s)
Alleles , HLA-C Antigens , High-Throughput Nucleotide Sequencing , Histocompatibility Testing , Humans , HLA-C Antigens/genetics , Denmark , Exons , HLA-B15 Antigen/genetics , HLA-B15 Antigen/immunology , Sequence Analysis, DNA/methods
12.
Int J Mol Sci ; 25(16)2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39201523

ABSTRACT

The HLA genes are associated with various autoimmune pathologies, with the control of the immune response also being significant in organs and cells transplantation. The aim of the study is to identify the HLA-A, HLA-B, and HLA-C alleles frequencies in the analyzed Romanian cohort. We performed HLA typing using next-generation sequencing (NGS) in a Romanian cohort to estimate class I HLA allele frequencies up to a six-digit resolution. A total of 420 voluntary donors from the National Registry of Voluntary Hematopoietic Stem Cell Donors (RNDVCSH) were included in the study for HLA genotyping. Peripheral blood samples were taken and brought to the Fundeni Clinical Institute during 2020-2021. HLA genotyping was performed using the Immucor Mia Fora NGS MFlex kit. A total of 109 different alleles were detected in 420 analyzed samples, out of which 31 were for HLA-A, 49 for HLA-B, and 29 for HLA-C. The most frequent HLA-A alleles were HLA-A*02:01:01 (26.11%), HLA-A*01:01:01 (12.5%), HLA-A*24:02:01 (11.67%), HLA-A*03:01:01 (9.72%), HLA-A*11:01:01, and HLA-A*32:01:01 (each with 8.6%). For the HLA-B locus, the most frequent allele was HLA-B*18:01:01 (11.25%), followed by HLA-B*51:01:01 (10.83%) and HLA-B*08:01:01 (7.78%). The most common HLA-C alleles were HLA-C*07:01:01 (17.36%), HLA-C*04:01:01 (13.47%), and HLA-C*12:03:01 (10.69%). Follow-up studies are ongoing for confirming the detected results.


Subject(s)
Gene Frequency , HLA-A Antigens , HLA-B Antigens , HLA-C Antigens , Tissue Donors , Humans , HLA-C Antigens/genetics , HLA-A Antigens/genetics , HLA-B Antigens/genetics , Male , Female , Alleles , Romania , Hematopoietic Stem Cells/metabolism , Hematopoietic Stem Cell Transplantation , Adult , High-Throughput Nucleotide Sequencing , Histocompatibility Testing/methods , Genotype , Middle Aged
13.
HLA ; 104(2): e15644, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39132706

ABSTRACT

HLA-C*17:78 differs from HLA-C*17:03:01:03 by one nucleotide change C>T in exon 3 (GCG>GTG).


Subject(s)
Alleles , Base Sequence , Exons , HLA-C Antigens , Humans , HLA-C Antigens/genetics , India , Histocompatibility Testing , Sequence Analysis, DNA , Sequence Alignment , Polymorphism, Single Nucleotide , Codon
14.
19.
HLA ; 104(1): e15629, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39073238

ABSTRACT

HLA-C*02 246 has one nucleotide change from HLA-C*02:02:02:01 at nucleotide 523 changing Arginine to Cysteine at residue 151.


Subject(s)
Alleles , Base Sequence , Exons , HLA-C Antigens , Histocompatibility Testing , Humans , HLA-C Antigens/genetics , Sequence Analysis, DNA/methods , Sequence Alignment , Amino Acid Substitution , Codon
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