ABSTRACT
The novel HLA-C*01:273 allele, first described in a potential bone marrow donor from Brazil.
Subject(s)
Alleles , Exons , HLA-C Antigens , Humans , HLA-C Antigens/genetics , Brazil , Histocompatibility Testing , Base Sequence , Tissue Donors , Sequence Analysis, DNA/methods , Sequence Alignment , CodonABSTRACT
HLA-C*04:01:01:182 differs from the HLA-C*04:01:01:06 allele by one nucleotide substitution in the 5'UTR.
Subject(s)
Alleles , HLA-C Antigens , High-Throughput Nucleotide Sequencing , Histocompatibility Testing , Tissue Donors , Humans , HLA-C Antigens/genetics , High-Throughput Nucleotide Sequencing/methods , Histocompatibility Testing/methods , 5' Untranslated Regions , Exons , Base Sequence , Sequence Analysis, DNA/methods , Bone Marrow , Polymorphism, Single Nucleotide , Bone Marrow TransplantationABSTRACT
Characterisation of the novel HLA-C*14:02:01:31 allele in a 21-year-old Greek bone marrow donor.
Subject(s)
Alleles , Exons , HLA-C Antigens , High-Throughput Nucleotide Sequencing , Histocompatibility Testing , Tissue Donors , Humans , HLA-C Antigens/genetics , Young Adult , Bone Marrow Transplantation , Bone Marrow , Base Sequence , Polymorphism, Single Nucleotide , CodonABSTRACT
The newly discovered HLA-C*04:01:01:186 allele differs from HLA-C*04:01:01:01 by a single nucleotide substitution in intron 3.
Subject(s)
Alleles , HLA-C Antigens , High-Throughput Nucleotide Sequencing , Histocompatibility Testing , Introns , Humans , HLA-C Antigens/genetics , High-Throughput Nucleotide Sequencing/methods , Histocompatibility Testing/methods , Greece , Polymorphism, Single Nucleotide , Exons , Base Sequence , Sequence Analysis, DNA/methodsABSTRACT
Recurrent pregnancy loss (RPL) is a major reproductive health issue with multifactorial causes, affecting 2.6% of all pregnancies worldwide. Nearly half of the RPL cases lack clinically identifiable causes (e.g., antiphospholipid syndrome, uterine anomalies, and parental chromosomal abnormalities), referred to as unexplained RPL (uRPL). Here, we perform a genome-wide association study focusing on uRPL in 1,728 cases and 24,315 female controls of Japanese ancestry. We detect significant associations in the major histocompatibility complex (MHC) region at 6p21 (lead variant=rs9263738; P = 1.4 × 10-10; odds ratio [OR] = 1.51 [95% CI: 1.33-1.72]; risk allele frequency = 0.871). The MHC associations are fine-mapped to the classical HLA alleles, HLA-C*12:02, HLA-B*52:01, and HLA-DRB1*15:02 (P = 1.1 × 10-10, 1.5 × 10-10, and 1.2 × 10-9, respectively), which constitute a population-specific common long-range haplotype with a protective effect (P = 2.8 × 10-10; OR = 0.65 [95% CI: 0.57-0.75]; haplotype frequency=0.108). Genome-wide copy-number variation (CNV) calling demonstrates rare predicted loss-of-function (pLoF) variants of the cadherin-11 gene (CDH11) conferring the risk of uRPL (P = 1.3 × 10-4; OR = 3.29 [95% CI: 1.78-5.76]). Our study highlights the importance of reproductive immunology and rare variants in the uRPL etiology.
Subject(s)
Abortion, Habitual , Genetic Predisposition to Disease , Genome-Wide Association Study , Humans , Female , Abortion, Habitual/genetics , Pregnancy , Gene Frequency , HLA-DRB1 Chains/genetics , Polymorphism, Single Nucleotide , Adult , Alleles , Case-Control Studies , HLA-C Antigens/genetics , Major Histocompatibility Complex/genetics , Chromosomes, Human, Pair 6/genetics , DNA Copy Number Variations , Haplotypes , Japan/epidemiology , HLA-B Antigens/genetics , Genetic VariationABSTRACT
OBJECTIVE: To analyze a Chinese pedigree with a recombination occurring between the HLA-A/C loci in both parents. METHODS: A patient who was planning to undergo hematopoietic stem cell transplantation due to "aplastic anemia" in February 2022 was selected as the study subject. Peripheral blood samples were collected from the patient, his parents and brother. HLA-A/C/B/DRB1/DQB1 high-resolution typing was carried out by using sequence-based typing and sequence-specific oligonucleotides. The recombination was identified by pedigree analysis. The HLA haplotype of each individual was identified by genealogical analysis. The parentage possibility was determined by short tandem repeat analysis. HLA-A/C/B/DRB1/DRB345/DQA1/DQB1/DPA1/DPB1 were determined with next-generation high-throughput sequence-based typing. The recombination sites were analyzed by family study. RESULTS: The high parentage possibilities of the family was confirmed by short tandem repeat analysis. Recombination was found between the HLA-A*24:02 A*33:03/C*14:03 in the paternally transmitted haplotype, whilst HLA-A*01:01 A*03:01/C*08:02 was found in the maternally transmitted haplotype, which had resulted in two novel HLA haplotypes in the proband. CONCLUSION: A rare case with simultaneous recombination of the paternal and maternal HLA-A/C loci has been discovered, which may facilitate further study of the mechanisms of the HLA recombination.
Subject(s)
Asian People , HLA-A Antigens , Haplotypes , Pedigree , Recombination, Genetic , Adult , Female , Humans , Male , Asian People/genetics , East Asian People , Histocompatibility Testing , HLA-A Antigens/genetics , HLA-C Antigens/genetics , Microsatellite Repeats , ParentsABSTRACT
HLA-C*06:364 differs from HLA-C*06:02:01:01 by a non-synonymous nucleotide substitution in exon 3.
Subject(s)
Alleles , Exons , HLA-C Antigens , Humans , HLA-C Antigens/genetics , Histocompatibility Testing , Base Sequence , Sequence Analysis, DNA/methods , Codon , Sequence AlignmentABSTRACT
HLA (HLA) are a major barrier to transplant success, as HLA-A and -B molecules are principal ligands for T-cells, and HLA-C for Killer cell Immunoglobulin-like Receptors (KIR), directing Natural Killer (NK) cell function. HLA-C molecules are designated "C1" or "C2" ligands based on residues 77 and 80, which determine the NK cell responses. Here, we investigated donor/recipient HLA-C mismatch associations with the development of chronic lung allograft dysfunction (CLAD) following lung transplantation (LTx). 310 LTx donor/recipient pairs were Next Generation Sequenced and assessed for C1 and C2 allotypes. PIRCHE scores were used to quantify HLA mismatching between donor/recipients at amino acid level and stratify recipients into low, moderate or highly mismatched groups (n = 103-104). Associations between C ligands and freedom from CLAD was assessed with Cox regression models and survival curves. C2/C2 recipients (n = 42) had less CLAD than those with C1/C1 (n = 138) or C1/C2 genotypes (n = 130) (p < 0.05). Incidence of CLAD was lower in C2/C2 recipients receiving a mismatched C1/C1 allograft (n = 14), compared to matched (n = 8) or heterozygous (n = 20) allografts. Furthermore, ~80% of these recipients (C2/C2 recipients receiving C1/C1 transplants) remained CLAD-free for 10 years post-LTx. Recipients with higher HLA-C mismatching had less CLAD (p < 0.05) an observation not explained by linkage disequilibrium with other HLA loci. Our data implicates a role for HLA-C in CLAD development. HLA-C mismatching was not detrimental to LTx outcome, but potentially beneficial, representing a paradigm shift in assessing donor/recipient matching. This may inform better selection of donor/recipient pairs and potentially more targeted approaches to treating CLAD.
Subject(s)
HLA-C Antigens , Histocompatibility Testing , Lung Transplantation , Humans , Lung Transplantation/adverse effects , HLA-C Antigens/genetics , HLA-C Antigens/immunology , Male , Female , Middle Aged , Adult , Genotype , Tissue Donors , Graft Rejection/immunology , Killer Cells, Natural/immunology , Aged , Primary Graft Dysfunction/immunologyABSTRACT
HLA-C*04:520, a novel HLA-C allele, differs from HLA-C*04:01:01 by one mismatch in exon 5.
Subject(s)
Alleles , Base Sequence , Exons , HLA-C Antigens , Histocompatibility Testing , Humans , HLA-C Antigens/genetics , Sequence Analysis, DNA/methods , Sequence Alignment , Codon , Tissue DonorsABSTRACT
HLA-B*15:679 and HLA-C*15:02:01:61 differ from HLA-B*15:12:01 and HLA-C*15:02:01:01 by a single nucleotides.
Subject(s)
Alleles , Base Sequence , HLA-C Antigens , Histocompatibility Testing , Humans , HLA-C Antigens/genetics , India , Exons , Sequence Analysis, DNA/methods , Polymorphism, Single Nucleotide , HLA-B15 Antigen/genetics , HLA-B15 Antigen/immunology , Sequence Alignment , CodonABSTRACT
Allele variants HLA-C*01:02:01:74Q and -C*15:02:01:63 differ from -C*01:02:01:01 and -15:02:01:01 by a single nucleotide, respectively.
Subject(s)
Alleles , HLA-C Antigens , Histocompatibility Testing , Humans , HLA-C Antigens/genetics , Polymorphism, Single Nucleotide , Exons , India , Base Sequence , Sequence Analysis, DNA/methodsABSTRACT
Two nucleotide substitutions in codon 152 of HLA-C*08:01:01:01 result in a novel allele HLA-C*08:66.
Subject(s)
Exons , HLA-C Antigens , Histocompatibility Testing , Humans , Alleles , Base Sequence , Codon , Histocompatibility Testing/methods , HLA-C Antigens/genetics , Sequence Alignment , Sequence Analysis, DNA/methods , TaiwanABSTRACT
HLA-C*07:1089 differs from HLA-C*07:02:01:01 by one nucleotide in exon 3.
Subject(s)
Exons , HLA-C Antigens , Histocompatibility Testing , Humans , Alleles , Base Sequence , Codon , East Asian People , HLA-C Antigens/genetics , Sequence Alignment , Sequence Analysis, DNA/methodsABSTRACT
At position 778 (CâT) in exon 3, the new allele C*05:01:81 is distinct from C*05:01:01.
Subject(s)
Exons , HLA-C Antigens , Histocompatibility Testing , Humans , Alleles , Base Sequence , Codon , HLA-C Antigens/genetics , Polymorphism, Single Nucleotide , Sequence Alignment , Sequence Analysis, DNA/methodsABSTRACT
HLA-C*03:652 differs from the HLA-C*03:04:01:01 by one nucleotide in exon 3.
Subject(s)
Alleles , Asian People , Base Sequence , Exons , HLA-C Antigens , Histocompatibility Testing , Sequence Analysis, DNA , Humans , HLA-C Antigens/genetics , Asian People/genetics , Sequence Analysis, DNA/methods , Sequence Alignment , Codon , East Asian PeopleABSTRACT
HLA-C*14:155 differs from HLA-C*14:02:01:01 by one nucleotide in exon 1.
Subject(s)
Alleles , Asian People , Base Sequence , Exons , HLA-C Antigens , Histocompatibility Testing , Sequence Analysis, DNA , Humans , HLA-C Antigens/genetics , Asian People/genetics , Sequence Analysis, DNA/methods , Sequence Alignment , Codon , East Asian PeopleABSTRACT
Nucleotide substitution in codon 238 of HLA-C*12:02:02:01 results in a novel allele, HLA-C*12:02:53.
Subject(s)
Alleles , Base Sequence , Codon , Exons , HLA-C Antigens , Histocompatibility Testing , Humans , HLA-C Antigens/genetics , Taiwan , Sequence Analysis, DNA , Asian People/genetics , Sequence Alignment , Polymorphism, Single Nucleotide , Amino Acid SubstitutionABSTRACT
Five novel HLA-C alleles detected by next-generation sequencing: HLA-C*02:02:73, -C*03:04:106, -C*06:382, -C*07:1114Q and -C*12:408.
Subject(s)
Alleles , HLA-C Antigens , High-Throughput Nucleotide Sequencing , Histocompatibility Testing , Humans , High-Throughput Nucleotide Sequencing/methods , HLA-C Antigens/genetics , Histocompatibility Testing/methods , Exons , Sequence Analysis, DNA/methodsABSTRACT
HLA-C*03:620 differs from the HLA-C*03:04:01:02 allele by one nucleotide substitution in the exon 3.
Subject(s)
Alleles , Asian People , Base Sequence , Exons , HLA-C Antigens , Histocompatibility Testing , Humans , HLA-C Antigens/genetics , Asian People/genetics , Sequence Analysis, DNA/methods , Codon , Sequence Alignment , Polymorphism, Single Nucleotide , East Asian PeopleABSTRACT
The novel HLA-C*15:274 allele, first described in a potential bone marrow donor from Brazil.