-
HLA Nov 2023The full length sequence of the HLA-B*08:01:71, HLA-B*51:382 and HLA-B*55:01:30 alleles are reported.
The full length sequence of the HLA-B*08:01:71, HLA-B*51:382 and HLA-B*55:01:30 alleles are reported.
Topics: Humans; Alleles; HLA-B Antigens; Genes, MHC Class I; Genomics; Sequence Analysis, DNA
PubMed: 37549885
DOI: 10.1111/tan.15184 -
HLA Aug 2023The HLA-C*01:242 allele differs from HLA-C*01:02:01:01 allele by a single nucleotide in codon 281.
The HLA-C*01:242 allele differs from HLA-C*01:02:01:01 allele by a single nucleotide in codon 281.
Topics: Humans; HLA-C Antigens; Alleles; Genes, MHC Class I; Codon; High-Throughput Nucleotide Sequencing
PubMed: 37009751
DOI: 10.1111/tan.15050 -
HLA Nov 2023Many specificities single out HLA-F: its structure, expression regulation at cell membrane and function. HLA-F mRNA is detected in the most cell types and the protein is...
Many specificities single out HLA-F: its structure, expression regulation at cell membrane and function. HLA-F mRNA is detected in the most cell types and the protein is localized in the ER and Golgi apparatus. When expressed at cell surface, HLA-F may be associated to β2-microglobulin and peptide or expressed as an open-conformer molecule. HLA-F reaches the membrane upon activation of different primary cell types and cell-lines. HLA-F has its highest affinity for the KIR3DS1-activating NK receptor, but also binds inhibitory immune receptors. Some studies reported that HLA-F expression is associated with its genotype. Higher HLA-F mRNA expression associated with F*01:01:02, and 3 noncoding SNPs, rs1362126, rs2523405, and rs2523393, located in HLA-F-AS1 or upstream the HLA-F sequence were associated with HLA-F mRNA expression. Given the implication of HLA-F in many clinical setting, and the undisclosed process of its expression regulation, we aim to confirm the effect of the aforementioned SNPs with HLA-F transcriptional and protein expression. We analyzed the distribution, frequency and linkage disequilibrium of these SNPs at worldwide scale in the 1000 Genomes Project samples. Influence on the genotype of each SNP on HLA-F expression was explored using RNAseq data from the 1000 Genomes Project, and using Q-PCR and intracellular cytometry in PBMC from healthy individuals. Our results show that the SNPs under studied displayed remarkably different allelic proportion according to geography and confirm that rs1362126, rs2523405, and rs2523393 displayed the most concordant results, with the highest effect size and a double-dose effect.
Topics: Humans; Leukocytes, Mononuclear; Alleles; Histocompatibility Antigens Class I; Polymorphism, Single Nucleotide; Genotype; RNA, Messenger
PubMed: 37166140
DOI: 10.1111/tan.15087 -
HLA Dec 2023HLA-C*01:225 has one nucleotide change compared with HLA-C*01:02:01:01 in codon 110 of exon 3.
HLA-C*01:225 has one nucleotide change compared with HLA-C*01:02:01:01 in codon 110 of exon 3.
Topics: Humans; Alleles; Codon; East Asian People; HLA-C Antigens; Sequence Analysis, DNA
PubMed: 37681350
DOI: 10.1111/tan.15218 -
HLA Sep 2023Characterization of three novel HLA-DPA1 alleles bearing null, synonymous, and non-synonymous mutations.
Characterization of three novel HLA-DPA1 alleles bearing null, synonymous, and non-synonymous mutations.
Topics: Humans; Alleles; HLA-DP alpha-Chains; High-Throughput Nucleotide Sequencing
PubMed: 37315941
DOI: 10.1111/tan.15125 -
Clinica Chimica Acta; International... Jan 2024HLA-B*15:02 is highly associated with carbamazepine-induced SJS/TEN; however, there is no rapid and accurate detecting method. Here, we present a method to distinguish...
BACKGROUND
HLA-B*15:02 is highly associated with carbamazepine-induced SJS/TEN; however, there is no rapid and accurate detecting method. Here, we present a method to distinguish HLA-B*15:02 from 16 highly homologous HLA-B*15 alleles.
METHODS
The high-throughput two-dimensional polymerase chain reaction (2D-PCR) technology was employed to identify HLA-B*15:02 in two-tube reaction. And, 2D-PCR accuracy was verified by PCR-sequence based typing (PCR-SBT).
RESULTS
HLA-B*15:02 heterozygotes were identified by 14 melting valleys in the first tube reaction and none in the second, or by 13 melting valleys in the first tube reaction and one in the second. HLA-B*15:02 homozygote was identified by 13 melting valleys in the first tube reaction and none in the second. Three (0.16%) HLA-B*15:02 homozygotes and 84 (4.59%) HLA-B*15:02 heterozygotes were detected in 1830 samples of clinical general population without detecting 16 highly homologous alleles to HLA-B*15:02. The kappa test showed 100% coincidence between the 2D-PCR and PCR-SBT.
CONCLUSIONS
2D-PCR in two-tube reaction method for identifying HLA-B*15:02 was successfully established. Identification of HLA-B*15:02 is necessary prior to taking CBZ based on HLA-B*15:02 allele frequency.
Topics: Humans; Alleles; HLA-B Antigens; Polymerase Chain Reaction; Carbamazepine; Gene Frequency; Genotype
PubMed: 37972805
DOI: 10.1016/j.cca.2023.117654 -
HLA Mar 2024HLA-A*01:01:01:112 differs from the HLA-A*01:01:01:01 allele by one nucleotide substitution in the 5'UTR.
HLA-A*01:01:01:112 differs from the HLA-A*01:01:01:01 allele by one nucleotide substitution in the 5'UTR.
Topics: Humans; Alleles; Bone Marrow; Greece; 5' Untranslated Regions; HLA-A Antigens
PubMed: 38433707
DOI: 10.1111/tan.15426 -
HLA Dec 2023The HLA-A*24:585:02 allele differs from HLA-A*24:02:01:01 allele by three nucleotides within codons -16 and -15.
The HLA-A*24:585:02 allele differs from HLA-A*24:02:01:01 allele by three nucleotides within codons -16 and -15.
Topics: Humans; Alleles; High-Throughput Nucleotide Sequencing; Nucleotides; HLA-A Antigens
PubMed: 37681294
DOI: 10.1111/tan.15224 -
JAMA Network Open Oct 2023The development of therapeutics for patients who are positive for specific human leukocyte antigen (HLA) subtypes evokes the question of whether certain racial and...
IMPORTANCE
The development of therapeutics for patients who are positive for specific human leukocyte antigen (HLA) subtypes evokes the question of whether certain racial and ethnic groups are more or less likely to be eligible for novel products.
OBJECTIVE
To determine whether racial and ethnic inequities were present with regard to trial eligibility in trials investigating a therapeutic restricted to patients with specific HLA subtypes.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional study included all clinical trials registered in ClinicalTrials.gov through March 18, 2022, that investigated an interventional study of a therapeutic strategy and restricted participants to those with at least 1 HLA subtype. Data were analyzed from May 8 to July 1, 2022.
MAIN OUTCOMES AND MEASURES
The type of therapeutics used in trials, the condition under study, the HLA subtypes used, and the likelihood of being enrolled in such a trial according to race and ethnicity.
RESULTS
Of 2135 trials identified, 263 met inclusion criteria. Overall, the estimated likelihood of being eligible for an HLA-based trial was 50.3%. Individuals of African American descent had the lowest likelihood of eligibility (33.0%), while being an individual of European descent conferred the highest (53.0%; 1.6 times more likely than African American individuals). Most trials studied anticancer therapeutics (258 [98.1%; 95% CI, 96.4%-99.7%]), and most were a therapeutic vaccine (179 [68.1%; 95% CI, 62.4%-73.7%]). The HLA-A*02:01 allele and the HLA-A2 serotype were the most frequent HLA subtypes for trial eligibility. The frequency of the HLA-A*02:01 allele in the population varied, with 11.9% (95% CI, 11.8%-12.0%) in African or African American individuals and 27.1% (95% CI, 27.1%-27.1%) in individuals of European descent.
CONCLUSIONS AND RELEVANCE
The findings of this cross-sectional study suggest that enrollment restrictions for clinical trials investigating novel HLA therapeutics may be associated with racial and ethnic inequities with regard to trial eligibility. Overcoming these restrictions poses biological challenges, but solutions must be implemented to provide equal access to innovative strategies regardless of race or ethnicity.
Topics: Humans; Ethnicity; Cross-Sectional Studies; HLA Antigens; Alleles; HLA-A Antigens
PubMed: 37883087
DOI: 10.1001/jamanetworkopen.2023.38612 -
Molecular Biology Reports Nov 2023Sindhi is a dual-purpose breed adapted to tropical environments. However, this breed has the smallest total population among indicine breeds in Brazil and the smallest...
BACKGROUND
Sindhi is a dual-purpose breed adapted to tropical environments. However, this breed has the smallest total population among indicine breeds in Brazil and the smallest effective number. In addition, the inbreeding coefficient is higher than 6.25% in ~ 60% of the population. Therefore, alternatives to increase genetic diversity are important. Within this context, the PRDM9 gene is particularly interesting since it is involved in meiotic recombination events, consequently enhancing genetic variability in the population by increasing the number of circulating haplotypes. Each allele of the gene induces recombination at a different hotspot. The larger the number of circulating alleles, the higher the recombination rate and the greater the genetic variability.
METHODS
The aim of this study was to characterize alleles of the PRDM9 gene in Sindhi cattle. The region of the zinc finger domains of the gene was amplified by PCR, genotyped, and sequenced for allele identification in 50 Sindhi animals.
RESULTS
Three alleles (A-cattle1, B-cattle14, and C-cattle19) and six genotypes (AA, BB, CC, AB, AC, and BC) were identified.
CONCLUSION
The allele variation of the PRDM9 gene in the Sindhi breed enables to guide the mating of animals with different genotypes/alleles and to promote genetic variability by recombination if there is intralocus variability.
Topics: Cattle; Animals; Genotype; Homologous Recombination; Haplotypes; Zinc Fingers; Base Sequence; Alleles
PubMed: 37658931
DOI: 10.1007/s11033-023-08778-7