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HLA Feb 2022The HLA system plays a pivotal role both in transplantation and immunology. While classical HLA genotypes matching is made at the allelic level, recent progresses were...
The HLA system plays a pivotal role both in transplantation and immunology. While classical HLA genotypes matching is made at the allelic level, recent progresses were developed to explore antibody-antigen recognition by studying epitopes. Donor to recipient matching at the epitopic level is becoming a trending topic in the transplantation research field because anti-HLA antibodies are epitope-specific rather than allele-specific. Indeed, different HLA alleles often share common epitopes. We present the HLA-Epi tool (hla.univ-nantes.fr) to study an HLA genotype at the epitope level. Using the international HLA epitope registry (Epregistry.com.br) as a reference, we developed HLA-Epi to easily determine epitopic and allelic compatibility levels between several HLA genotypes. The epitope database covers the most common HLA alleles (N = 2976 HLA alleles), representing more than 99% of the total observed frequency of HLA alleles. The freely accessible web tool HLA-Epi calculates an epitopic mismatch load between different sets of potential recipient-donor pairs at different resolution levels. We have characterized the epitopic mismatches distribution in a cohort of more than 10,000 kidney transplanted pairs from European ancestry, which showed low number of epitopic mismatches: 56.9 incompatibilities on average. HLA-Epi allows the exploration of epitope pairing matching to better understand epitopes contribution to immune responses regulation, particularly during transplantation. This free and ready-to-use bioinformatics tool not only addresses limitations of other related tools, but also offers a cost-efficient and reproducible strategy to analyze HLA epitopes as an alternative to HLA allele compatibility. In the future, this could improve sensitization prevention for allograft allocation decisions and reduce the risk of alloreactivity.
Topics: Alleles; Epitopes; Fluprednisolone; Graft Rejection; HLA Antigens; Histocompatibility Testing; Humans; Isoantibodies
PubMed: 34862850
DOI: 10.1111/tan.14505 -
Biomedica : Revista Del Instituto... Mar 2016The genetic variability present in the APOE gene polymorphism is considered an important factor associated with predisposition to diseases affecting lipid metabolism, as...
INTRODUCTION
The genetic variability present in the APOE gene polymorphism is considered an important factor associated with predisposition to diseases affecting lipid metabolism, as well as heart diseases and Alzheimer's disease, among others. Understanding it as a risk factor in different populations and ethnic groups is a useful tool.
OBJECTIVE
To analyze the APOE gene polymorphism and determine allelic and genotypic frequencies of a representative sample of population from Barranquilla, Colombia.
MATERIALS AND METHODS
We performed a descriptive and comparative study. The sample size was 227 unrelated individuals from Barranquilla, Colombia.
RESULTS
The most frequent allele was the ε3, with 85%, followed by the ε4 allele (13%) and ε2 (1.8%). The genotypes found were: ε3/ε3: 71.8%, ε3/ε4: 24.2%, ε2/ε3: 2.2%, ε2/ε4: 1.3% and ε4/ε4: 0.4%. The ε2/ε2 genotype was not found in this study. The sample exhibited the Hardy-Weinberg equilibrium.
CONCLUSION
The frequency of the ε3 allele and the ε3/ε3 genotype was similar to that reported in the literature in countries like Brazil, Mexico, Colombia, and in some Colombian Amerindian ethnic groups. The ε2/ε2 genotype was absent. This result is consistent with those found in other population groups worldwide. The frequency of the ε4 allele and the genotypes associated in this population could be related to the presence of diseases such as hypercholesterolemia, myocardial infarction and Alzheimer.
Topics: Adolescent; Adult; Alleles; Apolipoproteins E; Colombia; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Male; Middle Aged; Polymorphism, Genetic; Young Adult
PubMed: 27622438
DOI: 10.7705/biomedica.v36i1.2612 -
Heredity Mar 2021Selection pressure from parasites is thought to be a major force shaping the extreme polymorphism of the major histocompatibility complex (MHC) genes, but the modes and...
Selection pressure from parasites is thought to be a major force shaping the extreme polymorphism of the major histocompatibility complex (MHC) genes, but the modes and consequences of selection remain unclear. Here, we analyse MHC class II and microsatellite diversity in 16 guppy (Poecilia reticulata) populations from two islands (Trinidad and Tobago) that have been separated for at least 10 ky. Within-population MHC diversity was high, but allele sharing was limited within islands and even lower between islands, suggesting relatively fast turnover of alleles. Allelic lineages strongly supported in phylogenetic analyses tended to be island-specific, suggesting rapid lineage sorting, and an expansion of an allelic lineage private to Tobago was observed. New alleles appear to be generated locally at a detectably high frequency. We did not detect a consistent signature of local adaptation, but F outlier analysis suggested that balancing selection may be the more general process behind spatial variation in MHC allele frequencies in this system, particularly within Trinidad. We found no evidence for divergent allele advantage within populations, or for decreased genetic structuring of MHC supertypes compared to MHC alleles. The dynamic and complex nature of MHC evolution we observed in guppies, coupled with some evidence for balancing selection shaping MHC allele frequencies, are consistent with Red Queen processes of host-parasite coevolution.
Topics: Alleles; Animals; Genes, MHC Class II; Genetic Variation; Phylogeny; Poecilia; Selection, Genetic
PubMed: 32985616
DOI: 10.1038/s41437-020-00369-7 -
BMC Research Notes Nov 2021Allelic imbalance (AI) is the differential expression of the two alleles in a diploid. AI can vary between tissues, treatments, and environments. Methods for testing AI...
OBJECTIVE
Allelic imbalance (AI) is the differential expression of the two alleles in a diploid. AI can vary between tissues, treatments, and environments. Methods for testing AI exist, but methods are needed to estimate type I error and power for detecting AI and difference of AI between conditions. As the costs of the technology plummet, what is more important: reads or replicates?
RESULTS
We find that a minimum of 2400, 480, and 240 allele specific reads divided equally among 12, 5, and 3 replicates is needed to detect a 10, 20, and 30%, respectively, deviation from allelic balance in a condition with power > 80%. A minimum of 960 and 240 allele specific reads divided equally among 8 replicates is needed to detect a 20 or 30% difference in AI between conditions with comparable power. Higher numbers of replicates increase power more than adding coverage without affecting type I error. We provide a Python package that enables simulation of AI scenarios and enables individuals to estimate type I error and power in detecting AI and differences in AI between conditions.
Topics: Alleles; Allelic Imbalance; Bayes Theorem; Computer Simulation; Humans
PubMed: 34838135
DOI: 10.1186/s13104-021-05851-x -
BMC Plant Biology Jul 2022Pre-harvest sprouting (PHS) is a serious limiting factor for wheat (Triticum aestivum L.) grain yield and end-use quality. Identification of reliable molecular markers...
BACKGROUND
Pre-harvest sprouting (PHS) is a serious limiting factor for wheat (Triticum aestivum L.) grain yield and end-use quality. Identification of reliable molecular markers and PHS-resistant germplasms is vital to improve PHS resistance by molecular marker-assisted selection (MAS), but the effects of allelic variation and haplotypes in genes conferring PHS resistance in winter wheat cultivars are less understood.
RESULTS
Resistance to PHS was tested in 326 commercial winter wheat cultivars for three consecutive growing seasons from 2018-2020. The effects of alleles and haplotypes of 10 genes associated with PHS resistance were determined for all cultivars and were validated by introgressing the PHS-resistance allele and haplotype into a susceptible wheat cultivar. High level of phenotypic variation in PHS resistance was observed in this set of cultivars and 8 of them were highly resistant to PHS with stable germination index (GI) of less than 25% in each individual year. Allelic effects of nine genes and TaMFT haplotype analysis demonstrated that the haplotype Hap1 with low-GI alleles at five positions had the best PHS resistance. This haplotype has the priority to use in improving PHS resistance because of its high effectiveness and rare present in the current commercial cultivars. Among 14 main allelic combinations (ACs) identified, the AC1 carrying the haplotype Hap1 and the TaSdr-B1a allele had better PHS resistance than the other classes. The introgression of Hap1 and TaSdr-B1a is able to significantly improve the PHS resistance in the susceptible cultivar Lunxuan 13.
CONCLUSIONS
The effectiveness of alleles conferring PHS resistance in winter wheat cultivars was determined and the useful alleles and haplotypes were identified, providing valuable information for parental selection and MAS aiming at improving PHS-resistance in winter wheat. The identification of the PHS-resistant cultivars without known resistance alleles offers an opportunity to explore new PHS-resistant genes.
Topics: Alleles; Germination; Haplotypes; Seasons; Triticum
PubMed: 35790923
DOI: 10.1186/s12870-022-03710-w -
Genome Research Feb 2022Polyploidy is widespread in plants, allowing the different copies of genes to be expressed differently in a tissue-specific or developmentally specific way. This...
Polyploidy is widespread in plants, allowing the different copies of genes to be expressed differently in a tissue-specific or developmentally specific way. This allele-specific expression (ASE) has been widely reported, but the proportion and nature of genes showing this characteristic have not been well defined. We now report an analysis of the frequency and patterns of ASE at the whole-genome level in the highly polyploid sugarcane genome. Very high depth whole-genome sequencing and RNA sequencing revealed strong correlations between allelic proportions in the genome and in expressed sequences. This level of sequencing allowed discrimination of each of the possible allele doses in this 12-ploid genome. Most genes were expressed in direct proportion to the frequency of the allele in the genome with examples of polymorphisms being found with every possible discrete level of dose from 1:11 for single-copy alleles to 12:0 for monomorphic sites. The rarer cases of ASE were more frequent in the expression of defense-response genes, as well as in some processes related to the biosynthesis of cell walls. ASE was more common in genes with variants that resulted in significant disruption of function. The low level of ASE may reflect the recent origin of polyploid hybrid sugarcane. Much of the ASE present can be attributed to strong selection for resistance to diseases in both nature and domestication.
Topics: Alleles; Gene Expression; Polymorphism, Single Nucleotide; Polyploidy; Saccharum; Sequence Analysis, RNA
PubMed: 34949669
DOI: 10.1101/gr.275904.121 -
British Journal of Haematology Mar 2020
Topics: Adult; Alleles; Cohort Studies; Humans; Leukemia, Myeloid, Acute; Nuclear Proteins; Nucleophosmin
PubMed: 31580476
DOI: 10.1111/bjh.16240 -
Frontiers in Immunology 2023Patients in need of hematopoietic stem cell transplantation often rely on unrelated stem cell donors matched in certain human leukocyte antigen (HLA) genes. Donor search...
Patients in need of hematopoietic stem cell transplantation often rely on unrelated stem cell donors matched in certain human leukocyte antigen (HLA) genes. Donor search is complicated by the extensive allelic variability of the HLA system. Therefore, large registries of potential donors are maintained in many countries worldwide. Population-specific HLA characteristics determine the registry benefits for patients and also the need for further regional donor recruitment. In this work, we analyzed HLA allele and haplotype frequencies of donors of DKMS Chile, the first Chilean donor registry, with self-assessed "non-Indigenous" (=92,788) and "Mapuche" (=1,993) ancestry. We identified HLA alleles that were distinctly more abundant in the Chilean subpopulations than in worldwide reference populations, four of them particularly characteristic for the Mapuche subpopulation, namely B*39:09g, B*35:09, DRB1*04:07g, and DRB1*16:02g. Both population subsamples carried haplotypes of both Native American and European origin at high frequencies, reflecting Chile's complex history of admixture and immigration. Matching probability analysis revealed limited benefits for Chilean patients (both non-Indigenous and Mapuche) from donor registries of non-Chilean donors, thus indicating a need for ongoing significant donor recruitment efforts in Chile.
Topics: Humans; Chile; Alleles; Haplotypes; Hematopoietic Stem Cell Transplantation
PubMed: 37313414
DOI: 10.3389/fimmu.2023.1175135 -
Genetics Jul 2022Multigene families-immunity genes or sensory receptors, for instance-are often subject to diversifying selection. Allelic diversity may be favored not only through...
Multigene families-immunity genes or sensory receptors, for instance-are often subject to diversifying selection. Allelic diversity may be favored not only through balancing or frequency-dependent selection at individual loci but also by associating different alleles in multicopy gene families. Using a combination of analytical calculations and simulations, we explored a population genetic model of epistatic selection and unequal recombination, where a trade-off exists between the benefit of allelic diversity and the cost of copy abundance. Starting from the neutral case, where we showed that gene copy number is Gamma distributed at equilibrium, we derived also the mean and shape of the limiting distribution under selection. Considering a more general model, which includes variable population size and population substructure, we explored by simulations mean fitness and some summary statistics of the copy number distribution. We determined the relative effects of selection, recombination, and demographic parameters in maintaining allelic diversity and shaping the mean fitness of a population. One way to control the variance of copy number is by lowering the rate of unequal recombination. Indeed, when encoding recombination by a rate modifier locus, we observe exactly this prediction. Finally, we analyzed the empirical copy number distribution of 3 genes in human and estimated recombination and selection parameters of our model.
Topics: Alleles; Humans; Models, Genetic; Recombination, Genetic; Selection, Genetic
PubMed: 35460227
DOI: 10.1093/genetics/iyac052 -
International Journal of Molecular... Apr 2022Although Slavic populations account for over 4.5% of world inhabitants, no centralised, open-source reference database of genetic variation of any Slavic population...
Although Slavic populations account for over 4.5% of world inhabitants, no centralised, open-source reference database of genetic variation of any Slavic population exists to date. Such data are crucial for clinical genetics, biomedical research, as well as archeological and historical studies. The Polish population, which is homogenous and sedentary in its nature but influenced by many migrations of the past, is unique and could serve as a genetic reference for the Slavic nations. In this study, we analysed whole genomes of 1222 Poles to identify and genotype a wide spectrum of genomic variation, such as small and structural variants, runs of homozygosity, mitochondrial haplogroups, and variants. Common variant analyses showed that the Polish cohort is highly homogenous and shares ancestry with other European populations. In rare variant analyses, we identified 32 autosomal-recessive genes with significantly different frequencies of pathogenic alleles in the Polish population as compared to the non-Finish Europeans, including , , , , and . The allele frequencies for small and structural variants, calculated for 1076 unrelated individuals, are released publicly as The Thousand Polish Genomes database, and will contribute to the worldwide genomic resources available to researchers and clinicians.
Topics: Alleles; Gene Frequency; Genetics, Population; Genome, Human; Humans; Mitochondrial Proteins; Poland
PubMed: 35562925
DOI: 10.3390/ijms23094532