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HLA Jan 2023The novel HLA-B*52:01:01:23 allele differs from HLA-B*52:01:01:01 by a nucleotide change at gDNA-61 C➔A.
The novel HLA-B*52:01:01:23 allele differs from HLA-B*52:01:01:01 by a nucleotide change at gDNA-61 C➔A.
Topics: Humans; Alleles; India
PubMed: 36086925
DOI: 10.1111/tan.14812 -
American Journal of Human Genetics Oct 2023Pharmacogenomics (PGx) is an integral part of precision medicine and contributes to the maximization of drug efficacy and reduction of adverse drug event risk. Accurate...
Pharmacogenomics (PGx) is an integral part of precision medicine and contributes to the maximization of drug efficacy and reduction of adverse drug event risk. Accurate information on PGx allele frequencies improves the implementation of PGx. Nonetheless, curating such information from published allele data is time and resource intensive. The limited number of allelic variants in most studies leads to an underestimation of certain alleles. We applied the Pharmacogenomics Clinical Annotation Tool (PharmCAT) on an integrated 200K UK Biobank genetic dataset (N = 200,044). Based on PharmCAT results, we estimated PGx frequencies (alleles, diplotypes, phenotypes, and activity scores) for 17 pharmacogenes in five biogeographic groups: European, Central/South Asian, East Asian, Afro-Caribbean, and Sub-Saharan African. PGx frequencies were distinct for each biogeographic group. Even biogeographic groups with similar proportions of phenotypes were driven by different sets of dominant PGx alleles. PharmCAT also identified "no-function" alleles that were rare or seldom tested in certain groups by previous studies, e.g., SLCO1B131 in the Afro-Caribbean (3.0%) and Sub-Saharan African (3.9%) groups. Estimated PGx frequencies are disseminated via the PharmGKB (The Pharmacogenomics Knowledgebase: www.pharmgkb.org). We demonstrate that genetic biobanks such as the UK Biobank are a robust resource for estimating PGx frequencies. Improving our understanding of PGx allele and phenotype frequencies provides guidance for future PGx studies and clinical genetic test panel design, and better serves individuals from wider biogeographic backgrounds.
Topics: Humans; Pharmacogenetics; Alleles; Biological Specimen Banks; Precision Medicine; Gene Frequency; Liver-Specific Organic Anion Transporter 1
PubMed: 37757824
DOI: 10.1016/j.ajhg.2023.09.001 -
Archives of Razi Institute Nov 2021Based on 16 STR-loci, the allele pool and interbreed differentiation of goat breeds of Russian and foreign breeding were investigated in this study. These breeds...
Based on 16 STR-loci, the allele pool and interbreed differentiation of goat breeds of Russian and foreign breeding were investigated in this study. These breeds included Karachai (KRCH-K, n=73, mountain zone; KRCH-Z, n=33, foothill zone), Dagestan Downy (DAGD, n=30), Dagestan Wool (DAGW, n=30), Soviet Wool (SOVW, n=30), Saanen (SAAN, n=34), Murciano-Granadina (MURS, n=37), as well as wild goats, represented by three species of mountain goats (n=52): Siberian Capricorn (Capra sibirica) of Altai (CSIB-S, n=6), Tajikistan (CSIB-T, n=4), Kyrgyzstan (CSIB-K, n=6), and the Himalayas (CSIB-H, n=4); Bezoar goat (Capa aegagrus) of Turkey (CAEG, n=3) and Pakistan (CAEG-S, n=3); West Caucasian tur (): western Caucasian (Kuban, CCAU-K, n=10), central Caucasian (CCAU-M, n=8), and eastern Caucasian (Dagestan, CCAU-D, n=8). The highest genetic diversity was observed in the North Caucasus breeds, such as Karachai, Dagestan Downy, and Dagestan Wool. The mean numbers of alleles per locus and allelic diversity were 7.385-9.154 and 7.353-7.713, respectively. The genetic proximity of Caucasian breeds was confirmed by cluster analysis, and they formed a common branch with the highest genetic affinity, while the Orenburg and Soviet Wool breeds formed another branch, and the third branch with the least affinity was the dairy breed of foreign selection.The analysis of the phylogenetic tree of domestic and wild species established the formation of three clusters formed by the subspecies of the West Caucasian tur, Siberian ibex, and breeds of domestic goats. At the same time, populations of the Bezoar goats were localized at the root of the last cluster, which confirmed their role as the ancestors of domestic goats.
Topics: Alleles; Animals; Genetic Variation; Goats; Phylogeny
PubMed: 35355766
DOI: 10.22092/ari.2021.355684.1709 -
PeerJ 2024Whereas undetected species contribute to estimation of species diversity, undetected alleles have not been used to estimated genetic diversity. Although random sampling...
Whereas undetected species contribute to estimation of species diversity, undetected alleles have not been used to estimated genetic diversity. Although random sampling guarantees unbiased estimation of allele frequency and genetic diversity measures, using undetected alleles may provide biased but more precise estimators useful for conservation. We newly devised kernel density estimation (KDE) for allele frequency including undetected alleles and tested it in estimation of allele frequency and nucleotide diversity using population generated by coalescent simulation as well as well as real population data. Contrary to expectations, nucleotide diversity estimated by KDE had worse bias and accuracy. Allele frequency estimated by KDE was also worse except when the sample size was small. These might be due to finity of population and/or the curse of dimensionality. In conclusion, KDE of allele frequency does not contribute to genetic diversity estimation.
Topics: Gene Frequency; Alleles; Genetic Variation; Humans; Models, Genetic; Computer Simulation; Genetics, Population
PubMed: 38666077
DOI: 10.7717/peerj.17248 -
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 -
Cell Reports Jan 2023Genes are typically assumed to express both parental alleles similarly, yet cell lines show random allelic expression (RAE) for many autosomal genes that could shape...
Genes are typically assumed to express both parental alleles similarly, yet cell lines show random allelic expression (RAE) for many autosomal genes that could shape genetic effects. Thus, understanding RAE in human tissues could improve our understanding of phenotypic variation. Here, we develop a methodology to perform genome-wide profiling of RAE and biallelic expression in GTEx datasets for 832 people and 54 tissues. We report 2,762 autosomal genes with some RAE properties similar to randomly inactivated X-linked genes. We found that RAE is associated with rapidly evolving regions in the human genome, adaptive signaling processes, and genes linked to age-related diseases such as neurodegeneration and cancer. We define putative mechanistic subtypes of RAE distinguished by gene overlaps on sense and antisense DNA strands, aggregation in clusters near telomeres, and increased regulatory complexity and inputs compared with biallelic genes. We provide foundations to study RAE in human phenotypes, evolution, and disease.
Topics: Humans; Adult; Alleles; Human Body; Chromosomes; Phenotype; Cell Line
PubMed: 36640362
DOI: 10.1016/j.celrep.2022.111945 -
Western Journal of Nursing Research Apr 2017Twenty-three percent to 50% of heart failure (HF) patients have memory loss. Objectives were to (a) characterize major allelic frequency of 2 variants in apolipoprotein...
Twenty-three percent to 50% of heart failure (HF) patients have memory loss. Objectives were to (a) characterize major allelic frequency of 2 variants in apolipoprotein ( APOE) gene in HF patients, (b) evaluate differences in memory and serum brain-derived neurotrophic factor (BDNF) levels based on APOE ε4 allele(s), and (c) estimate effect sizes (ESs) and confidence intervals (CIs). In this pilot, 29 HF patients were enrolled and 26 completed. Recall and delayed recall memory were measured at baseline and 12 weeks. Serum was collected at baseline and 8 weeks. Seven (24.1%) patients had APOE ε4 allele. No significant differences were found in recall and delayed recall memory or serum BDNF levels based on APOE ε4 allele. ESs were small to medium; CIs indicated ES precision was small. Future studies are needed to fully understand how genotypic and neuropsychological phenotypic variables influence response to computerized cognitive training.
Topics: Alleles; Apolipoprotein E4; Brain-Derived Neurotrophic Factor; Cognition; Female; Genotype; Heart Failure; Humans; Male; Memory; Mental Recall; Middle Aged; Neuropsychological Tests
PubMed: 27733670
DOI: 10.1177/0193945916670145 -
HLA Jan 2024Two novel non-classical HLA class I alleles have been characterized, HLA-F*01:16 and -F*01:17.
Two novel non-classical HLA class I alleles have been characterized, HLA-F*01:16 and -F*01:17.
Topics: Humans; Alleles; Genes, MHC Class I; Tissue Donors
PubMed: 38073430
DOI: 10.1111/tan.15325 -
International Journal of Molecular... Nov 2023Huntington's disease (HD) is a genetic disorder caused by a CAG trinucleotide expansion in the huntingtin () gene. Juan de Acosta, Atlántico, a city located on the...
Huntington's disease (HD) is a genetic disorder caused by a CAG trinucleotide expansion in the huntingtin () gene. Juan de Acosta, Atlántico, a city located on the Caribbean coast of Colombia, is home to the world's second-largest HD pedigree. Here, we include 291 descendants of this pedigree with at least one family member with HD. Blood samples were collected, and genomic DNA was extracted. We quantified the CAG expansion using an amplicon sequencing protocol. The genetic heterogeneity was measured as the ratio of the mosaicism allele's read peak and the slippage ratio of the allele's read peak from our sequence data. The statistical and bioinformatic analyses were performed with a significance threshold of < 0.05. We found that the average CAG repeat length in all participants was 21.91 (SD = 8.92). Of the 291 participants, 33 (11.3%, 18 females) had a positive molecular diagnosis for HD. Most affected individuals were adults, and the most common primary and secondary alleles were 17/7 (CAG/CCG) and 17/10 (CAG/CCG), respectively. The mosaicism increased with age in the participants with HD, while the slippage analyses revealed differences by the HD allele type only for the secondary allele. The slippage tended to increase with the CAG repeat length in the participants with HD, but the increase was not statistically significant. This study analyzed the genetic and molecular features of 291 participants, including 33 with HD. We found that the mosaicism increased with age in the participants with HD, particularly for the secondary allele. The most common haplotype was 17/7_17/10. The slippage for the secondary allele varied by the HD allele type, but there was no significant difference in the slippage by sex. Our findings offer valuable insights into HD and could have implications for future research and clinical management.
Topics: Adult; Female; Humans; Huntington Disease; Colombia; Alleles; DNA; Pedigree; Huntingtin Protein; Trinucleotide Repeat Expansion
PubMed: 38003344
DOI: 10.3390/ijms242216154 -
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