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HLA Oct 2023Characterization of the novel HLA-A*02:09:01:04 allele in a 36-year-old Greek female.
Characterization of the novel HLA-A*02:09:01:04 allele in a 36-year-old Greek female.
Topics: Humans; Female; Adult; Alleles; Greece; High-Throughput Nucleotide Sequencing; HLA-A Antigens
PubMed: 37400620
DOI: 10.1111/tan.15147 -
The American Journal on Addictions Sep 2023This study examined how a promoter variant of TH (rs10770141) affects subjective effects of cocaine in 65 nontreatment-seeking individuals with cocaine dependence.
BACKGROUND AND OBJECTIVES
This study examined how a promoter variant of TH (rs10770141) affects subjective effects of cocaine in 65 nontreatment-seeking individuals with cocaine dependence.
METHODS
Participants received cocaine/saline intravenously, and TH genotypes were evaluated.
RESULTS
Homozygous individuals for the minor T allele reported greater "good" and "bad" subjective effects to cocaine than those with the major C allele.
DISCUSSION AND CONCLUSIONS
TH rs10770141 modulates subjective effects of cocaine in participants with cocaine dependence.
SCIENTIFIC SIGNIFICANCE
These results are among the first to indicate that homozygosity of the T allele of rs10770141 modulates greater sensitivity to cocaine.
Topics: Humans; Cocaine; Cocaine-Related Disorders; Genotype; Alleles; Promoter Regions, Genetic
PubMed: 37337750
DOI: 10.1111/ajad.13444 -
Genome Research Aug 2023An intricate network of - and -elements acts on RNA -methyladenosine (mA), which in turn may affect gene expression and, ultimately, human health. A complete...
An intricate network of - and -elements acts on RNA -methyladenosine (mA), which in turn may affect gene expression and, ultimately, human health. A complete understanding of this network requires new approaches to accurately measure the subtle mA differences arising from genetic variants, many of which have been associated with common diseases. To address this gap, we developed a method to accurately and sensitively detect transcriptome-wide allele-specific mA (ASmA) from MeRIP-seq data and applied it to uncover 12,056 high-confidence ASmA modifications from 25 human tissues. We also identified 1184 putative functional variants for ASmA regulation, a subset of which we experimentally validated. Importantly, we found that many of these ASmA-associated genetic variants were enriched for common disease-associated and complex trait-associated risk loci, and verified that two disease risk variants can change mA modification status. Together, this work provides a tool to detangle the dynamic network of RNA modifications at the allelic level and highlights the interplay of mA and genetics in human health and disease.
Topics: Humans; RNA; Alleles; Transcriptome
PubMed: 37714712
DOI: 10.1101/gr.277704.123 -
BMC Bioinformatics Mar 2024Uncovering functional genetic variants from an allele-specific perspective is of paramount importance in advancing our understanding of gene regulation and genetic...
BACKGROUND
Uncovering functional genetic variants from an allele-specific perspective is of paramount importance in advancing our understanding of gene regulation and genetic diseases. Recently, various allele-specific events, such as allele-specific gene expression, allele-specific methylation, and allele-specific binding, have been explored on a genome-wide scale due to the development of high-throughput sequencing methods. RNA secondary structure, which plays a crucial role in multiple RNA-associated processes like RNA modification, translation and splicing, has emerged as an essential focus of relevant research. However, tools to identify genetic variants associated with allele-specific RNA secondary structures are still lacking.
RESULTS
Here, we develop a computational tool called 'AStruct' that enables us to detect allele-specific RNA secondary structure (ASRS) from RT-stop based structuromic probing data. AStruct shows robust performance in both simulated datasets and public icSHAPE datasets. We reveal that single nucleotide polymorphisms (SNPs) with higher AStruct scores are enriched in coding regions and tend to be functional. These SNPs are highly conservative, have the potential to disrupt sites involved in m6A modification or protein binding, and are frequently associated with disease.
CONCLUSIONS
AStruct is a tool dedicated to invoke allele-specific RNA secondary structure events at heterozygous SNPs in RT-stop based structuromic probing data. It utilizes allelic variants, base pairing and RT-stop information under different cell conditions to detect dynamic and functional ASRS. Compared to sequence-based tools, AStruct considers dynamic cell conditions and outperforms in detecting functional variants. AStruct is implemented in JAVA and is freely accessible at: https://github.com/canceromics/AStruct .
Topics: RNA; Alleles; Gene Expression Regulation; RNA Splicing; High-Throughput Nucleotide Sequencing
PubMed: 38429654
DOI: 10.1186/s12859-024-05704-x -
Gastroenterology Mar 2024
Topics: Humans; Alleles; Glucagon-Like Peptides; Obesity; Polymorphism, Single Nucleotide; Non-alcoholic Fatty Liver Disease; Genetic Predisposition to Disease; Genotype
PubMed: 37972824
DOI: 10.1053/j.gastro.2023.11.018 -
Animal Biotechnology Dec 2023This paper reviews information about a unique and iconic breed of the Orenburg Oblast, the homeland and the only place where the best herds of Orenburg down-hair goats... (Review)
Review
This paper reviews information about a unique and iconic breed of the Orenburg Oblast, the homeland and the only place where the best herds of Orenburg down-hair goats in Russia are concentrated. Three types of these small ruminant animals are widespread on the territory of the region: Orenburg purebred gray goats, Orenburg purebred white goats, as well as crossbred white goats of F White Don × White Orenburg. Currently, at the farms of the Orenburg region, animals are selected according to their phenotype, with selected traits being color, weight and length of down hair. In recent years, the Orenburg goat breed has become an object of genetic research using various marker systems including immunogenetic, microsatellite, mtDNA and SNP markers. Overall, these studies evidence about the uniqueness of the allele pool in the landmark native breed of the Orenburg goats, which is a complex dynamic genetic system, prioritizing its further in-depth genome research and breeding applications.
Topics: Animals; Goats; Phenotype; Alleles; Hair
PubMed: 36495096
DOI: 10.1080/10495398.2022.2154221 -
ImmunoHorizons Nov 2023The polarization of naive Th cells into differentiated subsets in vitro was a powerful approach to define the development and function of Th cells in vivo. Th cell...
The polarization of naive Th cells into differentiated subsets in vitro was a powerful approach to define the development and function of Th cells in vivo. Th cell cultures identified cytokines that promote polarization and defined the phenotype and stability of differentiated cells. One of the limitations of this approach is the heterogeneity of the differentiated culture, essentially with regard to what proportion of the culture is secreting the hallmark cytokine of interest. This heterogeneity has always been puzzling because all cells in the culture have been exposed to identical culture conditions. We examined this phenomenon using an Il17f lineage-tracing allele (Cost, Cre on seventeen transcript) crossed to stop-flox Rosa-YFP (yellow fluorescent protein) mice. We found that less than half of the cells in a Th17 culture become lineage-positive during a differentiation culture and that it is primarily cells that are lineage-positive that produce cytokines when cultures are restimulated after differentiation. We sorted and analyzed YFP-positive and YFP-negative cells and found similar expression of many Th17 transcription factors, although YFP-negative cells had increased expression of other lineage-defining transcription factors. We observed that YFP-negative cells had diminished expression of Stat3 and Il6ra, as well as decreased STAT3 activation. YFP-negative cells transduced with active STAT3 had significant increases in IL-17A expression, without increases in Th17 transcription factors. Taken together, these data suggest that there is a threshold of STAT3 activation that is required for efficient Th17 differentiation, and that even in a culture of homogeneous naive T cells there is heterogeneity in the receipt of early cytokine signals.
Topics: Animals; Mice; Cytokines; Th17 Cells; Cell Differentiation; Alleles; Cell Movement
PubMed: 37938185
DOI: 10.4049/immunohorizons.2300072 -
Screening, Confirmation and Validation of Mismatch AS F-Primers for Hypertension-Related Genotyping.Studies in Health Technology and... Nov 2023In this study, screening, confirmation and validation of mismatch allele-specific (AS) forward (F)-primers are executed to establish a quadruplex amplification analysis...
In this study, screening, confirmation and validation of mismatch allele-specific (AS) forward (F)-primers are executed to establish a quadruplex amplification analysis (real-time PCR) for discrimination of CYP2D6*10, ADRB1, NPPA and CYP3A5*3 genotypes associated with hypertensive pharmacogenomics. To significantly distinguish heterozygote and homozygote, ΔCq (differences in threshold cycles between the wild-type F-primer amplification assay and the mutant-type F-primer amplification assay) was utilized to determine outcomes. Detection of plasmid by uniplex real-time PCR was used to screen the mismatch AS F-primers. Robustness assessment and agreement analysis were employed to confirm and validate initially selected F-primers, respectively. Robustness assessment confirmed that except of ADRB1 (0.7-0.9), amplification efficiency ranged from 0.9 to 1.1. No statistically significant difference was found between the analysis and NGS. Therefore, the optimized F-primer as polymorphism recognition molecules can benefit the genotyping guiding drug delivery in anti-hypertension treatment.
Topics: Genotype; Alleles; Polymorphism, Single Nucleotide; Pharmacogenetics
PubMed: 38007760
DOI: 10.3233/SHTI230860 -
Pharmacogenomics Sep 2023This work was designed to identify the pharmacogenetic profile of Brazilian psychiatric patients receiving psychoactive drug treatment according to ethnicity. Based on...
This work was designed to identify the pharmacogenetic profile of Brazilian psychiatric patients receiving psychoactive drug treatment according to ethnicity. Based on the GnTech database, this cross-sectional study analyzed data from self-reported sociodemographic and genetic results from the next-generation sequencing panel composed of 26 pharmacogenes from 359 psychotropic drug users. Variant frequencies of multiple pharmacogenes presented differences between ethnicities (, , , , , , , , , , , , , , , , , and ), endorsing the necessity of individual-level analyses in drug treatment. A discussion of pharmacogenomic test implementation in psychiatric clinical practice is needed to improve treatment choices, especially in Brazil, a multiethnic country.
Topics: Humans; Alleles; Brazil; Cross-Sectional Studies; Phenotype; Pharmacogenetics
PubMed: 37846556
DOI: 10.2217/pgs-2023-0075 -
HLA Oct 2023HLA-DPA1*02:102Q, a novel HLA class II allele detected by next-generation sequencing.
HLA-DPA1*02:102Q, a novel HLA class II allele detected by next-generation sequencing.
Topics: Humans; Alleles; HLA-DP alpha-Chains
PubMed: 37354083
DOI: 10.1111/tan.15140