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Keywords = D222G/N polymorphism

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17 pages, 4894 KB  
Article
Identification of Candidate Genes Related to SPAD Value Using Multi-Year Phenotypic Data in Rice Germplasms by Genome-Wide Association Study (GWAS)
by Dong-Hyun Baek, Tae-Heon Kim, Chang-Ju Lee, Jingli Gao, Woo-Geun Park and Suk-Man Kim
Agronomy 2025, 15(9), 2050; https://doi.org/10.3390/agronomy15092050 - 26 Aug 2025
Viewed by 505
Abstract
This study aimed to identify candidate genes associated with chlorophyll content in rice via genome-wide association studies (GWAS) and to develop molecular markers for the selection of genetic resources and breeding lines exhibiting high chlorophyll content. Measurement of the Soil and Plant Analysis [...] Read more.
This study aimed to identify candidate genes associated with chlorophyll content in rice via genome-wide association studies (GWAS) and to develop molecular markers for the selection of genetic resources and breeding lines exhibiting high chlorophyll content. Measurement of the Soil and Plant Analysis Development (SPAD) values, indicative of chlorophyll content and photosynthetic potential, were measured in 198 rice genetic resources across three years under consistent nitrogen conditions. Nitrogen fertilizer (as urea) was applied at a rate of 90 kg N ha−1. After analyzing the multi-year SPAD data, genetic resources with the coefficient of variation (CV) value exceeding 20% were excluded, and the remaining 175 accessions were used for subsequent analyses. Population structure analysis using the principal component analysis (PCA) and phylogenetic methods confirmed clear genetic differentiation, supporting the reliability of the GWAS. A GWAS using 289,569 SNPs identified 17 significant loci, among which four quantitative trait loci (QTLs)—qSV3-1, qSV3-2, qSV6, and qSV7—explained over 20% of phenotypic variance. Analysis of their additive effects revealed distinct SPAD distributions among QTL combination groups, with accessions harboring all four QTLs exhibiting the highest values. Candidate gene analysis within ± 200 kb of lead SNPs identified Os03g079100 (OsUCL8), involved in photosynthesis, near qSV3-2. A derived cleaved amplified polymorphic sequence (dCAPS) marker was developed to differentiate alleles at this locus and validated via restriction digestion. These results provide key genetic insights into chlorophyll accumulation and offer molecular markers for breeding high-yielding rice cultivars with enhanced chlorophyll content. The results of this study are expected to contribute to the development of sustainable rice varieties by utilizing the developed markers and identified candidate genes to increase SPAD values, thereby enhancing nitrogen use efficiency, improving photosynthetic capacity, and ultimately increasing rice productivity. Full article
(This article belongs to the Section Crop Breeding and Genetics)
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30 pages, 29722 KB  
Article
Modeling Possible G-Quadruplexes and i-Motifs at DNA–DNA Contact Sites: Strategy, Classification, and Examples
by Vladimir B. Tsvetkov
Int. J. Mol. Sci. 2025, 26(13), 5979; https://doi.org/10.3390/ijms26135979 - 21 Jun 2025
Cited by 1 | Viewed by 617
Abstract
Tetrahelical DNA structures, such as G-quadruplexes (G4s) or i-motifs (iMs), are adopted by sequences comprising several G/C tracts, exist in equilibria with respective duplexes, and may contribute to genomic instability upon helicase deficiency. To understand genomic rearrangements resulting from the juxtaposition of G/C-rich [...] Read more.
Tetrahelical DNA structures, such as G-quadruplexes (G4s) or i-motifs (iMs), are adopted by sequences comprising several G/C tracts, exist in equilibria with respective duplexes, and may contribute to genomic instability upon helicase deficiency. To understand genomic rearrangements resulting from the juxtaposition of G/C-rich DNA duplexes, models of possible intermediate structures are needed. In this study, a general strategy for creating and verifying in silico 3D models of tetrahelical DNA was proposed. This strategy was used to investigate contacts of two or more duplexes with n G3/C3 tracts (n = 2–6) separated by T/A nucleotides. The revealed viable structures of DNA–DNA contacts include stacks of right-handed and left-handed G-quadruplexes (G4s), Holliday structure-resembling assemblies with the G4 and iM opposite each other on the borders of the central “hole”, etc. Based on molecular dynamic simulations, the most probable variants were determined by estimating the contributions to the free energy. The results may be used to clarify the mechanisms of strand exchange and other rearrangements upon DNA breaks near prolonged G/C-rich sites in living systems. Additionally, they provide a balanced view on the polymorphic versus programmed DNA assemblies in artificial systems. Full article
(This article belongs to the Collection State-of-the-Art Macromolecules in Russia)
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11 pages, 735 KB  
Article
Effects of Hawthorn Fruit Supplementation on Facial Skin Phenotypes and Leukocyte Telomere Length Stratified by TERT Polymorphisms
by Minju Kim and Inkyung Baik
Nutrients 2025, 17(12), 1983; https://doi.org/10.3390/nu17121983 - 12 Jun 2025
Viewed by 942
Abstract
Objectives: A randomized, double-blind, placebo-controlled intervention study aimed to evaluate whether hawthorn fruit (HF) supplementation can influence facial skin phenotypes and leukocyte telomere length (TL) and whether these effects differ by genetic polymorphisms related to TL. Participants/Methods: Among 41 male and female adults [...] Read more.
Objectives: A randomized, double-blind, placebo-controlled intervention study aimed to evaluate whether hawthorn fruit (HF) supplementation can influence facial skin phenotypes and leukocyte telomere length (TL) and whether these effects differ by genetic polymorphisms related to TL. Participants/Methods: Among 41 male and female adults aged 25–75 years who participated in the study, 36 completed initial and follow-up examinations over 6 months. The HF supplementation group (n = 17) was instructed to take a powdered HF supplement (900 mg/day), while controls (n = 19) were to take a cornstarch placebo (900 mg/day). Facial skin phenotypes, including pigmentation, pores, hydration, wrinkles, and elasticity, were measured before and after the intervention, and changes in these phenotype scores were calculated. Sequencing of telomerase reverse transcriptase (TERT) polymorphisms, such as rs7705526 (C>A) and rs2853669 (A>G), was conducted. Results: The HF supplementation group exhibited significantly improved hydration scores compared to the control group; the mean changes (follow-up measure—baseline measure) [standard deviation] in hydration scores over 6 months were 1.71 [8.18] and −3.00 [8.42] for the supplementation group and control group, respectively (p < 0.05) (Cohen’s d = 0.57). However, changes in other phenotypes and leukocyte TL were similar between groups. The genotype-specific analysis revealed that the improvement of hydration state was most noticeable among carriers with the CC genotype of rs7705526 (p < 0.05) (Cohen’s d = 1.50) and that the HF supplementation group exhibited reduced wrinkle scores while the control group showed increased scores among carriers of the AA genotype of rs2853669 (p < 0.05) (Cohen’s d = 1.40). In correlation analysis for all participants, hydration scores were positively correlated with leukocyte TL (Spearman correlation coefficient: 0.36; p < 0.05). Conclusions: These findings suggest that HF consumption may have potential anti-skin-aging effects. Future studies may need to elucidate the biological mechanisms underlying these effects. Full article
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15 pages, 2576 KB  
Brief Report
Association of Novel Mutations in the Vasoactive Intestinal Peptide Receptor-1 Gene with Egg Shell Thickness in Three Strains of Laying-Type Quail
by Xinle Wang, Huricha Chen, Ying Lei, Qiankun Wang, Gan Li and Junyan Bai
Animals 2025, 15(10), 1373; https://doi.org/10.3390/ani15101373 - 9 May 2025
Viewed by 432
Abstract
This study aimed to investigate the potential role of the vasoactive intestinal peptide receptor-1 (VIPR-1) gene polymorphisms and haplotypes in influencing egg production performance and egg quality parameters in laying-type quail. Genomic DNA was extracted from 150 quail across three strains: [...] Read more.
This study aimed to investigate the potential role of the vasoactive intestinal peptide receptor-1 (VIPR-1) gene polymorphisms and haplotypes in influencing egg production performance and egg quality parameters in laying-type quail. Genomic DNA was extracted from 150 quail across three strains: Chinese yellow (CY, n = 50), Beijing white (BW, n = 50), and Korean (KO, n = 50). We designed two pairs of primers and initiated PCR amplification, after which the amplified products were sent to a testing company for purification. Sanger sequencing was employed to identify single nucleotide polymorphisms (SNPs) within the VIPR-1 gene. Two SNP sites were selected for genotyping; g.1603402T>G was analyzed using PCR-RFLP with the BsrD I enzyme, while g.1614884A>G was genotyped using the HpyCH4 IV enzyme. The association results revealed that the g.1603402T>G site showed significant association with egg shell thickness (EST) in the BW strain (p < 0.05). There were no significant associations between these two loci and the remaining egg quality traits in the BW and KO strains (p > 0.05). Differences in egg quality and laying performance among haplotype combinations were not significant (p > 0.05). In conclusion, the VIPR-1 gene, with its identified polymorphisms and haplotypes, has potential as a molecular marker that could improve egg shell thickness in BW quail. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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20 pages, 2783 KB  
Article
CYP2D6 Genotyping for Optimization of Tamoxifen Therapy in Indonesian Women with ER+ Breast Cancer
by Baitha Palanggatan Maggadani, Kathleen Irena Junusmin, Fatma Aldila, Jessica Audrienna, Bijak Rabbani, Yusuf Maulana, Sabrina Gabriel Tanu, Gabriella Gabriella, Margareta Amelia, Faustina Audrey Agatha, Marco Wijaya, Stevany Tiurma Sormin, Caroline Mahendra, Levana Laksmicitra Sani, Astrid Irwanto, Alexandre Chan, Harmita Harmita, Yahdiana Harahap and Samuel Johny Haryono
J. Pers. Med. 2025, 15(3), 93; https://doi.org/10.3390/jpm15030093 - 28 Feb 2025
Viewed by 2218
Abstract
Background: Certain CYP2D6 genotypes are linked to a lower efficacy of tamoxifen therapy. This study aimed to observe CYP2D6 polymorphisms and examine the impact of CYP2D6 genotyping among tamoxifen-treated breast cancer patients in Indonesia. Methods: 150 breast cancer participants were recruited. Buccal swab [...] Read more.
Background: Certain CYP2D6 genotypes are linked to a lower efficacy of tamoxifen therapy. This study aimed to observe CYP2D6 polymorphisms and examine the impact of CYP2D6 genotyping among tamoxifen-treated breast cancer patients in Indonesia. Methods: 150 breast cancer participants were recruited. Buccal swab samples were collected; gDNA was extracted and genotyped using the qPCR method. Blood samples were collected, and measurement of tamoxifen metabolite levels was performed using UPLC-MS/MS. Results: 43.3% (n = 65) of participants were IMs. *10 was the most common haplotype (n = 89, 29.7%), followed by *36 (n = 73, 29.7%), making *10/*36 the most common diplotype (n = 34, 22.7%) in this study. The difference in endoxifen levels between the NM and IM-PM groups at baseline was statistically significant (p ≤ 0.001). A dose increase in tamoxifen to 40 mg daily successfully increased endoxifen levels in IMs to a similar level with NMs at baseline (p > 0.05) without exposing IMs to serious side effects. No statistically significant differences were observed between the 20mg group and the 40 mg group on the adjusted OS (p > 0.05) and the adjusted PFS (p > 0.05). Conclusions: Our study observed a considerably high proportion of CYP2D6 IMs. The dose adjustment of tamoxifen was proven to significantly and safely improve the level of endoxifen and survival. Full article
(This article belongs to the Section Pharmacogenetics)
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23 pages, 1444 KB  
Article
Polymorphic Variants of Peptidylarginine Deiminase Gene from P. gingivalis—Searching for Targets for Supportive Therapy of Periodontitis
by Karolina Strzelec, Agata Dziedzic-Kowalska, Łukasz Sieron, Grzegorz P. Bereta, Karolina L. Stepien, Klara Ferenc, Katarzyna Łazarz-Bartyzel, Iwona Olszewska-Czyż, Iwona Rąpalska, Małgorzata Aptekorz, Tomasz Kaczmarzyk, Marta Cześnikiewicz-Guzik and Katarzyna Gawron
Int. J. Mol. Sci. 2025, 26(4), 1662; https://doi.org/10.3390/ijms26041662 - 15 Feb 2025
Viewed by 793
Abstract
Periodontitis (PD), an oral inflammatory disease, is primarily caused by P. gingivalis. Peptidylarginine deiminase (PPAD) is considered an attractive virulence factor because, due to protein citrullination, it may have deleterious effects on host tissues. In this study, the ppad gene sequences from [...] Read more.
Periodontitis (PD), an oral inflammatory disease, is primarily caused by P. gingivalis. Peptidylarginine deiminase (PPAD) is considered an attractive virulence factor because, due to protein citrullination, it may have deleterious effects on host tissues. In this study, the ppad gene sequences from P. gingivalis were analyzed in the context of its impact on bacterial virulence and potential targets for PD therapy. Analyses of ppad sequences from 58 patients with various clinical stages of PD, 20 controls, and 60 sequences from public databases were conducted. Overall, 55 substitutions assigned as polymorphic variants (4), missense mutations (10), or synonymous variants (35) were identified in PD, and 22 synonymous variants were identified in controls. Among them, the G231N, E232T, N235D variant was found in ~25% of P. gingivalis strains from PD samples. It was located close to the catalytic triad and had two-fold higher activity in comparison with reference P. gingivalis, upregulated expression of key inflammatory mediators, and contributed to worsening periodontium conditions in advanced PD, suggesting their unambiguous impact on P. gingivalis virulence. Our results indicate the G231N, E232T, N235D variant of the ppad gene as a potential candidate, opening a path to searching for novel targets for supportive therapy of PD. Further validation of the identified mutations is needed in future studies. Full article
(This article belongs to the Section Molecular Biology)
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14 pages, 2450 KB  
Article
Intraspecific Chloroplast Genome Genetic Polymorphism of Pinellia ternata (Xi Junecry) and Its Revelation of a Single Origin in Phylogeny
by Wenlong Xing, Weihan Yu, Yuanyuan Kong, Xian Ren, Liuying Zhu, Qingyang Li, Yujie Yang, Yueqin Cheng and Hongwei Wang
Genes 2024, 15(12), 1638; https://doi.org/10.3390/genes15121638 - 20 Dec 2024
Cited by 2 | Viewed by 843
Abstract
Background: Xi Junecry (Pinellia ternata), a perennial herb of the Araceae family, is indigenous to Xinxian County, Henan Province, China, and is regarded as a premium variety among similar medicinal materials. However, the lack of comprehensive genetic information on Xi [...] Read more.
Background: Xi Junecry (Pinellia ternata), a perennial herb of the Araceae family, is indigenous to Xinxian County, Henan Province, China, and is regarded as a premium variety among similar medicinal materials. However, the lack of comprehensive genetic information on Xi Junecry germplasm resources has constrained the cultivation and identification of high-quality varieties. Methods: In this study, six chloroplast genomes of Xi Junecry were assembled and annotated using high-throughput sequencing. Subsequently, comparative analyses were conducted, and a phylogenetic tree was constructed. Results: The six Xi Junecry chloroplast genome lengths ranged from 157,456 to 158,406 bp, and the GC content was between 36.0% and 36.2%. A total of 265 single nucleotide polymorphism sites were identified across the six genomes, with a whole-genome nucleotide diversity (Pi) value of 0.00084. Among the four genomic regions, the small single-copy region exhibited the highest Pi, followed by the large single-copy region, while the inverted repeat region showed the lowest. Nucleotide polymorphism in coding regions was significantly lower than in non-coding regions. Nine hypervariable regions were identified, as follows: ndhE-ndhG, trnN-GUU-ndhF, trnS-GCU-trnG-UCC, atpB-rbcL, psaI, accD-ycf4, psbE-petL, psaC-ndhE, and psbI-trnG-UCC. Positive selection sites were detected in the accD and rbcL genes. Phylogenetic analysis clustered the six Xi Junecry samples into a distinct clade, separating them from other regional Pinellia samples. Conclusions: These findings elucidate the genetic variation levels in Xi Junecry and provide high-variability loci for population history inference, genetic diversity assessment, species domestication studies, and new cultivar development. Full article
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19 pages, 1828 KB  
Article
A Comprehensive Analysis of CSN1S2 I and II Transcripts Reveals Significant Genetic Diversity and Allele-Specific Exon Skipping in Ragusana and Amiatina Donkeys
by Gianfranco Cosenza and Alfredo Pauciullo
Animals 2024, 14(20), 2918; https://doi.org/10.3390/ani14202918 - 10 Oct 2024
Cited by 2 | Viewed by 1279
Abstract
The αs2-casein is a phosphoprotein secreted in the milk of most mammals, and it is the most hydrophilic of all caseins. Contrary to genes found in ruminants, in donkeys two different encoding genes for donkey αs2-casein (CSN1S2 I and CSN1S2 II) have [...] Read more.
The αs2-casein is a phosphoprotein secreted in the milk of most mammals, and it is the most hydrophilic of all caseins. Contrary to genes found in ruminants, in donkeys two different encoding genes for donkey αs2-casein (CSN1S2 I and CSN1S2 II) have been identified. However, unlike in ruminants, the variability at these loci has not been characterized in detail in donkeys until now. In this study, we analyze the transcript profile of the donkey CSN1S2 I and CSN1S2 II genes, and we identify and describe the variability of these loci in the Ragusana and Amiatina breeds reared in Italy. The analysis of the CSN1S2 I Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) products and subsequent sequencing showed, in addition to correctly spliced mRNA, seven other minor mRNAs resulting from differential splicing events involving, in various combinations, entire exons (4, 5, 6, and 11), parts of exons (5′ or 3′ end of exon 17), or the recognition of intronic sequences as an exon (exon 12′). Similarly, the transcription analysis of the CSN1S2 II gene revealed a remarkable variability in splicing events, mainly concerning the alternative insertion of an extra exon 7 (named 7′); the first 33 bp of exon 13; or the alternative skipping of exons 9, 10, 11, 12, and 15, and their combinations. At the mRNA level for CSN1S2 I, seven SNPs were observed, five of which led to amino acid changes: p.T73>A, p.I109>V, p.I130>V, p.I146>T, and p.D217>Y. Similarly, nine SNPs were observed at the CSN1S2 II locus, seven of which are non-synonymous: p.L63>F, p.H70>Q, p.D90>N, p.129A>T, p.H131>Y, p.E144>G, and p.F157>S. In addition, the DNA sequencing of exon 17 and flanking introns of the CSN1S2 I gene revealed a G>A transition at the splice acceptor site of CSN1S2 I exon 17 (FM946022.1:c.375-1G>A), resulting in an allele-specific skipping of the first 15 nucleotides of this exon, which encode the peptide 176NKINQ180, and the recognition of an in-frame cryptic splicing acceptor site: arAACAAAATCAACCAG. A genotyping method based on restriction fragment length polymorphism (XbaI PCR-RFLP) was set up for this SNP. In the total population studied (105 Ragusana and 14 Amiatina donkeys), the A allele had a frequency of 0.2437 with no evidence of deviation from the Hardy–Weinberg equilibrium. This study adds new knowledge regarding the genetic variability of αs2-caseins in donkeys and may contribute significantly to the genetic improvement of milk production for this species. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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13 pages, 3153 KB  
Article
Sanger Sequencing Reveals Novel Variants in GLO-1, ACE, and CBR1 Genes in Patients of Early and Severe Diabetic Nephropathy
by Syed Zubair Hussain Shah, Amir Rashid, Asifa Majeed, Tariq Ghafoor and Nadeem Azam
Medicina 2024, 60(9), 1540; https://doi.org/10.3390/medicina60091540 - 20 Sep 2024
Viewed by 1645
Abstract
Background and Objectives: Diabetes is a global health issue, with approximately 50% of patients developing diabetic nephropathy (DN) and 25% experiencing early and severe forms of the disease. The genetic factors contributing to rapid disease progression in a subset of these patients are [...] Read more.
Background and Objectives: Diabetes is a global health issue, with approximately 50% of patients developing diabetic nephropathy (DN) and 25% experiencing early and severe forms of the disease. The genetic factors contributing to rapid disease progression in a subset of these patients are unclear. This study investigates genetic variations in the GLO-1, CBR-1, and ACE genes associated with early and severe DN. Materials and Methods: Sanger DNA sequencing of the exons of CBR1, GLO1, and ACE genes was conducted in 113 patients with early and severe DN (defined as occurring within 10 years of the diagnosis of diabetes and with eGFR < 45 mL/min/1.73 m2) and 100 controls. The impact of identified genetic variations was analyzed using computational protein models created in silico with SWISS-Model and SWISS-Dock for ligand binding interactions. Results: In GLO1, two heterozygous missense mutations, c.102G>T and c.147C>G, and one heterozygous nonsense mutation, c.148G>T, were identified in patients. The SNP rs1049346 (G>A) at location 6:38703061 (GRCh38) was clinically significant. The c.147C>G mutation (C19S) was associated with ligand binding disruption in the GLO1 protein, while the nonsense mutation resulted in a truncated, non-functional protein. In CBR1, two heterozygous variations, one missense c.358G>A, and one silent mutation c.311G>C were observed, with the former (D120N) affecting the active site. No significant changes were noted in ACE gene variants concerning protein structure or function. Conclusions: The study identifies four novel and five recurrent mutations/polymorphisms in GLO1, ACE, and CBR1 genes associated with severe DN in Pakistani patients. Notably, a nonsense mutation in GLO1 led to a truncated, non-functional protein, while missense mutations in GLO1 and CBR1 potentially disrupt enzyme function, possibly accelerating DN progression. Full article
(This article belongs to the Section Urology & Nephrology)
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13 pages, 730 KB  
Article
Development and Optimization of Oligonucleotide Ligation Assay (OLA) Probes for Detection of HIV-1 Resistance to Dolutegravir
by Ingrid A. Beck, Ceejay L. Boyce, Marley D. Bishop, Yen L. Vu, Amanda Fung, Sheila Styrchak, Nuttada Panpradist, Barry R. Lutz and Lisa M. Frenkel
Viruses 2024, 16(7), 1162; https://doi.org/10.3390/v16071162 - 19 Jul 2024
Cited by 4 | Viewed by 2125
Abstract
The WHO currently recommends dolutegravir (DTG)-based ART for persons living with HIV infection in resource-limited-settings (RLS). To expand access to testing for HIV drug resistance (DR) to DTG in RLS, we developed probes for use in the oligonucleotide ligation assay (OLA)-Simple, a near-point [...] Read more.
The WHO currently recommends dolutegravir (DTG)-based ART for persons living with HIV infection in resource-limited-settings (RLS). To expand access to testing for HIV drug resistance (DR) to DTG in RLS, we developed probes for use in the oligonucleotide ligation assay (OLA)-Simple, a near-point of care HIV DR kit. Genotypic data from clinical trials and case reports were used to determine the mutations in HIV-1 integrase critical to identifying individuals with DTG-resistance at virologic failure of DTG-based ART. Probes to detect G118R, Q148H/K/R, N155H and R263K in HIV-1 subtypes A, B, C, D and CRF01_AE were designed using sequence alignments from the Los Alamos database and validated using 61 clinical samples of HIV-1 subtypes A, B, C, D, CRF01_AE genotyped by PacBio (n = 15) or Sanger (n = 46). Initial OLA probes failed to ligate for 16/244 (6.5%) codons (9 at G118R and 7 at Q148H/K/R). Probes revised to accommodate polymorphisms interfering with ligation at codons G118R and Q148R reduced indeterminates to 3.7% (5 at G118R and 4 at Q148H/K/R) and detected DTG-mutations with a sensitivity of 96.5% and 100% specificity. These OLA DTG resistance probes appear highly sensitive and specific across HIV-1 subtypes common in RLS with high burden of HIV infection. Full article
(This article belongs to the Special Issue Antiviral Resistance Mutations)
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18 pages, 2609 KB  
Article
An Investigation of Severe Influenza Cases in Russia during the 2022–2023 Epidemic Season and an Analysis of HA-D222G/N Polymorphism in Newly Emerged and Dominant Clade 6B.1A.5a.2a A(H1N1)pdm09 Viruses
by Natalia P. Kolosova, Nikita D. Boldyrev, Svetlana V. Svyatchenko, Alexey V. Danilenko, Natalia I. Goncharova, Kyunnei N. Shadrinova, Elena I. Danilenko, Galina S. Onkhonova, Maksim N. Kosenko, Maria E. Antonets, Ivan M. Susloparov, Tatiana N. Ilyicheva, Vasily Y. Marchenko and Alexander B. Ryzhikov
Pathogens 2024, 13(1), 1; https://doi.org/10.3390/pathogens13010001 - 19 Dec 2023
Cited by 7 | Viewed by 2881
Abstract
In Russia, during the COVID-19 pandemic, a decrease in influenza circulation was initially observed. Influenza circulation re-emerged with the dominance of new clades of A(H3N2) viruses in 2021–2022 and A(H1N1)pdm09 viruses in 2022–2023. In this study, we aimed to characterize influenza viruses during [...] Read more.
In Russia, during the COVID-19 pandemic, a decrease in influenza circulation was initially observed. Influenza circulation re-emerged with the dominance of new clades of A(H3N2) viruses in 2021–2022 and A(H1N1)pdm09 viruses in 2022–2023. In this study, we aimed to characterize influenza viruses during the 2022–2023 season in Russia, as well as investigate A(H1N1)pdm09 HA-D222G/N polymorphism associated with increased disease severity. PCR testing of 780 clinical specimens showed 72.2% of them to be positive for A(H1N1)pdm09, 2.8% for A(H3N2), and 25% for influenza B viruses. The majority of A(H1N1)pdm09 viruses analyzed belonged to the newly emerged 6B.1A.5a.2a clade. The intra-sample predominance of HA-D222G/N virus variants was observed in 29% of the specimens from A(H1N1)pdm09 fatal cases. The D222N polymorphic variant was registered more frequently than D222G. All the B/Victoria viruses analyzed belonged to the V1A.3a.2 clade. Several identified A(H3N2) viruses belonged to one of the four subclades (2a.1b, 2a.3a.1, 2a.3b, 2b) within the 3C.2a1b.2a.2 group. The majority of antigenically characterized viruses bore similarities to the corresponding 2022–2023 NH vaccine strains. Only one influenza A(H1N1)pdm09 virus showed reduced inhibition by neuraminidase inhibitors. None of the influenza viruses analyzed had genetic markers of reduced susceptibility to baloxavir. Full article
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10 pages, 289 KB  
Article
The Polymorphism rs17300539 in the Adiponectin Promoter Gene Is Related to Metabolic Syndrome, Insulin Resistance, and Adiponectin Levels in Caucasian Patients with Obesity
by Daniel de Luis Roman, Olatz Izaola Jauregui and David Primo Martin
Nutrients 2023, 15(24), 5028; https://doi.org/10.3390/nu15245028 - 7 Dec 2023
Cited by 1 | Viewed by 2570
Abstract
Background and Aims: The present study was designed to investigate SNP rs17300539 in the ADIPOQ gene and its relationships with obesity, metabolic syndrome (MS), and serum circulating adiponectin. Methods: The present design involved a Caucasian population of 329 subjects with obesity. [...] Read more.
Background and Aims: The present study was designed to investigate SNP rs17300539 in the ADIPOQ gene and its relationships with obesity, metabolic syndrome (MS), and serum circulating adiponectin. Methods: The present design involved a Caucasian population of 329 subjects with obesity. Anthropometric and adiposity parameters, blood pressure, biochemical parameters, and the percentage of patients with metabolic syndrome were recorded. The ADIPOQ gene variant (rs17300539) genotype was evaluated. Results: The percentage of patients with different genotypes of the rs17300539 polymorphism in this sample was 86.0% (n = 283) (GG), 11.2% (n = 37) (GA), and 2.7% (n = 9) (AA). The allele frequency was G (0.76) and A (0.24). Applying the dominant genetic model (GG vs. GA + AA), we reported differences between genotype GG and genotype GA + AA for serum adiponectin levels (Delta: 7.5 ± 1.4 ng/mL; p = 0.03), triglycerides (Delta: 41.1 ± 3.4 mg/dL; p = 0.01), fastingcirculating insulin (Delta: 4.9 ± 1.1 mUI/L; p = 0.02), and insulin resistance as HOMA-IR (Delta: 1.4 ± 0.1 units; p = 0.02). The remaining biochemical parameters were not related to the genotype of obese patients. The percentages of individuals with MS (OR = 2.07, 95% CI = 1.3–3.88; p = 0.01), hypertriglyceridaemia (OR = 2.66, 95% CI = 1.43–5.01; p = 0.01), and hyperglycaemia (OR = 3.31, 95% CI = 1.26–8.69; p = 0.02) were higher in GG subjects than patients with A allele. Logistic regression analysis reported an important risk of the presence of metabolic syndrome in GG subjects (OR = 1.99, 95% CI = 1.21–4.11; p = 0.02) after adjusting for adiponectin, dietary energy intakes, gender, weight, and age. Conclusions: The GG genotype of rs17300539 is associated with hypertriglyceridaemia, insulin resistance, low adiponectin levels, and a high risk of metabolic syndrome and its components. Full article
(This article belongs to the Special Issue Recent Advances in Nutrigenomics and Nutrigenetics)
14 pages, 1135 KB  
Article
Impacts of Natural Selection on Evolution of Core and Symbiotically Specialized (sym) Genes in the Polytypic Species Neorhizobium galegae
by Evgeny S. Karasev, Sergey L. Hosid, Tatiana S. Aksenova, Olga P. Onishchuk, Oksana N. Kurchak, Nikolay I. Dzyubenko, Evgeny E. Andronov and Nikolay A. Provorov
Int. J. Mol. Sci. 2023, 24(23), 16696; https://doi.org/10.3390/ijms242316696 - 24 Nov 2023
Cited by 2 | Viewed by 1431
Abstract
Nodule bacteria (rhizobia) represent a suitable model to address a range of fundamental genetic problems, including the impacts of natural selection on the evolution of symbiotic microorganisms. Rhizobia possess multipartite genomes in which symbiotically specialized (sym) genes differ from core genes [...] Read more.
Nodule bacteria (rhizobia) represent a suitable model to address a range of fundamental genetic problems, including the impacts of natural selection on the evolution of symbiotic microorganisms. Rhizobia possess multipartite genomes in which symbiotically specialized (sym) genes differ from core genes in their natural histories. Diversification of sym genes is responsible for rhizobia microevolution, which depends on host-induced natural selection. By contrast, diversification of core genes is responsible for rhizobia speciation, which occurs under the impacts of still unknown selective factors. In this paper, we demonstrate that in goat’s rue rhizobia (Neorhizobium galegae) populations collected at North Caucasus, representing two host-specific biovars orientalis and officianalis (N2-fixing symbionts of Galega orientalis and G. officinalis), the evolutionary mechanisms are different for core and sym genes. In both N. galegae biovars, core genes are more polymorphic than sym genes. In bv. orientalis, the evolution of core genes occurs under the impacts of driving selection (dN/dS > 1), while the evolution of sym genes is close to neutral (dN/dS ≈ 1). In bv. officinalis, the evolution of core genes is neutral, while for sym genes, it is dependent on purifying selection (dN/dS < 1). A marked phylogenetic congruence of core and sym genes revealed using ANI analysis may be due to a low intensity of gene transfer within and between N. galegae biovars. Polymorphism in both gene groups and the impacts of driving selection on core gene evolution are more pronounced in bv. orientalis than in bv. officianalis, reflecting the diversities of their respective host plant species. In bv. orientalis, a highly significant (P0 < 0.001) positive correlation is revealed between the p-distance and dN/dS values for core genes, while in bv. officinalis, this correlation is of low significance (0.05 < P0 < 0.10). For sym genes, the correlation between p-distance and dN/dS values is negative in bv. officinalis but is not revealed in bv. orientalis. These data, along with the functional annotation of core genes implemented using Gene Ontology tools, suggest that the evolution of bv. officinalis is based mostly on adaptation for in planta niches while in bv. orientalis, evolution presumably depends on adaptation for soil niches. New insights into the tradeoff between natural selection and genetic diversity are presented, suggesting that gene nucleotide polymorphism may be extended by driving selection only in ecologically versatile organisms capable of supporting a broad spectrum of gene alleles in their gene pools. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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23 pages, 6402 KB  
Article
In Silico Evaluation of Coding and Non-Coding nsSNPs in the Thrombopoietin Receptor (MPL) Proto-Oncogene: Assessing Their Influence on Protein Stability, Structure, and Function
by Hakeemah H. Al-nakhle, Hind S. Yagoub, Sadin H. Anbarkhan, Ghadah A. Alamri and Norah M. Alsubaie
Curr. Issues Mol. Biol. 2023, 45(12), 9390-9412; https://doi.org/10.3390/cimb45120589 - 23 Nov 2023
Cited by 2 | Viewed by 2156
Abstract
The thrombopoietin receptor (MPL) gene is a critical regulator of hematopoiesis, and any alterations in its structure or function can result in a range of hematological disorders. Non-synonymous single nucleotide polymorphisms (nsSNPs) in MPL have the potential to disrupt normal protein [...] Read more.
The thrombopoietin receptor (MPL) gene is a critical regulator of hematopoiesis, and any alterations in its structure or function can result in a range of hematological disorders. Non-synonymous single nucleotide polymorphisms (nsSNPs) in MPL have the potential to disrupt normal protein function, prompting our investigation into the most deleterious MPL SNPs and the associated structural changes affecting protein–protein interactions. We employed a comprehensive suite of bioinformatics tools, including PredictSNP, InterPro, ConSurf, I-Mutant2.0, MUpro, Musitedeep, Project HOPE, STRING, RegulomeDB, Mutpred2, CScape, and CScape Somatic, to analyze 635 nsSNPs within the MPL gene. Among the analyzed nsSNPs, PredictSNP identified 28 as significantly pathogenic, revealing three critical functional domains within MPL. Ten of these nsSNPs exhibited high conservation scores, indicating potential effects on protein structure and function, while 14 were found to compromise MPL protein stability. Although the most harmful nsSNPs did not directly impact post-translational modification sites, 13 had the capacity to substantially alter the protein’s physicochemical properties. Some mutations posed a risk to vital protein–protein interactions crucial for hematological functions, and three non-coding region nsSNPs displayed significant regulatory potential with potential implications for hematopoiesis. Furthermore, 13 out of 21 nsSNPs evaluated were classified as high-risk pathogenic variants by Mutpred2. Notably, amino acid alterations such as C291S, T293N, D295G, and W435C, while impactful on protein stability and function, were deemed non-oncogenic “passenger” mutations. Our study underscores the substantial impact of missense nsSNPs on MPL protein structure and function. Given MPL’s central role in hematopoiesis, these mutations can significantly disrupt hematological processes, potentially leading to a variety of disorders. The identified high-risk pathogenic nsSNPs may hold promise as potential biomarkers or therapeutic targets for hematological diseases. This research lays the foundation for future investigations into the MPL gene’s role in the realm of hematological health and diseases. Full article
(This article belongs to the Special Issue Structure and Function of Proteins: From Bioinformatics Insights)
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16 pages, 440 KB  
Article
Interleukin Variants Are Associated with the Development and Progression of IgA Nephropathy: A Candidate-Gene Association Study and Meta-Analysis
by Ioanna Chronopoulou, Maria Tziastoudi, Georgios Pissas, Efthimios Dardiotis, Maria Dardioti, Spyridon Golfinopoulos, Georgios Filippidis, Peter R. Mertens, Evangelia E. Tsironi, Vassilios Liakopoulos, Theodoros Eleftheriadis and Ioannis Stefanidis
Int. J. Mol. Sci. 2023, 24(22), 16347; https://doi.org/10.3390/ijms242216347 - 15 Nov 2023
Cited by 4 | Viewed by 1998
Abstract
The interleukin-1 gene cluster encodes cytokines, which modulate mesangial cell proliferation and matrix expansion, both constituting central factors in the development and progression of immunoglobulin A nephropathy (IgAN). A candidate-gene study was performed to examine the association of polymorphisms of the interleukin-1 gene [...] Read more.
The interleukin-1 gene cluster encodes cytokines, which modulate mesangial cell proliferation and matrix expansion, both constituting central factors in the development and progression of immunoglobulin A nephropathy (IgAN). A candidate-gene study was performed to examine the association of polymorphisms of the interleukin-1 gene cluster with the risk of progressive IgAN. To gain deeper insights into the involvement of interleukin genes in IgAN, a meta-analysis of genetic association studies (GAS) that examine the association between interleukin variants and IgAN was conducted. Association study: The case-control study consisted of 121 unrelated Caucasians with sporadic, histologically diagnosed IgAN and of 246 age- and sex-matched healthy controls. Persistent proteinuria (>2 g/24 h) and/or impaired kidney function (serum creatinine > 1.5 mg/dL) defined progressive (n = 67) vs. non-progressive (n = 54) IgAN cases. Genotypes were assessed for two promoter-region single-nucleotide polymorphisms, C-899T (rs1800587) in IL1A and C-511T (rs16944) in IL1B, and for one penta-allelic variable-length tandem repeat polymorphism (VNTR 86 bp intron 2) in IL1RN. The association of these variants with the susceptibility of IgAN and the development of progressive IgAN (healthy status, IgAN, progressive IgAN) was tested using the generalized odds ratio (ORG) metric. Linkage disequilibrium and haplotype analysis were also performed. Meta-analysis: We included in the meta-analysis 15 studies investigating association between 14 interleukin variants harbored in eight different genes and IgAN. The ORG was used to evaluate the association between interleukin variants and IgAN using random effects models. The present case-control study revealed association of IL1B C-511T (rs16944) with the progression of IgAN (p = 0.041; ORG = 2.11 (1.09–4.07)). On haplotype analysis, significant results were derived for the haplotypes C-C-1 (p = 0.005; OR = 0.456 (0.261~0.797)) and C-T-2 (p = 0.003; OR = 4.208 (1.545–11.50)). Regarding association and meta-analysis results, variants in IL1B (rs1143627 and rs16944), IL1RN (rs928940, rs439154, and rs315951) and IL10 (rs1800871) were associated with IgAN based on either genotype or allele counts. Genetic variants and haplotypes in the IL1B, IL1RN, and IL10 genes might contribute to an increased risk for development and progression of IgAN. Full article
(This article belongs to the Section Molecular Immunology)
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