Search Results (804)

The global impact of COVID-19 was staggering, with millions of cases and related mortality reported worldwide. Genetic variations play a significant role in determining an individual’s susceptibility to SARS-CoV-2 infection and progress to severe disease. This pilot study provides an experimental approach using WES to identify certain rare and novel genetic variants that might affect an individual’s susceptibility to the risk of SARS-CoV-2 infection, offering an initial exploration of these genetic variants. In the study cohort with 16 patients, the mortality rate was higher in male patients due to severe disease. There was a substantial burden of comorbidity, including hypertension, ischemic heart disease, and T2DM, conditions which independently increase the risk of adverse outcomes in COVID-19 patients. A total of 4478 variants were identified, distributed across 322 genes within the cohort. The majority of these variants were missense substitutions along with frameshift variants, inframe insertions/deletions (indels), and nonsense variants. The variants were further categorized by types to include single-nucleotide polymorphisms (SNPs), deletions (DEL), and insertions (INS). The gene with the highest number of variants was HLA-DRB1, followed by HLA-B, ABO, HPS4, and SP110 displaying both common polymorphisms and rare variants. Moreover, the HLA-B gene exhibited the highest number of rare candidate variants, followed by AK2, IRF7, KMT2D, TAP1, and HLA-DRB1. Several genes harbored multiple novel variants, including TAP1, AK2, G6PC3, HLA-B, IL12RB2, and ITGB2. The frequencies of the identified variants were found to be either zero or extremely low (below 1% threshold) in the Middle Eastern or in the overall combined population, suggesting that these are indeed rare and do not represent common indigenous polymorphisms. Functional enrichment analysis of the constructed protein–protein interaction network in our preliminary findings revealed that the identified genes are primarily enriched in pathways associated with immune deficiency and DNA repair. This initial exploration of genetic variants in COVID-19 susceptibility provides a foundation for future large-scale studies. Full article

Splicing regulatory sequences are cornerstones for exon recognition. Mutations that modify them can severely compromise mRNA maturation and protein production. A wide range of mutations, including SNPs and InDels, can influence splicing regulatory signals either directly (e.g., altering canonical donor and acceptor dinucleotides) or indirectly (e.g., creating cryptic splice sites). CSN1S1 and CSN1S2 genes encode for the two main milk proteins, αs1 and αs2 caseins, respectively. They represent a remarkable and unique example of the possibilities for alternative splicing of individual genes, both due to the high number of alternative splices identified to date and for recognized allele-specific splicing events. To date, at least 13 alleles of CSN1S1 originating from mutations that affect canonical splice sites have been described in Bos taurus (CSN1S1 A, A1, and H), Ovis aries (E, H, and I), Capra hircus (D and G), Bubalus bubalis (E, F) and Camelidae (A, C, and D). Similarly, allele-specific splicing events have been described at the CSN1S2 locus in B. taurus. (CSN1S2 D), C. hircus (CSN1S2 D), B. bubalis (CSN1S2 B, B1, and B2), Equus asinus (CSN1S2 I B), and Camelidae. This review highlights that mutations affecting canonical splice sites, particularly donor sites, are significant sources of genetic variation impacting the casein production of the main dairy livestock species. Currently, a key limitation on this topic is the lack of detailed functional and proteomic studies. Future research should leverage advanced omics technologies like long-read transcriptomics and allele-resolved RNA sequencing to characterize these splicing mechanisms, guiding precision breeding strategies. Full article

The poultry industry, a globally fast growing agricultural sector, provides affordable animal protein due to high efficiency. Gallus gallus domesticus are the most common domestic birds. Hybrid chicken breeds (crosses) are widely used to achieve high productivity. Maintaining industry competitiveness requires constant genetic selection of parent stock to improve performance traits. Genetic studies, which are essential in modern breeding programs, help identify genome variants linked to economically important traits and preserve population health. Next-generation sequencing (NGS) has identified millions of single nucleotide polymorphisms (SNPs) and insertions/deletions (INDELs), enabling detection of genome-wide regions associated with selection traits. Recent studies have pinpointed such regions using broiler lines, laying hen lines, or pooled genomic data. This review discusses advances in chicken genomic and transcriptomic research focused on traits enhancing meat breed performance and reproductive abilities. Special attention is given to transcriptome studies revealing regulatory mechanisms and key signaling pathways involved in artificial molting, as well as metagenome studies investigating resistance to infectious diseases and climate adaptation. Finally, a dedicated section highlights CRISPR/Cas genomic editing techniques for targeted genome modification in chicken genomics. Full article

We previously demonstrated lipid nanoparticle-mediated CRISPR-Cas9 gene editing to disrupt the gene encoding cytochrome P450 oxidoreductase (Cypor), combined with transient administration of acetaminophen (APAP), to repopulate the liver with healthy hepatocytes and rescue a phenylketonuria mouse model. This study aimed to investigate electroporation-mediated delivery of Cypor-targeting CRISPR-Cas9 ribonucleoproteins into wild-type hepatocytes, combined with liver engraftment under APAP treatment, as an in vivo selection approach in a mouse model of homozygous familial hypercholesterolemia (Ldlr^−/−). Electroporation provides higher delivery efficiency compared to lipid nanoparticles. We observed engraftment levels up to 13% engraftment of electroporated Cypor-deficient hepatocytes with indels in the liver of Ldlr^−/− mice after transient APAP administration, while negligible engraftment was observed in no-APAP controls (mean 9% and 2%, respectively, p = 0.0121). The engraftment of Cypor-deficient Ldlr^+/+ hepatocytes was associated with reductions in LDL-cholesterol (18%) and triglycerides (52%) compared to the untransplanted control Ldlr^−/− mice fed a Western diet for 5 weeks, but offered no protection from the development of diet-induced aortic root atherosclerosis or liver steatosis. While biochemical markers for liver damage normalized after discontinuation of APAP, we observed persistent lipid accumulation in the liver of Ldlr^−/− mice grafted with Cypor-deficient Ldlr^+/+ hepatocytes, likely stemming from the impact of Cypor deficiency on cholesterol clearance. Therefore, the combination of CRISPR-Cas9-mediated Cypor knockdown to induce clonal expansion of gene-edited hepatocytes using transient APAP administration is not a viable therapeutic strategy for familial hypercholesterolemia due to the essential role of Cypor in cholesterol metabolism. Unlike findings from phenylketonuria mouse model studies, the loss of Cypor function could not be compensated by unedited native hepatocytes in Ldlr^−/− mice. Collectively, our results demonstrate that electroporation is a viable and informative approach for evaluating gene editing strategies for the treatment of inherited metabolic diseases that affect the liver. Our electroporation procedure revealed that a one-size-fits-all gene editing strategy may not be universally applicable for treating inherited metabolic liver disorders. Tailored gene editing and selection strategies may be needed for different liver disorders. Full article

Objectives: Sillago japonica is a commercially important marine fish species in the Northwestern Pacific, and understanding its genetic diversity and population structure is crucial for germplasm resource conservation and elucidating population evolution mechanisms. This study specifically aimed to systematically explore the genetic diversity and population structure of S. japonica across five geographic regions (DJW, YSW, ST, ZS, and RS) in its distribution range. Methods: A total of 50 S. japonica individuals from the five geographic regions were analyzed using high-throughput mitochondrial genome sequencing data. We identified single nucleotide polymorphisms (SNPs) and insertion-deletion (InDel) loci, followed by comprehensive population genetic analyses including phylogenetic tree construction, principal component analysis (PCA), ADMIXTURE analysis, and calculation of genetic differentiation indices (Fst) and genetic diversity parameters. Results: A total of 2966 SNPs and 414 insertion-deletion loci were identified. Phylogenetic tree topology, PCA, and ADMIXTURE 1.3.0 analysis consistently showed low genetic differentiation among the five populations, a pattern supported by low pairwise Fst values ranging from 0.00047 to 0.05589, indicating extensive gene flow across regions. Genetic diversity parameters varied slightly among populations: observed heterozygosity (0.00001–0.00528), expected heterozygosity (0.04552–0.07311), percentages of polymorphic loci (19.41–30.36%), and nucleotide diversity (0.04792–0.07697). Conclusions: The low genetic differentiation and diversity observed in S. japonica populations may result from the combined effects of historical bottleneck-induced gene pool reduction and extensive gene flow. These findings provide essential theoretical support for formulating targeted conservation strategies for S. japonica germplasm resources and further studies on its population evolution mechanisms. Full article

Flax (Linum usitatissimum L.) is a globally important oilseed crop, valued for its edible and industrial uses. Flax seeds are rich in unsaturated fatty acids. In this study, ethyl methyl sulfone was employed to construct a mutant library from the flax cultivar Longya 10 (WT). Screening efforts identified M45, a stable mutant with an oleic acid content of 43.22% at 40 days after flowering, representing a 21.23% increase over the wild-type. RNA-Seq analysis revealed the presence of two homologs of the SAD (stearoyl-ACP desaturase) family and two homologs of the FAD2 (fatty acid desaturase 2) family, which showed differential expression in a trend consistent with the phenotype of M45. A BSA-Seq analysis was conducted to identify genes with SNPs (single nucleotide polymorphisms) and Indel (insertions/deletions) variant loci that were associated with increased oleic acid. The combination of BSA-Seq, RNA-Seq, and metabolomic analyses identified L.us.o.g.scaffold122.86, a gene that may be co-expressed with L.us.o.g.scaffold7.26 to affect oleic acid accumulation via FAD2. Full article

The internal transcribed spacer (ITS) is one of the most extensively utilized in the taxonomy of the genus Morus due to its generally concerted evolution. Although non-concerted evolution of nuclear ribosomal DNA (nrDNA) has been reported in some species, genome-wide nrDNA characteristics in the genus Morus remain poorly understood. In this study, 158 single-nucleotide polymorphisms (SNPs) and 15 insertions and deletions (InDels) were identified within the nrDNA regions of 542 mulberry accessions representing sixteen Morus species. These wide occurrences of heterogeneous SNPs and InDels revealed the intra-individual polymorphism within the nrDNA region of Morus, indicating the incomplete concerted evolution of nrDNA. Notably, 66 out of 158 SNPs and 13 out of 15 InDels were localized within the ITS regions (ITS1-5.8S-ITS2), indicating a high degree of polymorphism in the ITS, which was further validated through classical cloning and Sanger sequencing methodologies. The 13/16 bp InDel located in the ITS1 region was utilized to develop a rapid and reliable cleaved amplified polymorphic sequence (CAPS) marker-based method for distinguishing M. alba and M. notabilis from other Morus species, eliminating the need for a clone-based sequencing step or comparative phenotypic analysis. Phylogenetic analysis based on nrDNA SNPs from 542 mulberry accessions revealed six distinct clades, corresponding to the six Morus species. These findings offer novel new insights into the taxonomy, conservation, and breeding improvement of Morus species. Full article

Prime editing (PE), a novel “search-and-replace” genome editing technology, demonstrates significant potential for crop genetic improvement due to its precision and versatility. However, since its initial application in plants, PE technology has consistently faced challenges of low and variable editing efficiency, representing a major bottleneck hindering its broader application. Therefore, this study conducted a systematic review following the PRISMA 2020 guidelines. We systematically searched databases—Web of Science, PubMed, and Google Scholar—for studies published up to June 2025 focusing on enhancing PE performance in crops. After a rigorous screening process, 38 eligible primary research articles were ultimately included for comprehensive analysis. Our analysis revealed that early PE systems such as PE2 could perform diverse edits, including all 12 base substitutions and small insertions or deletions (indels), but their efficiency was highly variable across species, targets, and edit types. To overcome this bottleneck, researchers developed four major optimization strategies: (1) engineering core components such as Cas9, reverse transcriptase (RT), and editor architecture; (2) enhancing expression and delivery via optimized promoters and vectors; (3) improving reaction processes by modulating DNA repair pathways or external conditions; and (4) enriching edited events through selectable or visual markers. These advancements broadened PE’s targeting scope with novel Cas9 variants and enabled complex, kilobase-scale DNA insertions and rearrangements. The application of PE technology in plants has evolved from basic functional validation, through systematic optimization for enhanced efficiency, to advanced stages of functional expansion. This review charts this trajectory and clarifies the key strategies driving these advancements. We posit that future breakthroughs will increasingly depend on synergistically integrating these strategies to enable the efficient, precise, and predictable application of PE technology across diverse crops and complex breeding objectives. This study provides an important theoretical framework and practical guidance for subsequent research and application in this field. Full article

Efficient and fast water uptake by seeds, facilitated by optimal soil moisture, plays a critical role in timely germination and early seedling vigor for foxtail millet production in arid and semi-arid regions. The husk, as a unique structure through which the seed contacts the soil, plays an important role in water uptake and germination. Many foxtail millet germplasm accessions have papillae on the epidermis of their husks, yet the role of this trait in water uptake and germination, as well as the genetic basis and regulatory mechanism related to this trait, remain unknown. In this study, we demonstrated that the water uptake by the seeds from accessions with papillae was significantly higher than that of accessions without papillae two hours and four hours after sowing during a 10 h experiment, resulting in faster germination. Analysis of segregating ratios from two F2 populations derived from crossing between accessions with and without papillae indicated that husk papilla density was of monogenic dominance. Bulked Segregant Analysis Sequencing (BSA-Seq) showed that candidate regions on chromosome 5 were significantly associated with husk papilla density. The mapped region overlapped by the two BSA populations for papilla density included 72 genes. In combination with the expression profiles of these genes, five candidate genes were identified, encoding aquaporins, fructose transporter, and glycoside hydrolase. This study elucidated the role of husk papillae in enhancing water uptake and germination in foxtail millet, provided genetic insights into the trait, and laid the foundation for further study on the mechanism of husk papilla differentiation. Full article

Background/Objectives: The non-small-cell lung cancer (NSCLC) therapeutic landscape has undergone a profound transformation with the introduction of multiple personalized treatment options. Mutations in ERBB2 (HER2) have recently emerged as promising novel targets for the treatment of non-squamous NSCLC (nsNSCLC). Accurate, rapid, and efficient molecular profiling is crucial for identifying patients who may benefit from targeted therapies, including HER2-directed agents. Materials and Methods: Here, we aimed to retrospectively assess the performance of the Oncomine™ Precision Assay* (OPA) in combination with the Ion Torrent Genexus™ Integrated Sequencer* (Thermo Fisher Scientific. Waltham, MA, USA) for detecting ERBB2 mutations in nsNSCLC. A total of 108 archived nsNSCLC samples, consisting of biopsies, resections, and cytological specimens, were used to assess concordance with in-house-validated orthogonal tests. Results: The OPA showed high sensitivity and specificity with an overall accuracy of 100% for single-nucleotide variants (SNVs) and insertions and deletions (Indels). SNVs and Indels with allele frequencies as low as 5% were correctly identified across samples with a tumor cell content ranging from 5% to 95%. Additionally, the assay demonstrated high reproducibility across the six participating laboratories. The turnaround time of the OPA was notably shorter compared to traditional orthogonal methods, facilitating rapid molecular report generation. Conclusions: The OPA in combination with the Ion Torrent Genexus™ System allows for highly sensitive and specific detection of relevant ERBB2 mutations. The assay’s streamlined workflow, coupled with its automated data analysis pipeline, enables a fast turnaround time for testing across a range of sample types. This includes samples with reduced tumor cell content and limited available input. This study demonstrates the future potential of using this assay in a clinical setting. Full article

In this study, we performed whole-genome resequencing (WGS) to investigate genomic variation and functional divergence among four wild Cymbidium species—C. ensifolium, C. sinense, C. kanran, and C. floribundum—collected from Fujian Province, China. A total of 350.58 Gbp of high-quality sequencing data was obtained from 13 samples, enabling comprehensive identification of SNPs and InDels. Genomic variants were unevenly distributed, with lower variation in gene-rich regions and higher levels in non-coding areas. Circos plots and variant density heatmaps revealed significant regional differences across chromosomes, with longer chromosomes exhibiting greater variant enrichment in 1 Mb windows. C. floribundum harbored the highest number of nonsynonymous SNPs and InDel-associated genes, whereas C. sinense and C. kanran had fewer mutations. KEGG pathway enrichment analysis revealed species-specific functional divergence, particularly in metabolism, stress response, and secondary metabolite biosynthesis. Population structure analysis and principal component analysis (PCA) indicated genetic differentiation among these species Notably, C. kanran exhibited high within-population genetic diversity. These findings provide essential genomic resources for the conservation and functional studies of wild Cymbidium species in subtropical China. Full article

This review synthesizes advances in livestock genomics by examining the interplay between candidate genes, molecular markers (MMs), signatures of selection (SSs), and quantitative trait loci (QTLs) in shaping economically vital traits across livestock species. By integrating advances in genomics, bioinformatics, and precision breeding, the study elucidates genetic mechanisms underlying productivity, reproduction, meat quality, milk yield, fibre characteristics, disease resistance, and climate resilience traits pivotal to meeting the projected 70% surge in global animal product demand by 2050. A critical synthesis of 1455 peer-reviewed studies reveals that targeted genetic markers (e.g., SNPs, Indels) and QTL regions (e.g., IGF2 for muscle development, DGAT1 for milk composition) enable precise selection for superior phenotypes. SSs, identified through genome-wide scans and haplotype-based analyses, provide insights into domestication history, adaptive evolution, and breed-specific traits, such as heat tolerance in tropical cattle or parasite resistance in sheep. Functional candidate genes, including leptin (LEP) for feed efficiency and myostatin (MSTN) for double-muscling, are highlighted as drivers of genetic gain in breeding programs. The review underscores the transformative role of high-throughput sequencing, genome-wide association studies (GWASs), and CRISPR-based editing in accelerating trait discovery and validation. However, challenges persist, such as gene interactions, genotype–environment interactions, and ethical concerns over genetic diversity loss. By advocating for a multidisciplinary framework that merges genomic data with phenomics, metabolomics, and advanced biostatistics, this work serves as a guide for researchers, breeders, and policymakers. For example, incorporating DGAT1 markers into dairy cattle programs could elevate milk fat content by 15-20%, directly improving farm profitability. The current analysis underscores the need to harmonize high-yield breeding with ethical practices, such as conserving heat-tolerant cattle breeds, like Sahiwal. Full article

Speed is not only the primary objective of racehorse breeding but also a crucial indicator for evaluating racehorse performance. This study investigates a newly developed racehorse breed in China. Through whole-genome resequencing, we selected 60 offspring obtained from the crossbreeding of Thoroughbred horses and Xilingol horses for this study. This breed is tentatively named “Grassland-Thoroughbred”, and the samples were divided into two groups based on racing ability: 30 racehorses and 30 non-racehorses. Based on whole-genome sequencing data, the study achieved an average sequencing depth of 25.63×. The analysis revealed strong selection pressure on chromosomes (Chr) 1 and 3. Selection signals were detected using methods such as the nucleotide diversity ratio (π ratio), integrated haplotype score (iHS), fixation index (Fst), and cross-population extended haplotype homozygosity (XP-EHH). Regions ranked in the top 5% by at least three methods were designated as candidate regions. This approach detected 215 candidate genes. Additionally, the Fst method was employed to detect Indels, and the top 1% regions detected were considered candidate regions, covering 661 candidate genes. Functional enrichment analysis of the candidate genes suggests that pathways related to immune regulation, neural signal transmission, muscle contraction, and energy metabolism may significantly influence differences in performance. Among these identified genes, PPARGC1A, FOXO1, SGCD, FOXP2, PRKG1, SLC25A15, CKMT2, and TRAP1 play crucial roles in muscle function, metabolism, sensory perception, and neurobiology, indicating their key significance in shaping racehorse phenotypes. This study not only enhances understanding of the molecular mechanisms underlying racehorse speed but also provides essential theoretical and practical references for the molecular breeding of Grassland-Thoroughbreds. Full article

 Porcine epidemic diarrhea virus (PEDV) continues to circulate globally, causing substantial economic losses to the swine industry. Historically, PEDV strains are classified into the classical G1, epidemic G2, and S-INDEL genotypes. Among these genotypes, the highly virulent and prevalent G2 genotype has been extensively studied. However, recent clinical outbreaks in China necessitate a reevaluation of the epidemiological and evolutionary dynamics of circulating strains. This study analyzed 37 newly sequenced S genes and public sequences to characterize the genetic variations of S-INDEL strains. Our analysis revealed that S-INDEL strains are endemic throughout China, with a phylogenetic analysis identifying two distinct clades: clade 1, comprising early endemic strains, and clade 2, representing a recently dominant, geographically restricted lineage in China. While inter-genotypic recombination has been documented, our findings also demonstrate that intra-genotypic and intra-clade recombination events contributed significantly to the emergence of clade 2, distinguishing its evolutionary pattern from clade 1. A comparative analysis identified 22 clade-specific amino acid changes, 11 of which occurred in the D0 domain. Notably, mutations at positively selected sites—113 and 114 within the D0 domain, a domain associated with pathogenicity—were specific to clade 2. A phylodynamic analysis indicated Germany as the epicenter of S-INDEL dispersal, with China acting as a sink population characterized by localized transmission networks and frequent recombination events. These results demonstrate that contemporary S-INDEL strains, specifically clade 2, exhibit unique recombination patterns and mutations potentially impacting virulence. Continuous surveillance is essential to assess the pathogenic potential of these evolving recombinant variants and the efficacy of vaccines against them.  Full article

Acute lymphoblastic leukemia (ALL) is a heterogeneous hematologic malignancy defined by the uncontrolled proliferation of lymphoid precursors. Accurate diagnosis and effective therapeutic strategies hinge on a comprehensive understanding of the genetic and molecular landscape of ALL. This review synthesizes the latest updates in cytogenetic and molecular classifications, emphasizing the 2022 World Health Organization (WHO) and International Consensus Classification (ICC) revisions. Key chromosomal alterations such as BCR::ABL1 and ETV6::RUNX1 and emerging subtypes including Ph-like ALL, DUX4, and MEF2D rearrangements are examined for their prognostic significance. Furthermore, we assess novel diagnostic tools, notably next-generation sequencing (NGS) and optical genome mapping (OGM). While NGS excels at identifying point mutations and small indels, OGM offers high-resolution structural variant detection with 100% sensitivity in multiple validation studies. These advancements enhance our grasp of leukemogenesis and pave the way for precision medicine in both B- and T-cell ALL. Ultimately, integrating these innovations into routine diagnostics is crucial for personalized patient management and improving clinical outcomes. Full article