Genes

16 pages, 819 KiB

Open AccessArticle

Incidence of Homozygous SMN2 Deletion in Japan: Cross-Reactivity of SMN2 Primers with SMN1 Sequence Causes False Negatives in Real-Time PCR Screening

by Makoto Sakima, Yoshihiro Bouike, Shin-Ichi Wada, Masami Nakamae, Yoriko Noguchi, Ryosuke Bo, Hiroyuki Awano, Jumpei Oba and Hisahide Nishio

Genes 2025, 16(6), 712; https://doi.org/10.3390/genes16060712 - 16 Jun 2025

Abstract

Background: SMN1 and SMN2 are causative and modifier genes, respectively, for spinal muscular atrophy (SMA). The incidence of SMN1 homozygous deletion in Japan is 1 in 20,000. However, the incidence of SMN2 homozygous deletion in Japan remains unknown. Methods: To clarify [...] Read more.

Background: SMN1 and SMN2 are causative and modifier genes, respectively, for spinal muscular atrophy (SMA). The incidence of SMN1 homozygous deletion in Japan is 1 in 20,000. However, the incidence of SMN2 homozygous deletion in Japan remains unknown. Methods: To clarify the incidence of homozygous SMN2 deletion in Japan, real-time polymerase chain reaction (PCR) was performed on dried blood spot (DBS) samples collected from newborns nationwide. Samples with positive or ambiguous results were retested using PCR-restriction fragment length polymorphism (PCR-RFLP) and nucleotide sequence analysis. Results: Of the 1000 DBS samples that were screened using real-time PCR, 51 were positive. Retesting using PCR-RFLP analysis identified 10 false results: six false positives and four false negatives. Therefore, there were 49 true positives among the 1000 samples. Notably, nucleotide sequence analysis revealed that the false negatives were caused by the cross-reactivity of SMN2 primers with SMN1 sequences. Conclusions: The incidence of homozygous SMN2 deletion in Japan is approximately 1 in 20 people. This incidence is much higher than that of homozygous SMN1 deletion and may reflect the vulnerability of the SMN2 region. Importantly, the results of the present study suggest that false negatives in the screening process were caused by cross-reactivity with non-target gene sequences. Full article

(This article belongs to the Section Genetic Diagnosis)

20 pages, 5106 KiB

Open AccessArticle

Investigating the Sexual Dimorphism of Waist-to-Hip Ratio and Its Associations with Complex Traits

by Haochang Li, Shirong Hui, Xuehong Cai, Ran He, Meijie Yu, Yihao Li, Rongbin Yu and Peng Huang

Genes 2025, 16(6), 711; https://doi.org/10.3390/genes16060711 - 16 Jun 2025

Abstract

Background: Obesity significantly impacts disease burden, with waist-to-hip ratio (WHR) as a key obesity indicator, but the genetic and biological pathways underlying WHR, particularly its sex-specific differences, remain poorly understood. Methods: This study explored WHR’s sexual dimorphism and its links to complex traits [...] Read more.

Background: Obesity significantly impacts disease burden, with waist-to-hip ratio (WHR) as a key obesity indicator, but the genetic and biological pathways underlying WHR, particularly its sex-specific differences, remain poorly understood. Methods: This study explored WHR’s sexual dimorphism and its links to complex traits using cross-sectional surveys and genetic data from Giant and UK Biobank (UKB). We analyzed WHR heritability, performed tissue-specific transcriptome-wide association studies (TWAS) using FUSION, and conducted genetic correlation analyses with linkage disequilibrium score regression (LDSC) and Local Analysis of [co]Variant Association (LAVA). Polygenic scores (PGS) for WHR were constructed using the clumping and thresholding method (CT), and associations with complex traits were assessed via logistic or linear models. Results: The genetic analysis showed sex-specific heritability for WHR, with TWAS identifying female-specific (e.g., CCDC92) and male-specific (e.g., UQCC1) genes. Global genetic correlation analysis revealed sex-specific associations between WHR and 23 traits, while local analysis identified eight sex-specific loci across five diseases. Regression analysis highlighted sex-specific associations for 70 traits with WHR and 45 traits with WHR PGS, with stronger effects in females. Predictive models also performed better in females. Conclusions: This study underscores WHR’s sexual dimorphism and its distinct associations with complex traits, offering insights into sex-specific biological differences, health management, and clinical advancements. Full article

(This article belongs to the Section Molecular Genetics and Genomics)

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20 pages, 1987 KiB

Open AccessArticle

Genomic Anomaly Detection with Functional Data Analysis

by Ria Kanjilal, Andre Luiz Campelo dos Santos, Sandipan Paul Arnab, Michael DeGiorgio and Raquel Assis

Genes 2025, 16(6), 710; https://doi.org/10.3390/genes16060710 - 15 Jun 2025

Abstract

Background: Genetic variation provides a foundation for understanding evolution. With the rise of artificial intelligence, machine learning has emerged as a powerful tool for identifying genomic footprints of evolutionary processes through simulation-based predictive modeling. However, existing approaches require prior knowledge of the factors [...] Read more.

Background: Genetic variation provides a foundation for understanding evolution. With the rise of artificial intelligence, machine learning has emerged as a powerful tool for identifying genomic footprints of evolutionary processes through simulation-based predictive modeling. However, existing approaches require prior knowledge of the factors shaping genetic variation, whereas uncovering anomalous genomic regions regardless of their causes remains an equally important and complementary endeavor. Methods: To address this problem, we introduce ANDES (ANomaly DEtection using Summary statistics), a suite of algorithms that apply statistical techniques to extract features for unsupervised anomaly detection. A key innovation of ANDES is its ability to account for autocovariation due to linkage disequilibrium by fitting curves to contiguous windows and computing their first and second derivatives, thereby capturing the “velocity” and “acceleration” of genetic variation. These features are then used to train models that flag biologically significant or artifactual regions. Results: Application to human genomic data demonstrates that ANDES successfully detects anomalous regions that colocalize with genes under positive or balancing selection. Moreover, these analyses reveal a non-uniform distribution of anomalies, which are enriched in specific autosomes, intergenic regions, introns, and regions with low GC content, repetitive sequences, and poor mappability. Conclusions: ANDES thus offers a novel, model-agnostic framework for uncovering anomalous genomic regions in both model and non-model organisms. Full article

(This article belongs to the Section Technologies and Resources for Genetics)

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18 pages, 4371 KiB

Open AccessArticle

Exploring Runs of Homozygosity and Heterozygosity in Sheep Breeds Maintained in Poland

by Tomasz Szmatola, Katarzyna Ropka-Molik, Igor Jasielczuk, Aldona Kawęcka and Artur Gurgul

Genes 2025, 16(6), 709; https://doi.org/10.3390/genes16060709 - 14 Jun 2025

Abstract

Objectives: The study investigates runs of homozygosity (ROH) and heterozygosity (ROHet), and their patterns in nine sheep breeds (772 animals in total) maintained in Poland (native and conserved), corresponding to their genetic diversity, inbreeding levels, and selection signatures. Methods: Genotypes were [...] Read more.

Objectives: The study investigates runs of homozygosity (ROH) and heterozygosity (ROHet), and their patterns in nine sheep breeds (772 animals in total) maintained in Poland (native and conserved), corresponding to their genetic diversity, inbreeding levels, and selection signatures. Methods: Genotypes were obtained using the Illumina OvineSNP50 BeadChip and quality-filtered SNPs were used to detect ROH and ROHet segments with the detectRUNS R package, following stringent parameters for segment length, SNP density, and genotype quality. Results: Significant variation in ROH characteristics was observed across breeds. Short ROH segments were predominant in all breeds, indicating historical inbreeding events. In contrast, longer ROH segments signified recent inbreeding, particularly in Swiniarka (SW) and Polish Merino of Colored Variety (MPC). The ROH-based genomic inbreeding coefficient (F_ROH) varied across breeds, with SW exhibiting the highest levels, suggesting reduced genetic diversity. ROHet analysis revealed that Uhruska (UHR) had the highest heterozygous segments span, while Black-headed (BH) sheep exhibited the lowest ROHet extent. ROH islands identified across breeds revealed regions under selection, associated with traits such as reproductive performance, wool quality, and body condition. Genes located within these islands (e.g., U6, SPP1, ABCG2) were linked to economically significant traits including milk production, growth, and carcass quality. Conclusions: The presented results highlight the genetic adaptations shaped by selection pressures, while also providing insights into the genetic architecture of sheep breeds maintained in Poland. Full article

(This article belongs to the Section Animal Genetics and Genomics)

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23 pages, 3942 KiB

Open AccessArticle

Half the Chromosome It Used to Be: Identifying Cancer Treatments Targeting Aneuploid Losses

by Andrew O. Disharoon and Joe R. Delaney

Genes 2025, 16(6), 708; https://doi.org/10.3390/genes16060708 - 14 Jun 2025

Abstract

Background/Objectives: Aneuploidy is near-ubiquitous in cancer and can decrease chemotherapy efficacy while also sensitizing cells to other drugs. Methods: To systematically identify treatment strategies that target aneuploid cancers, data were integrated from The Cancer Genome Atlas (TCGA; 10,967 samples, 16,948 aneuploidy events) and [...] Read more.

Background/Objectives: Aneuploidy is near-ubiquitous in cancer and can decrease chemotherapy efficacy while also sensitizing cells to other drugs. Methods: To systematically identify treatment strategies that target aneuploid cancers, data were integrated from The Cancer Genome Atlas (TCGA; 10,967 samples, 16,948 aneuploidy events) and the Broad Institute’s Profiling Relative Inhibition Simultaneously in Mixtures (PRISM) screen of 578 cancer cell lines and 4518 compounds. Results: Our analyses uncovered 37,720 significant positive and negative associations linking specific aneuploidies and treatments with patient prognosis or cell viability. Within TCGA data, 22 treatments correlated with improved 5-year survival for specific aneuploid cancers, whereas 46 were linked to worse outcomes. A complementary analysis of PRISM identified 17,946 compound–aneuploidy associations and 16,189 mechanism of action (MOA)–aneuploidy associations. Pathway-altering compounds that selectively reduce viability in cells with aneuploidy profiles were discovered, including an unexpectedly prominent number of glucocorticoid receptor agonists. Conclusions: This integrated dataset provides a resource for designing therapeutic decision hypotheses, identifying drug-repurposing opportunities, and informing future studies aimed at targeting aneuploidy-induced vulnerabilities in cancer. Full article

(This article belongs to the Section Pharmacogenetics)

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13 pages, 1822 KiB

Open AccessArticle

MPDZ Pathogenic Variants Cause Obstructive Ventriculomegaly Related to Diencephalosynapsis and Third Ventricle Atresia

by Sara Cabet, Jean-François Ghersi-Egea, Suonavy Khung-Savatovsky, Fabien Guimiot, Audrey Putoux, Isabelle Sabatier, Carla Fernandez, Laure Raymond, Jérémie Mortreux, Hélène Laurichesse Delmas, Fabrice Eric Cuillier, Fabien Ho, Gaetan Lesca, Jean-Luc Alessandri and Laurent Guibaud

Genes 2025, 16(6), 707; https://doi.org/10.3390/genes16060707 - 13 Jun 2025

Viewed by 31

Abstract

Objective: Ventriculomegaly is the main prenatal imaging feature for diagnosing fetal central nervous system anomalies in humans. Many ventriculomegalies can be related to genetic causes, regardless of their imaging presentations. Among these, MPDZ variants have been reported to cause severe ventriculomegaly inherited in [...] Read more.

Objective: Ventriculomegaly is the main prenatal imaging feature for diagnosing fetal central nervous system anomalies in humans. Many ventriculomegalies can be related to genetic causes, regardless of their imaging presentations. Among these, MPDZ variants have been reported to cause severe ventriculomegaly inherited in an autosomal recessive manner (OMIM#615219). Several hypotheses have been put forward linking MPDZ variants to ventriculomegaly, but the precise underlying mechanisms, in particular whether its origin is obstructive or non-obstructive, are yet to be elucidated. Methods: To address this question, we retrospectively analyzed pre- and postnatal neuro-imaging and neuropathological data for cases of ventriculomegaly in which MPDZ variants were found through exome or genome sequencing. We performed anti-MPDZ immunostaining on fetal brain samples. Results: We analyzed six cases (four fetuses and two children) of ventriculomegaly of variable severities with MPDZ variants. The precise analysis of brain MRI data, corroborated by fetopathological examinations, demonstrated an obstructive pattern of ventriculomegaly upstream from partial fusion of the thalami, also called diencephalosynapsis, with partial atresia of the third ventricle, which could extend to Sylvius’s aqueduct. Conclusions: The morphological analysis using targeted brain magnetic resonance imaging (MRI) and neuropathological data allowed us to unravel the underlying mechanisms of congenital ventriculomegaly related to MDPZ variants. Full article

(This article belongs to the Section Neurogenomics)

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11 pages, 632 KiB

Open AccessArticle

Expansion of the Genotypic and Phenotypic Spectrum of TCTN3-Related Joubert Syndrome

by Mariangela Lo Giudice, Eugenia Borgione, Marika Giuliano, Sandro Santa Paola, Francesco Domenico Di Blasi, Rosa Pettinato, Corrado Romano and Carmela Scuderi

Genes 2025, 16(6), 706; https://doi.org/10.3390/genes16060706 - 13 Jun 2025

Viewed by 53

Abstract

Background/Objectives: Joubert syndrome (JS, MIM 213300) is a rare genetic condition characterized by respiratory control disturbances, abnormal eye movements, ataxia, cognitive impairment, and the notable agenesis of the cerebellar vermis. The molar tooth sign visible in magnetic resonance imaging of the brain serves [...] Read more.

Background/Objectives: Joubert syndrome (JS, MIM 213300) is a rare genetic condition characterized by respiratory control disturbances, abnormal eye movements, ataxia, cognitive impairment, and the notable agenesis of the cerebellar vermis. The molar tooth sign visible in magnetic resonance imaging of the brain serves as a diagnostic tool for JS. Variants in the TCTN3 gene can lead to the development of several diseases, including JS type 18, Orofaciodigital syndrome IV, and Meckel–Gruber syndrome. Methods: We performed whole-exome sequencing (WES) in a 49-year-old woman with JS characterized by severe intellectual disability, ataxic gait, agenesis of the cerebellar vermis leading to the molar tooth sign, dystonic movements, strabismus, and nystagmus. Moreover, the patient also showed a thickened corpus callosum. Results: Molecular analysis through WES revealed the heterozygous variants c.182dup (p.G62Wfs*18) and c.1452+4del in the TCTN3 gene, expanding our understanding of the genetic diversity and potential phenotypic implications associated with TCTN3 variations. Conclusions: To our knowledge, this is the first patient with JS and a thickened corpus callosum. Moreover, a thickened corpus callosum has never been identified in patients with pathogenic variants of the TCTN3 gene. Full article

(This article belongs to the Special Issue Molecular Basis and Genetics of Intellectual Disability)

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20 pages, 1211 KiB

Open AccessReview

Human CD36: Gene Regulation, Protein Function, and Its Role in Atherosclerosis Pathogenesis

by Monika Rac

Genes 2025, 16(6), 705; https://doi.org/10.3390/genes16060705 - 13 Jun 2025

Viewed by 29

Abstract

Human CD36 plays an important role in ligand binding, signalling, cell adhesion, and the regulation of angiogenesis. As a scavenging receptor, it is responsible for clearing long-chain fatty acids (LCFAs) and removing approximately 50% of oxidised low-density lipoprotein (ox-LDL) from plasma. The CD36 [...] Read more.

Human CD36 plays an important role in ligand binding, signalling, cell adhesion, and the regulation of angiogenesis. As a scavenging receptor, it is responsible for clearing long-chain fatty acids (LCFAs) and removing approximately 50% of oxidised low-density lipoprotein (ox-LDL) from plasma. The CD36 gene is alternatively spliced. It has several alternative promoters and first exons. The alternative transcripts are expressed in multiple tissues, and their expression patterns are highly variable. The molecular mechanisms that regulate CD36 gene expression are complex and reflect its multifunctional role in different tissues. CD36 activity has been linked to several metabolic processes, such as inflammation, angiogenesis, phagocytosis, and energy homeostasis. CD36 plays a key role in regulating vascular and cardiovascular health and in the pathogenesis of atherosclerosis. CD36 gene mutations in the Caucasian population are rare. Hence, it is extremely difficult to recruit a statistically significant group of CAD patients with these mutations. Nevertheless, this population is largely at risk of cardiovascular disease. Atherosclerosis is a multifactorial disease, but the role of the CD36 receptor in the development of ox-LDL is extremely important. This review aims to introduce readers to issues related to the relationship between CD36 and CAD. The activity of this receptor should be considered when exploring treatment options for atherosclerosis-related complications. Full article

(This article belongs to the Section Human Genomics and Genetic Diseases)

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15 pages, 2110 KiB

Open AccessArticle

The Integrative Taxonomy and Mitochondrial Genome Evolution of Freshwater Planarians (Platyhelminthes: Tricladida): The Discovery of a New Clade in Southern China

by Yimeng Yang, Zhizhuo Huang, Xiaowen Fang, Pinyi Li, Yexin Li, Xiuying Hou, Yongjun Li, Hengwen Yang, Chunxia Jing, Zhinan Yin and Guang Yang

Genes 2025, 16(6), 704; https://doi.org/10.3390/genes16060704 - 13 Jun 2025

Viewed by 132

Abstract

Background: The genus Dugesia (Platyhelminthes: Tricladida) includes a large diversity of free-living freshwater flatworms and is important for studies on regeneration and evolution. This study aims to describe a newly discovered asexual planarian species from southern China and explore its genetic characteristics and [...] Read more.

Background: The genus Dugesia (Platyhelminthes: Tricladida) includes a large diversity of free-living freshwater flatworms and is important for studies on regeneration and evolution. This study aims to describe a newly discovered asexual planarian species from southern China and explore its genetic characteristics and regenerative abilities. Methods: An integrative taxonomic analysis was conducted using morphology, karyology, histology, molecular phylogeny (18S, 28S, COI, mitogenome), and genome size estimation via flow cytometry. Regeneration was assessed by standardized amputations, and long-term asexual propagation was observed under laboratory conditions for three years. Results: Phylogenetic analyses using nuclear (18S, 28S rDNA) and mitochondrial (COI, mitogenome) markers confirmed that Dugesia cantonensis Guang Yang & Zhinan Yin, sp. nov. forms a distinct clade within Dugesia. Its 18,125 bp mitogenome contains 36 genes but lacks atp8. D. cantonensis displays a distinctive morphology, notably a pharynx located near the head. All body fragments regenerated into complete individuals within nine days. Remarkably, one individual produced ~10⁵ clonal descendants over three years via repeated amputation, maintaining stable regenerative ability and growth across generations. Karyological analysis revealed a diploid karyotype (2n = 16) consisting of eight chromosome pairs. The nuclear genome size was estimated at approximately 2.5 Gb using Danio rerio as an internal standard. Histological examination showed no detectable reproductive organs, confirming the species as an exclusively asexual lineage. Conclusions: D. cantonensis represents a new planarian strain with stable propagation and regeneration. These features make it a valuable resource for regenerative biology and comparative genomic studies. Full article

(This article belongs to the Section Population and Evolutionary Genetics and Genomics)

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9 pages, 204 KiB

Open AccessArticle

Several Proinflammatory Genes’ Variability and Phenotypes of Atopic Dermatitis in Czech Adult AD Patients

by Vladimír Vašků and Anna Vašků

Genes 2025, 16(6), 703; https://doi.org/10.3390/genes16060703 - 12 Jun 2025

Viewed by 149

Abstract

Background: The etiopathogenesis of atopic dermatitis is complicated, and it includes aspects such as dysfunction of the skin barrier, changes in immune responses, IgE-mediated hypersensitivity, and many characteristics of the environment. Regarding skin barrier dysfunction, a number of genetic changes have been described. [...] Read more.

Background: The etiopathogenesis of atopic dermatitis is complicated, and it includes aspects such as dysfunction of the skin barrier, changes in immune responses, IgE-mediated hypersensitivity, and many characteristics of the environment. Regarding skin barrier dysfunction, a number of genetic changes have been described. This genetic predisposition could be related to the phenotypes of atopic dermatitis. Aim: In this study, several polymorphisms in five proinflammatory genes were associated with certain phenotypes of AD patients (genotype–phenotype study). Methods: In total, 89 unrelated AD Czech (Caucasian) patients were genotyped regarding five proinflammatory gene polymorphisms (angiotensinogen AGT M235T, AGT-6 G/A, TNF-α-238 G/A, TNF-β Fok1, IL-6-174 C/G and IL-6-596 G/A). Genotyping was performed using PCR and restriction analysis. For phenotypes, patients’ sex, age and personal and family history of atopy, aero- and food allergies and other complex diseases were evaluated. Results: A significant association with transepidermal water loss (TEWL) measured on the forearm was found with the AGT M235T polymorphism (p = 0.02). For the AG genotype of TNF-α-238 G/A, a six-times higher risk for a family history of diabetes mellitus compared to other examined aspects of family history was found (p = 0.02). A family history of thyreopathy was associated with the IL-6-174 G/C polymorphism when compared to a family history of other complex diseases. The GG genotype had a ten-times higher risk for a family history of thyreopathy compared to the other genotypes (p = 0.004). This result was highly specific (0.914). The GG genotype of IL-6-596 G/A was associated with a family history of thyreopathy, with the same result (p = 0.004). Moreover, the G allele of IL-6-174 G/C was associated with a family history of thyreopathy compared to AD patients without a positive family history of complex diseases (p = 0.03). In AD men, the MM genotype of the AGT M235T gene was found to be associated with food allergies (p = 0.004). This result was highly sensitive (0.833). A family history of cardiovascular disease in AD men was associated with AGT-6 G/A variability. The A allele was found to be six times more frequent in patients with a positive family history of cardiovascular disease (p = 0.02, with high sensitivity and specificity (0.700 and 0.735, respectively)). A family history of diabetes mellitus was associated with the TNF-β Fok1 polymorphism, where the B1 allele was almost six times more frequent in AD men with a positive family history of diabetes mellitus (p = 0.02), with high sensitivity (0.85). A significant association between TEWL measured on the forearm and the AGT M235T polymorphism was found when AD women were carriers of the MM genotype, with a median of 25 and range 4–61; those patients with the MT genotype had a median of 10 and range of 0.3–39; and patients with the TT genotype had a median of 5 and range of 3–40, p = 0.003. The polymorphism AGT-6 G/A was associated with different ages of eczema onset. The AG genotype was almost nine times more risky for the youngest group (0–7 years) compared to the oldest group (more than 18 years) (p = 0.02), with high specificity for this result. Conclusions: Our results in the field of cytokine signaling in the immune system in patients with atopic dermatitis are in agreement with those of GWASs. We suggest that cost-effective and simple PCR tests may be the best approach for the rapid and optimal collection of valid genetic information in clinical practice. Full article

(This article belongs to the Section Molecular Genetics and Genomics)

21 pages, 1060 KiB

Open AccessReview

Origin and Evolution of Genes in Eukaryotes: Mechanisms, Dynamics, and Functional Implications

by Salvatore Saccone, Desiree Brancato, Francesca Bruno, Elvira Coniglio, Valentina Sturiale and Concetta Federico

Genes 2025, 16(6), 702; https://doi.org/10.3390/genes16060702 - 12 Jun 2025

Viewed by 216

Abstract

The origin and evolution of genes are central themes in evolutionary biology and genomics, shedding light on how molecular innovations shape biological complexity and adaptation. This review explores the principal mechanisms underlying gene emergence in eukaryotes, including gene duplication, de novo gene birth, [...] Read more.

The origin and evolution of genes are central themes in evolutionary biology and genomics, shedding light on how molecular innovations shape biological complexity and adaptation. This review explores the principal mechanisms underlying gene emergence in eukaryotes, including gene duplication, de novo gene birth, horizontal gene transfer, viral gene domestication, and exon shuffling. We examine the population dynamics that govern the fixation of new genes, their functional integration, and the selective forces acting upon them—from purifying selection to adaptive innovation. Examples such as NOTCH2NL and SRGAP2C, which originated through recent segmental duplications followed by neofunctionalization, illustrate how duplicate-derived de novo genes can play a key role in human brain development. In addition, we highlight the emerging relevance of nuclear architecture in determining the evolutionary fate of new genes, offering a spatial dimension to gene innovation. We also discuss methodological approaches for detecting new genes and inferring selection, and finally, we highlight the emerging role of the human pangenome in revealing hidden gene diversity and its implications for evolutionary and biomedical research. Understanding gene innovation not only enhances our grasp of evolutionary processes but also informs clinical studies on disease susceptibility and human uniqueness. Full article

(This article belongs to the Special Issue The Origins and Evolution of Genes, Genetic Code and Proteins)

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16 pages, 5772 KiB

Open AccessArticle

Integrated Analysis of miRNA and mRNA Expression Profiles Associated with Development of Skeletal Muscle of Jiangquan Black Pigs

by Yarui Gao, Shiyin Li, Wei Chen, Jianmin Zhang, Zhanchi Ren, Zhao Ma, Yunzhou Wang and Yongqing Zeng

Genes 2025, 16(6), 701; https://doi.org/10.3390/genes16060701 - 12 Jun 2025

Viewed by 157

Abstract

Background: Hypertrophy, myogenic differentiation, and mass gain of porcine skeletal muscle are key factors in meat production efficiency, regulated by miRNAs through post-transcriptional mechanisms. This study aims to identify miRNA-mRNA pairs linked to growth and muscle development in Jiangquan Black pigs with differing [...] Read more.

Background: Hypertrophy, myogenic differentiation, and mass gain of porcine skeletal muscle are key factors in meat production efficiency, regulated by miRNAs through post-transcriptional mechanisms. This study aims to identify miRNA-mRNA pairs linked to growth and muscle development in Jiangquan Black pigs with differing average daily gains (ADGs), providing a foundation for molecular breeding in this breed. Methods: This study divided eight pigs into two groups and analyzed the skeletal muscle characteristics of Jiangquan Black pigs with different average daily weight gains using HE staining. RNA-Seq was conducted to identify differentially expressed miRNAs and mRNAs, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed, and an integrated miRNA-mRNA regulatory network was subsequently constructed. Results: RNA sequencing analysis identified 255 differentially expressed genes (DEmRNAs, |FC| > 1.5) and 27 differentially expressed miRNAs (DE miRNAs, |FC| > 2). Bioinformatics analysis revealed 330 significantly negatively correlated miRNA-mRNA regulatory pairs, with key pathways, including the MAPK, mTOR, insulin, FoxO, Wnt, and TGF-β signaling pathways, being implicated in muscular development. Quantitative real-time PCR (qRT-PCR) validation confirmed the reliability of the sequencing data. Conclusions: Different ADGs among half-sibling Jiangquan Black pigs with the same diet may be due to the DE miRNAs and DEmRNAs related to skeletal muscle growth and development. These findings reveal the potential regulatory mechanisms of DE miRNAs and DEmRNAs in porcine skeletal muscle growth, providing valuable insights for the next steps in molecular breeding strategies for Jiangquan Black pigs. Full article

(This article belongs to the Section Animal Genetics and Genomics)

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19 pages, 1172 KiB

Open AccessArticle

Validating Single-Step Genomic Predictions for Growth Rate and Disease Resistance in Eucalyptus globulus with Metafounders

by Milena Gonzalez, Ignacio Aguilar, Matias Bermann, Marianella Quezada, Jorge Hidalgo, Ignacy Misztal, Daniela Lourenco and Gustavo Balmelli

Genes 2025, 16(6), 700; https://doi.org/10.3390/genes16060700 - 10 Jun 2025

Viewed by 304

Abstract

Background: Single-step genomic BLUP (ssGBLUP) has gained increasing interest from forest tree breeders. ssGBLUP combines phenotypic and pedigree data with marker data to enhance the prediction accuracy of estimated breeding values. However, potential errors in determining progeny relationships among open-pollinated species may result [...] Read more.

Background: Single-step genomic BLUP (ssGBLUP) has gained increasing interest from forest tree breeders. ssGBLUP combines phenotypic and pedigree data with marker data to enhance the prediction accuracy of estimated breeding values. However, potential errors in determining progeny relationships among open-pollinated species may result in lower accuracy of estimated breeding values. Unknown parent groups (UPG) and metafounders (MF) were developed to address missing pedigrees in a population. This study aimed to incorporate MF into ssGBLUP models to select the best parents for controlled mating and the best progenies for cloning in a tree breeding population of Eucalyptus globulus. Methods: Genetic groups were defined to include base individuals of similar genetic origin. Tree growth was measured as total height (TH) and diameter at breast height (DBH), while disease resistance was assessed through heteroblasty (the transition from juvenile to adult foliage: ADFO). All traits were evaluated at 14 and 21 months. Two genomic multi-trait threshold linear models were fitted, with and without MF. Also, two multi-trait threshold-linear models based on phenotypic and pedigree information (ABLUP) were used to evaluate the increase in accuracy when adding genomic information to the model. To test the quality of models by cross-validation, the linear regression method (LR) was used. Results: The LR statistics indicated that the ssGBLUP models without MF performed better, as the inclusion of MF increased the bias of predictions. The ssGBLUP accuracy for both validations ranged from 0.42 to 0.68. Conclusions: The best model to select parents for controlled matings and individuals for cloning is ssGBLUP without MF. Full article

(This article belongs to the Section Plant Genetics and Genomics)

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53 pages, 1863 KiB

Open AccessReview

The Role of Adiponectin and ADIPOQ Variation in Metabolic Syndrome: A Narrative Review

by Wiktoria Błażejewska, Justyna Dąbrowska, Joanna Michałowska and Paweł Bogdański

Genes 2025, 16(6), 699; https://doi.org/10.3390/genes16060699 - 10 Jun 2025

Viewed by 396

Abstract

Metabolic syndrome (MetS), a significant global health concern, is characterized as a cluster of metabolic abnormalities that elevate the risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Adiponectin, an adipokine secreted by adipose tissue, plays a crucial role in regulating [...] Read more.

Metabolic syndrome (MetS), a significant global health concern, is characterized as a cluster of metabolic abnormalities that elevate the risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Adiponectin, an adipokine secreted by adipose tissue, plays a crucial role in regulating glucose and lipid homeostasis while exhibiting protective effects against vascular alterations. Single-nucleotide variants (SNVs) in the ADIPOQ gene have significantly affected circulating adiponectin levels and metabolic parameters. This narrative review examines current evidence on the relationship between adiponectin, ADIPOQ gene variants, and metabolic syndrome. The findings indicate that lower adiponectin levels are associated with an increased risk of metabolic syndrome components, including elevated triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), and fasting glucose levels. In conclusion, adiponectin emerges as a key regulator of metabolic homeostasis, with SNVs in the ADIPOQ gene correlating with the development of metabolic-related complications. Full article

(This article belongs to the Section Human Genomics and Genetic Diseases)

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14 pages, 1182 KiB

Open AccessArticle

Direct Oral Anticoagulant-Related Bleeding in Atrial Fibrillation Patients Leads to ADAMTS7 Promoter Demethylation

by Georgia Ragia, Thomas Thomopoulos, Myria Pallikarou, Natalia Atzemian, Anthi Maslarinou, Georgios Chalikias, Athanasios Trikas, Dimitrios N. Tziakas and Vangelis G. Manolopoulos

Genes 2025, 16(6), 698; https://doi.org/10.3390/genes16060698 - 9 Jun 2025

Viewed by 190

Abstract

Background/Objectives: Among other substrates, the a disintegrin and metalloproteinase with thrombospondin motifs 7 (ADAMTS7) protease degrades thrombospondin-5 (the cartilage oligomeric protein, COMP), thrombospondin-1 (TSP-1) and the tissue inhibitor of metalloproteinases-1 (TIMP-1) indicating a potential role of ADAMTS7 expression on coagulation cascade, [...] Read more.

Background/Objectives: Among other substrates, the a disintegrin and metalloproteinase with thrombospondin motifs 7 (ADAMTS7) protease degrades thrombospondin-5 (the cartilage oligomeric protein, COMP), thrombospondin-1 (TSP-1) and the tissue inhibitor of metalloproteinases-1 (TIMP-1) indicating a potential role of ADAMTS7 expression on coagulation cascade, tissue remodeling and wound healing. We analyzed the potential effect of direct oral anticoagulant (DOAC) treatment on ADAMTS7 promoter methylation and followed it over time to assess whether DOACs epigenetically modulate ADAMTS7 and induce pathways associated with coagulation or endothelium repair machinery. Methods: Eighty-four DOAC-treated atrial fibrillation (AF) patients followed-up from baseline (t0) to 7 days (t1, n = 70) and 28 days of treatment (t2, n = 62) and 19 non-AF controls were included in the study. Genomic DNA was extracted from blood at all timepoints and was bisulfite-converted prior to methylation analysis. ADAMTS7 promoter DNA methylation was analyzed with MIP-qMSP-PCR. Results: A total of 16 minor bleeding events occurred. The baseline percentage of ADAMTS7 methylation did not differ between AF patients and controls (15.8% vs. 16.1%, p = 0.908). In the patient cohort, DOAC therapy marginally decreased ADAMTS7 methylation from t0 to t2 (15.2% vs. 14.0%, p = 0.044). This ADAMTS7 demethylation from t0 to t2 was statistically significant only in patients experiencing bleeding (17.1%. vs. 13.4%, p = 0.010 in bleedings, 14.5% vs. 14.2%, p = 0.561 in non-bleedings). No other differences were observed. Conclusions: ADAMTS7 is demethylated during DOAC-related bleedings, a mechanism potentially leading to COMP degradation and thus thrombin-induced platelet aggregation, as well as the induction of endothelium repair through different ADAMTS7-dependent pathways. Full article

(This article belongs to the Section Human Genomics and Genetic Diseases)

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3 pages, 147 KiB

Open AccessEditorial

Editorial on Genomic Mosaicism in Human Development and Diseases

by Xincen Xi and Xiaoxu Yang

Genes 2025, 16(6), 697; https://doi.org/10.3390/genes16060697 - 9 Jun 2025

Viewed by 182

Abstract

The individual genome continuously accumulates genetic variations from a zygote [...] Full article

(This article belongs to the Special Issue Genomic Mosaicism in Human Development and Diseases)

18 pages, 3630 KiB

Open AccessArticle

Identifying CDCA4 as a Radiotherapy Resistance-Associated Gene in Colorectal Cancer by an Integrated Bioinformatics Analysis Approach

by Lin Chen, Yawei Gao, Zhiqing Hu, Jingwen Si, Yuchao Zhang and Qingping Cai

Genes 2025, 16(6), 696; https://doi.org/10.3390/genes16060696 - 9 Jun 2025

Viewed by 177

Abstract

Background: Colorectal cancer (CRC) remains one of the most prevalent and fatal malignancies globally, with radiotherapy playing a crucial role in the treatment of locally advanced rectal cancer (LARC). However, the efficacy of radiotherapy is limited by significant resistance, with only a small [...] Read more.

Background: Colorectal cancer (CRC) remains one of the most prevalent and fatal malignancies globally, with radiotherapy playing a crucial role in the treatment of locally advanced rectal cancer (LARC). However, the efficacy of radiotherapy is limited by significant resistance, with only a small proportion of patients achieving a pathologic complete response (PCR) to neoadjuvant chemoradiotherapy (nCRT). This study aims to uncover the genetic and molecular factors contributing to radiotherapy resistance in CRC through an integrated analysis of germline mutations, transcriptomic data, and immune microenvironment characteristics. Methods: Whole-exome sequencing (WES) was performed on tumor samples from 12 LARC patients. Transcriptomic data from the TCGA-READ and GSE150082 (LARC with chemoradiotherapy) cohorts were integrated with WES findings. The independent cohort GSE190826 (neoadjuvant therapy in rectal cancer) dataset was utilized to validate the WES data. Single-cell RNA sequencing (scRNA-seq) analysis of GSE132465 (primary CRC) resolved cellular heterogeneity. A random forest algorithm was employed to develop a predictive gene signature. Results: Our findings reveal a mutational landscape associated with radiotherapy resistance, identifying specific germline mutations linked to treatment outcomes. Differential gene expression analysis highlighted pathways involved in DNA replication, DNA repair, and immune regulation, with a focus on the tumor immune microenvironment (TIME). A gene signature, including CDCA4, FANCA, PBRM1, RPL13, and C12orf43, was developed to predict radiotherapy response. Notably, CDCA4 expression was significantly associated with tumor mutation burden (TMB) and microsatellite instability (MSI), and it plays a crucial role in regulating B cell infiltration in the tumor microenvironment. Conclusions: Our study provides novel insights into the molecular mechanisms of radiotherapy resistance in CRC and proposes CDCA4 and B cell-related immune features as potential biomarkers for patient stratification and personalized treatment strategies. Full article

(This article belongs to the Section Bioinformatics)

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12 pages, 1158 KiB

Open AccessArticle

ChromoCheck: Predicting Postnatal Chromosomal Trisomy Cases Using a Support Vector Machine Learning Model

by Nabras Al-Mahrami, Nuha Al Jabri, Amal A. W. Sallam, Najwa Al Jahdhami and Fahad Zadjali

Genes 2025, 16(6), 695; https://doi.org/10.3390/genes16060695 - 8 Jun 2025

Viewed by 317

Abstract

Introduction: Chromosomal study via karyotype is one of the historical gold-standard procedures used to provide a clearer view of chromosomal trisomy abnormalities. It has been used to correlate several phenotypic manifestations that require immediate medical intervention. However, the laboratory procedure persisted with various [...] Read more.

Introduction: Chromosomal study via karyotype is one of the historical gold-standard procedures used to provide a clearer view of chromosomal trisomy abnormalities. It has been used to correlate several phenotypic manifestations that require immediate medical intervention. However, the laboratory procedure persisted with various drawbacks. The recent machine learning model shed light on prediction capabilities in the medical field. In this study, we aimed to use a support vector machine model for predicting postnatal chromosomal trisomy cases. Methods: A dataset of 946 neonatal records from the Royal Hospital, Muscat, Oman, covering the period from 2013 to 2023, has been used in this model. The model is based on features such as thyroxine hormone levels and thyroid-stimulating hormone levels. With different R packages, we used a support vector machine model with leave-one-out cross-validation and ten iterations to test three kernel functions: linear, radial, and polynomial. Results: Among the obtained kernel performances, the linear kernel has optimal classification performance. The training accuracy was 81%, and the testing accuracy was 82%. Sensitivity ranged from 97 to 98%, and specificity ranged from 79 to 80%. The area under the curve in relation to the training dataset came to 0.89, and it came to 0.90 for the test dataset. We deployed the trained models in a website tool called ChromoCheck. Conclusions: Our study is an example of how machine learning can be instrumental in augmenting conventional methods of cytogenetics diagnosis and decision-making in a clinical setup. Full article

(This article belongs to the Special Issue Cytogenetics and Cytogenomics in Clinical Diagnostics: Innovations and Applications)

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19 pages, 2361 KiB

Open AccessArticle

Genetic Variation and Metapopulation Structure Inform Recovery Goals in a Threatened Species

by Molly J. Garrett, Courtney J. Conway, Lisette P. Waits and Paul A. Hohenlohe

Genes 2025, 16(6), 694; https://doi.org/10.3390/genes16060694 - 8 Jun 2025

Viewed by 293

Abstract

Background: Monitoring genetic parameters is important for setting effective conservation and management strategies, particularly for small, fragmented, and isolated populations. Small, isolated populations face increased rates of genetic drift and inbreeding, which increase extinction risk especially when gene flow is limited. Methods: Here, [...] Read more.

Background: Monitoring genetic parameters is important for setting effective conservation and management strategies, particularly for small, fragmented, and isolated populations. Small, isolated populations face increased rates of genetic drift and inbreeding, which increase extinction risk especially when gene flow is limited. Methods: Here, we applied a Genotyping-in-Thousands by sequencing (GT-seq) panel to inform recovery action for the federally threatened northern Idaho ground squirrel (Urocitellus brunneus). We evaluated genetic diversity, structure, connectivity, and effective population size to address species recovery goals. Results: We delineated three types of conservation units: (1) three evolutionarily significant units that represent long-term population structure and variation, (2) nine management units that reflect current demographic connectivity and restrictions to gene flow, and (3) three adaptive units that capture adaptive differentiation across the species range. Effective population sizes per management unit were small overall (mean 38.16, range 2.3–220.9), indicating that recovery goals of 10 subpopulations with N_e > 500 have not been reached. Conclusions: Our results support the maintenance of connectivity within evolutionarily significant units through the restoration of dispersal corridors. Next steps could include further sampling of some subpopulations with low sample sizes, unsampled subpopulations, and subpopulations that are geographically isolated. Genotyping future samples with the same GT-seq panel would help to detect dispersal, assess effective population size, monitor the effects of inbreeding, and evaluate adaptive differentiation to monitor the effects of management action and environmental change. Full article

(This article belongs to the Special Issue Advances of Genetics in Wildlife Conservation and Management)

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21 pages, 1452 KiB

Open AccessArticle

Swertianin Suppresses M1 Macrophage Polarization and Inflammation in Metabolic Dysfunction-Associated Fatty Liver Disease via PPARG Activation

by Jing Xia, Wei Xiong, Ce Yang, Ying Tan, Xiaoyuan Peng and Wenxiang Wang

Genes 2025, 16(6), 693; https://doi.org/10.3390/genes16060693 - 6 Jun 2025

Viewed by 293

Abstract

Background: Metabolic dysfunction-associated fatty liver disease (MASLD) is closely associated with immune dysregulation and macrophage-driven inflammation. The activation of PPARG plays a critical role in modulating macrophage polarization and lipid metabolism, suggesting its potential as a therapeutic target for MASLD. Methods: We used [...] Read more.

Background: Metabolic dysfunction-associated fatty liver disease (MASLD) is closely associated with immune dysregulation and macrophage-driven inflammation. The activation of PPARG plays a critical role in modulating macrophage polarization and lipid metabolism, suggesting its potential as a therapeutic target for MASLD. Methods: We used UPLC-Q/TOF-MS and network pharmacology to investigate the key components and targets of Swertia davidi Franch, focusing on Swertianin. In vitro experiments on macrophages were conducted to assess the modulation of M1 polarization, and a mouse model of MASLD was utilized to explore the therapeutic effects of Swertianin. Results: Swertianin activated PPARG, leading to significant inhibition of M1 macrophage polarization, a reduction in lipid accumulation, and decreased inflammatory marker levels both in vitro and in vivo. The treatment significantly improved liver pathology in mice, indicating its therapeutic potential for MASLD. Conclusions: Swertianin’s activation of PPARG provides a novel mechanism for treating MASLD, targeting both macrophage polarization and inflammation. Full article

(This article belongs to the Section Molecular Genetics and Genomics)

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19 pages, 5771 KiB

Open AccessArticle

Identifying Candidate Genes Related to the Nutritional Components of Soybean (Glycine max) Sprouts Based on the Transcriptome and Co-Expression Network

by Cheng Wang, Qiaoli Hu, Yan Wang, Shulin Lan, Xueting Li, Hui Liu, Xue Feng, Qiaoxia Shang and Weiyu Li

Genes 2025, 16(6), 692; https://doi.org/10.3390/genes16060692 - 6 Jun 2025

Viewed by 334

Abstract

Background: During the germination of soybean seeds, many biochemical metabolic reactions become extremely active, resulting in a series of physiological and biochemical activities, and the seeds being rich in nutrients. Studying the network and key genes that regulate the nutritional content of bean [...] Read more.

Background: During the germination of soybean seeds, many biochemical metabolic reactions become extremely active, resulting in a series of physiological and biochemical activities, and the seeds being rich in nutrients. Studying the network and key genes that regulate the nutritional content of bean sprouts is particularly important. Methods: In this study, the nutrient contents of Dongnong 254 and Heze small beans were measured when the bean sprouts were 1 cm, 3 cm, 5 cm and 7 cm long, and transcriptome sequencing was performed. Results: Clustering and principal component analysis (PCA) revealed that the samples could be divided into three groups. The differences between Dongnong 254 and Heze small bean samples with sprout lengths of 5 cm and 7 cm were greater than those between materials. Through differential expression analysis, 18,472 differentially expressed genes (DEGs) in the material included 1816 unique DEGs, and a total of six clusters with statistical significance were identified, which were enriched in pathways related to photosynthesis and sugar metabolism. The 6938 DEGs among the materials included 1044 unique DEGs, and a total of nine statistically significant clusters were identified, which were mainly annotated in pathways related to photosynthesis, hormones and flavonoids. Three specific modules that were significantly related to the nutritional content of bean sprouts were identified via WGCNA. The connectivity and functional annotation of genes within the modules were calculated, and nine candidate genes were found, nine of which encoded transcription factors (Glyma.16G071900 (WD40), Glyma.17G172400 (bHLH), Glyma.18G148000 (AP2) and Glyma.01G003000 (MYB)). Conclusions: These research results provide a theoretical basis for an in-depth understanding of the molecular mechanisms of soybean sprout development and nutritional components and provide new genetic resources for the study of nutritional components in soybean sprouts. Full article

(This article belongs to the Section Plant Genetics and Genomics)

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12 pages, 2331 KiB

Open AccessArticle

Regulation of Petal Coloration by the Auxin Amide Hydrolase Gene RhILL1 in Rose (Rosa hybrida)

by Dan Wang, Yiping Zhang, Daliang Li, Xujun Ma, Xiao Yang, Hongying Jian, Huichun Wang, Lihua Wang, Hao Zhang, Qigang Wang and Xianqin Qiu

Genes 2025, 16(6), 691; https://doi.org/10.3390/genes16060691 - 6 Jun 2025

Viewed by 322

Abstract

Objective: This study aimed to elucidate the regulatory mechanism of an auxin amide hydrolase gene (IAA-Leucine Resistant1-like Hydrolase, RhILL1) in the petal pigmentation of rose (Rosa hybrida), providing theoretical insight into the hormonal regulation of flower coloration at the molecular [...] Read more.

Objective: This study aimed to elucidate the regulatory mechanism of an auxin amide hydrolase gene (IAA-Leucine Resistant1-like Hydrolase, RhILL1) in the petal pigmentation of rose (Rosa hybrida), providing theoretical insight into the hormonal regulation of flower coloration at the molecular level. Methods: Using petals at Stage 3 (S3) of the cut rose cultivar ‘Pink Floyd’ as experimental material, we cloned the rose auxin amide hydrolase gene RhILL1 and validated its function via virus-induced gene silencing (VIGS). The expression levels of anthocyanin biosynthetic genes, anthocyanin content, and auxin (IAA) levels were analyzed to assess the role of RhILL1 in petal pigmentation. Results: The full-length open reading frame (ORF) of RhILL1 was cloned, spanning 1326 bp and encoding a 441-amino-acid protein harboring two conserved domains, Peptidase_M20 and M20_dimer, characteristic of the ILL1 protein family. Functional characterization was performed using VIGS. Quantitative real-time PCR (qRT-PCR) revealed that RhILL1 expression progressively increased from the Green (G) stage to S3, correlating with intensified petal coloration. Silencing RhILL1 resulted in visibly lighter petals, the reduced expression of anthocyanin biosynthetic genes, and a significant decrease in endogenous indole-3-acetic acid (IAA) levels compared with controls. Moreover, exogenous application of 10 μM naphthaleneacetic acid (NAA) to petals significantly preserved petal pigmentation. Conclusion: These findings suggest that RhILL1 contributes to the development and maintenance of petal coloration in rose, likely by modulating IAA levels, thereby influencing the expression of anthocyanin biosynthesis-related genes. Full article

(This article belongs to the Section Plant Genetics and Genomics)

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12 pages, 1284 KiB

Open AccessCommunication

Deficiency in KPNA4, but Not in KPNA3, Causes Attention Deficit/Hyperactivity Disorder like Symptoms in Mice

by Franziska Rother, Amishaben R. Parmar, Julia S. Bodenhagen, Letizia Marvaldi, Enno Hartmann and Michael Bader

Genes 2025, 16(6), 690; https://doi.org/10.3390/genes16060690 - 6 Jun 2025

Viewed by 356

Abstract

Nucleocytoplasmic transport is crucial for neuronal cell physiology and defects are involved in neurodegenerative diseases like amyotrophic lateral sclerosis and Alzheimer’s disease, but also in ageing. Recent studies have suggested, that the classic nuclear import factor adapters KPNA3 (also named importin alpha4) and [...] Read more.

Nucleocytoplasmic transport is crucial for neuronal cell physiology and defects are involved in neurodegenerative diseases like amyotrophic lateral sclerosis and Alzheimer’s disease, but also in ageing. Recent studies have suggested, that the classic nuclear import factor adapters KPNA3 (also named importin alpha4) and KPNA4 (also named importin alpha3) could be associated with the development of motor neuron diseases, a condition specifically affecting the neurons projecting from brain to spinal cord or from spinal cord to the muscles. Here we set out to analyze the neuronal function of mice deficient in KPNA3 (Kpna3-KO) or KPNA4 (Kpna4-KO). The motoric abilities and locomotion at different time points in ageing were tested to study the role of these two genes on motor neuron function. While we did not find deficits related to motor neurons in both mouse models, we discovered a hypermotoric phenotype in KPNA4-deficient mice. Attention deficit/hyperactivity disorder (ADHD) is caused by a combination of genetic, environmental and neurobiological factors and a number of genes have been suggested in genome-wide association studies to contribute to ADHD, including KPNA4. Here we provide supportive evidence for KPNA4 as a candidate pathogenic factor in ADHD, by analysing Kpna4-KO mice which show ADHD-like symptoms. Full article

(This article belongs to the Section Molecular Genetics and Genomics)

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9 pages, 227 KiB

Open AccessCase Report

Mixed Segmental Uniparental Disomy of Chromosome 15q11-q1 Coexists with Homozygous Variant in GNB5 Gene in Child with Prader–Willi and Lodder–Merla Syndrome

by Tomasz Marczyk, Maria Libura, Beata Wikiera, Magdalena Góralska, Agnieszka Pollak, Marlena Telenga, Rafał Płoski and Robert Śmigiel

Genes 2025, 16(6), 689; https://doi.org/10.3390/genes16060689 - 5 Jun 2025

Viewed by 355

Abstract

Background: Uniparental disomy (UPD) refers to the condition in which both chromosomes (or part of chromosome) of a pair are inherited from the same parent. There are two types of UPD: uniparental isodisomy (both chromosomes inherited from one parent are identical copies) and [...] Read more.

Background: Uniparental disomy (UPD) refers to the condition in which both chromosomes (or part of chromosome) of a pair are inherited from the same parent. There are two types of UPD: uniparental isodisomy (both chromosomes inherited from one parent are identical copies) and uniparental heterodisomy (two different chromosomes are inherited from one parent). UPD presents two primary developmental risks: recessive trait inheritance or an imprinting disorder. These risks may coexist, leading to an ultra-rare comorbidity. Managing the comorbidities associated with rare diseases presents unique clinical challenges. Results: The existence of such phenomena is evidenced by our case report of a boy who was ultimately diagnosed with two rare diseases: Prader–Willi syndrome (PWS), due to the maternal uniparental disomy of chromosome 15 (UPD), and autosomal recessive Lodder–Merla type 1 syndrome, linked to a novel pathogenic variant in the G protein subunit β 5 (GNB5) gene, as detailed in this paper. Conclusions: An unusual or severe phenotype in a patient diagnosed with PWS should invariably prompt the consideration of a comorbid genetic disease attributable to genes located in the PWS critical region of chromosome 15q, or elsewhere on chromosome 15. In cases of epileptic encephalopathy with cardiac arrhythmia, prompt consultation with a cardiologist and comprehensive genetic testing are essential to reduce the risks associated with untreated arrhythmia and ensure the provision of appropriate and safe anti-epileptic therapy. The presented case provides further support for the hypothesis that uniparental disomy may serve as an underlying cause of Lodder–Merla syndrome. This underscores the significance of comprehensive genetic testing, encompassing parental testing and familial cascade testing (in selected cases where there is consanguinity, or the likelihood of close common ancestral background between partners) to establish the recurrence risk. Full article

(This article belongs to the Section Human Genomics and Genetic Diseases)

12 pages, 2588 KiB

Open AccessReview

Integration of Newer Genomic Technologies into Clinical Cytogenetics Laboratories

by Patrick R. Gonzales

Genes 2025, 16(6), 688; https://doi.org/10.3390/genes16060688 - 4 Jun 2025

Viewed by 442

Abstract

Over the past several decades, clinical cytogenetics has branched out from the use of light microscopy and examination of banded chromosomes to embrace multiple newer techniques, including fluorescence in situ hybridization (FISH), multiple generations of microarray designs, as well as the newest technologies, [...] Read more.

Over the past several decades, clinical cytogenetics has branched out from the use of light microscopy and examination of banded chromosomes to embrace multiple newer techniques, including fluorescence in situ hybridization (FISH), multiple generations of microarray designs, as well as the newest technologies, namely, optical genome mapping (OGM) and genomic proximity mapping (GPM). While these newer technologies have had an increasingly molecular genetic focus over time, they are still rooted in the field of cytogenetics, the genetics of the single cell. This review provides a brief overview of the earliest, as well as the most recent, techniques available to clinical cytogenetics laboratories for both constitutional and neoplastic testing and discusses some advantages and disadvantages of each. Full article

(This article belongs to the Special Issue Clinical Cytogenetics: Current Advances and Future Perspectives)

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30 pages, 2841 KiB

Open AccessReview

Progress in the Genetics of Myelodysplastic Syndromes with a Latin American Perspective

by Ana Lisa Basquiera, Verónica Andreoli, Sofía Grille and Carolina Bárbara Belli

Genes 2025, 16(6), 687; https://doi.org/10.3390/genes16060687 - 2 Jun 2025

Viewed by 480

Abstract

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematological malignancies characterized by ineffective hematopoiesis, resulting in cytopenias, morphologic dysplasia in hematopoietic lineages, and a variable risk of progression to acute myeloid leukemia. Significant advances in the understanding of MDS have been made in [...] Read more.

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematological malignancies characterized by ineffective hematopoiesis, resulting in cytopenias, morphologic dysplasia in hematopoietic lineages, and a variable risk of progression to acute myeloid leukemia. Significant advances in the understanding of MDS have been made in recent years, largely due to the implementation of molecular tools. Latin America is a highly diverse region, both ethnically and racially, and often faces resource limitations that challenge the broad applicability of recent advances in MDS. In this review, we discuss the key genes implicated in the pathogenesis and classification of MDS, and their relevance to diagnosis, prognosis, and potential therapeutic targets. We also explore the challenges associated with the identification of germline predisposition to MDS in Latin America and discuss the current availability and limitations of molecular diagnostic tools in the region. Full article

(This article belongs to the Special Issue Progress in Hematology: Non-Malignant, Pre-Malignant, and Malignant Disorders, and Genetically Based Therapies)

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18 pages, 5530 KiB

Open AccessArticle

In Silico Genomic Analysis of Chloroplast DNA in Vitis Vinifera L.: Identification of Key Regions for DNA Coding

by Francisca Peña, Luciano Univaso, Celián Román-Figueroa and Manuel Paneque

Genes 2025, 16(6), 686; https://doi.org/10.3390/genes16060686 - 31 May 2025

Viewed by 420

Abstract

Background/Objectives: The genus Vitis comprises approximately 70 species with high genetic diversity, among which Vitis vinifera is the most economically significant. Despite numerous studies on the genetic characterizations of V. vinifera, selecting optimal chloroplast DNA barcoding regions for intraspecific differentiation remains unresolved. [...] Read more.

Background/Objectives: The genus Vitis comprises approximately 70 species with high genetic diversity, among which Vitis vinifera is the most economically significant. Despite numerous studies on the genetic characterizations of V. vinifera, selecting optimal chloroplast DNA barcoding regions for intraspecific differentiation remains unresolved. Most studies have focused on nuclear markers (SSRs, SNPs) or widely used chloroplast loci (e.g., matk, rbcl), which have shown limited resolution at the subspecies level. In this study, the complete chloroplast genomes of 34 V. vinifera accessions from different varieties and hybrids (vinifera, sylvestris, caucasica, and labrusca) were analyzed to identify the key genomic regions for DNA barcoding. Methods: Using bioinformatics tools, we assessed the genome structure, nucleotide variability, microsatellites, codon usage bias, and phylogenetic relationships among the investigated varieties. Results: The chloroplast genomes displayed a quadripartite structure, with lengths ranging from 160,906 to 160,929 bp and a guanine–cytosine (GC) content of ~37.4%. Phylogenetic analysis revealed an unusual position for VV-5 vini and VVVL-3 lab, suggesting potential taxonomic misclassification or hybridization effects. A single locus showed low discrimination power, but the concatenation of five loci (ccsA-trnN-GUU, rpl16, rpl2-rps19, rpoC2, and trnM-CAU) exhibited significantly improved resolution (44.11% K2P), surpassing traditional markers. Conclusions: This study addresses the gap in the literature regarding the use of concatenated chloroplast loci for subspecies research; the results validate these markers across a broader range of Vitis accessions and integrate nuclear and mitochondrial data to achieve a more comprehensive understanding of the evolutionary history and genetic diversity of V. vinifera. Full article

(This article belongs to the Section Plant Genetics and Genomics)

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13 pages, 1150 KiB

Open AccessReview

The Emergence of Artificial Intelligence-Guided Karyotyping: A Review and Reflection

by Lynne S. Rosenblum, Julia Holmes and Agshin F. Taghiyev

Genes 2025, 16(6), 685; https://doi.org/10.3390/genes16060685 - 31 May 2025

Viewed by 555

Abstract

Artificial intelligence (AI) has entered the medical subspecialty of cytogenetics with the recent introduction of AI-guided karyotyping into the clinical laboratory. Karyotyping is an essential component of the cytogenetic analysis process; however, it is both labor-intensive and time-consuming. The introduction of AI algorithms [...] Read more.

Artificial intelligence (AI) has entered the medical subspecialty of cytogenetics with the recent introduction of AI-guided karyotyping into the clinical laboratory. Karyotyping is an essential component of the cytogenetic analysis process; however, it is both labor-intensive and time-consuming. The introduction of AI algorithms into karyotyping software streamlines this process to provide accurate and abundant auto-karyotyped images for laboratory professionals to review and, also, alters the paradigm for chromosome analysis. Herein, we provide an overview of the AI-guided karyotyping products currently available for clinical use, discuss their utilization in the cytogenetics laboratory, and highlight changes AI-guided karyotyping has brought for early users. Finally, we reflect on our own laboratory observations and experience to discuss issues and practices that may need to adapt to best utilize this promising new technology. Full article

(This article belongs to the Special Issue Clinical Cytogenetics: Current Advances and Future Perspectives)

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16 pages, 2312 KiB

Open AccessArticle

A Modified FLT3 PCR Assay Using a TapeStation Readout

by Elizabeth Adele Blake, Madhurya Ramineni and Zoltán N. Oltvai

Genes 2025, 16(6), 684; https://doi.org/10.3390/genes16060684 - 31 May 2025

Viewed by 377

Abstract

Background: FLT3 mutation testing is a key ancillary molecular assay for diagnosing and managing patients with acute myeloid leukemia (AML), including assessing the utility of FLT3 inhibitors during induction chemotherapy. FLT3 PCR utilizing fluorescently labeled primers and capillary electrophoresis readout is the most [...] Read more.

Background: FLT3 mutation testing is a key ancillary molecular assay for diagnosing and managing patients with acute myeloid leukemia (AML), including assessing the utility of FLT3 inhibitors during induction chemotherapy. FLT3 PCR utilizing fluorescently labeled primers and capillary electrophoresis readout is the most used technique for the rapid detection of FLT3 internal tandem duplications (ITDs) (including very small ITDs) and tyrosine kinase domain (TKD) mutations. However, capillary electrophoresis (CE) is a relatively lengthy and technically demanding result readout mode that could potentially be replaced by faster alternatives. Methods: Here, we describe the validation of a modified FLT3 PCR assay that uses the Agilent 4200 TapeStation platform for result readouts. This platform generates quantifiable electropherograms and gel images in under two minutes and at a low cost. We validated its ability to detect FLT3-ITD and -TKD mutations using 22 and 18 previously tested patient samples, respectively. Results: The TapeStation 4200 instrument is 100% sensitive, specific, and highly reproducible for post-PCR fragment analysis in detecting FLT3-ITD (greater than 15 bp in size) and TKD mutations in AML patients. Its results are nearly 100% concordant with those obtained from our previously validated NGS and PAGE methods. However, the limitation of this readout mode is its inability to reliably detect FLT3-ITDs smaller than 15 bp in size. Conclusions: Given the widespread use of TapeStation instruments in molecular diagnostics laboratories as part of next-generation sequencing (NGS) workflows, this modified assay is well-suited as a companion test for rapid NGS platforms to detect larger FLT3-ITDs, which are NGS often miscalledor under-called by the NGS bioinformatics algorithms. However, it is not suitable for use as a standalone assay, as it is unable to reliably detect very short FLT3-ITDs. Full article

(This article belongs to the Special Issue Genetic Diagnostics: Precision Tools for Disease Detection)

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17 pages, 1663 KiB

Open AccessArticle

Salt Tolerance Diversity in Citrus Rootstocks Agrees with Genotypic Diversity at the LCl-6 Quantitative Trait Locus

by Maria J. Asins, M. Verónica Raga, Maria R. Romero-Aranda, Emilio Jaime-Fernández, Emilio A. Carbonell and Andres Belver

Genes 2025, 16(6), 683; https://doi.org/10.3390/genes16060683 - 30 May 2025

Viewed by 350

Abstract

Background/Objective: Salinity is a growing problem affecting a large portion of global agricultural land, particularly in areas where water resources are scarce. The objective of this study was to provide physiological and molecular information on salt-tolerant citrus rootstocks to mitigate the detrimental effects [...] Read more.

Background/Objective: Salinity is a growing problem affecting a large portion of global agricultural land, particularly in areas where water resources are scarce. The objective of this study was to provide physiological and molecular information on salt-tolerant citrus rootstocks to mitigate the detrimental effects of salinity on citriculture. Methods: Ten accessions belonging to eight Citrus species and four to Poncirus trifoliata Raf. were tested for salinity tolerance (0 and 15 mM NaCl for 1 year) in terms of vegetative and Cl⁻ tissue distribution traits. In addition, most accessions were evaluated for leaf Na⁺ and other cations. Results: All salt tolerant accessions tended to restrict the leaf Cl⁻ content, although in a lower degree than the Cleopatra mandarin. However, differences in their ability to restrict leaf [Na⁺] were evident, contributing to a classification of trifoliate and sour orange accessions that matched their genotypic grouping based on allele sharing at a marker targeting candidate gene coding for the NPF5.9 transporter within LCL-6 quantitative trait locus. Conclusions: Our markers targeting LCl-6 candidate genes coding for NPF5.9, PIP2.1, and CHX20 (citrus GmSALT3 ortholog) could be efficient tools for managing the detected salt tolerance diversity in terms of both Cl⁻ and Na⁺ homeostasis in rootstock breeding programs derived from these species, in addition to Citrus reshni. Full article

(This article belongs to the Section Plant Genetics and Genomics)

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