Genes

14 pages, 2696 KiB

Open AccessEditor’s ChoiceArticle

Phenotypic and Genetic Heterogeneity of a Pakistani Cohort of 15 Consanguineous Families Segregating Variants in Leber Congenital Amaurosis-Associated Genes

by Zainab Akhtar, Sumaira Altaf, Yumei Li, Sana Bibi, Jamal Shah, Kiran Afshan, Meng Wang, Hafiz Muhammad Jafar Hussain, Nadeem Qureshi, Rui Chen and Sabika Firasat

Genes 2024, 15(12), 1646; https://doi.org/10.3390/genes15121646 - 21 Dec 2024

Viewed by 1605

Abstract

Background: Leber congenital amaurosis (LCA) is a congenital onset severe form of inherited retinal dystrophy (IRD) and a common cause of pediatric blindness. Disease-causing variants in at least 14 genes are reported to predispose LCA phenotype. LCA is inherited as an autosomal recessive [...] Read more.

Background: Leber congenital amaurosis (LCA) is a congenital onset severe form of inherited retinal dystrophy (IRD) and a common cause of pediatric blindness. Disease-causing variants in at least 14 genes are reported to predispose LCA phenotype. LCA is inherited as an autosomal recessive disease. It can be an isolated eye disorder or as part of a syndrome, such as Senior Loken or Joubert syndrome. Sequencing studies from consanguineous populations have proven useful for novel variants identification; thus, the present study aimed to explore the genetic heterogeneity of 15 consanguineous Pakistani families, each segregating a severe IRD phenotype using targeted next generation sequencing. Methods: This study enrolled 15 consanguineous families, each with multiple affected cases of retinal dystrophy phenotype. DNA was extracted from blood samples. Targeted panel sequencing of 344 known genes for IRDs was performed, followed by Sanger sequencing for segregation analysis. Results: Data analysis revealed a total of eight reported (c.316C>T and c.506G>A in RDH12; c.864dup and c.1012C>T in SPATA7, as well as c.1459T>C, c.1062_1068del, c.1495+1G>A, c.998G>A in the CRB1, LCA5, TULP1, and IFT140 genes, respectively) and four novel homozygous (c.720+1G>T in LCA5, c.196G>C in LRAT, c.620_625del in PRPH2, and c.3411_3414del in CRB1) variants segregating with disease phenotype in each respective family. Furthermore, a novel heterozygous variant of CRB1 gene, i.e., c.1935delC in compound heterozygous condition was found segregating with disease phenotype in one large family with multiple consanguinity loops. Conclusion: Comprehensive molecular diagnosis of 15 consanguineous Pakistani families led to the identification of a total of 5 novel variants contributing to genetic heterogeneity of LCA-associated genes and helped to provide genetic counseling to the affected families. Full article

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

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9 pages, 725 KiB

Open AccessEditor’s ChoiceArticle

Impact of Long-Term Cannabidiol (CBD) Treatment on Mouse Kidney Transcriptome

by Mikołaj Rokicki, Jakub Żurowski, Sebastian Sawicki, Ewa Ocłoń, Tomasz Szmatoła, Igor Jasielczuk, Karolina Mizera-Szpilka, Ewelina Semik-Gurgul and Artur Gurgul

Genes 2024, 15(12), 1640; https://doi.org/10.3390/genes15121640 - 21 Dec 2024

Cited by 1 | Viewed by 1674

Abstract

Background: Cannabidiol, which is one of the main cannabinoids present in Cannabis sativa plants, has been shown to have therapeutic properties, including anti-inflammatory and antioxidant effects that may be useful for treatment of various kidney conditions. Objectives: This article investigates the effect of [...] Read more.

Background: Cannabidiol, which is one of the main cannabinoids present in Cannabis sativa plants, has been shown to have therapeutic properties, including anti-inflammatory and antioxidant effects that may be useful for treatment of various kidney conditions. Objectives: This article investigates the effect of long-term cannabidiol (CBD) treatment on changes in the renal transcriptome in a mouse model. The main hypothesis was that systematic CBD treatment would affect gene expression associated with those processes in the kidney. Methods: The study was conducted on male C57BL/6J mice. Mice in the experimental groups received daily intraperitoneal injections of CBD at doses of 10 mg/kg or 20 mg/kg body weight (b.w.) for 28 days. After the experiment, kidney tissues were collected, RNA was isolated, and RNA-Seq sequencing was performed. Results: The results show CBD’s effects on changes in gene expression, including the regulation of genes related to circadian rhythm (e.g., Ciart, Nr1d1, Nr1d2, Per2, and Per3), glucocorticoid receptor function (e.g., Cyp1b1, Ddit4, Foxo3, Gjb2, and Pck1), lipid metabolism (e.g., Cyp2d22, Cyp2d9, Decr2 Hacl1, and Sphk1), and inflammatory response (e.g., Cxcr4 and Ccl28). Conclusions: The obtained results suggest that CBD may be beneficial for therapeutic purposes in treating kidney disease, and its effects should be further analyzed in clinical trials. Full article

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

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17 pages, 2764 KiB

Open AccessEditor’s ChoiceArticle

Drought Stress Inhibits the Accumulation of Rotenoids and the Biosynthesis of Drought-Responsive Phytohormones in Mirabilis himalaica (Edgew.) Heim Calli

by Shiyi Zhang, Jiaqi Gao, Xiaozhong Lan, Linfan Zhang, Weipeng Lian, Chenglin Wang, Zhanyun Shen, Xiang Li and Juan Liu

Genes 2024, 15(12), 1644; https://doi.org/10.3390/genes15121644 - 21 Dec 2024

Viewed by 1048

Abstract

Background: Mirabilis himalaica, distributed in the high-altitude, arid, and semi-arid regions of Xizang, exhibits great tolerance to drought, which is rich in rotenoids and other secondary metabolites. It is still unknown, though, how drought stress influences rotenoid synthesis in M. himalaica [...] Read more.

Background: Mirabilis himalaica, distributed in the high-altitude, arid, and semi-arid regions of Xizang, exhibits great tolerance to drought, which is rich in rotenoids and other secondary metabolites. It is still unknown, though, how drought stress influences rotenoid synthesis in M. himalaica. Methods: In this study, the calli of M. himalaica were subjected to 5% PEG6000 for 0, 20, and 40 h and divided into control group (CK), mild-drought-treated group (M), and high-drought-treated group (H), respectively. We then analyzed the relative content of three main rotenoids in M. himalaica using high-performance liquid chromatography–electrospray ionization–tandem mass spectrometry (HPLC-ESI-MS/MS). Results: Our findings demonstrated that the content of rotenoids was significantly reduced under drought stress. Transcriptome analysis subsequently revealed 14,525 differentially expressed genes (DEGs) between the different treatments. Furthermore, these DEGs exhibited enrichment in pathways associated with isoflavone biosynthesis and hormone signaling pathways. Key genes with decreased expression patterns during drought stress were also found to be involved in rotenoid accumulation and drought-responsive phytohormone signaling, including abscisic acid (ABA), auxin (IAA), and jasmonic acid (JA). Conclusions: These findings elucidate the molecular processes of drought resistance in M. himalaica and shed light on the relationship between rotenoid production and drought stress in M. himalaica. Full article

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

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17 pages, 7574 KiB

Open AccessEditor’s ChoiceArticle

Identification of Retrocopies in Lepidoptera and Impact on Domestication of Silkworm

by Lingzi Bie, Jiahe Sun, Yi Wang and Chunfang Wang

Genes 2024, 15(12), 1641; https://doi.org/10.3390/genes15121641 - 21 Dec 2024

Viewed by 627

Abstract

Background: During the domestication of silkworm, an economic insect, its physiological characteristics have changed greatly. RNA-based gene duplication, known as retrocopy, plays an important role in the formation of new genes and genome evolution, but the retrocopies of lepidopteran insects have not been [...] Read more.

Background: During the domestication of silkworm, an economic insect, its physiological characteristics have changed greatly. RNA-based gene duplication, known as retrocopy, plays an important role in the formation of new genes and genome evolution, but the retrocopies of lepidopteran insects have not been fully identified and analyzed, which not only severely limits researchers from exploring the effects of retrocopies on lepidopteran insects but also affects the studies on the domestication of silkworm. Methods: We compared the genomes and proteomes of eight lepidopteran insects and used a series of screening criteria for auxiliary screening to obtain the retrocopies in lepidopteran insects and explored their characteristics. In addition, based on the silkworm transcriptome data from the SilkDB3.0 website, we explored the functions of the retrocopies on the domestication of the silkworm. Results: A total of 1993 retrocopies and 1208 parental genes in lepidopteran insects were obtained. We revealed that the retrocopies in Lepidoptera do not conform to the “out of X” hypothesis but fit the “out of testis” hypothesis. These retrocopies were subject to strong functional constraints and performed important functions in growth and development. Transcriptome analysis revealed that the expression pattern of the retrocopies and their parental genes were irrelevant. Through the analysis of the retrocopies in silkworm generated after domestication and located in the candidate domestication regions, the possible universal connection between the retrocopies and the domestication of silkworm were found. Conclusions: Our study pioneered the exploration of retrocopies in multiple Lepidoptera species and found the potential association between the retrocopies and the domestication of silkworm. Full article

(This article belongs to the Special Issue Genomics, Transcriptomics, and Proteomics of Insects)

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16 pages, 1226 KiB

Open AccessEditor’s ChoiceArticle

House Mice in the Atlantic Region: Genetic Signals of Their Human Transport

by Sofia I. Gabriel, Jonathan J. Hughes, Jeremy S. Herman, John F. Baines, Mabel D. Giménez, Melissa M. Gray, Emilie A. Hardouin, Bret A. Payseur, Peter G. Ryan, Alejandro Sánchez-Chardi, Rainer G. Ulrich, Maria da Luz Mathias and Jeremy B. Searle

Genes 2024, 15(12), 1645; https://doi.org/10.3390/genes15121645 - 21 Dec 2024

Viewed by 1289

Abstract

Background/Objectives: The colonization history of house mice reflects the maritime history of humans that passively transported them worldwide. We investigated western house mouse colonization in the Atlantic region through studies of mitochondrial D-loop DNA sequences from modern specimens. Methods: We assembled a dataset [...] Read more.

Background/Objectives: The colonization history of house mice reflects the maritime history of humans that passively transported them worldwide. We investigated western house mouse colonization in the Atlantic region through studies of mitochondrial D-loop DNA sequences from modern specimens. Methods: We assembled a dataset of 758 haplotypes derived from 2765 mice from 47 countries/oceanic archipelagos (a combination of new and published data). Our maximum likelihood phylogeny recovered five previously identified clades, and we used the haplotype affinities within the phylogeny to infer house mouse colonization history, employing statistical tests and indices. From human history, we predefined four European source areas for mice in the Atlantic region (Northern Europe excluding Scandinavia, Southern Europe, Scandinavia, and Macaronesia) and we investigated the colonization from these source areas to different geographic areas in the Atlantic region. Results: Our inferences suggest mouse colonization of Scandinavia itself from Northern Europe, and Macaronesia from both Southern Europe and Scandinavia/Germany (the latter likely representing the transport of mice by Vikings). Mice on North Atlantic islands apparently derive primarily from Scandinavia, while for South Atlantic islands, North America, and Sub-Saharan Africa, the clearest source is Northern Europe, although mice on South Atlantic islands also had genetic inputs from Macaronesia and Southern Europe (for Tristan da Cunha). Macaronesia was a stopover for Atlantic voyages, creating an opportunity for mouse infestation. Mice in Latin America also apparently had multiple colonization sources, with a strong Southern European signal but also input from Northern Europe and/or Macaronesia. Conclusions: D-loop sequences help discern the broad-scale colonization history of house mice and new perspectives on human history. Full article

(This article belongs to the Collection Feature Papers in ‘Animal Genetics and Genomics’)

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22 pages, 4014 KiB

Open AccessEditor’s ChoiceArticle

Genomic Analysis of Talaromyces verruculosus SJ9: An Efficient Tetracycline-, Enrofloxacin-, and Tylosin-Degrading Fungus

by Jing Fu, Xiaoqing Wu, Chi Zhang, Yuhan Tang, Fangyuan Zhou, Xinjian Zhang and Susu Fan

Genes 2024, 15(12), 1643; https://doi.org/10.3390/genes15121643 - 21 Dec 2024

Viewed by 896

Abstract

Background/Objectives: Many fungi related to Talaromyces verruculosus can degrade a wide range of pollutants and are widely distributed globally. T. verruculosus SJ9 was enriched from fresh strawberry inter-root soil to yield fungi capable of degrading tetracycline, enrofloxacin, and tylosin. Methods: T. verruculosus SJ9 [...] Read more.

Background/Objectives: Many fungi related to Talaromyces verruculosus can degrade a wide range of pollutants and are widely distributed globally. T. verruculosus SJ9 was enriched from fresh strawberry inter-root soil to yield fungi capable of degrading tetracycline, enrofloxacin, and tylosin. Methods: T. verruculosus SJ9 genome was sequenced, assembled, and annotated in this study utilizing bioinformatics software, PacBio, and the Illumina NovaSeq PE150 technology. Results: The genome size is 40.6 Mb, the N50 scaffold size is 4,534,389 bp, and the predicted number of coding genes is 8171. The T. verruculosus TS63-9 genome has the highest resemblance to the T. verruculosus SJ9 genome, according to a comparative genomic analysis of seven species. In addition, we annotated many genes encoding antibiotic-degrading enzymes in T. verruculosus SJ9 through genomic databases, which also provided strong evidence for its ability to degrade antibiotics. Conclusions: Through the correlation analysis of the whole-genome data of T. verruculosus SJ9, we identified a number of genes capable of encoding antibiotic-degrading enzymes in its gene function annotation database. These antibiotic-related enzymes provide some evidence that T. verruculosus SJ9 can degrade fluoroquinolone antibiotics, tetracycline antibiotics, and macrolide antibiotics. In summary, the complete genome sequence of T. verruculosus SJ9 has now been published, and this resource constitutes a significant dataset that will inform forthcoming transcriptomic, proteomic, and metabolic investigations of this fungal species. In addition, genomic studies of other filamentous fungi can utilize it as a reference. Thanks to the discoveries made in this study, the future application of this fungus in industrial production will be more rapid. Full article

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

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14 pages, 2450 KiB

Open AccessEditor’s ChoiceArticle

Intraspecific Chloroplast Genome Genetic Polymorphism of Pinellia ternata (Xi Junecry) and Its Revelation of a Single Origin in Phylogeny

by Wenlong Xing, Weihan Yu, Yuanyuan Kong, Xian Ren, Liuying Zhu, Qingyang Li, Yujie Yang, Yueqin Cheng and Hongwei Wang

Genes 2024, 15(12), 1638; https://doi.org/10.3390/genes15121638 - 20 Dec 2024

Cited by 2 | Viewed by 735

Abstract

Background: Xi Junecry (Pinellia ternata), a perennial herb of the Araceae family, is indigenous to Xinxian County, Henan Province, China, and is regarded as a premium variety among similar medicinal materials. However, the lack of comprehensive genetic information on Xi [...] Read more.

Background: Xi Junecry (Pinellia ternata), a perennial herb of the Araceae family, is indigenous to Xinxian County, Henan Province, China, and is regarded as a premium variety among similar medicinal materials. However, the lack of comprehensive genetic information on Xi Junecry germplasm resources has constrained the cultivation and identification of high-quality varieties. Methods: In this study, six chloroplast genomes of Xi Junecry were assembled and annotated using high-throughput sequencing. Subsequently, comparative analyses were conducted, and a phylogenetic tree was constructed. Results: The six Xi Junecry chloroplast genome lengths ranged from 157,456 to 158,406 bp, and the GC content was between 36.0% and 36.2%. A total of 265 single nucleotide polymorphism sites were identified across the six genomes, with a whole-genome nucleotide diversity (Pi) value of 0.00084. Among the four genomic regions, the small single-copy region exhibited the highest Pi, followed by the large single-copy region, while the inverted repeat region showed the lowest. Nucleotide polymorphism in coding regions was significantly lower than in non-coding regions. Nine hypervariable regions were identified, as follows: ndhE-ndhG, trnN-GUU-ndhF, trnS-GCU-trnG-UCC, atpB-rbcL, psaI, accD-ycf4, psbE-petL, psaC-ndhE, and psbI-trnG-UCC. Positive selection sites were detected in the accD and rbcL genes. Phylogenetic analysis clustered the six Xi Junecry samples into a distinct clade, separating them from other regional Pinellia samples. Conclusions: These findings elucidate the genetic variation levels in Xi Junecry and provide high-variability loci for population history inference, genetic diversity assessment, species domestication studies, and new cultivar development. Full article

(This article belongs to the Special Issue Plant Genetic Resources: Genetic Diversity, Conservation, and Utilization)

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17 pages, 3928 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Dynamic Chromatin Accessibility and Gene Expression Regulation During Maize Leaf Development

by Yiduo Wang, Shuai Wang, Yufeng Wu, Jiawen Cheng and Haiyan Wang

Genes 2024, 15(12), 1630; https://doi.org/10.3390/genes15121630 - 20 Dec 2024

Viewed by 1109

Abstract

Background/Objectives: Chromatin accessibility is closely associated with transcriptional regulation during maize (Zea mays) leaf development. However, its precise role in controlling gene expression at different developmental stages remains poorly understood. This study aimed to investigate the dynamics of chromatin accessibility and [...] Read more.

Background/Objectives: Chromatin accessibility is closely associated with transcriptional regulation during maize (Zea mays) leaf development. However, its precise role in controlling gene expression at different developmental stages remains poorly understood. This study aimed to investigate the dynamics of chromatin accessibility and its influence on genome-wide gene expression during the BBCH_11, BBCH_13, and BBCH_17 stages of maize leaf development. Methods: Maize leaves were collected at the BBCH_11, BBCH_13, and BBCH_17 developmental stages, and chromatin accessibility was assessed using ATAC-seq. RNA-seq was performed to profile gene expression. Integrated analysis of ATAC-seq and RNA-seq data was conducted to elucidate the relationship between chromatin accessibility and transcriptional regulation. Results: A total of 46,808, 38,242, and 41,084 accessible chromatin regions (ACRs) were identified at the BBCH_11, BBCH_13, and BBCH_17 stages, respectively, with 23.4%, 12.2%, and 21.9% of these regions located near transcription start sites (TSSs). Integrated analyses revealed that both the number and intensity of ACRs significantly influence gene expression levels. Motif analysis identified key transcription factors associated with leaf development and potential transcriptional repressors among genes, showing divergent regulation patterns in ATAC-seq and RNA-seq datasets. Conclusions: These findings demonstrate that chromatin accessibility plays a crucial role in regulating the spatial and temporal expression of key genes during maize leaf development by modulating transcription factor binding. This study provides novel insights into the regulatory mechanisms underlying maize leaf development, contributing to a deeper understanding of chromatin-mediated gene expression. Full article

(This article belongs to the Special Issue Advances in Genetics and Genomics of Plants: 2nd Edition)

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20 pages, 459 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Neutral Genetic Diversity in Mixed Mating Systems

by Marcy K. Uyenoyama

Genes 2024, 15(12), 1635; https://doi.org/10.3390/genes15121635 - 20 Dec 2024

Viewed by 604

Abstract

Background/Objectives: Systems of reproduction differ with respect to the magnitude of neutral genetic diversity maintained in a population. In particular, the partitioning of reproductive organisms into mating types and regular inbreeding have long been recognized as key factors that influence effective population number. [...] Read more.

Background/Objectives: Systems of reproduction differ with respect to the magnitude of neutral genetic diversity maintained in a population. In particular, the partitioning of reproductive organisms into mating types and regular inbreeding have long been recognized as key factors that influence effective population number. Here, a range of reproductive systems are compared with respect to the maintenance of neutral genetic diversity. This study addresses full gonochorism, full hermaphroditism, androdioecy (male and hermaphroditic reproductives), and gynodioecy (female and hermaphroditic reproductives). Methods: Coalescence theory is used to determine the level of diversity maintained under each mating system considered. Results: For each mating system, the nature of the dependence of the level of neutral diversity on inbreeding depression, sex-specific viability, and other factors is described. In particular, the models account for the effects of sex-specific viability on the evolutionarily stable sex ratio and the collective contribution of each mating type (sex) to the offspring generation. Conclusions: Within the context of conservation biology, population genetic and quantitative genetic theory has addressed the determination of the target minimum effective population size. In contrast, this study proposes and explores a summary statistic (a ratio of effective numbers) as a means of characterizing the context in which evolution occurs. Full article

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

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15 pages, 1837 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Association Analysis of Growth Traits in Hu Sheep

by Tingting Li, Feng Xing, Na Zhang, Jieran Chen, Yuting Zhang, Hengqian Yang, Shiyu Peng, Runlin Ma, Qiuyue Liu, Shangquan Gan and Haitao Wang

Genes 2024, 15(12), 1637; https://doi.org/10.3390/genes15121637 - 20 Dec 2024

Cited by 2 | Viewed by 1302

Abstract

(1) Background: The Hu sheep is a renowned breed characterized by high reproduction, year-round estrus, and resistance to high humidity and temperature conditions. However, the breed exhibits lower growth rates and meat yields, which necessitate improvements through selective breeding. The integration of molecular [...] Read more.

(1) Background: The Hu sheep is a renowned breed characterized by high reproduction, year-round estrus, and resistance to high humidity and temperature conditions. However, the breed exhibits lower growth rates and meat yields, which necessitate improvements through selective breeding. The integration of molecular markers in sheep breeding programs has the potential to enhance growth performance, reduce breeding cycles, and increase meat production. Currently, the applications of SNP chips for genotyping in conjunction with genome-wide association studies (GWAS) have become a prevalent approach for identifying candidate genes associated with economically significant traits in livestock. (2) Methods: To pinpoint candidate genes influencing growth traits in Hu sheep, we recorded the birth weight, weaning weight, and weights at 3, 4, 5, 6, and 7 months for a total of 567 Hu sheep, and genotyping was performed using the Ovine 40K SNP chip. (3) Results: Through GWAS analysis and KEGG pathway enrichment, we identified three candidate genes associated with birth weight (CAMK2B, CACNA2D1, and CACNA1C). Additionally, we found two candidate genes linked to weaning weight (FGF9 and BMPR1B), with CACNA2D1 also serving as a shared gene between birth weight and weaning weight traits. Furthermore, we identified eight candidate genes related to monthly weight (FIGF, WT1, KCNIP4, JAK2, WWP1, PLCL1, GPRIN3, and CCSER1). (4) Conclusion: Our findings revealed a total of 13 candidate genetic markers that can be utilized for molecular marker-assisted selection, aiming to improve meat production in sheep breeding programs. Full article

(This article belongs to the Special Issue Advances in Cattle, Sheep, and Goats Molecular Genetics and Breeding)

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13 pages, 299 KiB

Open AccessEditor’s ChoiceReview

Role of the PPARGC1A Gene and Its rs8192678 Polymorphism on Sport Performance, Aerobic Capacity, Muscle Adaptation and Metabolic Diseases: A Narrative Review

by David Varillas-Delgado

Genes 2024, 15(12), 1631; https://doi.org/10.3390/genes15121631 - 20 Dec 2024

Cited by 5 | Viewed by 3013

Abstract

Background/Objectives: The PPARGC1A gene, encoding the PGC-1α protein, is a critical regulator of energy metabolism, influencing mitochondrial biogenesis, fatty acid oxidation, and carbohydrate metabolism. This narrative review aims to evaluate the role of the PPARGC1A gene, with a specific focus on the c.1444G<A [...] Read more.

Background/Objectives: The PPARGC1A gene, encoding the PGC-1α protein, is a critical regulator of energy metabolism, influencing mitochondrial biogenesis, fatty acid oxidation, and carbohydrate metabolism. This narrative review aims to evaluate the role of the PPARGC1A gene, with a specific focus on the c.1444G<A polymorphism (rs8192678), in sports performance, including its impact on aerobic capacity, muscle adaptation, and its potential implications for metabolic health. Methods: A comprehensive literature search was conducted using databases such as PubMed, Scopus, Science Direct, and Web of Science, following PRISMA guidelines. Studies investigating the rs8192678 polymorphism in athletes, its relationship with physical performance, and its broader metabolic effects were included. Data were synthesized qualitatively, and heterogeneity among findings was assessed. The rs8192678 polymorphism influences sports performance differently. Results: the G allele is associated with enhanced mitochondrial efficiency, higher aerobic capacity, and a greater proportion of fatigue-resistant type I muscle fibers, benefiting endurance sports like cycling and triathlon. Conversely, the A allele correlates with reduced mitochondrial biogenesis and oxidative capacity, potentially impairing endurance but showing possible utility in strength-based sports. Furthermore, the A allele is linked to increased risks of metabolic conditions, including type 2 diabetes and obesity. Discrepancies in results highlight the influence of genetic, environmental, and training interactions. Conclusions: the PPARGC1A rs8192678 polymorphism plays a significant role in athletic performance and metabolic regulation. While the G allele confers advantages in endurance sports, the A allele presents mixed implications for strength and metabolic health. These findings support the potential for genetic profiling in personalized training and health interventions but emphasize the need for further research to clarify genotype-environment interactions. Full article

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

11 pages, 2480 KiB

Open AccessEditor’s ChoiceArticle

Expanding the Genotypic and Phenotypic Spectrum of OFD1-Related Conditions: Three More Cases

by Tatiana Kyian, Artem Borovikov, Inga Anisimova, Oksana Ryzhkova, Maria Bulakh, Elizabeth Bragina, Maria Avakyan, Anna Demchenko, Victoria Zabnenkova, Victor Kovalev, Artem Bukhonin, Elena Kondratyeva and Sergey Kutsev

Genes 2024, 15(12), 1633; https://doi.org/10.3390/genes15121633 - 20 Dec 2024

Cited by 1 | Viewed by 1667

Abstract

Introduction: Pathogenic variants in the OFD1 gene are linked to a spectrum of syndromes that exhibit partial clinical overlap. Hemizygous loss-of-function variants are considered lethal in males, while heterozygous loss-of-function variants generally result in oro-facial-digital syndrome type 1. A reported phenotype, Simpson–Golabi–Behmel syndrome [...] Read more.

Introduction: Pathogenic variants in the OFD1 gene are linked to a spectrum of syndromes that exhibit partial clinical overlap. Hemizygous loss-of-function variants are considered lethal in males, while heterozygous loss-of-function variants generally result in oro-facial-digital syndrome type 1. A reported phenotype, Simpson–Golabi–Behmel syndrome type 2, was published once but remains controversial, with many specialists questioning its validity and arguing about its continued listing in the OMIM database. Methods: To investigate the genetic and phenotypic characteristics of the patients, we performed clinical exome sequencing, family-based genetic analysis, X-inactivation studies, electron microscopy, and detailed clinical assessments. Results: Three patients from unrelated families carrying loss-of-function variants in the OFD1 gene were identified, emphasizing the diverse phenotypic spectrum of OFD1-associated disorders. The first patient, a female with a heterozygous frameshift variant p.(Gln398LeufsTer2), was diagnosed with oro-facial-digital syndrome type 1. The second patient, a male with a heterozygous nonsense variant p.(Gln892Ter), presented with features resembling Simpson–Golabi–Behmel syndrome type 2, as previously reported under this diagnosis. The third patient, a male with another heterozygous nonsense variant p.(Glu879Ter), exhibited isolated primary ciliary dyskinesia without any syndromic features. Conclusions: This study contributes to the growing body of evidence on the expanding phenotypic spectrum of OFD1-associated disorders. It underscores the need for further investigation into the molecular mechanisms underlying the diverse presentations and the necessity of re-evaluating diagnostic classifications for conditions such as SGBS2 in the context of variants in the OFD1 gene. Full article

(This article belongs to the Special Issue Genes and Variants in Human Rare Genetic Diseases)

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11 pages, 705 KiB

Open AccessEditor’s ChoiceArticle

Novel Intragenic and Genomic Variants Highlight the Phenotypic Variability in HCCS-Related Disease

by Linda M. Reis, Donald Basel, Pierre Bitoun, David S. Walton, Tom Glaser and Elena V. Semina

Genes 2024, 15(12), 1636; https://doi.org/10.3390/genes15121636 - 20 Dec 2024

Viewed by 655

Abstract

Background: Disruption of HCCS results in microphthalmia with linear skin lesions (MLS) characterized by microphthalmia/anophthalmia, corneal opacity, aplastic skin lesions, variable central nervous system and cardiac anomalies, intellectual disability, and poor growth in heterozygous females. Structural variants consisting of chromosomal rearrangements or [...] Read more.

Background: Disruption of HCCS results in microphthalmia with linear skin lesions (MLS) characterized by microphthalmia/anophthalmia, corneal opacity, aplastic skin lesions, variable central nervous system and cardiac anomalies, intellectual disability, and poor growth in heterozygous females. Structural variants consisting of chromosomal rearrangements or deletions are the most common variant type, but a small number of intragenic variants have been reported. Methods: Exome sequencing identified variants affecting HCCS. Results: Three novel intragenic variants and two genomic deletions of HCCS were found in individuals with primarily ocular features of MLS. X-inactivation was highly skewed in affected individuals with all three intragenic variants. Corneal opacity was the most penetrant feature (100%). In addition, a duplication of uncertain significance including both HCCS and AMELX was identified in a male with corneal anomalies, glaucoma, an atrial septal defect, and enamel hypoplasia along with a family history of developmental ocular disorders consistent with X-linked inheritance. Conclusion: Although variable expressivity is a known feature of MLS, our findings provide additional support for including HCCS in testing for individuals with isolated ocular anomalies and provide further evidence for its association with congenital aphakia, aniridia/other iris defects, and corneal staphyloma/ectasia. Full article

(This article belongs to the Special Issue Genetics of Eye Development and Diseases)

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14 pages, 4107 KiB

Open AccessEditor’s ChoiceArticle

Polymorphism of Genes Potentially Affecting Growth and Body Size Suggests Genetic Divergence in Wild and Domestic Reindeer (Rangifer tarandus) Populations

by Anna A. Krutikova, Natalia V. Dementieva, Yuri S. Shcherbakov, Vasiliy V. Goncharov, Darren K. Griffin and Michael N. Romanov

Genes 2024, 15(12), 1629; https://doi.org/10.3390/genes15121629 - 20 Dec 2024

Viewed by 1457

Abstract

Background/Objectives: A combination of increased human presence in the Arctic zone alongside climate change has led to a decrease in the number of wild reindeer (Rangifer tarandus). Studying the genetic potential of this species will aid in conservation efforts, while [...] Read more.

Background/Objectives: A combination of increased human presence in the Arctic zone alongside climate change has led to a decrease in the number of wild reindeer (Rangifer tarandus). Studying the genetic potential of this species will aid in conservation efforts, while simultaneously promoting improved meat productivity in domestic reindeer. Alongside reducing feed costs, increasing disease resistance, etc., acquiring genetic variation information is a crucial task for domestic reindeer husbandry. This study thus identified highly informative molecular genetic markers usable for assessing genetic diversity and breeding purposes in reindeer. Methods: We analyzed gene polymorphism that may potentially affect animal growth and development in populations of wild (Taimyr Peninsula) and domestic reindeer, including Nenets and Evenk breeds. We screened these populations for polymorphisms by sequencing the GH, GHR, LCORL and BMP2 genes. Results: Following generation of gene sequences, we compared the alleles frequency in the surveyed populations and their genetic divergence. Some loci lacked polymorphism in wild reindeer, unlike domestic breeds. This could suggest a selection-driven microevolutionary divergence in domestic reindeer populations. An isolated domestic population from Kolguyev Island appeared to be genetically remote from continental reindeer. Conclusions: Molecular genetic markers associated with economically important traits in reindeer can be further developed using the data obtained. Monitoring wild reindeer populations and better utilizing the genetic potential of domestic animals will depend on a panel of these marker genes. By using this marker panel, the amount of time spent on selection efforts will be greatly reduced to enhance meat performance during reindeer breeding. Full article

(This article belongs to the Special Issue Wildlife Genetic Diversity and Genomics)

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14 pages, 261 KiB

Open AccessEditor’s ChoiceArticle

Multiplex Detection of SNPs for Genetic Monitoring in Laboratory Mice by Luminex xTAG Assay

by Jiaqi Zhou, Jie Wei, Hong Wang, Huan Li, Lan Zhao, Rui Fu and Bingfei Yue

Genes 2024, 15(12), 1622; https://doi.org/10.3390/genes15121622 - 19 Dec 2024

Viewed by 748

Abstract

Background: The genetic quality of laboratory mice may have a direct impact on the results of research. Therefore, it is essential to improve genetic monitoring methods to guarantee research quality. However, few current methods boast high efficiency, high throughput, low cost, and general [...] Read more.

Background: The genetic quality of laboratory mice may have a direct impact on the results of research. Therefore, it is essential to improve genetic monitoring methods to guarantee research quality. However, few current methods boast high efficiency, high throughput, low cost, and general applicability at the same time. Methods: First, we got 34 SNP loci from previous studies for inbred strains and screened out 15 loci with good polymorphism for outbred groups from these 34 loci. Then, by using the Luminex xTAG assay, we tested inbred strains and outbred groups. Results: We tested commonly used inbred strains and five DNA samples from the International Council for Laboratory Animal Science, obtaining correct genotyping results. Additionally, some loci were potentially confirmed to be useful for distinguishing C57BL/6 and BALB/c mouse substrains. Furthermore, we tested three outbred groups and analyzed the genetic structure, and we compared the results of the SNP markers by xTAG assay to the STR markers by PCR, the trends of the three groups are the same. Conclusions: In our studies, the panels could meet the requirements for method promotion and provide a good choice for the genetic monitoring of inbred and outbred mice. Full article

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

18 pages, 6611 KiB

Open AccessEditor’s ChoiceArticle

The Impact of Bevacizumab and miR200c on EMT and EGFR-TKI Resistance in EGFR-Mutant Lung Cancer Organoids

by Nobuaki Kobayashi, Seigo Katakura, Nobuhiko Fukuda, Kohei Somekawa, Ayami Kaneko and Takeshi Kaneko

Genes 2024, 15(12), 1624; https://doi.org/10.3390/genes15121624 - 19 Dec 2024

Cited by 1 | Viewed by 1439

Abstract

Objectives: This research aims to investigate the mechanisms of resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in non-small-cell lung cancer (NSCLC), particularly focusing on the role of the epithelial–mesenchymal transition (EMT) within the tumor microenvironment (TME). Materials and Methods [...] Read more.

Objectives: This research aims to investigate the mechanisms of resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in non-small-cell lung cancer (NSCLC), particularly focusing on the role of the epithelial–mesenchymal transition (EMT) within the tumor microenvironment (TME). Materials and Methods: We employed an in vitro three-dimensional organoid model that mirrors the physiology of human lung cancer. These organoids consist of lung cancer cells harboring specific EGFR mutations, human mesenchymal stem cells, and human umbilical vein endothelial cells. We analyzed EMT and drug resistance markers, and evaluated the effects of the anti-angiogenic agent Bevacizumab and micro-RNA miR200c. Results: The study identified a significant link between EMT and EGFR-TKI resistance. Notable findings included a decrease in E-cadherin and an increase in Zinc Finger E-Box Binding Homeobox 1 (ZEB1), both of which influenced EMT and resistance to treatment. Bevacizumab showed promise in improving drug resistance and mitigating EMT, suggesting an involvement of the Vascular Endothelial Growth Factor (VEGF) cascade. Transfection with miR200c was associated with improved EMT and drug resistance, further highlighting the role of EMT in TKI resistance. Conclusions: Our research provides significant insights into the EMT-driven EGFR-TKI resistance in NSCLC and offers potential strategies to overcome resistance, including the use of Bevacizumab and miR200c. However, due to the limitations in organoid models in replicating precise human cancer TME and the potential influence of specific EGFR mutations, further in vivo studies and clinical trials are necessary for validation. Full article

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

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13 pages, 3696 KiB

Open AccessEditor’s ChoiceArticle

MicroRNA Screening Reveals Upregulation of FoxO-Signaling in Relapsed Acute Myeloid Leukemia Patients

by Paula Reichelt, Stephan Bernhart, Uwe Platzbecker and Michael Cross

Genes 2024, 15(12), 1625; https://doi.org/10.3390/genes15121625 - 19 Dec 2024

Viewed by 880

Abstract

Background/Objectives: AML is an aggressive malignant disease characterized by aberrant proliferation and accumulation of immature blast cells in the patient’s bone marrow. Chemotherapeutic treatment can effectively induce remission and re-establish functional hematopoiesis. However, many patients experience chemoresistance-associated relapse and disease progression with [...] Read more.

Background/Objectives: AML is an aggressive malignant disease characterized by aberrant proliferation and accumulation of immature blast cells in the patient’s bone marrow. Chemotherapeutic treatment can effectively induce remission and re-establish functional hematopoiesis. However, many patients experience chemoresistance-associated relapse and disease progression with a poor prognosis. The identification of molecular determinants of chemoresistance that could serve as potential targets for the therapeutic restoration of chemosensitivity has proven to be challenging. Methods: To address this, we have analyzed longitudinal changes in the expression of microRNAs during disease progression in a small set of four AML patients, combined with gene ontology (GO) pathway analysis and evaluation of gene expression data in patient databases. Results: MicroRNA profiling of bone marrow samples at diagnosis and after relapse revealed significant differential expression of a large number of microRNAs between the two time points. Subsequent GO pathway analysis identified 11 signal transduction pathways likely to be affected by the differential miRNA signatures. Exemplary validation of the FoxO signaling pathway by gene expression analysis confirmed significant upregulation of FOXO1 and the target genes GADD45 and SOD2. Conclusions: Here, we show how a microRNA-based pathway prediction strategy can be used to identify differentially regulated signaling pathways that represent potential targets for therapeutic intervention. Full article

(This article belongs to the Special Issue MicroRNA in Cancers)

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15 pages, 712 KiB

Open AccessEditor’s ChoiceArticle

Association Among MCT1 rs1049434 Polymorphism, Athlete Status, and Physiological Parameters in Japanese Long-Distance Runners

by Shotaro Seki, Tetsuro Kobayashi, Kenji Beppu, Manabu Nojo, Kosaku Hoshina, Naoki Kikuchi, Takanobu Okamoto, Koichi Nakazato and Inkwan Hwang

Genes 2024, 15(12), 1627; https://doi.org/10.3390/genes15121627 - 19 Dec 2024

Viewed by 1041

Abstract

Background/Objectives: Monocarboxylate transporters (MCTs) comprise 14 known isoforms, with MCT1 being particularly important for lactate transport. Variations in lactate metabolism capacity and aerobic performance are associated with the T1470A polymorphism in MCT1. We aimed to investigate the frequency of the T1470A polymorphism [...] Read more.

Background/Objectives: Monocarboxylate transporters (MCTs) comprise 14 known isoforms, with MCT1 being particularly important for lactate transport. Variations in lactate metabolism capacity and aerobic performance are associated with the T1470A polymorphism in MCT1. We aimed to investigate the frequency of the T1470A polymorphism and compare relevant physiological parameters among long-distance runners, wherein these parameters are fundamental to athletic performance. Methods: We included 158 Japanese long-distance runners (LD) and 649 individuals from the general Japanese population (CON). The frequency of the T1470A polymorphism was compared between these groups and across athletic levels using the chi-square test. Additionally, physiological data were collected from 57 long-distance runners, and respiratory gas measurements were obtained using the mixing-chamber method during a graded incremental exercise test. Results: We observed a significant difference between the LD and CON groups in the dominant model and between the sub-28 min group and 28 min or above group in the recessive model. As the competitive level increased, the frequency of the AA genotype also increased. When comparing physiological parameters between the AA genotype and T allele, subjects with the AA genotype showed significantly higher values for oxygen uptake at lactate threshold (p = 0.001), oxygen uptake at onset of blood lactate accumulation (p = 0.01), maximal oxygen uptake (p = 0.005), and maximal blood lactate concentration (p = 0.038). Conclusions: These results suggest that the AA genotype of the T1470A polymorphism of MCT1 is an effective genotype associated with athletic status and aerobic capacity in Japanese long-distance runners. Full article

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

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19 pages, 7309 KiB

Open AccessEditor’s ChoiceArticle

Side- and Disease-Dependent Changes in Human Aortic Valve Cell Population and Transcriptomic Heterogeneity Determined by Single-Cell RNA Sequencing

by Nicolas Villa-Roel, Christian Park, Aitor Andueza, Kyung In Baek, Ally Su, Mark C. Blaser, Bradley G. Leshnower, Ajit Yoganathan, Elena Aikawa and Hanjoong Jo

Genes 2024, 15(12), 1623; https://doi.org/10.3390/genes15121623 - 19 Dec 2024

Viewed by 1652

Abstract

Background: Calcific aortic valve disease (CAVD) is a highly prevalent disease, especially in the elderly population, but there are no effective drug therapies other than aortic valve repair or replacement. CAVD develops preferentially on the fibrosa side, while the ventricularis side remains relatively [...] Read more.

Background: Calcific aortic valve disease (CAVD) is a highly prevalent disease, especially in the elderly population, but there are no effective drug therapies other than aortic valve repair or replacement. CAVD develops preferentially on the fibrosa side, while the ventricularis side remains relatively spared through unknown mechanisms. We hypothesized that the fibrosa is prone to the disease due to side-dependent differences in transcriptomic patterns and cell phenotypes. Methods: To test this hypothesis, we performed single-cell RNA sequencing using a new method to collect endothelial-enriched samples independently from the fibrosa and ventricularis sides of freshly obtained human aortic valve leaflets from five donors, ranging from non-diseased to fibrocalcific stages. Results: From the 82,356 aortic valve cells analyzed, we found 27 cell clusters, including seven valvular endothelial cell (VEC), nine valvular interstitial cell (VIC), and seven immune, three transitional, and one stromal cell population. We identified several side-dependent VEC subtypes with unique gene expression patterns. Homeostatic VIC clusters were abundant in non-diseased tissues, while VICs enriched with fibrocalcific genes and pathways were more prevalent in diseased leaflets. Furthermore, homeostatic macrophage (MΦ) clusters decreased while inflammatory MΦ and T-cell clusters increased with disease progression. A foamy MΦ cluster was increased in the fibrosa of mildly diseased tissues. Some side-dependent VEC clusters represented non-diseased, protective phenotypes, while others were CAVD-associated and were characterized by genes enriched in pathways of inflammation, endothelial–mesenchymal transition, apoptosis, proliferation, and fibrosis. Interestingly, we found several activator protein-1 (AP-1)-related transcription factors (FOSB, FOS, JUN, JUNB) and EGR1 to be upregulated in the fibrosa and diseased aortic valve leaflets. Conclusions: Our results showed that VECs are highly heterogeneous in a side- and CAVD-dependent manner. Unique VEC clusters and their differentially regulated genes and pathways found in the fibrosa of diseased tissues may represent novel pathogenic mechanisms and potential therapeutic targets. Full article

(This article belongs to the Special Issue Cardiovascular Disease: From Genetics to Therapeutics)

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18 pages, 5689 KiB

Open AccessEditor’s ChoiceArticle

Comparative Transcriptome Analysis Reveals Mechanisms of Differential Salinity Tolerance Between Suaeda glauca and Suaeda salsa

by Qidong Yan, Shang Gao, Xianglun Zhang, Guoping Liu, Peitao Chen, Xuanyi Gao, Li Yuan, Yucheng Tian, Dapeng Li, Xuepeng Zhang and Huan Zhang

Genes 2024, 15(12), 1628; https://doi.org/10.3390/genes15121628 - 19 Dec 2024

Viewed by 1122

Abstract

Background: Suaeda glauca and Suaeda salsa have obvious morphological features and strongly tolerate saline–alkali environments. However, the mechanisms that lead to the differences in saline–alkali tolerance between them remain unclear. Methods: In this study, we employed comparative transcriptome analysis to investigate S. glauca [...] Read more.

Background: Suaeda glauca and Suaeda salsa have obvious morphological features and strongly tolerate saline–alkali environments. However, the mechanisms that lead to the differences in saline–alkali tolerance between them remain unclear. Methods: In this study, we employed comparative transcriptome analysis to investigate S. glauca and S. salsa under saline–alkali stress. Results: Our sequencing efforts resulted in the identification of 99,868 unigenes. We obtained 12,021 and 6227 differentially expressed genes (DEGs) from the S. glauca and S. salsa under salt stress compared with plants in the control. Notably, 1189 and 1864 were specifically upregulated DEGs in the roots and leaves of S. salsa under saline–alkali conditions, respectively. These genes were enriched in pathways such as “Plant hormone signal transduction”, “Carbon metabolism” and “Starch and sucrose metabolism”. Further analysis of stress-related pathways and gene expression levels revealed that key genes involved in abscisic acid (ABA) and jasmonic acid (JA) biosynthesis, ABA signal transduction, and their downstream transcription factors were upregulated in the roots of S. salsa under saline–alkali conditions. Additionally, 24 DEGs associated with stress response were identified in the roots and leaves of both species. The expression levels of these pathways and related genes were higher in S. salsa than in S. glauca, suggesting that S. salsa enhances its saline–alkali tolerance by elevating the expression of these genes. Conclusions: This study provides a new research perspective for revealing the differences in saline–alkali tolerance mechanisms between S. glauca and S. salsa, bringing forth important candidate genes for studying their saline–alkali tolerance. Full article

(This article belongs to the Special Issue Abiotic Stress in Plants: Molecular Genetics and Genomics—2nd Edition)

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11 pages, 19493 KiB

Open AccessEditor’s ChoiceArticle

Transcriptomic Changes in Human Tonsil-Derived Mesenchymal Stem Cells Across Culture Passages

by Moon Sik Oh, Heesun Hong, Ok Joo Lee, Su Hyeon Yi, Hae Sang Park, Jae-Jun Lee, Chan Hum Park and Sun-Wha Im

Genes 2024, 15(12), 1626; https://doi.org/10.3390/genes15121626 - 19 Dec 2024

Cited by 1 | Viewed by 741

Abstract

Background/Objectives: Tonsil-derived mesenchymal stem cells (TMSCs) are in the limelight in regenerative medicine due to their high proliferation and differentiation potential. It is important to conduct studies to determine the optimal conditions for achieving the maximum yield while maintaining the optimal differentiation capacity [...] Read more.

Background/Objectives: Tonsil-derived mesenchymal stem cells (TMSCs) are in the limelight in regenerative medicine due to their high proliferation and differentiation potential. It is important to conduct studies to determine the optimal conditions for achieving the maximum yield while maintaining the optimal differentiation capacity of TMSCs. Methods: This study explores the impact of serial subculture on TMSCs by analyzing gene expression at passages 2, 4, 6, and 8. For each culture passage, genes with significant differences in RNA expression from previous passages were selected and their characteristics were observed performing enrichment analysis including KEGG (Kyoto Encyclopedia of Genes and Genomes) and Reactome pathway. Results: At each passage, a “cell cycle” term was ranked high with statistical significance in the KEGG and Reactome pathway. Cell cycle gene expression, including Cyclin-dependent kinases (CDKs) and cyclins, increased until passage 6, then decreased by passage 8. The cell cycle is known to be important not only for proliferation but also for determining whether stem cells maintain pluripotency or differentiate into various lineages. Conclusions: The results suggest that cell cycle gene expression can guide the timing for differentiation induction, with passage 6 potentially being a critical point for initiating differentiation. Full article

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

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17 pages, 3080 KiB

Open AccessEditor’s ChoiceArticle

The Complete Mitochondrial Genome of the Luciocyprinus langsoni (Cypriniformes: Cyprinidae): Characterization, Phylogeny, and Genetic Diversity Analysis

by Tiezhu Yang, Chenxi Tan, Liangjie Zhao, Zhiguo Hu, Chaoqun Su, Fan Li, Yuanye Ma, Wenchao Zhang, Xiaoyu Hao, Wenxu Zou, Jiayin Kang and Qingqing He

Genes 2024, 15(12), 1621; https://doi.org/10.3390/genes15121621 - 18 Dec 2024

Viewed by 766

Abstract

Background: Luciocyprinus langsoni is a species belonging to the Cyprinidae family. The objective of this study is to gain a comprehensive understanding of its evolutionary history and genetic characteristics. Methods: The complete mitochondrial genome of L. langsoni was determined using [...] Read more.

Background: Luciocyprinus langsoni is a species belonging to the Cyprinidae family. The objective of this study is to gain a comprehensive understanding of its evolutionary history and genetic characteristics. Methods: The complete mitochondrial genome of L. langsoni was determined using overlapping PCR. A phylogenetic analysis was conducted based on 13 protein-coding genes from 48 species. A population genetic diversity analysis using the COI gene and a selection analysis of 13 protein-coding genes were also performed. Results: The mitogenome is 16,586 base pairs long and consists of 13 protein-coding genes, two ribosomal RNAs, 22 transfer RNAs, and two control regions. It has a high adenine-thymine (A + T) content. The phylogenetic analysis confirms the placement of L. langsoni within the subfamily Cyprininae. The population genetic diversity analysis reveals low variability in the Hechi Longjiang population. The selection analysis shows that all 13 protein-coding genes have evolved under purifying selection with Ka/Ks ratios below 1. Conclusions: These results enhance our understanding of L. langsoni’s evolutionary history and lay a genetic foundation for future studies in population genetics and phylogenetics. Full article

(This article belongs to the Special Issue Advances in Genes and Genomics of Aquatic Animals and Pathogens)

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11 pages, 3489 KiB

Open AccessEditor’s ChoiceArticle

Endurance Effort Affected Expression of Actinin 3 and Klotho Different Isoforms Basing on the Arabian Horses Model

by Grzegorz Myćka, Katarzyna Ropka-Molik, Anna Cywińska and Monika Stefaniuk-Szmukier

Genes 2024, 15(12), 1618; https://doi.org/10.3390/genes15121618 - 18 Dec 2024

Viewed by 868

Abstract

Background: Among numerous genes that have been a focus of equine genetic research, the KL (Klotho) and ACTN3 (Alpha-actinin-3) genes stand out due to their significant roles in muscle function and overall health, as well as performance ability. Previous studies on Arabian horses [...] Read more.

Background: Among numerous genes that have been a focus of equine genetic research, the KL (Klotho) and ACTN3 (Alpha-actinin-3) genes stand out due to their significant roles in muscle function and overall health, as well as performance ability. Previous studies on Arabian horses and other mammalians have shown that both KL and ACTN3 occur in different isoforms that seem to have different roles in metabolism. The main purpose of this present study was to describe different isoforms (ACTN3, ACTN3-201, ACTN3-202, KL, KL-202, KL-203) expression levels affected by the endurance effort in Arabian horses. Methods: Blood samples were taken from a group of n = 10 Arabian horses taking part in a long-distance 120 km endurance ride. After RNA isolation and reverse transcription, real-time PCR was performed. The expression levels (Relative Quantity, RQ) were calculated using the delta-delta CT method. The results showed surprisingly large differences between different isoforms expression levels which brought us to the conclusion that both KL and ACTN3 genes are suitable genetic markers to measure endurance performance. Moreover, the correlation network analyses showed that the MIOX (myo-inositol oxygenase), SH3RH2 (SH3 domain-containing ring finger 2) and TNNI2 (Troponin I2, fast skeletal type) genes are significantly involved in the endurance effort metabolism. Full article

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

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15 pages, 3634 KiB

Open AccessEditor’s ChoiceArticle

Chemogenetic Inhibition of Prefrontal Cortex Ameliorates Autism-Like Social Deficits and Absence-Like Seizures in a Gene-Trap Ash1l Haploinsufficiency Mouse Model

by Kaijie Ma, Kylee McDaniel, Daoqi Zhang, Maria Webb and Luye Qin

Genes 2024, 15(12), 1619; https://doi.org/10.3390/genes15121619 - 18 Dec 2024

Viewed by 1069

Abstract

Background: ASH1L (absent, small, or homeotic-like 1), a histone methyltransferase, has been identified as a high-risk gene for autism spectrum disorder (ASD). We previously showed that postnatal Ash1l severe deficiency in the prefrontal cortex (PFC) of male and female mice caused seizures. However, [...] Read more.

Background: ASH1L (absent, small, or homeotic-like 1), a histone methyltransferase, has been identified as a high-risk gene for autism spectrum disorder (ASD). We previously showed that postnatal Ash1l severe deficiency in the prefrontal cortex (PFC) of male and female mice caused seizures. However, the synaptic mechanisms underlying autism-like social deficits and seizures need to be elucidated. Objective: The goal of this study is to characterize the behavioral deficits and reveal the synaptic mechanisms in an Ash1l haploinsufficiency mouse model using a targeted gene-trap knockout (gtKO) strategy. Method: A series of behavioral tests were used to examine behavioral deficits. Electrophysiological and chemogenetic approaches were used to examine and manipulate the excitability of pyramidal neurons in the PFC of Ash1l^+/GT mice. Results: Ash1l^+/GT mice displayed social deficits, increased self-grooming, and cognitive impairments. Epileptiform discharges were found on electroencephalograms (EEGs) of Ash1l^+/GT mice, indicating absence-like seizures. Ash1l haploinsufficiency increased the susceptibility for convulsive seizures when Ash1l^+/GT mice were challenged by pentylenetetrazole (PTZ, a competitive GABA_A receptor antagonist). Whole-cell patch-clamp recordings showed that Ash1l haploinsufficiency increased the excitability of pyramidal neurons in the PFC by altering intrinsic neuronal properties, enhancing glutamatergic synaptic transmission, and diminishing GABAergic synaptic inhibition. Chemogenetic inhibition of pyramidal neurons in the PFC of Ash1l^+/GT mice ameliorated autism-like social deficits and abolished absence-like seizures. Conclusions: We demonstrated that increased neural activity in the PFC contributed to the autism-like social deficits and absence-like seizures in Ash1l^+/GT mice, which provides novel insights into the therapeutic strategies for patients with ASH1L-associated ASD and epilepsy. Full article

(This article belongs to the Special Issue The Genetic and Epigenetic Basis of Neurodevelopmental Disorders)

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17 pages, 7699 KiB

Open AccessEditor’s ChoiceSystematic Review

Long Non-Coding RNAs as Diagnostic Biomarkers for Ischemic Stroke: A Systematic Review and Meta-Analysis

by Jianwei Pan, Weijian Fan, Chenjie Gu, Yongmei Xi, Yu Wang and Peter Wang

Genes 2024, 15(12), 1620; https://doi.org/10.3390/genes15121620 - 18 Dec 2024

Viewed by 1374

Abstract

Ischemic stroke is a serious cerebrovascular disease, highlighting the urgent need for reliable biomarkers for early diagnosis. Recent reports suggest that long non-coding RNAs (lncRNAs) can be potential biomarkers for ischemic stroke. Therefore, our study seeks to investigate the potential diagnostic value of [...] Read more.

Ischemic stroke is a serious cerebrovascular disease, highlighting the urgent need for reliable biomarkers for early diagnosis. Recent reports suggest that long non-coding RNAs (lncRNAs) can be potential biomarkers for ischemic stroke. Therefore, our study seeks to investigate the potential diagnostic value of lncRNAs for ischemic stroke by analyzing existing research. A comprehensive literature search was conducted across the PubMed, ScienceDirect, Wiley Online Library, and Web of Science databases for articles published up to July 10, 2024. Statistical analyses were performed using Stata 17.0 software to calculate pooled sensitivity, specificity, positive likelihood ratio (PLR), diagnostic odds ratio (DOR), negative likelihood ratio (NLR), and area under the curve (AUC). Heterogeneity was explored with the Cochran-Q test and the I² statistical test, and publication bias was assessed with Deeks’ funnel plot. A total of 44 articles were included, involving 4302 ischemic stroke patients and 3725 healthy controls. Results demonstrated that lncRNAs H19, GAS5, PVT1, TUG1, and MALAT1 exhibited consistent trends across multiple studies. The pooled sensitivity of lncRNAs in the diagnosis of ischemic stroke was 79% (95% CI: 73–84%), specificity was 88% (95% CI: 77–94%), PLR was 6.63 (95% CI: 3.11–14.15), NLR was 0.23 (95% CI: 0.16–0.33), DOR was 28.5 (95% CI: 9.88–82.21), and AUC was 0.88 (95% CI: 0.85–0.90). Furthermore, the results of subgroup analysis indicated that lncRNA H19 had superior diagnostic performance. LncRNAs demonstrated strong diagnostic accuracy in distinguishing ischemic stroke patients from healthy controls, underscoring their potential as reliable biomarkers. Because most of the articles included in this study originate from China, large-scale, high-quality, multi-country prospective studies are required to further validate the reliability of lncRNAs as biomarkers for ischemic stroke. Full article

(This article belongs to the Special Issue The Epigenetic Roles of lncRNAs)

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22 pages, 1564 KiB

Open AccessEditor’s ChoiceArticle

Heritability and Genome-Wide Association Study of Dog Behavioral Phenotypes in a Commercial Breeding Cohort

by Nayan Bhowmik, Shawna R. Cook, Candace Croney, Shanis Barnard, Aynsley C. Romaniuk and Kari J. Ekenstedt

Genes 2024, 15(12), 1611; https://doi.org/10.3390/genes15121611 - 17 Dec 2024

Viewed by 1970

Abstract

Background: Canine behavior plays an important role in the success of the human–dog relationship and the dog’s overall welfare, making selection for behavior a vital part of any breeding program. While behaviors are complex traits determined by gene × environment interactions, genetic [...] Read more.

Background: Canine behavior plays an important role in the success of the human–dog relationship and the dog’s overall welfare, making selection for behavior a vital part of any breeding program. While behaviors are complex traits determined by gene × environment interactions, genetic selection for desirable behavioral phenotypes remains possible. Methods: No genomic association studies of dog behavior to date have been reported on a commercial breeding (CB) cohort; therefore, we utilized dogs from these facilities (n = 615 dogs). Behavioral testing followed previously validated protocols, resulting in three phenotypes/variables [social fear (SF), non-social fear (NSF), and startle response (SR)]. Dogs were genotyped on the 710 K Affymetrix Axiom CanineHD SNP array. Results: Inbreeding coefficients indicated that dogs from CB facilities are statistically less inbred than dogs originating from other breeding sources. Heritability estimates for behavioral phenotypes ranged from 0.042 ± 0.045 to 0.354 ± 0.111. A genome-wide association analysis identified genetic loci associated with SF, NSF, and SR; genes near many of these loci have been previously associated with behavioral phenotypes in other populations of dogs. Finally, genetic risk scores demonstrated differences between dogs that were more or less fearful in response to test stimuli, suggesting that these behaviors could be subjected to genetic improvement. Conclusions: This study confirms several canine genetic behavioral loci identified in previous studies. It also demonstrates that inbreeding coefficients of dogs in CB facilities are typically lower than those in dogs originating from other breeding sources. SF and NSF were more heritable than SR. Risk allele and weighted risk scores suggest that fearful behaviors could be subjected to genetic improvement. Full article

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

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11 pages, 780 KiB

Open AccessEditor’s ChoiceArticle

Conventional Cytogenetic Analysis of Solid Tumor Abnormalities: A 25-Year Review of Proficiency Test Results from the College of American Pathologists/American College of Medical Genetics and Genomics Cytogenetics Committee

by Rachel K. Vanderschelden, William R. Sukov, Juli-Anne Gardner, Catherine W. Rehder, Brynn Levy, Gopalrao V. Velagaleti, Reha M. Toydemir, Guilin Tang, Brittany Boles, Yang Cao, Christopher Mixon, Ying S. Zou, Caroline Astbury, Karen D. Tsuchiya and Jess F. Peterson

Genes 2024, 15(12), 1612; https://doi.org/10.3390/genes15121612 - 17 Dec 2024

Viewed by 1286

Abstract

Background: The joint College of American Pathologists/American College of Medical Genetics and Genomics Cytogenetics Committee works to ensure the competency and proficiency of clinical cytogenetic testing laboratories through proficiency testing (PT) programs for various clinical tests offered by such laboratories, including the evaluation [...] Read more.

Background: The joint College of American Pathologists/American College of Medical Genetics and Genomics Cytogenetics Committee works to ensure the competency and proficiency of clinical cytogenetic testing laboratories through proficiency testing (PT) programs for various clinical tests offered by such laboratories, including the evaluation of cytogenetic abnormalities in solid tumors. Methods: Review and analyze 25 years (1999–2023) of solid tumor chromosome analysis PT results, utilizing G-banded karyograms. A retrospective review of results from 1999 to 2023 was performed, identifying the challenges addressing solid tumors. The chromosomal abnormalities and overall performance were evaluated. Results: A total of 21 solid tumor challenges were administered during the period 1999–2018. No solid tumor challenges were administered during the period 2019–2023. Challenges consisted of metaphase images and accompanying clinical history for the evaluation of numerical and/or structural abnormalities. All 21 cases reached 80% grading consensus for abnormality recognition. However, five cases (24%) failed to reach consensus for nomenclature reporting by participating laboratories. These cases illustrate errors in reporting chromosomal abnormalities, including whole-arm translocations and those involving sex chromosomes. In addition, they highlight the challenges with differentiation of terminal and interstitial deletions, difficulties in identifying correct breakpoints, and omission of brackets in neoplastic cases. Conclusions: This comprehensive 25-year review demonstrates the exceptional proficiency of cytogenetic laboratories in accurately identifying chromosome abnormalities in solid tumors, while also highlighting the challenges of reporting specific types of chromosomal abnormalities. Full article

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

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22 pages, 11986 KiB

Open AccessEditor’s ChoiceArticle

The Finnic Peoples of Russia: Genetic Structure Inferred from Genome-Wide and Y-Chromosome Data

by Anastasia Agdzhoyan, Georgy Ponomarev, Vladimir Pylev, Zhaneta Autleva (Kagazezheva), Igor Gorin, Igor Evsyukov, Elvira Pocheshkhova, Sergey Koshel, Viacheslav Kuleshov, Dmitry Adamov and Natalia Kuznetsova

Genes 2024, 15(12), 1610; https://doi.org/10.3390/genes15121610 - 17 Dec 2024

Viewed by 5883

Abstract

Background: Eastern Finnic populations, including Karelians, Veps, Votes, Ingrians, and Ingrian Finns, are a significant component of the history of Finnic populations, which have developed over ~3 kya. Yet, these groups remain understudied from a genetic point of view. Methods: In this work, [...] Read more.

Background: Eastern Finnic populations, including Karelians, Veps, Votes, Ingrians, and Ingrian Finns, are a significant component of the history of Finnic populations, which have developed over ~3 kya. Yet, these groups remain understudied from a genetic point of view. Methods: In this work, we explore the gene pools of Karelians (Northern, Tver, Ludic, and Livvi), Veps, Ingrians, Votes, and Ingrian Finns using Y-chromosome markers (N = 357) and genome-wide autosomes (N = 67) and in comparison with selected Russians populations of the area (N = 763). The data are analyzed using statistical, bioinformatic, and cartographic methods. Results: The autosomal gene pool of Eastern Finnic populations can be divided into two large categories based on the results of the PCA and ADMIXTURE modeling: (a) “Karelia”: Veps, Northern, Ludic, Livvi, and Tver Karelians; (b) “Ingria”: Ingrians, Votes, Ingrian Finns. The Y-chromosomal gene pool of Baltic Finns is more diverse and is composed of four genetic components. The “Northern” component prevails in Northern Karelians and Ingrian Finns, the “Karelian” in Livvi, Ludic, and Tver Karelians, the “Ingrian-Veps” in Ingrians and Veps (a heterogeneous cluster occupying an intermediate position between the “Northern” and the “Karelian” ones), and the “Southern” in Votes. Moreover, our phylogeographic analysis has found that the Y-haplogroup N3a4-Z1927 carriers are frequent among most Eastern Finnic populations, as well as among some Northern Russian and Central Russian populations. Conclusions: The autosomal clustering reflects the major areal groupings of the populations in question, while the Y-chromosomal gene pool correlates with the known history of these groups. The overlap of the four Y-chromosomal patterns may reflect the eastern part of the homeland of the Proto-Finnic gene pool. The carriers of the Y-haplogroup N3a4-Z1927, frequent in the sample, had a common ancestor at ~2.4 kya, but the active spread of N3a4-Z1927 happened only at ~1.7–2 kya, during the “golden” age of the Proto-Finnic culture (the archaeological period of the “typical” Tarand graves). A heterogeneous Y-chromosomal cluster containing Ingrians, Veps, and Northern Russian populations, should be further studied. Full article

(This article belongs to the Special Issue Genetics and Genomics of Human Population History)

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8 pages, 263 KiB

Open AccessEditor’s ChoiceArticle

Swedish Genome-Wide Haplotype Association Analysis Suggests Breast Cancer Loci with Varying Risk-Modifying Effects

by Litika Vermani, Elin Barnekow, Wen Liu, Camilla Wendt, Per Hall, Sara Margolin and Annika Lindblom

Genes 2024, 15(12), 1616; https://doi.org/10.3390/genes15121616 - 17 Dec 2024

Cited by 1 | Viewed by 732

Abstract

Background: To find support for risk-modifying genes in breast cancer, a haplotype GWAS in sporadic breast cancer cases was undertaken. The results were compared with the results from previous analyses in familial cases and all cases from the same Swedish cohort. Methods: In [...] Read more.

Background: To find support for risk-modifying genes in breast cancer, a haplotype GWAS in sporadic breast cancer cases was undertaken. The results were compared with the results from previous analyses in familial cases and all cases from the same Swedish cohort. Methods: In total, 2550 women with sporadic invasive breast cancer and 5021 healthy controls were included in a sliding-window haplotype GWAS using PLINK 1.07. Results: The analysis of sporadic cases confirmed the loci on chromosomes 10q26.13, 11q13.3, and 16q12.1 and suggested one novel locus on chromosome 12p11.21 (OR = 1.42 p = 4.55 × 10⁻⁸). A comparison between these loci and the same loci in the analyses of familial cases and all breast cancer cases was undertaken. Conclusions: Haplotype GWAS in sporadic cases of Swedish breast cancer cases supported known risk loci and suggested another risk locus. The loci identified in the analysis of sporadic and all breast cancer cases were suggested to act as modifiers of the risk of breast cancer. Haplotype analysis identified other loci with higher odds ratios than single-variant analysis. Further studies are needed to find out how to best include the findings in breast cancer prevention. Full article

(This article belongs to the Special Issue Genetics and Genomics of Human Breast Cancer)

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18 pages, 20472 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Identification and Evolutionary Analysis of Functional BBM-like Genes in Plant Species

by Zhengyuan Hong, Linghong Zhu, Chaolei Liu, Kejian Wang, Yuchun Rao and Hongwei Lu

Genes 2024, 15(12), 1614; https://doi.org/10.3390/genes15121614 - 17 Dec 2024

Cited by 1 | Viewed by 1236

Abstract

Background/Objectives: BABY BOOM (BBM), a transcription factor from the APETALA2 (AP2) protein family, plays a critical role in somatic embryo induction and apomixis. BBM has now been widely applied to induce apomixis or enhance plant transformation and regeneration efficiency through overexpression or [...] Read more.

Background/Objectives: BABY BOOM (BBM), a transcription factor from the APETALA2 (AP2) protein family, plays a critical role in somatic embryo induction and apomixis. BBM has now been widely applied to induce apomixis or enhance plant transformation and regeneration efficiency through overexpression or ectopic expression. However, the structural and functional evolutionary history of BBM genes in plants is still not well understood. Methods: The protein sequences of 10 selected plant species were used to locate the branch of BBM-Like by key domain identification and phylogenetic tree construction. The identified BBML genes were used for further conserved motif identification, gene structural analysis, miRNA binding site prediction, cis-acting element prediction, collinear analysis, protein–protein interaction network construction, three-dimensional structure modeling, molecular docking, and expression pattern analysis. Results: A total of 24 BBML proteins were identified from 10 representative plant species. Phylogenetic relationship analysis displayed that BBML proteins from eudicots and monocots were divided into two clusters, with monocots exhibiting a higher number of BBMLs. Gene duplication events indicated that whole genome/segmental duplication were the primary drivers of BBML genes’ evolution in the tested species, with purifying selection playing a key role during evolution processes. Comparative analysis of motif, domains, and gene structures revealed that most BBMLs were highly evolutionarily conserved. The expression patterns of BBML genes revealed significant tissue specificity, particularly in the root and embryo. We also constructed protein–protein interaction networks and molecular docking models to identify functional pathways and key amino acid residues of BBML proteins. The functions of BBMLs may differ between monocots and eudicots, as suggested by the functional enrichment of interacting proteins. Conclusions: Our research delved into the molecular mechanism, evolutionary relationships, functional differentiation, and expression patterns of BBML genes across plants, laying the groundwork for further investigations into the molecular properties and biological roles of BBMLs. Full article

(This article belongs to the Special Issue Genetics and Genomics of Rice)

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15 pages, 1116 KiB

Open AccessEditor’s ChoiceReview

Mutant p53-Mediated Tumor Secretome: Bridging Tumor Cells and Stromal Cells

by Lei Qiu, Zelong Ma and Xiaoming Wu

Genes 2024, 15(12), 1615; https://doi.org/10.3390/genes15121615 - 17 Dec 2024

Viewed by 1696

Abstract

The tumor secretome comprises the totality of protein factors secreted by various cell components within the tumor microenvironment, serving as the primary medium for signal transduction between tumor cells and between tumor cells and stromal cells. The deletion or mutation of the p53 [...] Read more.

The tumor secretome comprises the totality of protein factors secreted by various cell components within the tumor microenvironment, serving as the primary medium for signal transduction between tumor cells and between tumor cells and stromal cells. The deletion or mutation of the p53 gene leads to alterations in cellular secretion characteristics, contributing to the construction of the tumor microenvironment in a cell non-autonomous manner. This review discusses the critical roles of mutant p53 in regulating the tumor secretome to remodel the tumor microenvironment, drive tumor progression, and influence the plasticity of cancer-associated fibroblasts (CAFs) as well as the dynamics of tumor immunity by focusing on both secreted protein expression and secretion pathways. The aim is to provide new insights for targeted cancer therapies. Full article

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

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20 pages, 957 KiB

Open AccessEditor’s ChoiceArticle

Unearthing Genetic Treasures: Exploring Lost Autochthonous Vitis vinifera Varieties in Lebanon

by Carole Saliba, Alba María Vargas, María Teresa de Andrés, Françoise Lamy, Liliane Boukhdoud, Rhea Kahale, Thierry Robert, Rani Azzi, Noel Abinader and Magda Bou Dagher Kharrat

Genes 2024, 15(12), 1617; https://doi.org/10.3390/genes15121617 - 17 Dec 2024

Viewed by 1170

Abstract

Background/Objectives: Lebanon, one of the oldest centers of grapevine (Vitis vinifera L.) cultivation, is home to a rich diversity of local grape varieties. This biodiversity is linked to the country’s unique topography and millennia of cultural history. However, the wine industry primarily [...] Read more.

Background/Objectives: Lebanon, one of the oldest centers of grapevine (Vitis vinifera L.) cultivation, is home to a rich diversity of local grape varieties. This biodiversity is linked to the country’s unique topography and millennia of cultural history. However, the wine industry primarily utilizes international varieties, putting many local varieties at risk of extinction. Methods: In this study, we analyzed 202 samples from old vineyards, home gardens, and private collections using 21 microsatellite markers to assess their identity and genetic diversity. Results: A total of 67 different genotypes were identified, with 34 not matching any existing profiles in the consulted databases, based on comparisons with the European Vitis Database, the Vitis International Variety Catalogue (VIVC), and the databases established in two previous studies conducted in Armenia and Lebanon. Cluster analyses revealed Lebanon’s rich diversity of local grape varieties, highlighting cases of synonymy, homonymy, and misnaming. All loci were polymorphic, with 228 alleles and an average of 11.4 alleles being detected. The highest number of alleles was observed at the VVIV67 locus (19 alleles), while the lowest was found at the VVIQ52 and VVIN73 loci (5 alleles). The observed heterozygosity was 0.732, slightly below the expected value of 0.757, with gene diversity varying among the markers. Conclusions: Of the 67 genetic profiles identified, 34 are absent from national and international databases, underscoring Lebanon as a hotspot for grapevine genetic diversity. This unique genetic variation, which includes several synonyms due to geographic isolation, could provide valuable opportunities for producing distinctive wines and emphasizes the need for further research and documentation. Full article

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

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12 pages, 2010 KiB

Open AccessEditor’s ChoiceArticle

Genetic Variations on Chromosome 6p21 Are Associated with Asthma Risk and Disease Severity: A Case–Control Study from Pakistan

by Aqsa Aslam, Susanne J. H. Vijverberg, Anke-Hilse Maitland-van der Zee and Muhammad Farooq Sabar

Genes 2024, 15(12), 1608; https://doi.org/10.3390/genes15121608 - 17 Dec 2024

Viewed by 749

Abstract

Background: Genetic factors play a role in asthma severity. However, low- and middle-income countries have minimal contribution to genomic asthma research. The current study investigates the influence of an important genetic asthma region (6p21) on severe asthma in a cohort of asthmatics in [...] Read more.

Background: Genetic factors play a role in asthma severity. However, low- and middle-income countries have minimal contribution to genomic asthma research. The current study investigates the influence of an important genetic asthma region (6p21) on severe asthma in a cohort of asthmatics in Pakistan. Materials and Methods: In this case–control study, mild to severe asthmatic patients (n = 255) and controls (n = 260) were enrolled from Lahore, Pakistan. Blood samples were collected, and genomic DNA was extracted for the genotyping of 11 single nucleotide polymorphisms located in the 6p21 region. Severe asthma was defined based on the defined daily dose of inhaled corticosteroids equivalent to 200 mcg of beclomethasone dipropionate (as per the global initiative for asthma guidelines). An additive genetic model was followed to find the associations between these variants and the outcome. Univariate and multivariate logistic regression, adjusted for confounders, was performed. Odds ratio (OR), 95% confidence interval (95% CI), p-value, and q-values after FDR adjustment were estimated. Results: The genetic variants rs3025028, rs987870, and rs3025039 showed strong associations with the incidence of asthma with odds ratios of 1.58, 1.62, and 2.70 (95% CI = 1.16–2.16, 1.15–2.30, and 1.40–5.39, respectively). Further stratification analysis to study the risk of severe asthma also revealed markedly significant associations for rs3025020 and rs1799964 (OR = 2.28 and 2.99; 95% CI = 1.39–3.86 and 1.75–5.33, respectively). However, the SNPs rs2070600, rs987870, and rs3025039 also showed a significant relationship with the severity (OR = 2.34, 1.75, and 2.72; 95% CI = 1.02–5.97, 1.07–2.98, and 1.11–7.71, respectively), but FDR-adjusted q-values were insignificant (0.10, 0.07, and 0.07, respectively). Conclusions: The 6p21 region variants rs3025028, rs987870, and rs3025039 are associated with the incidence, whereas rs3025020 and rs1799964 are associated with the risk of more severe asthma in the Pakistani population. Full article

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

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12 pages, 944 KiB

Open AccessEditor’s ChoiceArticle

Genetic Composition of Polish Hucul Mare Families: mtDNA Diversity

by Aleksandra Błaszczak, Monika Stefaniuk-Szmukier, Bogusława Długosz, Adrianna Dominika Musiał, Katarzyna Olczak and Katarzyna Ropka-Molik

Genes 2024, 15(12), 1607; https://doi.org/10.3390/genes15121607 - 17 Dec 2024

Viewed by 879

Abstract

Backround: The Hucul horse breed formed in the region of the Eastern Carpathians, likely through the natural crossbreeding of oriental horses. After World War II, their population significantly decreased, leading to the breeding being based on only 14 female lines, whose founders often [...] Read more.

Backround: The Hucul horse breed formed in the region of the Eastern Carpathians, likely through the natural crossbreeding of oriental horses. After World War II, their population significantly decreased, leading to the breeding being based on only 14 female lines, whose founders often had unknown origins. To preserve the breed’s unique characteristics, it is now part of a Genetic Resources Conservation Program, which prioritizes the maintenance of genetic diversity. This study aims to clarify the maternal relatedness of founder mares and assess genetic diversity using mitochondrial DNA (mtDNA). Methods: The hyper-variable region of the mitochondrial genome was analyzed in 57 horses. Pedigree records were used to trace genealogical lines, and molecular analysis focused on identifying maternal relationships between founder mares. Results: The analysis revealed close maternal kinships between the lines of Jagoda and Bajkałka, as well as Sekunda and Sroczka. In the Hucul population, seventeen mitochondrial haplotypes were identified, with three that did not match any established lines. The findings reveal discrepancies between pedigree records and mitochondrial DNA data, suggesting potential inaccuracies in the Hucul horse studbook. Conclusions: The findings highlight the importance of combining pedigree and molecular data to refine strategies to preserving genetic diversity, minimizing inbreeding, and improving the management the Genetic Resources Conservation Program. Full article

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

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20 pages, 2240 KiB

Open AccessEditor’s ChoiceArticle

Calcium Signaling and Molecular Adhesion Processes May Hold the Key to Genetic Risk for Autism: A Molecular Pathway Analysis on Two Independent Samples

by Antonio Drago, Marco Calabro and Concetta Crisafulli

Genes 2024, 15(12), 1609; https://doi.org/10.3390/genes15121609 - 17 Dec 2024

Cited by 2 | Viewed by 968

Abstract

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by limited interests, difficulties in social interactions, repetitive behaviors, and impairments in social communication. ASD tends to run in families, and twin studies suggest a strong genetic basis for the disorder. However, the [...] Read more.

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by limited interests, difficulties in social interactions, repetitive behaviors, and impairments in social communication. ASD tends to run in families, and twin studies suggest a strong genetic basis for the disorder. However, the definition of a genetic profile that indicates a risk for ASD remains unclear. Methods: This analysis includes an investigation (Autism Dataset 4 from the NIMH repository, n = 2890) and a replication (Autism Dataset 3 from the NIMH repository, n = 1233) of trio samples with GWAS data. In Phase 1, a molecular pathway analysis is conducted on the investigation sample to test for the enrichment of specific Gene Ontology (GO) terms associated with autism. In Phase 2, the identified pathways are tested for enrichment in the replication sample. Permutation tests are performed to reduce the risk of false-positive findings. Quality assessment is conducted using QQ-plots and λ values, with Plink and R utilized for the Transmission Disequilibrium Test (TDT) and permutation tests. Results: The GO term GO:0007417 was found to be enriched in both the investigation and replication samples. SNPs associated with this pathway were observed at a frequency higher than expected in the replication sample. Conclusions: The GO term GO:0007417 (development of the nervous system) was associated with autism in both trio samples. Variations in the genes TMPRSS4, TRPC4, and PCDH9 were consistently linked to autism across the two independent samples, highlighting the role of calcium signaling and cell adhesion molecules in the risk of autism-related disorders. The pathways and variations associated with autism are described in detail, which can contribute to the engineering of new pharmacological treatments for ASD. Full article

(This article belongs to the Special Issue Advances in Pharmacogenetics of Diseases)

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16 pages, 1584 KiB

Open AccessEditor’s ChoiceReview

Advancements and Challenges in Preimplantation Genetic Testing for Aneuploidies: In the Pathway to Non-Invasive Techniques

by Ana del Arco de la Paz, Carla Giménez-Rodríguez, Aikaterini Selntigia, Marcos Meseguer and Daniela Galliano

Genes 2024, 15(12), 1613; https://doi.org/10.3390/genes15121613 - 17 Dec 2024

Cited by 1 | Viewed by 2875

Abstract

The evolution of preimplantation genetic testing for aneuploidy (PGT-A) techniques has been crucial in assisted reproductive technologies (ARTs), improving embryo selection and increasing success rates in in vitro fertilization (IVF) treatments. Techniques ranging from fluorescence in situ hybridization (FISH) to next-generation sequencing (NGS) [...] Read more.

The evolution of preimplantation genetic testing for aneuploidy (PGT-A) techniques has been crucial in assisted reproductive technologies (ARTs), improving embryo selection and increasing success rates in in vitro fertilization (IVF) treatments. Techniques ranging from fluorescence in situ hybridization (FISH) to next-generation sequencing (NGS) have relied on cellular material extraction through biopsies of blastomeres at the cleavage stage on day three or from trophectoderm (TE) cells of the blastocyst. However, this has raised concerns about its potential impact on embryo development. As a result, there has been growing interest in developing non-invasive techniques for detecting aneuploidies, such as the analysis of blastocoel fluid (BF), spent culture medium (SCM), and artificial intelligence (AI) models. Non-invasive methods represent a promising advancement in PGT-A, offering the ability to detect aneuploidies without compromising embryo viability. This article reviews the evolution and principles of PGT-A, analyzing both traditional techniques and emerging non-invasive approaches, while highlighting the advantages and challenges associated with these methodologies. Furthermore, it explores the transformative potential of these innovations, which could optimize genetic screening and significantly improve clinical outcomes in the field of assisted reproduction. Full article

(This article belongs to the Special Issue Current Advances and Future Perspectives on Preimplantation Genetic Testing)

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18 pages, 693 KiB

Open AccessEditor’s ChoiceReview

A Global Perspective of GBA1-Related Parkinson’s Disease: A Narrative Review

by Christos Koros, Anastasia Bougea, Ioanna Alefanti, Athina Maria Simitsi, Nikolaos Papagiannakis, Ioanna Pachi, Evangelos Sfikas, Roubina Antonelou and Leonidas Stefanis

Genes 2024, 15(12), 1605; https://doi.org/10.3390/genes15121605 - 16 Dec 2024

Cited by 3 | Viewed by 2172

Abstract

Parkinson’s disease (PD) is considered to be the second most prominent neurodegenerative disease and has a global prevalence. Glucocerebrosidase (GBA1) gene mutations represent a significant hereditary risk factor for the development of PD and have a profound impact on the motor [...] Read more.

Parkinson’s disease (PD) is considered to be the second most prominent neurodegenerative disease and has a global prevalence. Glucocerebrosidase (GBA1) gene mutations represent a significant hereditary risk factor for the development of PD and have a profound impact on the motor and cognitive progression of the disease. The aim of this review is to summarize the literature data on the prevalence, type, and peculiarities of GBA1 mutations in populations of different ethnic backgrounds. We reviewed articles spanning the 2000–2024 period. GBA1-related PD has a worldwide distribution. It has long been recognized that pathogenic GBA1 mutations are particularly common in certain ethnic populations, including PD patients of Ashkenazi Jewish ancestry. Moreover, a considerable number of studies focused on European ancestry patients from Europe and North America have revealed a high proportion (up to 15%) of carriers among the PD population. GBA1 mutations also appear to play an important role in patient groups with an East Asian background, although the frequency of specific variants may differ as compared to those of European ancestry. Notably, the assessment of underrepresented populations in other parts of Asia (including India) and Latin America is in the spotlight of current research, while a variant with a newly described pathogenic mechanism has been reported in Sub-Saharan Africans. Given the importance of GBA1 mutations for PD genetics and clinical phenotype, a focused assessment of the prevalence and type of GBA1 variants in distinct ethnic populations will possibly inform ongoing PD-related clinical studies and facilitate upcoming therapeutic trials. Full article

(This article belongs to the Special Issue Genetics of Parkinson’s Disease Around the World)

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22 pages, 1509 KiB

Open AccessEditor’s ChoiceReview

Mechanisms, Machinery, and Dynamics of Chromosome Segregation in Zea mays

by Marissa E. Duffy, Michael Ngaw, Shayna E. Polsky, Abby E. Marzec, Sean S. Zhang, Owen R. Dzierzgowski and Natalie J. Nannas

Genes 2024, 15(12), 1606; https://doi.org/10.3390/genes15121606 - 16 Dec 2024

Cited by 1 | Viewed by 2153

Abstract

Zea mays (maize) is both an agronomically important crop and a powerful genetic model system with an extensive molecular toolkit and genomic resources. With these tools, maize is an optimal system for cytogenetic study, particularly in the investigation of chromosome segregation. Here, we [...] Read more.

Zea mays (maize) is both an agronomically important crop and a powerful genetic model system with an extensive molecular toolkit and genomic resources. With these tools, maize is an optimal system for cytogenetic study, particularly in the investigation of chromosome segregation. Here, we review the advances made in maize chromosome segregation, specifically in the regulation and dynamic assembly of the mitotic and meiotic spindle, the inheritance and mechanisms of the abnormal chromosome variant Ab10, the regulation of chromosome–spindle interactions via the spindle assembly checkpoint, and the function of kinetochore proteins that bridge chromosomes and spindles. In this review, we discuss these processes in a species-specific context including features that are both conserved and unique to Z. mays. Additionally, we highlight new protein structure prediction tools and make use of these tools to identify several novel kinetochore and spindle assembly checkpoint proteins in Z. mays. Full article

(This article belongs to the Special Issue Maize Molecular Genetics and Functional Genomics in 2024)

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13 pages, 3637 KiB

Open AccessEditor’s ChoiceArticle

Esterase-Mediated Pyrethroid Resistance in Populations of an Invasive Malaria Vector Anopheles stephensi from Ethiopia

by Daibin Zhong, Teshome Degefa, Guofa Zhou, Ming-Chieh Lee, Chloe Wang, Jiale Chen, Delenasaw Yewhalaw and Guiyun Yan

Genes 2024, 15(12), 1603; https://doi.org/10.3390/genes15121603 - 15 Dec 2024

Viewed by 1323

Abstract

Background: The swift expansion of the invasive malaria vector Anopheles stephensi throughout Africa presents a major challenge to malaria control initiatives. Unlike the native African vectors, An. stephensi thrives in urban settings and has developed resistance to multiple classes of insecticides, including pyrethroids, [...] Read more.

Background: The swift expansion of the invasive malaria vector Anopheles stephensi throughout Africa presents a major challenge to malaria control initiatives. Unlike the native African vectors, An. stephensi thrives in urban settings and has developed resistance to multiple classes of insecticides, including pyrethroids, organophosphates, and carbamates. Methods: Insecticide susceptibility tests were performed on field-collected An. stephensi mosquitoes from Awash Sebac Kilo, Ethiopia, to assess insecticide resistance levels. Illumina RNA-seq analysis was then employed to compare the transcriptomes of field-resistant populations and susceptible laboratory strains (STE2). Results: An. stephensi populations exhibited high levels of resistance to both deltamethrin (mortality, 39.4 ± 6.0%) and permethrin (mortality, 59.3 ± 26.3%) in WHO tube bioassays. RNA-seq analysis revealed that both field-resistant and field-unexposed populations exhibited increased expressions of genes associated with pyrethroid resistance, including esterases, P450s, and GSTs, compared to the susceptible STE2 strain. Notably, esterase E4 and venom carboxylesterase-6 were significantly overexpressed, up to 70-fold, compared to the laboratory strain. Functional enrichment analysis revealed a significant overrepresentation of genes associated with catalytic activity under molecular functions and metabolic process under biological process. Using weighted gene co-expression network analysis (WGCNA), we identified two co-expression modules (green and blue) that included 48 genes strongly linked to pyrethroid insecticide resistance. A co-expression network was subsequently built based on the weight values within these modules. Conclusions: This study highlights the role of esterases in the pyrethroid resistance of an An. stephensi population. The identification of candidate genes associated with insecticide resistance will facilitate the development of rapid diagnostic tools to monitor resistance trends. Full article

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

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17 pages, 3493 KiB

Open AccessEditor’s ChoiceArticle

Transfer RNA Levels Are Tuned to Support Differentiation During Drosophila Neurogenesis

by Rhondene Wint and Michael D. Cleary

Genes 2024, 15(12), 1602; https://doi.org/10.3390/genes15121602 - 15 Dec 2024

Viewed by 1056

Abstract

Background/Objectives: Neural differentiation requires a multifaceted program to alter gene expression along the proliferation to the differentiation axis. While critical changes occur at the level of transcription, post-transcriptional mechanisms allow fine-tuning of protein output. We investigated the role of tRNAs in regulating gene [...] Read more.

Background/Objectives: Neural differentiation requires a multifaceted program to alter gene expression along the proliferation to the differentiation axis. While critical changes occur at the level of transcription, post-transcriptional mechanisms allow fine-tuning of protein output. We investigated the role of tRNAs in regulating gene expression during neural differentiation in Drosophila larval brains. Methods: We quantified tRNA abundance in neural progenitor-biased and neuron-biased brains using the hydrotRNA-seq method. These tRNA data were combined with cell type-specific mRNA decay measurements and transcriptome profiles in order to model how tRNA abundance affects mRNA stability and translation efficiency. Results: We found that (1) tRNA abundance is largely constant between neural progenitors and neurons but significant variation exists for 10 nuclear tRNA genes and 8 corresponding anticodon groups, (2) tRNA abundance correlates with codon-mediated mRNA decay in neuroblasts and neurons, but does not completely explain the different stabilizing or destabilizing effects of certain codons, and (3) changes in tRNA levels support a shift in translation optimization from a program supporting proliferation to a program supporting differentiation. Conclusions: These findings reveal coordination between tRNA expression and codon usage in transcripts that regulate neural development. Full article

(This article belongs to the Section RNA)

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4 pages, 176 KiB

Open AccessEditor’s ChoiceEditorial

Genetic Research and Plant Breeding 2.0

by Kwon-Kyoo Kang, Yu-Jin Jung and Yong-Gu Cho

Genes 2024, 15(12), 1604; https://doi.org/10.3390/genes15121604 - 15 Dec 2024

Viewed by 942

Abstract

Recent advances in next-generation sequencing technologies have significantly reduced sequencing costs, resulting in the creation of large-scale genomic data that can be utilized for plant breeding [...] Full article

(This article belongs to the Special Issue Genetic Research and Plant Breeding 2.0)

35 pages, 570 KiB

Open AccessEditor’s ChoiceReview

Epigenetic Mechanisms in Aging: Extrinsic Factors and Gut Microbiome

by Alejandro Borrego-Ruiz and Juan J. Borrego

Genes 2024, 15(12), 1599; https://doi.org/10.3390/genes15121599 - 14 Dec 2024

Cited by 4 | Viewed by 3262

Abstract

Background/Objectives: Aging is a natural physiological process involving biological and genetic pathways. Growing evidence suggests that alterations in the epigenome during aging result in transcriptional changes, which play a significant role in the onset of age-related diseases, including cancer, cardiovascular disease, diabetes, and [...] Read more.

Background/Objectives: Aging is a natural physiological process involving biological and genetic pathways. Growing evidence suggests that alterations in the epigenome during aging result in transcriptional changes, which play a significant role in the onset of age-related diseases, including cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. For this reason, the epigenetic alterations in aging and age-related diseases have been reviewed, and the major extrinsic factors influencing these epigenetic alterations have been identified. In addition, the role of the gut microbiome and its metabolites as epigenetic modifiers has been addressed. Results: Long-term exposure to extrinsic factors such as air pollution, diet, drug use, environmental chemicals, microbial infections, physical activity, radiation, and stress provoke epigenetic changes in the host through several endocrine and immune pathways, potentially accelerating the aging process. Diverse studies have reported that the gut microbiome plays a critical role in regulating brain cell functions through DNA methylation and histone modifications. The interaction between genes and the gut microbiome serves as a source of adaptive variation, contributing to phenotypic plasticity. However, the molecular mechanisms and signaling pathways driving this process are still not fully understood. Conclusions: Extrinsic factors are potential inducers of epigenetic alterations, which may have important implications for longevity. The gut microbiome serves as an epigenetic effector influencing host gene expression through histone and DNA modifications, while bidirectional interactions with the host and the underexplored roles of microbial metabolites and non-bacterial microorganisms such as fungi and viruses highlight the need for further research. Full article

(This article belongs to the Section Epigenomics)

16 pages, 7493 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Identification and Expression Analysis of PaNRT Gene Family Under Various Nitrogen Conditions in Avocado (Persea americana Mill.)

by Yuan Tian, Ruiyuan Jiang and Jian Qin

Genes 2024, 15(12), 1600; https://doi.org/10.3390/genes15121600 - 14 Dec 2024

Cited by 1 | Viewed by 935

Abstract

Background: Avocado is an important economic fruit tree that requires a lot of nitrogen (N) to support growth and development. Nitrate transporter (NRT) gene family plays an essential role in N uptake and use in plants. However, no systematic identification of the NRT [...] Read more.

Background: Avocado is an important economic fruit tree that requires a lot of nitrogen (N) to support growth and development. Nitrate transporter (NRT) gene family plays an essential role in N uptake and use in plants. However, no systematic identification of the NRT gene family has been reported in avocado. Methods: Bioinformatic analysis was used to identify and characterize the NRT gene family in avocado. The five N additions (29.75, 59.50, 119.00, 178.50, and 238.00 mg/L N) were used to identify the N requirement of avocado seedlings based on physiological indexes, while RNA-seq was conducted to analyze the response of PaNRTs under low-N and high-N conditions. Results: Sixty-one members of the NRT gene family were identified and dispersed on 12 chromosomes in avocado. Many cis-regulatory elements (CREs) related to phytohormonal and stress response were found in the PaNRTs promoter regions. The avocado leaves in N3 have the highest activities of N-assimilating enzymes and N content as well as the lowest activities of antioxidant enzymes. Thus, 29.75 mg/L and 119.00 mg/L were chosen as low-N supply and normal-N supply for transcriptome analysis. The transcriptome analysis showed that PaNRT1.11, PaNRT1.22, PaNRT1.32, PaNRT1.33, PaNRT1.38, and PaNRT1.52 and PaNRT1.56 among PaNRT1 members were up-regulated under normal-N condition in the leaves or roots, suggesting that these genes might affect N absorption under nitrate-sufficient conditions in avocado. RT-qPCR analysis found the relative expression patterns of selected genes among four samples were consistent with transcriptome data, suggesting that transcriptome data were reliable. Conclusions: This study would provide valuable information for identifying the functions of the NRT gene family in avocado. Full article

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

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23 pages, 4617 KiB

Open AccessEditor’s ChoiceReview

Analyses of Human Genetic Data to Identify Clinically Relevant Domains of Neuroligins

by Alexander W. Lehr, Kathryn F. McDaniel and Katherine W. Roche

Genes 2024, 15(12), 1601; https://doi.org/10.3390/genes15121601 - 14 Dec 2024

Viewed by 1296

Abstract

Background/Objectives: Neuroligins (NLGNs) are postsynaptic adhesion molecules critical for neuronal development that are highly associated with autism spectrum disorder (ASD). Here, we provide an overview of the literature on NLGN rare variants. In addition, we introduce a new approach to analyze human variation [...] Read more.

Background/Objectives: Neuroligins (NLGNs) are postsynaptic adhesion molecules critical for neuronal development that are highly associated with autism spectrum disorder (ASD). Here, we provide an overview of the literature on NLGN rare variants. In addition, we introduce a new approach to analyze human variation within NLGN genes to identify sensitive regions that have an increased frequency of ASD-associated variants to better understand NLGN function. Methods: To identify critical protein subdomains within the NLGN gene family, we developed an algorithm that assesses tolerance to missense mutations in human genetic variation by comparing clinical variants from ClinVar to reference variants from gnomAD. This approach provides tolerance values to subdomains within the protein. Results: Our algorithm identified several critical regions that were conserved across multiple NLGN isoforms. Importantly, this approach also identified a previously reported cluster of pathogenic variants in NLGN4X (also conserved in NLGN1 and NLGN3) as well as a region around the highly characterized NLGN3 R451C ASD-associated mutation. Additionally, we highlighted other, as of yet, uncharacterized regions enriched with mutations. Conclusions: The systematic analysis of NLGN ASD-associated variants compared to variants identified in the unaffected population (gnomAD) reveals conserved domains in NLGN isoforms that are tolerant to variation or are enriched in clinically relevant variants. Examination of databases also allows for predictions of the presumed tolerance to loss of an allele. The use of the algorithm we developed effectively allowed the evaluation of subdomains of NLGNs and can be used to examine other ASD-associated genes. Full article

(This article belongs to the Special Issue Unraveling Genetic Complexity: Integrative Approaches in Variant Interpretation)

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13 pages, 275 KiB

Open AccessEditor’s ChoiceReview

Wnt Signaling Pathway in Tumor Biology

by Sabina Iluta, Madalina Nistor, Sanda Buruiana and Delia Dima

Genes 2024, 15(12), 1597; https://doi.org/10.3390/genes15121597 - 13 Dec 2024

Cited by 3 | Viewed by 1204

Abstract

Relapse and metastasis are the major challenges that stand in the way of cancer healing and survival, mainly attributed to cancer stem cells (CSCs). Their capabilities of self-renewal and tumorigenic potential leads to treatment resistance development. CSCs function through signaling pathways such as [...] Read more.

Relapse and metastasis are the major challenges that stand in the way of cancer healing and survival, mainly attributed to cancer stem cells (CSCs). Their capabilities of self-renewal and tumorigenic potential leads to treatment resistance development. CSCs function through signaling pathways such as the Wnt/β-catenin cascade. While commonly involved in embryogenesis and adult tissues homeostasis, the dysregulation of the Wnt pathway has direct correlations with tumorigenesis, metastasis, and drug resistance. The development of therapies that target CSCs and bulk tumors is both crucial and urgent. However, the extensive crosstalk present between Wnt and other signaling networks (Hedgehog and Notch) complicates the development of efficient long-term therapies with minimal side-effects on normal tissues. Despite the obstacles, the emergence of Wnt inhibitors and subsequent modulation of the signaling pathways would provide dynamic therapeutic approaches to impairing CSCs and reversing resistance mechanisms. Full article

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

13 pages, 2302 KiB

Open AccessEditor’s ChoiceArticle

Neuroblastoma Breakpoint Family 3mer Higher Order Repeats/Olduvai Triplet Pattern in the Complete Genome of Human and Nonhuman Primates and Relation to Cognitive Capacity

by Matko Glunčić, Ines Vlahović, Marija Rosandić and Vladimir Paar

Genes 2024, 15(12), 1598; https://doi.org/10.3390/genes15121598 - 13 Dec 2024

Viewed by 1172

Abstract

Background/Objectives: The ~1.6 kb NBPF repeat units in neuroblastoma breakpoint family (NBPF) genes are specific to humans and are associated with cognitive capacity in higher primates. While the number of NBPF monomers/Olduvai sequences in humans is approximately 2–3 times greater than in great [...] Read more.

Background/Objectives: The ~1.6 kb NBPF repeat units in neuroblastoma breakpoint family (NBPF) genes are specific to humans and are associated with cognitive capacity in higher primates. While the number of NBPF monomers/Olduvai sequences in humans is approximately 2–3 times greater than in great apes, the difference in copy number values of canonical NBPF 3mer Higher-order repeats (HORs)/Olduvai triplets between humans and great apes is substantially larger. This study aims to analyze the organization and evolutionary significance of NBPF 3mer HORs/Olduvai triplets in fully sequenced primate genomes. Methods: We applied the global repeat map (GRM) algorithm to identify canonical and variant NBPF 3mer HORs/Olduvai triplets in the complete genomes of humans, chimpanzees, gorillas, and orangutans. The resulting monomer arrays were analyzed using the GRMhor algorithm to generate detailed schematic representations of NBPF HOR organization. Results: The analysis reveals a distinct difference in NBPF-related patterns among these primates, particularly in the number of tandemly organized canonical 3mer HORs/Olduvai triplets: 61 tandemly organized canonical NBPF 3mer HORs/Olduvai triplets in humans, compared to 0 in chimpanzees and orangutans, and 9 in gorillas. When considering only tandemly organized 3mer HORs/Olduvai triplets with more than three copies, the numbers adjust to 36 in humans and 0 in great apes. Furthermore, the divergence between individual NBPF monomers in humans and great apes is twice as high as that observed within great apes. Conclusions: These findings support the hypothesis that the tandem organization of NBPF 3mer HORs/Olduvai triplets plays a crucial role in enhancing cognitive capacity in humans compared to great apes, potentially providing a significant evolutionary advantage. This effect complements the impact of the increased number of individual NBPF monomers/Olduvai sequences, together contributing to a synergistic amplification effect. Full article

(This article belongs to the Section Bioinformatics)

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18 pages, 2052 KiB

Open AccessEditor’s ChoiceReview

Exploring the Molecular Link Between Diabetes and Erectile Dysfunction Through Single-Cell Transcriptome Analysis

by Mahmuda Begum, Mayank Choubey, Munichandra Babu Tirumalasetty, Shahida Arbee, Sibly Sadik, Mohammad Mohabbulla Mohib, Shivani Srivastava, Naofel Minhaz, Riffat Alam and Mohammad Sarif Mohiuddin

Genes 2024, 15(12), 1596; https://doi.org/10.3390/genes15121596 - 13 Dec 2024

Cited by 1 | Viewed by 2892

Abstract

Erectile dysfunction (ED) is a pathophysiological condition in which the patients cannot achieve an erection during sexual activity, and it is often overlooked yet prevalent among diabetic men, globally affecting approximately 35–75% of diabetic individuals. The precise mechanisms through which diabetes contributes to [...] Read more.

Erectile dysfunction (ED) is a pathophysiological condition in which the patients cannot achieve an erection during sexual activity, and it is often overlooked yet prevalent among diabetic men, globally affecting approximately 35–75% of diabetic individuals. The precise mechanisms through which diabetes contributes to ED remain elusive, but the existing literature suggests the potential involvement of nerve and vascular damage that affects the penile supply. In the present review, we reanalyze the existing human single-cell transcriptomic data from patients having diabetes mellitus-associated ED with normal erections. The analysis validates the expression of genes associated with antioxidative pathways, growth factors, adipokines, angiogenesis, vascular functions, penile erection, sexual function, and inflammation in diverse cell types from healthy individuals and those with ED. Our transcriptomic analysis reveals alterations in the expression of adiponectin receptors in the pathogenesis of ED compared to their counterparts in healthy subjects. This comprehensive review sheds light on the molecular underpinnings of ED in the context of diabetes, providing an in-depth understanding of the biological and cellular alterations involved and paving the way for possible targeted therapeutic discoveries in the field of diabetes-associated male infertility. Full article

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

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15 pages, 5760 KiB

Open AccessEditor’s ChoiceArticle

Retinal Dystrophy Associated with Homozygous Variants in NRL

by Jordi Maggi, James V. M. Hanson, Lisa Kurmann, Samuel Koller, Silke Feil, Christina Gerth-Kahlert and Wolfgang Berger

Genes 2024, 15(12), 1594; https://doi.org/10.3390/genes15121594 - 12 Dec 2024

Viewed by 1376

Abstract

Background/Objectives: Neural retina leucine zipper (NRL) is a transcription factor involved in the differentiation of rod photoreceptors. Pathogenic variants in the gene encoding NRL have been associated with autosomal dominant retinitis pigmentosa and autosomal recessive clumped pigmentary retinal degeneration. Only a dozen [...] Read more.

Background/Objectives: Neural retina leucine zipper (NRL) is a transcription factor involved in the differentiation of rod photoreceptors. Pathogenic variants in the gene encoding NRL have been associated with autosomal dominant retinitis pigmentosa and autosomal recessive clumped pigmentary retinal degeneration. Only a dozen unrelated families affected by recessive NRL-related retinal dystrophy have been described. The purpose of this study was to expand the genotypic spectrum of this disease by reporting clinical and genetic findings of two unrelated families. Methods: Index patients affected by retinal dystrophy were genetically tested by whole-exome sequencing (WES) and whole-genome sequencing (WGS). Segregation analysis within the families was performed for candidate variants. A minigene assay was performed to functionally characterize a variant suspected to affect splicing. Results: Variant filtering revealed homozygous NRL variants in both families. The variant in patient A was a small deletion encompassing the donor splice site of exon 1 of transcript NM_006177.3. The minigene assay revealed that this variant led to two aberrant transcripts that used alternative cryptic donor splice sites located in intron 1. In patient B, a stop-gain variant was identified in the last exon of NRL in a homozygous state due to maternal uniparental disomy of chromosome 14. Conclusions: Our study expands the genotypic spectrum of autosomal recessive NRL-related retinal dystrophy. Moreover, it underscores the importance of actively maintaining bioinformatic pipelines for variant detection and the utility of minigene assays in functionally characterizing candidate splicing variants. Full article

(This article belongs to the Special Issue Study of Inherited Retinal Diseases—Volume II)

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12 pages, 794 KiB

Open AccessEditor’s ChoiceArticle

Patients with a Wide Range of Disorders Related to WFS1 Gene Variants: Novel Mutations and Genotype–Phenotype Correlations

by Julia Grzybowska-Adamowicz, Karolina Gadzalska, Paulina Jakiel, Ewa Juścińska, Monika Gorządek, Sebastian Skoczylas, Tomasz Płoszaj, Przemysława Jarosz-Chobot, Irina Kowalska, Małgorzata Myśliwiec, Agnieszka Szadkowska and Agnieszka Zmysłowska

Genes 2024, 15(12), 1592; https://doi.org/10.3390/genes15121592 - 12 Dec 2024

Viewed by 1568

Abstract

Background: WFS1-spectrum disorders are caused by a mutation in the WFS1 gene. The term includes a wide range of rare disorders, from the most severe Wolfram syndrome with autosomal recessive inheritance to milder clinical manifestations with a single causative variant in [...] Read more.

Background: WFS1-spectrum disorders are caused by a mutation in the WFS1 gene. The term includes a wide range of rare disorders, from the most severe Wolfram syndrome with autosomal recessive inheritance to milder clinical manifestations with a single causative variant in the WFS1 gene, such as Wolfram-like syndrome, low-frequency sensorineural hearing loss (LFSNHL), isolated diabetes mellitus (DM), nonsyndromic optic atrophy (OA), and isolated congenital cataracts. Methods: The aim of this study was to evaluate genotype–phenotype correlations in Polish patients with WFS1-spectrum disorders. The study group constituted 22 patients (10 F; 12 M), including 10 patients (3 F; 7 M) referred to the Outpatient Clinic for Rare Diseases in Children and Adolescents and Diabetogenetics between 2019 and 2024 with clinical symptoms suggestive of WFS1-spectrum disorders, and 12 of their first-degree relatives (7 F; 5 M) from 10 families in Poland. Molecular testing was performed using tNGS (Targeted Next Generation Sequencing; Illumina) and analyzed for variants in the WFS1 gene. Results: Thirteen different variants in the WFS1 gene were found in 22 individuals (10 patients and family members), including the identification of two new variants (c.1535T>C and c.2485C>G). All patients had hyperglycemia or DM, hearing impairment, OA, or a combination of these symptoms. Four patients in the study group were diagnosed with Wolfram syndrome and all were compound heterozygotes for variants in the WFS1 gene. Conclusions: The evaluation of molecular characteristics in combination with clinical symptoms broadens the understanding of WFS1-spectrum disorders and allows more accurate management and prognosis for patients with this diagnosis. Full article

(This article belongs to the Section Genetic Diagnosis)

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16 pages, 3901 KiB

Open AccessEditor’s ChoiceArticle

Comparative Genomic Analysis of Bacillus velezensis BRI3 Reveals Genes Potentially Associated with Efficient Antagonism of Sclerotinia sclerotiorum (Lib.) de Bary

by Yaoyao Liu, Changyan Yin, Min Zhu, Yuhua Zhan, Min Lin and Yongliang Yan

Genes 2024, 15(12), 1588; https://doi.org/10.3390/genes15121588 - 11 Dec 2024

Viewed by 1651

Abstract

Background/Objectives: Bacillus velezensis has recently received increased attention as a potential biological agent because of its broad-spectrum antagonistic capacity against harmful bacteria and fungi. This study aims to thoroughly analyze the genomic characteristics of B. velezensis BRI3, thereby providing theoretical groundwork for the [...] Read more.

Background/Objectives: Bacillus velezensis has recently received increased attention as a potential biological agent because of its broad-spectrum antagonistic capacity against harmful bacteria and fungi. This study aims to thoroughly analyze the genomic characteristics of B. velezensis BRI3, thereby providing theoretical groundwork for the agronomic utilization of this strain. Methods: In this work, we evaluated the beneficial traits of the newly isolated strain B. velezensis BRI3 via in vitro experiments, whole-genome sequencing, functional annotation, and comparative genomic analysis. Results: B. velezensis BRI3 exhibits broad-spectrum antifungal activity against various soilborne pathogens, displays inhibitory effects comparable to those of the type strain FZB42, and exhibits particularly effective antagonism against Sclerotinia sclerotiorum (Lib.) de Bary. Whole-genome sequencing and assembly revealed that the genome of BRI3 contains one chromosome and two plasmids, which carry a large amount of genetic information. Moreover, 13 biosynthetic gene clusters (BGCs) involved in the biosynthesis of secondary metabolites were predicted within the BRI3 genome. Among these, two unique BGCs (cluster 11 and cluster 13), which were not previously reported in the genomes of other strains and could potentially encode novel metabolic products, were identified. The results of the comparative genomic analysis demonstrated the genomic structural conservation and genetic homogeneity of BRI3. Conclusions: The unique characteristics and genomic data provide insights into the potential application of BRI3 as a biocontrol and probiotic agent. Full article

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

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