Genes

19 pages, 1563 KiB

Open AccessEditor’s ChoiceReview

Advances in Understanding Fusarium graminearum: Genes Involved in the Regulation of Sexual Development, Pathogenesis, and Deoxynivalenol Biosynthesis

by Gang Niu, Qing Yang, Yihui Liao, Daiyuan Sun, Zhe Tang, Guanghui Wang, Ming Xu, Chenfang Wang and Jiangang Kang

Genes 2024, 15(4), 475; https://doi.org/10.3390/genes15040475 - 9 Apr 2024

Cited by 4 | Viewed by 3583

Abstract

The wheat head blight disease caused by Fusarium graminearum is a major concern for food security and the health of both humans and animals. As a pathogenic microorganism, F. graminearum produces virulence factors during infection to increase pathogenicity, including various macromolecular and small [...] Read more.

The wheat head blight disease caused by Fusarium graminearum is a major concern for food security and the health of both humans and animals. As a pathogenic microorganism, F. graminearum produces virulence factors during infection to increase pathogenicity, including various macromolecular and small molecular compounds. Among these virulence factors, secreted proteins and deoxynivalenol (DON) are important weapons for the expansion and colonization of F. graminearum. Besides the presence of virulence factors, sexual reproduction is also crucial for the infection process of F. graminearum and is indispensable for the emergence and spread of wheat head blight. Over the last ten years, there have been notable breakthroughs in researching the virulence factors and sexual reproduction of F. graminearum. This review aims to analyze the research progress of sexual reproduction, secreted proteins, and DON of F. graminearum, emphasizing the regulation of sexual reproduction and DON synthesis. We also discuss the application of new gene engineering technologies in the prevention and control of wheat head blight. Full article

(This article belongs to the Special Issue Pathogenesis of Wheat Pathogens, Pathogen-Wheat Interaction, and Molecular Design and Breeding of Disease Resistance Wheat)

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15 pages, 865 KiB

Open AccessEditor’s ChoiceReview

A Summary of Two Decades of QTL and Candidate Genes That Control Seed Tocopherol Contents in Maize (Zea mays L.)

by My Abdelmajid Kassem, Dounya Knizia and Khalid Meksem

Genes 2024, 15(4), 472; https://doi.org/10.3390/genes15040472 - 9 Apr 2024

Cited by 1 | Viewed by 1386

Abstract

Tocopherols are secondary metabolites synthesized through the shikimate biosynthetic pathway in the plastids of most plants. It is well known that α–Tocopherol (vitamin E) has many health benefits for humans and animals; therefore, it is highly used in human and animal diets. Tocopherols [...] Read more.

Tocopherols are secondary metabolites synthesized through the shikimate biosynthetic pathway in the plastids of most plants. It is well known that α–Tocopherol (vitamin E) has many health benefits for humans and animals; therefore, it is highly used in human and animal diets. Tocopherols vary considerably in most crop (and plant) species and within cultivars of the same species depending on environmental and growth conditions; tocopherol content is a polygenic, complex traits, and its inheritance is poorly understood. The objective of this review paper was to summarize all identified quantitative trait loci (QTL) that control seed tocopherols and related contents identified in maize (Zea mays) during the past two decades (2002–2022). Candidate genes identified within these QTL regions are also discussed. The QTL described here, and candidate genes identified within these genomic regions could be used in breeding programs to develop maize cultivars with high, beneficial levels of seed tocopherol contents. Full article

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

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12 pages, 433 KiB

Open AccessEditor’s ChoiceArticle

Factors Influencing Mortality in Children with Central Nervous System Tumors: A Cohort Study on Clinical Characteristics and Genetic Markers

by Luz María Torres-Espíndola, Juan Carlos Pérez-De Marcos, Manuel Castillejos-López, Liliana Velasco-Hidalgo, Rocío Cárdenas-Cardós, Armando De Uña-Flores, Citlaltepetl Salinas-Lara, Silvia Caballero-Salazar, Rosario Fernández-Plata and Arnoldo Aquíno-Gálvez

Genes 2024, 15(4), 473; https://doi.org/10.3390/genes15040473 - 9 Apr 2024

Viewed by 1474

Abstract

Multidrug resistance (MDR) commonly leads to cancer treatment failure because cancer cells often expel chemotherapeutic drugs using ATP-binding cassette (ABC) transporters, which reduce drug levels within the cells. This study investigated the clinical characteristics and single nucleotide variant (SNV) in ABCB1, ABCC1 [...] Read more.

Multidrug resistance (MDR) commonly leads to cancer treatment failure because cancer cells often expel chemotherapeutic drugs using ATP-binding cassette (ABC) transporters, which reduce drug levels within the cells. This study investigated the clinical characteristics and single nucleotide variant (SNV) in ABCB1, ABCC1, ABCC2, ABCC4, and ABCG2, and their association with mortality in pediatric patients with central nervous system tumors (CNST). Using TaqMan probes, a real-time polymerase chain reaction genotyped 15 SNPs in 111 samples. Patients were followed up until death or the last follow-up day using the Cox proportional hazards model. An association was found between the rs1045642 (ABCB1) in the recessive model (HR = 2.433, 95% CI 1.098–5.392, p = 0.029), and the ICE scheme in the codominant model (HR = 9.810, 95% CI 2.74–35.06, p ≤ 0.001), dominant model (HR = 6.807, 95% CI 2.87–16.103, p ≤ 0.001), and recessive model (HR = 6.903, 95% CI 2.915–16.544, p = 0.038) significantly increased mortality in this cohort of patients. An association was also observed between the variant rs3114020 (ABCG2) and mortality in the codominant model (HR = 5.35, 95% CI 1.83–15.39, p = 0.002) and the dominant model (HR = 4.421, 95% CI 1.747–11.185, p = 0.002). A significant association between the ICE treatment schedule and increased mortality risk in the codominant model (HR = 6.351, 95% CI 1.831–22.02, p = 0.004, HR = 9.571, 95% CI 2.856–32.07, p ≤ 0.001), dominant model (HR = 6.592, 95% CI 2.669–16.280, p ≤ 0.001), and recessive model (HR = 5.798, 95% CI 2.411–13.940, p ≤ 0.001). The genetic variants rs3114020 in the ABCG2 gene and rs1045642 in the ABCB1 gene and the ICE chemotherapy schedule were associated with an increased mortality risk in this cohort of pediatric patients with CNST. Full article

(This article belongs to the Section Pharmacogenetics)

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11 pages, 1279 KiB

Open AccessEditor’s ChoiceArticle

Detection of Macrolide and/or Fluoroquinolone Resistance Genes in Mycoplasma genitalium Strains Isolated from Men in the Northwest Region of Croatia in 2018–2023

by Sunčanica Ljubin-Sternak, Tomislav Meštrović, Tatjana Marijan, Maja Anušić, Sandra Šuto and Jasmina Vraneš

Genes 2024, 15(4), 470; https://doi.org/10.3390/genes15040470 - 8 Apr 2024

Cited by 1 | Viewed by 1919

Abstract

Mycoplasma genitalium (M. genitalium) poses a significant public health challenge due to its association with non-gonococcal urethritis (particularly in men) and antimicrobial resistance. However, despite the prevalence of M. genitalium infections and the rise in resistance rates, routine testing and surveillance [...] Read more.

Mycoplasma genitalium (M. genitalium) poses a significant public health challenge due to its association with non-gonococcal urethritis (particularly in men) and antimicrobial resistance. However, despite the prevalence of M. genitalium infections and the rise in resistance rates, routine testing and surveillance remain limited. This is the first study from Croatia that aimed to assess the prevalence and trends of resistance in M. genitalium strains isolated from male individuals by detecting macrolide and fluoroquinolone resistance genes. The study also aimed to explore the factors associated with resistance and changes in resistance patterns over time. Urine samples collected from male individuals in the Zagreb County and northwest region of Croatia between 2018 and 2023 were tested for M. genitalium with the use of molecular methods. Positive samples were subjected to DNA extraction and multiplex tandem polymerase chain reaction (MT-PCR) targeting genetic mutations associated with macrolide (23S rRNA gene) and fluoroquinolone (parC gene) resistance. Of the 8073 urine samples tested from 6480 male individuals (and following the exclusion of repeated specimens), we found that the prevalence of M. genitalium infection was 2.2%. Macrolide resistance was observed in 60.4% of strains, while fluoroquinolone resistance was found in 19.2%. Co-resistance to both antibiotics was present in 18.2% of cases. A statistically significant increase in fluoroquinolone resistance was noted over the study period (p = 0.010), but this was not evident for azithromycin resistance (p = 0.165). There were no statistically significant differences in resistance patterns between age groups, whereas re-testing of patients revealed dynamic changes in resistance profiles over time. The high burden of macrolide resistance and increasing fluoroquinolone resistance underscore the urgent need for comprehensive resistance testing and surveillance programs. The implementation of resistance-guided treatment strategies, along with enhanced access to molecular diagnostics, is pivotal for effectively managing M. genitalium infections. Full article

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

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20 pages, 9633 KiB

Open AccessEditor’s ChoiceArticle

Redirect Tropism of Fowl Adenovirus 4 Vector by Modifying Fiber2 with Variable Domain of Heavy-Chain Antibody

by Yongjin Wang, Xiaohui Zou, Xiaojuan Guo, Zhichao Zhang, Min Wang, Tao Hung and Zhuozhuang Lu

Genes 2024, 15(4), 467; https://doi.org/10.3390/genes15040467 - 8 Apr 2024

Viewed by 1355

Abstract

The variable domain of a heavy-chain antibody (VHH) has the potential to be used to redirect the cell tropism of adenoviral vectors. Here, we attempted to establish platforms to simplify the screening of VHHs for their specific targeting function when being incorporated into [...] Read more.

The variable domain of a heavy-chain antibody (VHH) has the potential to be used to redirect the cell tropism of adenoviral vectors. Here, we attempted to establish platforms to simplify the screening of VHHs for their specific targeting function when being incorporated into the fiber of adenovirus. Both fowl adenovirus 4 (FAdV-4) and simian adenovirus 1 (SAdV-1) have two types of fiber, one of which is dispensable for virus propagation and is a proper site for VHH display. An intermediate plasmid, pMD-FAV4Fs, was constructed as the start plasmid for FAdV-4 fiber2 modification. Foldon from phage T4 fibritin, a trigger for trimerization, was employed to bridge the tail/shaft domain of fiber2 and VHHs against human CD16A, a key membrane marker of natural killer (NK) cells. Through one step of restriction-assembly, the modified fiber2 was transferred to the adenoviral plasmid, which was linearized and transfected to packaging cells. Five FAdV-4 viruses carrying the GFP gene were finally rescued and amplified, with three VHHs being displayed. One recombinant virus, FAdV4FC21-EG, could hardly transduce human 293 or Jurkat cells. In contrast, when it was used at a multiplicity of infection of 1000 viral particles per cell, the transduction efficiency reached 51% or 34% for 293 or Jurkat cells expressing exogenous CD16A. Such a strategy of fiber modification was transplanted to the SAdV-1 vector to construct SAdV1FC28H-EG, which moderately transduced primary human NK cells while the parental virus transduced none. Collectively, we reformed the strategy of integrating VHH to fiber and established novel platforms for screening VHHs to construct adenoviral vectors with a specific tropism. Full article

(This article belongs to the Section Viral Genomics)

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18 pages, 804 KiB

Open AccessEditor’s ChoiceReview

A Unifying Hypothesis for the Genome Dynamics Proposed to Underlie Neuropsychiatric Phenotypes

by George Sebastian Gericke

Genes 2024, 15(4), 471; https://doi.org/10.3390/genes15040471 - 8 Apr 2024

Viewed by 1801

Abstract

The sheer number of gene variants and the extent of the observed clinical and molecular heterogeneity recorded in neuropsychiatric disorders (NPDs) could be due to the magnified downstream effects initiated by a smaller group of genomic higher-order alterations in response to endogenous or [...] Read more.

The sheer number of gene variants and the extent of the observed clinical and molecular heterogeneity recorded in neuropsychiatric disorders (NPDs) could be due to the magnified downstream effects initiated by a smaller group of genomic higher-order alterations in response to endogenous or environmental stress. Chromosomal common fragile sites (CFS) are functionally linked with microRNAs, gene copy number variants (CNVs), sub-microscopic deletions and duplications of DNA, rare single-nucleotide variants (SNVs/SNPs), and small insertions/deletions (indels), as well as chromosomal translocations, gene duplications, altered methylation, microRNA and L1 transposon activity, and 3-D chromosomal topology characteristics. These genomic structural features have been linked with various NPDs in mostly isolated reports and have usually only been viewed as areas harboring potential candidate genes of interest. The suggestion to use a higher level entry point (the ‘fragilome’ and associated features) activated by a central mechanism (‘stress’) for studying NPD genetics has the potential to unify the existing vast number of different observations in this field. This approach may explain the continuum of gene findings distributed between affected and unaffected individuals, the clustering of NPD phenotypes and overlapping comorbidities, the extensive clinical and molecular heterogeneity, and the association with certain other medical disorders. Full article

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

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17 pages, 7143 KiB

Open AccessEditor’s ChoiceArticle

The Genome of Bifidobacterium longum subsp. infantis YLGB-1496 Provides Insights into Its Carbohydrate Utilization and Genetic Stability

by Xiaoxia Li, Jianjun Yang, Shaoqi Shi, Hanglian Lan, Wen Zhao, Weilian Hung, Jian He and Ran Wang

Genes 2024, 15(4), 466; https://doi.org/10.3390/genes15040466 - 8 Apr 2024

Cited by 2 | Viewed by 2262

Abstract

Bifidobacterium longum subsp. infantis YLGB-1496 (YLGB-1496) is a probiotic strain isolated from human breast milk. The application of YLGB-1496 is influenced by carbohydrate utilization and genetic stability. This study used genome sequencing and morphology during continuous subculture to determine the carbohydrate utilization characteristics [...] Read more.

Bifidobacterium longum subsp. infantis YLGB-1496 (YLGB-1496) is a probiotic strain isolated from human breast milk. The application of YLGB-1496 is influenced by carbohydrate utilization and genetic stability. This study used genome sequencing and morphology during continuous subculture to determine the carbohydrate utilization characteristics and genetic stability of YLGB-1496. The complete genome sequence of YLGB-1496 consists of 2,758,242 base pairs, 2442 coding sequences, and a GC content of 59.87%. A comparison of carbohydrate transport and metabolism genes of Bifidobacterium longum subsp. infantis (B. infantis) showed that YLGB-1496 was rich in glycosyl hydrolase 13, 20, 25, and 109 gene families. During continuous subculture, the growth characteristics and fermentation activity of the strain were highly stable. The bacterial cell surface and edges of the 1000th-generation strains were progressively smoother and well-defined, with no perforations or breaks in the cell wall. There were 20 SNP loci at the 1000th generation, fulfilling the requirement of belonging to the same strain. The presence of genes associated with cell adhesion and the absence of resistance genes supported the probiotic characteristics of the strain. The data obtained in this study provide insights into broad-spectrum carbohydrate utilization, genomic stability, and probiotic properties of YLGB-1496, which provide theoretical support to promote the use of YLGB-1496. Full article

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

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8 pages, 752 KiB

Open AccessEditor’s ChoiceCase Report

Therapeutic Management and Outcomes of Hepatoblastoma in a Pediatric Patient with Mosaic Edwards Syndrome

by Patrycja Sosnowska-Sienkiewicz, Alicja Kamińska, Iwona Anderko, Gabriela Telman-Kołodziejczyk, Przemysław Mańkowski and Danuta Januszkiewicz-Lewandowska

Genes 2024, 15(4), 463; https://doi.org/10.3390/genes15040463 - 7 Apr 2024

Cited by 2 | Viewed by 2260

Abstract

The mosaic form of Edwards syndrome affects 5% of all children with Edwards syndrome. The clinical phenotype is highly variable, ranging from the full spectrum of trisomy 18 to the normal phenotype. The purpose of this publication was to present the therapeutic process [...] Read more.

The mosaic form of Edwards syndrome affects 5% of all children with Edwards syndrome. The clinical phenotype is highly variable, ranging from the full spectrum of trisomy 18 to the normal phenotype. The purpose of this publication was to present the therapeutic process in an 18-month-old girl with the mosaic form of Edwards syndrome and hepatoblastoma, against the background of other cases of simultaneous occurrence of this syndrome and hepatoblastoma described so far. It appears that this particular group of patients with hepatoblastoma and Edwards syndrome can have good outcomes, provided they do not have life-threatening cardiac or other severe defects. Due to the prematurity of our patient and the defects associated with Edwards syndrome, the child required constant multidisciplinary care, but Edwards syndrome itself was not a reason to discontinue therapy for a malignant neoplasm of the liver. Regular abdominal ultrasound examination, along with AFP testing, may be helpful in the early detection of liver tumors in children with Edwards syndrome Full article

(This article belongs to the Special Issue Molecular Genetics and Clinical Diagnosis of Rare Diseases)

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11 pages, 2180 KiB

Open AccessEditor’s ChoiceBrief Report

Different Nuclear Architecture in Human Sperm According to Their Morphology

by Nino-Guy Cassuto, Nesrine Ogal, Said Assou, Lea Ruoso, Eli-Jonathan Rogers, Miguel-José Monteiro, Daniel Thomas, Jean-Pierre Siffroi and Alexandre Rouen

Genes 2024, 15(4), 464; https://doi.org/10.3390/genes15040464 - 7 Apr 2024

Viewed by 1715

Abstract

Human sperm parameters serve as a first step in diagnosing male infertility, but not in determining the potential for successful pregnancy during assisted reproductive technologies (ARTs) procedures. Here, we investigated the relationship between sperm head morphology at high magnification, based on strict morphologic [...] Read more.

Human sperm parameters serve as a first step in diagnosing male infertility, but not in determining the potential for successful pregnancy during assisted reproductive technologies (ARTs) procedures. Here, we investigated the relationship between sperm head morphology at high magnification, based on strict morphologic criteria, and the nuclear architecture analyzed by fluorescence in situ hybridization (FISH). We included five men. Two of them had an elevated high-magnification morphology score of 6 points (Score 6) indicating high fertility potential, whereas three had a low score of 0 points (Score 0), indicating low fertility potential. We used FISH to study the inter-telomeric distance and the chromosomal territory area of chromosome 1 (Chr. 1). We then compared these two parameters between subjects with high and low scores. FISH data analysis showed that the inter-telomeric distance (ITD) and chromosomal territory area (CTA) of Chr. 1 were significantly higher in subjects with low scores (score 0) than high scores (score 6). Our results suggest that (i) there is a link between nuclear architecture and sperm head abnormalities, particularly vacuoles; and (ii) it is possible to select spermatozoa with normal nuclear architecture, which might indirectly explain the positive ART outcomes observed with this technique. Full article

(This article belongs to the Special Issue Genetic Causes of Human Infertility)

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18 pages, 6581 KiB

Open AccessEditor’s ChoiceArticle

Transcriptomic Changes and Regulatory Networks Associated with Resistance to Mastitis in Xinjiang Brown Cattle

by Dan Wang, Haiyan Yang, Shengchao Ma, Tingting Liu, Mengjie Yan, Mingming Dong, Menghua Zhang, Tao Zhang, Xiaoxue Zhang, Lei Xu, Xixia Huang and Hong Chen

Genes 2024, 15(4), 465; https://doi.org/10.3390/genes15040465 - 7 Apr 2024

Cited by 2 | Viewed by 1554

Abstract

Xinjiang brown cattle are highly resistant to disease and tolerant of roughage feeding. The identification of genes regulating mastitis resistance in Xinjiang brown cattle is a novel means of genetic improvement. In this study, the blood levels of IL-1β, IL-6, IL-10, TNF-α, and [...] Read more.

Xinjiang brown cattle are highly resistant to disease and tolerant of roughage feeding. The identification of genes regulating mastitis resistance in Xinjiang brown cattle is a novel means of genetic improvement. In this study, the blood levels of IL-1β, IL-6, IL-10, TNF-α, and TGF-β in Xinjiang brown cattle with high and low somatic cell counts (SCCs) were investigated, showing that cytokine levels were higher in cattle with high SCCs. The peripheral blood transcriptomic profiles of healthy and mastitis-affected cattle were constructed by RNA-seq. Differential expression analysis identified 1632 differentially expressed mRNAs (DE-mRNAs), 1757 differentially expressed lncRNAs (DE-lncRNAs), and 23 differentially expressed circRNAs (DE-circRNAs), which were found to be enriched in key pathways such as PI3K/Akt, focal adhesion, and ECM-receptor interactions. Finally, ceRNA interaction networks were constructed using the differentially expressed genes and ceRNAs. It was found that keynote genes or mRNAs were also enriched in pathways such as PI3K-Akt, cholinergic synapses, cell adhesion molecules, ion binding, cytokine receptor activity, and peptide receptor activity, suggesting that the key genes and ncRNAs in the network may play an important role in the regulation of bovine mastitis. Full article

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

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14 pages, 1258 KiB

Open AccessEditor’s ChoiceArticle

Impact of 12-SNP and 6-SNP Polygenic Scores on Predisposition to High LDL-Cholesterol Levels in Patients with Familial Hypercholesterolemia

by Giovanna Cardiero, Martina Ferrandino, Ilenia Lorenza Calcaterra, Gabriella Iannuzzo, Matteo Nicola Dario Di Minno, Raffaele Buganza, Ornella Guardamagna, Renata Auricchio, Maria Donata Di Taranto and Giuliana Fortunato

Genes 2024, 15(4), 462; https://doi.org/10.3390/genes15040462 - 6 Apr 2024

Cited by 3 | Viewed by 1746

Abstract

Background: Familial hypercholesterolemia (FH) comprises high LDL-cholesterol (LDL-c) levels and high cardiovascular disease risk. In the absence of pathogenic variants in causative genes, a polygenic basis was hypothesized. Methods: In a population of 418 patients (excluding homozygotes) with clinical suspicion of FH, the [...] Read more.

Background: Familial hypercholesterolemia (FH) comprises high LDL-cholesterol (LDL-c) levels and high cardiovascular disease risk. In the absence of pathogenic variants in causative genes, a polygenic basis was hypothesized. Methods: In a population of 418 patients (excluding homozygotes) with clinical suspicion of FH, the FH-causative genes and the regions of single nucleotide polymorphisms (SNPs) included in 12-SNP and 6-SNP scores were sequenced by next-generation sequencing, allowing for the detection of pathogenic variants (V+) in 220 patients. To make a comparison, only patients without uncertain significance variants (V−/USV−) were considered (n = 162). Results: Higher values of both scores were observed in V+ than in V−. Considering a cut-off leading to 80% of V−/USV− as score-positive, a lower prevalence of patients positive for both 12-SNP and 6-SNP scores was observed in V+ (p = 0.010 and 0.033, respectively). Mainly for the 12-SNP score, among V+ patients, higher LDL-c levels were observed in score-positive (223 mg/dL -IQR 187-279) than in negative patients (212 mg/dL -IQR 162–240; p = 0.006). Multivariate analysis confirmed the association of scores and LDL-c levels independently of age, sex, and presence of pathogenic variants and revealed a greater association in children. Conclusions: The 12-SNP and 6-SNP polygenic scores could explain hypercholesterolemia in patients without pathogenic variants as well as the variability of LDL-c levels among patients with FH-causative variants. Full article

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

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7 pages, 732 KiB

Open AccessEditor’s ChoiceCase Report

Clinical and Molecular Characterization of a Novel Homozygous Frameshift Variant in AEBP1-Related Classical-like Ehlers Danlos Syndrome Type 2 with Comparison to Previously Reported Rare Cases

by Zong Yi Ha, Chieko Chijiwa and Suzanne Lewis

Genes 2024, 15(4), 461; https://doi.org/10.3390/genes15040461 - 6 Apr 2024

Cited by 1 | Viewed by 2043

Abstract

Recently, an autosomal recessive subtype of connective tissue disorder within the spectrum of Ehlers–Danlos syndrome (EDS), named classical-like EDS type 2 (clEDS2), was identified. clEDS2 is associated with biallelic variants in the adipocyte enhancer binding protein 1 (AEBP1) gene, specifically, affecting [...] Read more.

Recently, an autosomal recessive subtype of connective tissue disorder within the spectrum of Ehlers–Danlos syndrome (EDS), named classical-like EDS type 2 (clEDS2), was identified. clEDS2 is associated with biallelic variants in the adipocyte enhancer binding protein 1 (AEBP1) gene, specifically, affecting its aortic carboxypeptidase-like protein (ACLP) isoform. We described the 15th patient (13th family) diagnosed with clEDS2. This patient presented with notable similarities in phenotype to the documented cases, along with additional characteristics such as significant prematurity and short stature. An EDS sequencing panel-based analysis revealed homozygous AEBP1: NM_001129.5:c.2923del, p.Ala975Profs*22 likely pathogenic variants, and maternally inherited heterozygous COL11A1: NM_001854.4:c.1160A>G, p.Lys387Arg variant of uncertain significance in our patient. Upon comprehensive review of all previously reported clEDS2 patients, our patient exhibited the following overlapping phenotypes, including cutaneous features: hyperextensibility, atrophic scars/delayed wound healing (100%), easy bruising (100%), excessive skin (93%); skeletal features: generalized joint hypermobility (93%), pes planus (93%), dislocation/subluxation (93%); and cardiovascular features (86%). Our patient did not display symptoms of the critical complications reported in a few individuals, including superior mesenteric artery aneurysms and ruptures, aortic root aneurysm/dissection, spontaneous pneumothoraxes, and bowel ruptures. Together, this case expands the genetic and clinical phenotypic spectrum of AEBP1-related clEDS2. Full article

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

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15 pages, 3656 KiB

Open AccessEditor’s ChoiceArticle

Wasabi Gone Wild? Origin and Characterization of the Complete Plastomes of Ulleung Island Wasabi (Eutrema japonicum; Brassicaceae) and Other Cultivars in Korea

by JiYoung Yang, Cheon Gyoo Park, Myong-Suk Cho and Seung-Chul Kim

Genes 2024, 15(4), 457; https://doi.org/10.3390/genes15040457 - 5 Apr 2024

Cited by 1 | Viewed by 2042

Abstract

Korean wasabi occurs naturally on the young oceanic, volcanic Ulleung Island off the east coast of the Korean Peninsula. Although the Ulleung Island wasabi is reported as Eutrema japonicum and has been suggested to be morphologically identical to cultivars in Korea, very little [...] Read more.

Korean wasabi occurs naturally on the young oceanic, volcanic Ulleung Island off the east coast of the Korean Peninsula. Although the Ulleung Island wasabi is reported as Eutrema japonicum and has been suggested to be morphologically identical to cultivars in Korea, very little is known about its taxonomic identity and relationship with other cultivars. In this study, we sequenced the complete chloroplast DNA sequences of three naturally occurring Ulleung Island wasabi plants and six cultivars (‘Daewang’, ‘Daruma’, ‘Micado’, ‘Orochi’, ‘Green Thumb’, and ‘Shogun’) from continental Korea and determined the taxonomic identity of Korean wasabi on Ulleung Island. The size and organization of the complete chloroplast genomes of the nine accessions were nearly identical to those of previously reported wasabi cultivars. In addition, phylogenetic analysis based on the complete plastomes suggested that Ulleung Island wasabi most likely comprises various wasabi cultivars with three chlorotypes (‘Shogun’, ‘Green Thumb’, and a unique Chusan type). Based on the complete plastomes, we identified eight chlorotypes for the major wasabi cultivars and the Ulleung Island wasabi. Two major groups (1—‘Mazuma’ and ‘Daruma’, and 2—‘Fujidaruma’/‘Shimane No. 3’/Ulleung Island wasabi/five cultivars in Korea) were also identified based on mother line genealogical history. Furthermore, different types of variations (mutations, insertions/deletions (indels), mononucleotide repeats, and inversions) in plastomes were identified to distinguish different cultivar lines and five highly divergent hotspots. The nine newly obtained complete plastomes are valuable organelle genomic resources for species identification and infraspecific phylogeographic studies on wild and cultivated wasabi. Full article

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

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13 pages, 1181 KiB

Open AccessEditor’s ChoiceArticle

Characteristics of the Genetic Spread of Carbapenem-Resistant Acinetobacter baumannii in a Tertiary Greek Hospital

by Martha Papadopoulou, Ioannis Deliolanis, Michalis Polemis, Alkiviadis Vatopoulos, Mina Psichogiou and Panagiota Giakkoupi

Genes 2024, 15(4), 458; https://doi.org/10.3390/genes15040458 - 5 Apr 2024

Cited by 7 | Viewed by 2080

Abstract

Acinetobacter baumannii (Ab) has increasingly been identified as a cause of hospital-acquired infections and epidemics. The rise of carbapenem-resistant Acinetobacter baumannii (CRAB) poses significant challenges in treatment. Nosocomial outbreaks linked to CRAΒ A. baumannii strains have been reported worldwide, including in Greece. This [...] Read more.

Acinetobacter baumannii (Ab) has increasingly been identified as a cause of hospital-acquired infections and epidemics. The rise of carbapenem-resistant Acinetobacter baumannii (CRAB) poses significant challenges in treatment. Nosocomial outbreaks linked to CRAΒ A. baumannii strains have been reported worldwide, including in Greece. This study aimed to analyze the molecular epidemiology trends of multidrug-resistant A. baumannii isolates in a tertiary hospital in Athens, Greece. A total of 43 clinical isolates of extensively drug-resistant (XDRAB), pan-drug-resistant (PDRAB), and CRAB were collected from patients suffering from blood infection, hospitalized between 2016 and 2020 at the internal medicine clinics and the ICU. A.baumannii isolates underwent testing for Ambler class B and D carbapenemases and the detection of ISAba1, and were typed, initially, using pulsed-field gel electrophoresis, and, subsequently, using sequence-based typing and multiplex PCR to determine European Clone lineages. The bla_OXA-23 gene accompanied by ISAba1 was prevalent in nearly all A. baumannii isolates, except for one carrying bla_OXA-58. The intrinsic bla_OXA-51-like gene was found in all isolates. No Ambler class B carbapenemases (VIM, NDM) were detected. Isolates were grouped into four PF-clusters and no one-cluster spread was documented, consistent with the absence of outbreak. The study indicated that XDR/PDR-CRAB isolates predominantly produce OXA-23 carbapenemase and belong to European Clone II. Further research is needed to understand the distribution of resistant bacteria and develop effective prevention and control strategies. Full article

(This article belongs to the Topic Advances in Genetics and Precision Medicine in Human Diseases)

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18 pages, 1640 KiB

Open AccessEditor’s ChoiceArticle

Relevance of PNPLA3, TM6SF2, HSD17B13, and GCKR Variants to MASLD Severity in an Egyptian Population

by Nehal Elmansoury, Ahmed A. Megahed, Ahmed Kamal, Nefertiti El-Nikhely, Marina Labane, Manal Abdelmageed, Ann K. Daly and Ahmed Wahid

Genes 2024, 15(4), 455; https://doi.org/10.3390/genes15040455 - 4 Apr 2024

Cited by 3 | Viewed by 2942

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is a frequent clinical condition globally. Single nucleotide polymorphisms (SNPs) associated with NAFLD have been proposed in the literature and based on bioinformatic screening. The association between NAFLD and [...] Read more.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is a frequent clinical condition globally. Single nucleotide polymorphisms (SNPs) associated with NAFLD have been proposed in the literature and based on bioinformatic screening. The association between NAFLD and genetic variants in Egyptians is still unclear. Hence, we sought to investigate the association of some genetic variants with NAFLD in Egyptians. Egyptians have been categorized into either the MASLD group (n = 205) or the healthy control group (n = 187). The severity of hepatic steatosis and liver fibrosis was assessed by a Fibroscan device. TaqMan-based genotyping assays were employed to explore the association of selected SNPs with MASLD. PNPLA3 rs738409 C>G variant is associated with the presence of MASLD with liver fibrosis, the severity of both hepatic steatosis and liver fibrosis, increased systolic and diastolic blood pressure and increased alanine aminotransferase (all p < 0.05), while the TM6SF2 rs58542926 C>T, HSD17B13 rs9992651 G>A, and GCKR rs1260326 T>C variants were not (all p > 0.05). The TM6SF2 rs58542926 T allele is associated with increased fasting blood glucose and a decreased waist circumference. The GCKR rs1260326 C allele is associated with decreased aspartate transaminase and diastolic blood pressure (all p < 0.05). Only after adjusting for the risk factors (age, sex, BMI, WC, HDL, TG, diabetes mellitus, and hypertension) F2 liver fibrosis score is negatively correlated with the HSD17B13 rs9992651 GA genotype. This study offers evidence for the association of the PNPLA3 rs738409 C>G variant with MASLD among Egyptians and for the association of the PNPLA3 rs738409 G allele, the TM6SF2 rs58542926 T allele, and the GCKR rs1260326 C allele with some parameters of cardiometabolic criteria. Full article

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

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12 pages, 3156 KiB

Open AccessEditor’s ChoiceArticle

Development and Characterization of a Novel FVB-Prkdc^R2140C Mouse Model for Adriamycin-Induced Nephropathy

by Masaki Watanabe, Yuki Ishii, Kazuki Hashimoto, Hayato R. Takimoto and Nobuya Sasaki

Genes 2024, 15(4), 456; https://doi.org/10.3390/genes15040456 - 4 Apr 2024

Cited by 1 | Viewed by 1655

Abstract

The Adriamycin (ADR) nephropathy model, which induces podocyte injury, is limited to certain mouse strains due to genetic susceptibilities, such as the Prkdc^R2140C polymorphism. The FVB/N strain without the R2140C mutation resists ADR nephropathy. Meanwhile, a detailed analysis of the progression of [...] Read more.

The Adriamycin (ADR) nephropathy model, which induces podocyte injury, is limited to certain mouse strains due to genetic susceptibilities, such as the Prkdc^R2140C polymorphism. The FVB/N strain without the R2140C mutation resists ADR nephropathy. Meanwhile, a detailed analysis of the progression of ADR nephropathy in the FVB/N strain has yet to be conducted. Our research aimed to create a novel mouse model, the FVB-Prkdc^R2140C, by introducing Prkdc^R2140C into the FVB/NJcl (FVB) strain. Our study showed that FVB-Prkdc^R2140C mice developed severe renal damage when exposed to ADR, as evidenced by significant albuminuria and tubular injury, exceeding the levels observed in C57BL/6J (B6)-Prkdc^R2140C. This indicates that the FVB/N genetic background, in combination with the R2140C mutation, strongly predisposes mice to ADR nephropathy, highlighting the influence of genetic background on disease susceptibility. Using RNA sequencing and subsequent analysis, we identified several genes whose expression is altered in response to ADR nephropathy. In particular, Mmp7, Mmp10, and Mmp12 were highlighted for their differential expression between strains and their potential role in influencing the severity of kidney damage. Further genetic analysis should lead to identifying ADR nephropathy modifier gene(s), aiding in early diagnosis and providing novel approaches to kidney disease treatment and prevention. Full article

(This article belongs to the Topic Animal Models of Human Disease 2.0)

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13 pages, 2044 KiB

Open AccessEditor’s ChoiceArticle

Marker Density and Models to Improve the Accuracy of Genomic Selection for Growth and Slaughter Traits in Meat Rabbits

by Wenjie Li, Wenqiang Li, Zichen Song, Zihao Gao, Kerui Xie, Yubing Wang, Bo Wang, Jiaqing Hu, Qin Zhang, Chao Ning, Dan Wang and Xinzhong Fan

Genes 2024, 15(4), 454; https://doi.org/10.3390/genes15040454 - 3 Apr 2024

Cited by 5 | Viewed by 1652

Abstract

The selection and breeding of good meat rabbit breeds are fundamental to their industrial development, and genomic selection (GS) can employ genomic information to make up for the shortcomings of traditional phenotype-based breeding methods. For the practical implementation of GS in meat rabbit [...] Read more.

The selection and breeding of good meat rabbit breeds are fundamental to their industrial development, and genomic selection (GS) can employ genomic information to make up for the shortcomings of traditional phenotype-based breeding methods. For the practical implementation of GS in meat rabbit breeding, it is necessary to assess different marker densities and GS models. Here, we obtained low-coverage whole-genome sequencing (lcWGS) data from 1515 meat rabbits (including parent herd and half-sibling offspring). The specific objectives were (1) to derive a baseline for heritability estimates and genomic predictions based on randomly selected marker densities and (2) to assess the accuracy of genomic predictions for single- and multiple-trait linear mixed models. We found that a marker density of 50 K can be used as a baseline for heritability estimation and genomic prediction. For GS, the multi-trait genomic best linear unbiased prediction (GBLUP) model results in more accurate predictions for virtually all traits compared to the single-trait model, with improvements greater than 15% for all of them, which may be attributed to the use of information on genetically related traits. In addition, we discovered a positive correlation between the performance of the multi-trait GBLUP and the genetic correlation between the traits. We anticipate that this approach will provide solutions for GS, as well as optimize breeding programs, in meat rabbits. Full article

(This article belongs to the Special Issue Livestock Genomics, Genetics and Breeding)

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23 pages, 3682 KiB

Open AccessEditor’s ChoiceArticle

Early Chronic Fluoxetine Treatment of Ts65Dn Mice Rescues Synaptic Vesicular Deficits and Prevents Aberrant Proteomic Alterations

by S. Hossein Fatemi, Elysabeth D. Otte, Timothy D. Folsom, Arthur C. Eschenlauer, Randall J. Roper, Justin W. Aman and Paul D. Thuras

Genes 2024, 15(4), 452; https://doi.org/10.3390/genes15040452 - 3 Apr 2024

Viewed by 2347

Abstract

Down syndrome (DS) is the most common form of inherited intellectual disability caused by trisomy of chromosome 21, presenting with intellectual impairment, craniofacial abnormalities, cardiac defects, and gastrointestinal disorders. The Ts65Dn mouse model replicates many abnormalities of DS. We hypothesized that investigation of [...] Read more.

Down syndrome (DS) is the most common form of inherited intellectual disability caused by trisomy of chromosome 21, presenting with intellectual impairment, craniofacial abnormalities, cardiac defects, and gastrointestinal disorders. The Ts65Dn mouse model replicates many abnormalities of DS. We hypothesized that investigation of the cerebral cortex of fluoxetine-treated trisomic mice may provide proteomic signatures that identify therapeutic targets for DS. Subcellular fractionation of synaptosomes from cerebral cortices of age- and brain-area-matched samples from fluoxetine-treated vs. water-treated trisomic and euploid male mice were subjected to HPLC-tandem mass spectrometry. Analysis of the data revealed enrichment of trisomic risk genes that participate in regulation of synaptic vesicular traffic, pre-synaptic and post-synaptic development, and mitochondrial energy pathways during early brain development. Proteomic analysis of trisomic synaptic fractions revealed significant downregulation of proteins involved in synaptic vesicular traffic, including vesicular endocytosis (CLTA, CLTB, CLTC), synaptic assembly and maturation (EXOC1, EXOC3, EXOC8), anterograde axonal transport (EXOC1), neurotransmitter transport to PSD (SACM1L), endosomal-lysosomal acidification (ROGDI, DMXL2), and synaptic signaling (NRXN1, HIP1, ITSN1, YWHAG). Additionally, trisomic proteomes revealed upregulation of several trafficking proteins, involved in vesicular exocytosis (Rab5B), synapse elimination (UBE3A), scission of endocytosis (DBN1), transport of ER in dendritic spines (MYO5A), presynaptic activity-dependent bulk endocytosis (FMR1), and NMDA receptor activity (GRIN2A). Chronic fluoxetine treatment of Ts65Dn mice rescued synaptic vesicular abnormalities and prevented abnormal proteomic changes in adult Ts65Dn mice, pointing to therapeutic targets for potential treatment of DS. Full article

(This article belongs to the Special Issue Molecular Genetics of Neurodevelopmental Disorders)

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20 pages, 4663 KiB

Open AccessEditor’s ChoiceArticle

Identification, Classification, and Transcriptional Analysis of Rab GTPase Genes from Tomato (Solanum lycopersicum) Reveals Salt Stress Response Genes

by Flavia Soto, Alex San Martín-Davison, Josselyn Salinas-Cornejo, José Madrid-Espinoza and Simón Ruiz-Lara

Genes 2024, 15(4), 453; https://doi.org/10.3390/genes15040453 - 3 Apr 2024

Cited by 2 | Viewed by 1809

Abstract

Salinity in plants generates an osmotic and ionic imbalance inside cells that compromises the viability of the plant. Rab GTPases, the largest family within the small GTPase superfamily, play pivotal roles as regulators of vesicular trafficking in plants, including the economically important and [...] Read more.

Salinity in plants generates an osmotic and ionic imbalance inside cells that compromises the viability of the plant. Rab GTPases, the largest family within the small GTPase superfamily, play pivotal roles as regulators of vesicular trafficking in plants, including the economically important and globally cultivated tomato (Solanum lycopersicum). Despite their significance, the specific involvement of these small GTPases in tomato vesicular trafficking and their role under saline stress remains poorly understood. In this work, we identified and classified 54 genes encoding Rab GTPases in cultivated tomato, elucidating their genomic distribution and structural characteristics. We conducted an analysis of duplication events within the S. lycopersicum genome, as well as an examination of gene structure and conserved motifs. In addition, we investigated the transcriptional profiles for these Rab GTPases in various tissues of cultivated and wild tomato species using microarray-based analysis. The results showed predominantly low expression in most of the genes in both leaves and vegetative meristem, contrasting with notably high expression levels observed in seedling roots. Also, a greater increase in gene expression in shoots from salt-tolerant wild tomato species was observed under normal conditions when comparing Solanum habrochaites, Solanum pennellii, and Solanum pimpinellifolium with S. lycopersicum. Furthermore, an expression analysis of Rab GTPases from Solanum chilense in leaves and roots under salt stress treatment were also carried out for their characterization. These findings revealed that specific Rab GTPases from the endocytic pathway and the trans-Golgi network (TGN) showed higher induction in plants exposed to saline stress conditions. Likewise, disparities in gene expression were observed both among members of the same Rab GTPase subfamily and between different subfamilies. Overall, this work emphasizes the high degree of conservation of Rab GTPases, their high functional diversification in higher plants, and the essential role in mediating salt stress tolerance and suggests their potential for further exploration of vesicular trafficking mechanisms in response to abiotic stress conditions. Full article

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

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11 pages, 453 KiB

Open AccessEditor’s ChoiceArticle

The Effect of Genome Parametrization and SNP Marker Subsetting on Genomic Selection in Autotetraploid Alfalfa

by Nelson Nazzicari, Nicolò Franguelli, Barbara Ferrari, Luciano Pecetti and Paolo Annicchiarico

Genes 2024, 15(4), 449; https://doi.org/10.3390/genes15040449 - 2 Apr 2024

Cited by 2 | Viewed by 1641

Abstract

Background: Alfalfa, the most economically important forage legume worldwide, features modest genetic progress due to long selection cycles and the extent of the non-additive genetic variance associated with its autotetraploid genome. Methods: To improve the efficiency of genomic selection in alfalfa, we explored [...] Read more.

Background: Alfalfa, the most economically important forage legume worldwide, features modest genetic progress due to long selection cycles and the extent of the non-additive genetic variance associated with its autotetraploid genome. Methods: To improve the efficiency of genomic selection in alfalfa, we explored the effects of genome parametrization (as tetraploid and diploid dosages, plus allele ratios) and SNP marker subsetting (all available SNPs, only genic regions, and only non-genic regions) on genomic regressions, together with various levels of filtering on reading depth and missing rates. We used genotyping by sequencing-generated data and focused on traits of different genetic complexity, i.e., dry biomass yield in moisture-favorable (FE) and drought stress (SE) environments, leaf size, and the onset of flowering, which were assessed in 143 genotyped plants from a genetically broad European reference population and their phenotyped half-sib progenies. Results: On average, the allele ratio improved the predictive ability compared with other genome parametrizations (+7.9% vs. tetraploid dosage, +12.6% vs. diploid dosage), while using all the SNPs offered an advantage compared with any specific SNP subsetting (+3.7% vs. genic regions, +7.6% vs. non-genic regions). However, when focusing on specific traits, different combinations of genome parametrization and subsetting achieved better performances. We also released Legpipe2, an SNP calling pipeline tailored for reduced representation (GBS, RAD) in medium-sized genotyping experiments. Full article

(This article belongs to the Collection Feature Papers in Bioinformatics)

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4 pages, 160 KiB

Open AccessEditor’s ChoiceEditorial

Feature Papers in Population and Evolutionary Genetics and Genomics 2023: Unraveling Population Dynamics, Diversity, and Evolutionary Paths

by Maria-Anna Kyrgiafini and Zissis Mamuris

Genes 2024, 15(4), 446; https://doi.org/10.3390/genes15040446 - 1 Apr 2024

Viewed by 2920

Abstract

The dialogue between population genetics and evolutionary biology, which historically followed separate paths, has now developed into a complex and interdisciplinary field of study [...] Full article

(This article belongs to the Special Issue Feature Papers in Population and Evolutionary Genetics and Genomics 2023)

32 pages, 510 KiB

Open AccessEditor’s ChoiceReview

Unravelling the Genetic Landscape of Hemiplegic Migraine: Exploring Innovative Strategies and Emerging Approaches

by Mohammed M. Alfayyadh, Neven Maksemous, Heidi G. Sutherland, Rod A. Lea and Lyn R. Griffiths

Genes 2024, 15(4), 443; https://doi.org/10.3390/genes15040443 - 31 Mar 2024

Cited by 1 | Viewed by 3963

Abstract

Migraine is a severe, debilitating neurovascular disorder. Hemiplegic migraine (HM) is a rare and debilitating neurological condition with a strong genetic basis. Sequencing technologies have improved the diagnosis and our understanding of the molecular pathophysiology of HM. Linkage analysis and sequencing studies in [...] Read more.

Migraine is a severe, debilitating neurovascular disorder. Hemiplegic migraine (HM) is a rare and debilitating neurological condition with a strong genetic basis. Sequencing technologies have improved the diagnosis and our understanding of the molecular pathophysiology of HM. Linkage analysis and sequencing studies in HM families have identified pathogenic variants in ion channels and related genes, including CACNA1A, ATP1A2, and SCN1A, that cause HM. However, approximately 75% of HM patients are negative for these mutations, indicating there are other genes involved in disease causation. In this review, we explored our current understanding of the genetics of HM. The evidence presented herein summarises the current knowledge of the genetics of HM, which can be expanded further to explain the remaining heritability of this debilitating condition. Innovative bioinformatics and computational strategies to cover the entire genetic spectrum of HM are also discussed in this review. Full article

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

13 pages, 1799 KiB

Open AccessEditor’s ChoiceArticle

Molecular Mechanisms Associated with the Development of the Metritis Complex in Dairy Cattle

by Leanna Sanchez, Fernando Campos-Chillon, Mehdi Sargolzaei, Daniel G. Peterson, Kim A. Sprayberry, Garry McArthur, Paul Anderson, Bruce Golden, Siroj Pokharel and Mohammed K. Abo-Ismail

Genes 2024, 15(4), 439; https://doi.org/10.3390/genes15040439 - 30 Mar 2024

Viewed by 1999

Abstract

The metritis complex (MC), a group of post-partum uterine diseases, is associated with increased treatment costs and reduced milk yield and fertility. The goal of this study was to identify genetic variants, genes, or genomic regions that modulate MC disease. A genome-wide association [...] Read more.

The metritis complex (MC), a group of post-partum uterine diseases, is associated with increased treatment costs and reduced milk yield and fertility. The goal of this study was to identify genetic variants, genes, or genomic regions that modulate MC disease. A genome-wide association study was performed using a single-locus mixed linear model of 1967 genotypes (624,460 SNPs) and metritis complex records. Then, in-silico functional analyses were performed to detect biological mechanisms and pathways associated with the development of MC. The ATP8A2, COX16, AMN, and TRAF3 genes, located on chromosomes 12, 10, and 21, were associated with MC at p ≤ 0.0001. These genes are involved in the regulation of cholesterol metabolism in the stromal tissue of the uterus, which can be directly associated with the mode of transmission for pathogens causing the metritis complex. The modulation of cholesterol abundance alters the efficiency of virulence factors and may affect the susceptibility of the host to infection. The SIPA1L1, DEPDC5, and RNF122 genes were also significantly associated with MC at p ≤ 0.0001 and are involved in the PI3k-Akt pathway, responsible for activating the autophagic processes. Thus, the dysregulation of these genes allows for unhindered bacterial invasion, replication, and survival within the endometrium. Full article

(This article belongs to the Special Issue Research on Genetics and Genomics of Cattle)

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14 pages, 6013 KiB

Open AccessEditor’s ChoiceArticle

Exploring Plastomic Resources in Sempervivum (Crassulaceae): Implications for Phylogenetics

by Junhu Kan, Shuo Zhang, Zhiqiang Wu and De Bi

Genes 2024, 15(4), 441; https://doi.org/10.3390/genes15040441 - 30 Mar 2024

Cited by 3 | Viewed by 1567

Abstract

The plastid organelle is vital for photosynthesis and energy production. Advances in sequencing technology have enabled the exploration of plastomic resources, offering insights into plant evolution, diversity, and conservation. As an important group of horticultural ornamentals in the Crassulaceae family, Sempervivum plants are [...] Read more.

The plastid organelle is vital for photosynthesis and energy production. Advances in sequencing technology have enabled the exploration of plastomic resources, offering insights into plant evolution, diversity, and conservation. As an important group of horticultural ornamentals in the Crassulaceae family, Sempervivum plants are known for their unique rosette-like structures and reproduction through offsets. Despite their popularity, the classification status of Sempervivum remains uncertain, with only a single plastome sequence currently available. Furthermore, codon usage bias (CUB) is a widespread phenomenon of the unbalanced usage of synonymous codons in the coding sequence (CDS). However, due to the limited available plastid data, there has been no research that focused on the CUB analysis among Sempervivum until now. To address these gaps, we sequenced and released the plastomes of seven species and one subspecies from Sempervivum, revealing several consistent patterns. These included a shared 110 bp extension of the rps19 gene, 14 hypervariable regions (HVRs) with distinct nucleotide diversity (π: 0.01173 to 0.02702), and evidence of selective pressures shaping codon usage. Notably, phylogenetic analysis robustly divided the monophyletic clade into two sections: Jovibarba and Sempervivum. In conclusion, this comprehensive plastomic resource provides valuable insights into Sempervivum evolution and offers potential molecular markers for DNA barcoding. Full article

(This article belongs to the Special Issue Advances in Evolution of Plant Organelle Genome—2nd Edition)

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20 pages, 355 KiB

Open AccessEditor’s ChoiceReview

Neuroanatomical Correlates of Cognitive Dysfunction in 22q11.2 Deletion Syndrome

by Simon Smerconish and James Eric Schmitt

Genes 2024, 15(4), 440; https://doi.org/10.3390/genes15040440 - 30 Mar 2024

Cited by 2 | Viewed by 1783

Abstract

22q11.2 Deletion Syndrome (22q11.2DS), the most common chromosomal microdeletion, presents as a heterogeneous phenotype characterized by an array of anatomical, behavioral, and cognitive abnormalities. Individuals with 22q11.2DS exhibit extensive cognitive deficits, both in overall intellectual capacity and focal challenges in executive functioning, attentional [...] Read more.

22q11.2 Deletion Syndrome (22q11.2DS), the most common chromosomal microdeletion, presents as a heterogeneous phenotype characterized by an array of anatomical, behavioral, and cognitive abnormalities. Individuals with 22q11.2DS exhibit extensive cognitive deficits, both in overall intellectual capacity and focal challenges in executive functioning, attentional control, perceptual abilities, motor skills, verbal processing, as well as socioemotional operations. Heterogeneity is an intrinsic factor of the deletion’s clinical manifestation in these cognitive domains. Structural imaging has identified significant changes in volume, thickness, and surface area. These alterations are closely linked and display region-specific variations with an overall increase in abnormalities following a rostral-caudal gradient. Despite the extensive literature developing around the neurocognitive and neuroanatomical profiles associated with 22q11.2DS, comparatively little research has addressed specific structure–function relationships between aberrant morphological features and deficient cognitive processes. The current review attempts to categorize these limited findings alongside comparisons to populations with phenotypic and structural similarities in order to answer to what degree structural findings can explain the characteristic neurocognitive deficits seen in individuals with 22q11.2DS. In integrating findings from structural neuroimaging and cognitive assessments, this review seeks to characterize structural changes associated with the broad neurocognitive challenges faced by individuals with 22q11.2DS. Full article

(This article belongs to the Special Issue Phenotype and Pathogenetic Mechanisms in 22q11.2 Deletion/DiGeorge Syndrome)

14 pages, 1212 KiB

Open AccessEditor’s ChoiceArticle

Gene Dosage of F5 c.3481C>T Stop-Codon (p.R1161Ter) Switches the Clinical Phenotype from Severe Thrombosis to Recurrent Haemorrhage: Novel Hypotheses for Readthrough Strategy

by Donato Gemmati, Elisabetta D’Aversa, Bianca Antonica, Miriana Grisafi, Francesca Salvatori, Stefano Pizzicotti, Patrizia Pellegatti, Maria Ciccone, Stefano Moratelli, Maria Luisa Serino and Veronica Tisato

Genes 2024, 15(4), 432; https://doi.org/10.3390/genes15040432 - 29 Mar 2024

Viewed by 1893

Abstract

Inherited defects in the genes of blood coagulation essentially express the severity of the clinical phenotype that is directly correlated to the number of mutated alleles of the candidate leader gene (e.g., heterozygote vs. homozygote) and of possible additional coinherited traits. The F5 [...] Read more.

Inherited defects in the genes of blood coagulation essentially express the severity of the clinical phenotype that is directly correlated to the number of mutated alleles of the candidate leader gene (e.g., heterozygote vs. homozygote) and of possible additional coinherited traits. The F5 gene, which codes for coagulation factor V (FV), plays a two-faced role in the coagulation cascade, exhibiting both procoagulant and anticoagulant functions. Thus, defects in this gene can be predisposed to either bleeding or thrombosis. A Sanger sequence analysis detected a premature stop-codon in exon 13 of the F5 gene (c.3481C>T; p.R1161Ter) in several members of a family characterised by low circulating FV levels and contrasting clinical phenotypes. The propositus, a 29 y.o. male affected by recurrent haemorrhages, was homozygous for the F5 stop-codon and for the F5 c.1691G>A (p.R506Q; FV-Leiden) inherited from the heterozygous parents, which is suggestive of combined cis-segregation. The homozygous condition of the stop-codon completely abolished the F5 gene expression in the propositus (FV:Ag < 1%; FV:C < 1%; assessed by ELISA and PT-based one-stage clotting assay respectively), removing, in turn, any chance for FV-Leiden to act as a prothrombotic molecule. His father (57 y.o.), characterised by severe recurrent venous thromboses, underwent a complete molecular thrombophilic screening, revealing a heterozygous F2 G20210A defect, while his mother (56 y.o.), who was negative for further common coagulation defects, reported fully asymptomatic anamnesis. To dissect these conflicting phenotypes, we performed the ProC^®Global (Siemens Helthineers) coagulation test aimed at assessing the global pro- and anticoagulant balance of each family member, investigating the responses to the activated protein C (APC) by means of an APC-sensitivity ratio (APC-sr). The propositus had an unexpectedly poor response to APC (APC-sr: 1.09; n.v. > 2.25), and his father and mother had an APC-sr of 1.5 and 2.0, respectively. Although ProC^®Global prevalently detects the anticoagulant side of FV, the exceptionally low APC-sr of the propositus and his discordant severe–moderate haemorrhagic phenotype could suggest a residual expression of mutated FV p.506QQ through a natural readthrough or possible alternative splicing mechanisms. The coagulation pathway may be physiologically rebalanced through natural and induced strategies, and the described insights might be able to track the design of novel treatment approaches and rebalancing molecules. Full article

(This article belongs to the Special Issue Feature Papers in Human Genomics and Genetic Diseases 2023)

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22 pages, 2125 KiB

Open AccessEditor’s ChoiceReview

PCR in Forensic Science: A Critical Review

by Caitlin McDonald, Duncan Taylor and Adrian Linacre

Genes 2024, 15(4), 438; https://doi.org/10.3390/genes15040438 - 29 Mar 2024

Cited by 11 | Viewed by 13247

Abstract

The polymerase chain reaction (PCR) has played a fundamental role in our understanding of the world, and has applications across a broad range of disciplines. The introduction of PCR into forensic science marked the beginning of a new era of DNA profiling. This [...] Read more.

The polymerase chain reaction (PCR) has played a fundamental role in our understanding of the world, and has applications across a broad range of disciplines. The introduction of PCR into forensic science marked the beginning of a new era of DNA profiling. This era has pushed PCR to its limits and allowed genetic data to be generated from trace DNA. Trace samples contain very small amounts of degraded DNA associated with inhibitory compounds and ions. Despite significant development in the PCR process since it was first introduced, the challenges of profiling inhibited and degraded samples remain. This review examines the evolution of the PCR from its inception in the 1980s, through to its current application in forensic science. The driving factors behind PCR evolution for DNA profiling are discussed along with a critical comparison of cycling conditions used in commercial PCR kits. Newer PCR methods that are currently used in forensic practice and beyond are examined, and possible future directions of PCR for DNA profiling are evaluated. Full article

(This article belongs to the Section Bioinformatics)

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9 pages, 1042 KiB

Open AccessEditor’s ChoiceArticle

An Ultra-Rare Mixed Phenotype with Combined AP-4 and ERF Mutations: The First Report in a Pediatric Patient and a Literature Review

by Alessandro Orsini, Andrea Santangelo, Alessandra Carmignani, Anna Camporeale, Francesco Massart, Nina Tyutyusheva, Diego Giampietro Peroni, Thomas Foiadelli, Alessandro Ferretti, Benedetta Toschi, Silvia Romano and Alice Bonuccelli

Genes 2024, 15(4), 436; https://doi.org/10.3390/genes15040436 - 29 Mar 2024

Cited by 1 | Viewed by 1789

Abstract

The adaptor protein 4 (AP-4) constitutes a conserved hetero-tetrameric complex within the family of adaptor protein (AP) complex, crucial for the signal-mediated trafficking of integral membrane proteins. Mutations affecting all subunits of the AP-4 complex have been linked to autosomal-recessive cerebral palsy and [...] Read more.

The adaptor protein 4 (AP-4) constitutes a conserved hetero-tetrameric complex within the family of adaptor protein (AP) complex, crucial for the signal-mediated trafficking of integral membrane proteins. Mutations affecting all subunits of the AP-4 complex have been linked to autosomal-recessive cerebral palsy and a complex hereditary spastic paraparesis (HSP) phenotype. Our report details the case of a 14-year-old boy born to consanguineous parents, presenting psychomotor delay, severe intellectual disability, microcephaly, and trigonocephaly. Despite a history of febrile seizures, subsequent years were devoid of seizures, with normal EEG. Exome sequencing revealed pathogenic variants in both the AP4B1 and ERF genes. Significantly, the patient exhibited features associated with AP4B1 mutations, including distinctive traits such as cranial malformations. The ERF gene variant, linked to craniosynostosis, likely contributes to the observed trigonocephaly. This case represents the initial documentation of a concurrent mutation in the AP4B1 and ERF genes, underscoring the critical role of exome analysis in unraveling complex phenotypes. Understanding these complex genotypes offers valuable insights into broader syndromic conditions, facilitating comprehensive patient management. Full article

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

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8 pages, 732 KiB

Open AccessEditor’s ChoiceCase Report

Phenotypic Description of A Patient with ODLURO Syndrome and Functional Characterization of the Pathogenetic Role of A Synonymous Variant c.186G>A in KMT2E Gene

by Mario Benvenuto, Sofia Cesarini, Giulia Severi, Enrico Ambrosini, Angelo Russo, Marco Seri, Pietro Palumbo, Orazio Palumbo, Marco Castori, Emanuele Panza and Massimo Carella

Genes 2024, 15(4), 430; https://doi.org/10.3390/genes15040430 - 29 Mar 2024

Cited by 6 | Viewed by 2521

Abstract

O’Donnell-Luria-Rodan (ODLURO) syndrome is an autosomal dominant disorder caused by mutations in the KMT2E gene. The clinical phonotype of the affected individuals is typically characterized by global developmental delay, autism, epilepsy, hypotonia, macrocephaly, and very mild dysmorphic facial features. In this report, we [...] Read more.

O’Donnell-Luria-Rodan (ODLURO) syndrome is an autosomal dominant disorder caused by mutations in the KMT2E gene. The clinical phonotype of the affected individuals is typically characterized by global developmental delay, autism, epilepsy, hypotonia, macrocephaly, and very mild dysmorphic facial features. In this report, we describe the case of a 6-year-old boy with ODLURO syndrome who is a carrier of the synonymous mutation c.186G>A (p.Ala62=) in the KMT2E gene, predicted to alter splicing by in silico tools. Given the lack of functional studies on the c.186G>A variant, in order to assess its potential functional effect, we sequenced the patient’s cDNA demonstrating its impact on the mechanism of splicing. To the best of our knowledge, our patient is the second to date reported carrying this synonymous mutation, but he is the first whose functional investigation has confirmed the deleterious consequence of the variant, resulting in exon 4 skipping. Additionally, we suggest a potential etiological mechanism that could be responsible for the aberrant splicing mechanism in KMT2E. Full article

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

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23 pages, 11868 KiB

Open AccessEditor’s ChoiceEssay

Resequencing Analyses Revealed Genetic Diversity and Selection Signatures during Rabbit Breeding and Improvement

by Kerui Xie, Chao Ning, Aiguo Yang, Qin Zhang, Dan Wang and Xinzhong Fan

Genes 2024, 15(4), 433; https://doi.org/10.3390/genes15040433 - 29 Mar 2024

Cited by 4 | Viewed by 3197

Abstract

Domestication has shaped the diverse characteristics of rabbits, including coat color, fur structure, body size, and various physiological traits. Utilizing whole-genome resequencing (DNBSEQ-T7), we analyzed the genetic diversity, population structure, and genomic selection across 180 rabbits from 17 distinct breeds to uncover the [...] Read more.

Domestication has shaped the diverse characteristics of rabbits, including coat color, fur structure, body size, and various physiological traits. Utilizing whole-genome resequencing (DNBSEQ-T7), we analyzed the genetic diversity, population structure, and genomic selection across 180 rabbits from 17 distinct breeds to uncover the genetic basis of these traits. We conducted whole-genome sequencing on 17 rabbit breeds, identifying 17,430,184 high-quality SNPs and analyzing genomic diversity, patterns of genomic variation, population structure, and selection signatures related to coat color, coat structure, long hair, body size, reproductive capacity, and disease resistance. Through PCA and NJ tree analyses, distinct clusters emerged among Chinese indigenous rabbits, suggesting varied origins and domestication histories. Selective sweep testing pinpointed regions and genes linked to domestication and key morphological and economic traits, including those affecting coat color (TYR, ASIP), structure (LIPH), body size (INSIG2, GLI3), fertility (EDNRA, SRD5A2), heat stress adaptation (PLCB1), and immune response (SEC31A, CD86, LAP3). Our study identified key genomic signatures of selection related to traits such as coat color, fur structure, body size, and fertility; these findings highlight the genetic basis underlying phenotypic diversification in rabbits and have implications for breeding programs aiming to improve productive, reproductive, and adaptive traits. The detected genomic signatures of selection also provide insights into rabbit domestication and can aid conservation efforts for indigenous breeds. Full article

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

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18 pages, 1776 KiB

Open AccessEditor’s ChoiceArticle

Novel Synergistic Probiotic Intervention: Transcriptomic and Metabolomic Analysis Reveals Ameliorative Effects on Immunity, Gut Barrier, and Metabolism of Mice during Salmonella typhimurium Infection

by Muhammad Junaid, Hongyu Lu, Yixiang Li, Yu Liu, Ahmad Ud Din, Zhongquan Qi, Yi Xiong and Jianhua Yan

Genes 2024, 15(4), 435; https://doi.org/10.3390/genes15040435 - 29 Mar 2024

Cited by 5 | Viewed by 2508

Abstract

Salmonella typhimurium (S. typhimurium), a prevalent cause of foodborne infection, induces significant changes in the host transcriptome and metabolome. The lack of therapeutics with minimal or no side effects prompts the scientific community to explore alternative therapies. This study investigates the therapeutic [...] Read more.

Salmonella typhimurium (S. typhimurium), a prevalent cause of foodborne infection, induces significant changes in the host transcriptome and metabolome. The lack of therapeutics with minimal or no side effects prompts the scientific community to explore alternative therapies. This study investigates the therapeutic potential of a probiotic mixture comprising Lactobacillus acidophilus (L. acidophilus 1.3251) and Lactobacillus plantarum (L. plantarum 9513) against S. typhimurium, utilizing transcriptome and metabolomic analyses, a novel approach that has not been previously documented. Twenty-four SPF-BALB/c mice were divided into four groups: control negative group (CNG); positive control group (CPG); probiotic-supplemented non-challenged group (LAPG); and probiotic-supplemented Salmonella-challenged group (LAPST). An RNA-sequencing analysis of small intestinal (ileum) tissue revealed 2907 upregulated and 394 downregulated DEGs in the LAPST vs. CPG group. A functional analysis of DEGs highlighted their significantly altered gene ontology (GO) terms related to metabolism, gut integrity, cellular development, and immunity (p ≤ 0.05). The KEGG analysis showed that differentially expressed genes (DEGs) in the LAPST group were primarily involved in pathways related to gut integrity, immunity, and metabolism, such as MAPK, PI3K-Akt, AMPK, the tryptophan metabolism, the glycine, serine, and threonine metabolism, ECM–receptor interaction, and others. Additionally, the fecal metabolic analysis identified 1215 upregulated and 305 downregulated metabolites in the LAPST vs. CPG group, implying their involvement in KEGG pathways including bile secretion, propanoate metabolism, arginine and proline metabolism, amino acid biosynthesis, and protein digestion and absorption, which are vital for maintaining barrier integrity, immunity, and metabolism. In conclusion, these findings suggest that the administration of a probiotic mixture improves immunity, maintains gut homeostasis and barrier integrity, and enhances metabolism in Salmonella infection. Full article

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

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16 pages, 2740 KiB

Open AccessEditor’s ChoiceArticle

Analysis of the Overlength Main Noncoding Region in Metacarcinus magister (Decapoda: Brachyura) and a Phylogenetic Study of the Cancroidea Species

by Zhengfei Wang, Xinyi Xu, Yuqing Zheng, Zhiwen Xu, Yunjie Li and Huohuo Chen

Genes 2024, 15(4), 437; https://doi.org/10.3390/genes15040437 - 29 Mar 2024

Cited by 1 | Viewed by 1440

Abstract

Complete mitochondrial genomes (mitogenomes) can provide important information regarding the molecular evolution and phylogenetic relationships of marine invertebrates, especially in Brachyura. Only one Cancroidea species of mitogenomes has been sequenced before; in this research, the mitogenomic characteristics of Metacarcinus magister (Cancridae: Cancroidea) are newly [...] Read more.

Complete mitochondrial genomes (mitogenomes) can provide important information regarding the molecular evolution and phylogenetic relationships of marine invertebrates, especially in Brachyura. Only one Cancroidea species of mitogenomes has been sequenced before; in this research, the mitogenomic characteristics of Metacarcinus magister (Cancridae: Cancroidea) are newly studied. The length of the M. magister mitogenome was 48,820 bp, and it contained the typical 13 protein-coding genes, 2 ribosomal RNA genes, and 22 transfer RNA genes. We performed a series of analyses on the characteristics of the mNCR of M. magister. The phylogenetics, life circumstances, and selective pressures were all analyzed to explain the formation of this length, which revealed the length of the M. magister mitogenome to be approximately three times greater than the normal length of Brachyuran mitogenomes. Phylogenetic analyses based on a dataset of 215 Decapodan mitogenomes indicated that all Eriphioidea crabs were clustered together as a group. Moreover, the rearrangement mechanism of the Cancroidea species was predicted to provide stronger evidence for the phylogenetic analysis. In general, the results obtained in this study will contribute to a better understanding of the cause of the unusual length of the M. magister mitogenome and provide new insights into the phylogeny of Brachyura. Full article

(This article belongs to the Special Issue Molecular Evolution, Mitochondrial Genomics and Mitochondrial Genome Expression in Animals—2nd Edition)

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18 pages, 892 KiB

Open AccessEditor’s ChoiceReview

Innovations in Medicine: Exploring ChatGPT’s Impact on Rare Disorder Management

by Stefania Zampatti, Cristina Peconi, Domenica Megalizzi, Giulia Calvino, Giulia Trastulli, Raffaella Cascella, Claudia Strafella, Carlo Caltagirone and Emiliano Giardina

Genes 2024, 15(4), 421; https://doi.org/10.3390/genes15040421 - 28 Mar 2024

Cited by 11 | Viewed by 3102

Abstract

Artificial intelligence (AI) is rapidly transforming the field of medicine, announcing a new era of innovation and efficiency. Among AI programs designed for general use, ChatGPT holds a prominent position, using an innovative language model developed by OpenAI. Thanks to the use of [...] Read more.

Artificial intelligence (AI) is rapidly transforming the field of medicine, announcing a new era of innovation and efficiency. Among AI programs designed for general use, ChatGPT holds a prominent position, using an innovative language model developed by OpenAI. Thanks to the use of deep learning techniques, ChatGPT stands out as an exceptionally viable tool, renowned for generating human-like responses to queries. Various medical specialties, including rheumatology, oncology, psychiatry, internal medicine, and ophthalmology, have been explored for ChatGPT integration, with pilot studies and trials revealing each field’s potential benefits and challenges. However, the field of genetics and genetic counseling, as well as that of rare disorders, represents an area suitable for exploration, with its complex datasets and the need for personalized patient care. In this review, we synthesize the wide range of potential applications for ChatGPT in the medical field, highlighting its benefits and limitations. We pay special attention to rare and genetic disorders, aiming to shed light on the future roles of AI-driven chatbots in healthcare. Our goal is to pave the way for a healthcare system that is more knowledgeable, efficient, and centered around patient needs. Full article

(This article belongs to the Collection Genetics and Genomics of Rare Disorders)

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15 pages, 2997 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Identification, Characterization, and Expression Analysis of the HD-Zip Gene Family in Lagerstroemia for Regulating Plant Height

by Hang Lin, Xinqiang Jiang, Cheng Qian, Yue Zhang, Xin Meng, Nairui Liu, Lulu Li, Jingcai Wang and Yiqian Ju

Genes 2024, 15(4), 428; https://doi.org/10.3390/genes15040428 - 28 Mar 2024

Cited by 2 | Viewed by 1438

Abstract

The Homeodomain leucine zipper (HD-Zip) family of transcription factors is crucial in helping plants adapt to environmental changes and promoting their growth and development. Despite research on the HD-Zip family in various plants, studies in Lagerstroemia (crape myrtle) have not been reported. This [...] Read more.

The Homeodomain leucine zipper (HD-Zip) family of transcription factors is crucial in helping plants adapt to environmental changes and promoting their growth and development. Despite research on the HD-Zip family in various plants, studies in Lagerstroemia (crape myrtle) have not been reported. This study aimed to address this gap by comprehensively analyzing the HD-Zip gene family in crape myrtle. This study identified 52 HD-Zip genes in the genome of Lagerstroemia indica, designated as LinHDZ1-LinHDZ52. These genes were distributed across 22 chromosomes and grouped into 4 clusters (HD-Zip I-IV) based on their phylogenetic relationships. Most gene structures and motifs within each cluster were conserved. Analysis of protein properties, gene structure, conserved motifs, and cis-acting regulatory elements revealed diverse roles of LinHDZs in various biological contexts. Examining the expression patterns of these 52 genes in 6 tissues (shoot apical meristem, tender shoot, and mature shoot) of non-dwarf and dwarf crape myrtles revealed that 2 LinHDZs (LinHDZ24 and LinHDZ14) and 2 LinHDZs (LinHDZ9 and LinHDZ35) were respectively upregulated in tender shoot of non-dwarf crape myrtles and tender and mature shoots of dwarf crape myrtles, which suggested the important roles of these genes in regulate the shoot development of Lagerstroemia. In addition, the expression levels of 2 LinHDZs (LinHDZ23 and LinHDZ34) were significantly upregulated in the shoot apical meristem of non-dwarf crape myrtle. These genes were identified as key candidates for regulating Lagerstroemia plant height. This study enhanced the understanding of the functions of HD-Zip family members in the growth and development processes of woody plants and provided a theoretical basis for further studies on the molecular mechanisms underlying Lagerstroemia plant height. Full article

(This article belongs to the Special Issue Forest Genetics and Forest-Tree Breeding)

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10 pages, 2413 KiB

Open AccessEditor’s ChoiceBrief Report

A Case Study of a Rare Undifferentiated Spindle Cell Sarcoma of the Penis: Establishment and Characterization of Patient-Derived Models

by Ariane Cavalcante dos Santos Sousa, Bruno Leonardo Nascimento Correa Fernandes, Jeronimo Paulo Assis da Silva, Paulo Roberto Stevanato Filho, Luiza Bitencourt de Carvalho Terci Coimbra, Adriano de Oliveira Beserra, Ana Luiza Alvarenga, Giovanna Maida, Camila Tokumoto Guimaraes, Ingrid Martinez Nakamuta, Fabio Albuquerque Marchi, Camila Alves, Martina Lichtenfels, Caroline Brunetto de Farias, Bruna Elisa Catin Kupper, Felipe D’Almeida Costa, Celso Abdon Lopes de Mello, Dirce Maria Carraro, Giovana Tardin Torrezan, Ademar Lopes and Tiago Goss dos Santos Show full author list Hide full author list

Genes 2024, 15(4), 424; https://doi.org/10.3390/genes15040424 - 28 Mar 2024

Viewed by 2587

Abstract

Rare sarcomas present significant treatment challenges compared to more prevalent soft tissue sarcomas due to limited treatment options and a poor understanding of their biology. This study investigates a unique case of penile sarcoma, providing a comprehensive morphological and molecular analysis. Through the [...] Read more.

Rare sarcomas present significant treatment challenges compared to more prevalent soft tissue sarcomas due to limited treatment options and a poor understanding of their biology. This study investigates a unique case of penile sarcoma, providing a comprehensive morphological and molecular analysis. Through the creation of experimental patient-derived models—including patient-derived xenograft (PDX), 3D, and monolayer primary cultures—we successfully replicated crucial molecular traits observed in the patient’s tumor, such as smooth muscle actin and CD99 expression, along with specific mutations in genes like TSC2 and FGFR4. These models are helpful in assessing the potential for an in-depth exploration of this tumor’s biology. This comprehensive approach holds promise in identifying potential therapeutic avenues for managing this exceedingly rare soft tissue sarcoma. Full article

(This article belongs to the Special Issue Molecular Genetic Investigation of Rare Cancers)

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16 pages, 4455 KiB

Open AccessEditor’s ChoiceArticle

Cytogenetic Analysis of Satellitome of Madagascar Leaf-Tailed Geckos

by Alona Yurchenko, Tomáš Pšenička, Pablo Mora, Juan Alberto Marchal Ortega, Antonio Sánchez Baca and Michail Rovatsos

Genes 2024, 15(4), 429; https://doi.org/10.3390/genes15040429 - 28 Mar 2024

Cited by 1 | Viewed by 1542

Abstract

Satellite DNA (satDNA) consists of sequences of DNA that form tandem repetitions across the genome, and it is notorious for its diversity and fast evolutionary rate. Despite its importance, satDNA has been only sporadically studied in reptile lineages. Here, we sequenced genomic DNA [...] Read more.

Satellite DNA (satDNA) consists of sequences of DNA that form tandem repetitions across the genome, and it is notorious for its diversity and fast evolutionary rate. Despite its importance, satDNA has been only sporadically studied in reptile lineages. Here, we sequenced genomic DNA and PCR-amplified microdissected W chromosomes on the Illumina platform in order to characterize the monomers of satDNA from the Henkel’s leaf-tailed gecko U. henkeli and to compare their topology by in situ hybridization in the karyotypes of the closely related Günther’s flat-tail gecko U. guentheri and gold dust day gecko P. laticauda. We identified seventeen different satDNAs; twelve of them seem to accumulate in centromeres, telomeres and/or the W chromosome. Notably, centromeric and telomeric regions seem to share similar types of satDNAs, and we found two that seem to accumulate at both edges of all chromosomes in all three species. We speculate that the long-term stability of all-acrocentric karyotypes in geckos might be explained from the presence of specific satDNAs at the centromeric regions that are strong meiotic drivers, a hypothesis that should be further tested. Full article

(This article belongs to the Special Issue Commemorating the Launch of the Section "Cytogenomics")

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7 pages, 225 KiB

Open AccessEditor’s ChoiceBrief Report

GSDMB/ORMDL3 Rare/Common Variants Are Associated with Inhaled Corticosteroid Response among Children with Asthma

by Kirsten Voorhies, Akram Mohammed, Lokesh Chinthala, Sek Won Kong, In-Hee Lee, Alvin T. Kho, Michael McGeachie, Kenneth D. Mandl, Benjamin Raby, Melanie Hayes, Robert L. Davis, Ann Chen Wu and Sharon M. Lutz

Genes 2024, 15(4), 420; https://doi.org/10.3390/genes15040420 - 28 Mar 2024

Cited by 3 | Viewed by 3509

Abstract

Inhaled corticosteroids (ICS) are efficacious in the treatment of asthma, which affects more than 300 million people in the world. While genome-wide association studies have identified genes involved in differential treatment responses to ICS in asthma, few studies have evaluated the effects of [...] Read more.

Inhaled corticosteroids (ICS) are efficacious in the treatment of asthma, which affects more than 300 million people in the world. While genome-wide association studies have identified genes involved in differential treatment responses to ICS in asthma, few studies have evaluated the effects of combined rare and common variants on ICS response among children with asthma. Among children with asthma treated with ICS with whole exome sequencing (WES) data in the PrecisionLink Biobank (91 White and 20 Black children), we examined the effect and contribution of rare and common variants with hospitalizations or emergency department visits. For 12 regions previously associated with asthma and ICS response (DPP10, FBXL7, NDFIP1, TBXT, GLCCI1, HDAC9, TBXAS1, STAT6, GSDMB/ORMDL3, CRHR1, GNGT2, FCER2), we used the combined sum test for the sequence kernel association test (SKAT) adjusting for age, sex, and BMI and stratified by race. Validation was conducted in the Biorepository and Integrative Genomics (BIG) Initiative (83 White and 134 Black children). Using a Bonferroni threshold for the 12 regions tested (i.e., 0.05/12 = 0.004), GSDMB/ORMDL3 was significantly associated with ICS response for the combined effect of rare and common variants (p-value = 0.003) among White children in the PrecisionLink Biobank and replicated in the BIG Initiative (p-value = 0.02). Using WES data, the combined effect of rare and common variants for GSDMB/ORMDL3 was associated with ICS response among asthmatic children in the PrecisionLink Biobank and replicated in the BIG Initiative. This proof-of-concept study demonstrates the power of biobanks of pediatric real-life populations in asthma genomic investigations. Full article

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

8 pages, 210 KiB

Open AccessEditor’s ChoiceArticle

Expansion of the Genotypic and Phenotypic Spectrum of ASH1L-Related Syndromic Neurodevelopmental Disorder

by Ineke Cordova, Alyssa Blesson, Juliann M. Savatt, Abigail Sveden, Sonal Mahida, Heather Hazlett, Erin Rooney Riggs and Maya Chopra

Genes 2024, 15(4), 423; https://doi.org/10.3390/genes15040423 - 28 Mar 2024

Cited by 5 | Viewed by 2658

Abstract

Pathogenic ASH1L variants have been reported in probands with broad phenotypic presentations, including intellectual disability, autism spectrum disorder, attention deficit hyperactivity disorder, seizures, congenital anomalies, and other skeletal, muscular, and sleep differences. Here, we review previously published individuals with pathogenic ASH1L variants and [...] Read more.

Pathogenic ASH1L variants have been reported in probands with broad phenotypic presentations, including intellectual disability, autism spectrum disorder, attention deficit hyperactivity disorder, seizures, congenital anomalies, and other skeletal, muscular, and sleep differences. Here, we review previously published individuals with pathogenic ASH1L variants and report three further probands with novel ASH1L variants and previously unreported phenotypic features, including mixed receptive language disorder and gait disturbances. These novel data from the Brain Gene Registry, an accessible repository of clinically derived genotypic and phenotypic data, have allowed for the expansion of the phenotypic and genotypic spectrum of this condition. Full article

(This article belongs to the Special Issue Genetics of Rare Monogenic Neurodevelopmental Syndromes)

17 pages, 791 KiB

Open AccessEditor’s ChoiceArticle

Genetic Alterations in a Large Population of Italian Patients Affected by Neurodevelopmental Disorders

by Annaluisa Ranieri, Ilaria La Monica, Maria Rosaria Di Iorio, Barbara Lombardo and Lucio Pastore

Genes 2024, 15(4), 427; https://doi.org/10.3390/genes15040427 - 28 Mar 2024

Cited by 1 | Viewed by 2370

Abstract

Neurodevelopmental disorders are a group of complex multifactorial disorders characterized by cognitive impairment, communication deficits, abnormal behaviour, and/or motor skills resulting from abnormal neural development. Copy number variants (CNVs) are genetic alterations often associated with neurodevelopmental disorders. We evaluated the diagnostic efficacy of [...] Read more.

Neurodevelopmental disorders are a group of complex multifactorial disorders characterized by cognitive impairment, communication deficits, abnormal behaviour, and/or motor skills resulting from abnormal neural development. Copy number variants (CNVs) are genetic alterations often associated with neurodevelopmental disorders. We evaluated the diagnostic efficacy of the array-comparative genomic hybridization (a-CGH) method and its relevance as a routine diagnostic test in patients with neurodevelopmental disorders for the identification of the molecular alterations underlying or contributing to the clinical manifestations. In the present study, we analysed 1800 subjects with neurodevelopmental disorders using a CGH microarray. We identified 208 (7%) pathogenetic CNVs, 2202 (78%) variants of uncertain significance (VOUS), and 504 (18%) benign CNVs in the 1800 patients analysed. Some alterations contain genes potentially related to neurodevelopmental disorders including CHRNA7, ANKS1B, ANKRD11, RBFOX1, ASTN2, GABRG3, SHANK2, KIF1A SETBP1, SNTG2, CTNNA2, TOP3B, CNTN4, CNTN5, and CNTN6. The identification of interesting significant genes related to neurological disorders with a-CGH is therefore an essential step in the diagnostic procedure, allowing a better understanding of both the pathophysiology of these disorders and the mechanisms underlying their clinical manifestations. Full article

(This article belongs to the Special Issue Genetics of Multifactorial Diseases)

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15 pages, 11044 KiB

Open AccessEditor’s ChoiceArticle

Cytogenomic Characterization of Transposable Elements and Satellite DNA in Passiflora L. Species

by Gonçalo Santos Silva, Margarete Magalhães Souza, Vanessa de Carvalho Cayres Pamponét, Fabienne Micheli, Cláusio Antônio Ferreira de Melo, Sárah Gomes de Oliveira and Eduardo Almeida Costa

Genes 2024, 15(4), 418; https://doi.org/10.3390/genes15040418 - 27 Mar 2024

Cited by 1 | Viewed by 1475

Abstract

The species Passiflora alata, P. cincinnata, and P. edulis have great economic value due to the use of their fruits for human consumption. In this study, we compared the repetitive genome fractions of these three species. The compositions of the repetitive [...] Read more.

The species Passiflora alata, P. cincinnata, and P. edulis have great economic value due to the use of their fruits for human consumption. In this study, we compared the repetitive genome fractions of these three species. The compositions of the repetitive DNA of these three species’ genomes were analyzed using clustering and identification of the repetitive sequences with RepeatExplorer. It was found that repetitive DNA content represents 74.70%, 66.86%, and 62.24% of the genome of P. alata, P. edulis, and P. cincinnata, respectively. LTR Ty3/Gypsy retrotransposons represent the highest genome proportions in P. alata and P. edulis, while Ty1/Copia comprises the largest proportion of P. cincinnata genome. Chromosomal mapping by Fluorescent In Situ Hybridization (FISH) showed that LTR retrotransposons have a dispersed distribution along chromosomes. The subtelomeric region of chromosomes is where 145 bp satellite DNA is located, suggesting that these elements may play important roles in genome structure and organization in these species. In this work, we obtained the first global characterization of the composition of repetitive DNA in Passiflora, showing that an increase in genome size is related to an increase in repetitive DNA, which represents an important evolutionary route for these species. Full article

(This article belongs to the Section Cytogenomics)

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19 pages, 3099 KiB

Open AccessEditor’s ChoiceArticle

DRANetSplicer: A Splice Site Prediction Model Based on Deep Residual Attention Networks

by Xueyan Liu, Hongyan Zhang, Ying Zeng, Xinghui Zhu, Lei Zhu and Jiahui Fu

Genes 2024, 15(4), 404; https://doi.org/10.3390/genes15040404 - 26 Mar 2024

Cited by 2 | Viewed by 1947

Abstract

The precise identification of splice sites is essential for unraveling the structure and function of genes, constituting a pivotal step in the gene annotation process. In this study, we developed a novel deep learning model, DRANetSplicer, that integrates residual learning and attention mechanisms [...] Read more.

The precise identification of splice sites is essential for unraveling the structure and function of genes, constituting a pivotal step in the gene annotation process. In this study, we developed a novel deep learning model, DRANetSplicer, that integrates residual learning and attention mechanisms for enhanced accuracy in capturing the intricate features of splice sites. We constructed multiple datasets using the most recent versions of genomic data from three different organisms, Oryza sativa japonica, Arabidopsis thaliana and Homo sapiens. This approach allows us to train models with a richer set of high-quality data. DRANetSplicer outperformed benchmark methods on donor and acceptor splice site datasets, achieving an average accuracy of (96.57%, 95.82%) across the three organisms. Comparative analyses with benchmark methods, including SpliceFinder, Splice2Deep, Deep Splicer, EnsembleSplice, and DNABERT, revealed DRANetSplicer’s superior predictive performance, resulting in at least a (4.2%, 11.6%) relative reduction in average error rate. We utilized the DRANetSplicer model trained on O. sativa japonica data to predict splice sites in A. thaliana, achieving accuracies for donor and acceptor sites of (94.89%, 94.25%). These results indicate that DRANetSplicer possesses excellent cross-organism predictive capabilities, with its performance in cross-organism predictions even surpassing that of benchmark methods in non-cross-organism predictions. Cross-organism validation showcased DRANetSplicer’s excellence in predicting splice sites across similar organisms, supporting its applicability in gene annotation for understudied organisms. We employed multiple methods to visualize the decision-making process of the model. The visualization results indicate that DRANetSplicer can learn and interpret well-known biological features, further validating its overall performance. Our study systematically examined and confirmed the predictive ability of DRANetSplicer from various levels and perspectives, indicating that its practical application in gene annotation is justified. Full article

(This article belongs to the Special Issue Advances and Applications of Machine Learning in Biomedical Genomics)

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18 pages, 430 KiB

Open AccessEditor’s ChoiceArticle

New Empirical Bayes Models to Jointly Analyze Multiple RNA-Sequencing Data in a Hypophosphatasia Disease Study

by Dawson Kinsman, Jian Hu, Zhi Zhang and Gengxin Li

Genes 2024, 15(4), 407; https://doi.org/10.3390/genes15040407 - 26 Mar 2024

Cited by 1 | Viewed by 1352

Abstract

Hypophosphatasia is a rare inherited metabolic disorder caused by the deficiency of tissue-nonspecific alkaline phosphatase. More severe and early onset cases present symptoms of muscle weakness, diminished motor coordination, and epileptic seizures. These neurological manifestations are poorly characterized. Thus, it is urgent to [...] Read more.

Hypophosphatasia is a rare inherited metabolic disorder caused by the deficiency of tissue-nonspecific alkaline phosphatase. More severe and early onset cases present symptoms of muscle weakness, diminished motor coordination, and epileptic seizures. These neurological manifestations are poorly characterized. Thus, it is urgent to discover novel differentially expressed genes for investigating the genetic mechanisms underlying the neurological manifestations of hypophosphatasia. RNA-sequencing data offer a high-resolution and highly accurate transcript profile. In this study, we apply an empirical Bayes model to RNA-sequencing data acquired from the spinal cord and neocortex tissues of a mouse model, individually, to more accurately estimate the genetic effects without bias. More importantly, we further develop two integration methods, weighted gene approach and weighted Z method, to incorporate two RNA-sequencing data into a model for enhancing the effects of genetic markers in the diagnostics of hypophosphatasia disease. The simulation and real data analysis have demonstrated the effectiveness of our proposed integration methods, which can maximize genetic signals identified from the spinal cord and neocortex tissues, minimize the prediction error, and largely improve the prediction accuracy in risk prediction. Full article

(This article belongs to the Section RNA)

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23 pages, 10438 KiB

Open AccessEditor’s ChoiceArticle

Comparative Analysis of Chloroplast Genomes for the Genus Manglietia Blume (Magnoliaceae): Molecular Structure and Phylogenetic Evolution

by Tingzhang Li, Shuangyu Zhang, Yunfei Deng and Yuling Li

Genes 2024, 15(4), 406; https://doi.org/10.3390/genes15040406 - 26 Mar 2024

Cited by 2 | Viewed by 1446

Abstract

Manglietia Blume, belonging to the Magnoliaceae family and mainly distributed in tropical and subtropical regions of Asia, has great scientific and economic value. In this study, we employed next-generation sequencing followed by de novo assembly to investigate the adaptive evolution of Manglietia using [...] Read more.

Manglietia Blume, belonging to the Magnoliaceae family and mainly distributed in tropical and subtropical regions of Asia, has great scientific and economic value. In this study, we employed next-generation sequencing followed by de novo assembly to investigate the adaptive evolution of Manglietia using plastid genetic information. We newly sequenced the complete or nearly complete plastomes of four Manglietia species (Manglietia aromatica, Manglietia calcarea, Manglietia kwangtungensis, and Manglietia glauca) and conducted comparative analysis with seventeen published plastomes to examine the evolutionary pattern within this genus. The plastomes of these five newly sequenced Manglietia species range from 157,093 bp (M. calcarea2) to 160,493 bp (M. kwangtungensis), all exhibiting circular structures when mapped. Nucleotide diversity was observed across the plastomes, leading us to identify 13 mutational hotspot regions, comprising eight intergenic spacer regions and five gene regions. Our phylogenetic analyses based on 77 protein-coding genes generated phylogenetic relationships with high support and resolution for Manglietia. This genus can be divided into three clades, and the previously proposed infrageneric classifications are not supported by our studies. Furthermore, the close affinity between M. aromatica and M. calcarea is supported by the present work, and further studies are necessary to conclude the taxonomic treatment for the latter. These results provide resources for the comparative plastome, breeding, and plastid genetic engineering of Magnoliaceae and flowering plants. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Adaptive Evolution in Trees)

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14 pages, 4528 KiB

Open AccessEditor’s ChoiceArticle

Functional Differentiation of the Duplicated Gene BrrCIPK9 in Turnip (Brassica rapa var. rapa)

by Haotong Kang, Yunqiang Yang and Ying Meng

Genes 2024, 15(4), 405; https://doi.org/10.3390/genes15040405 - 26 Mar 2024

Cited by 2 | Viewed by 1463

Abstract

Gene duplication is a key biological process in the evolutionary history of plants and an important driving force for the diversification of genomic and genetic systems. Interactions between the calcium sensor calcineurin B-like protein (CBL) and its target, CBL-interacting protein kinase (CIPK), play [...] Read more.

Gene duplication is a key biological process in the evolutionary history of plants and an important driving force for the diversification of genomic and genetic systems. Interactions between the calcium sensor calcineurin B-like protein (CBL) and its target, CBL-interacting protein kinase (CIPK), play important roles in the plant’s response to various environmental stresses. As a food crop with important economic and research value, turnip (Brassica rapa var. rapa) has been well adapted to the environment of the Tibetan Plateau and become a traditional crop in the region. The BrrCIPK9 gene in turnip has not been characterized. In this study, two duplicated genes, BrrCIPK9.1 and BrrCIPK9.2, were screened from the turnip genome. Based on the phylogenetic analysis, BrrCIPK9.1 and BrrCIPK9.2 were found located in different sub-branches on the phylogenetic tree. Real-time fluorescence quantitative PCR analyses revealed their differential expression levels between the leaves and roots and in response to various stress treatments. The differences in their interactions with BrrCBLs were also revealed by yeast two-hybrid analyses. The results indicate that BrrCIPK9.1 and BrrCIPK9.2 have undergone Asparagine–alanine–phenylalanine (NAF) site divergence during turnip evolution, which has resulted in functional differences between them. Furthermore, BrrCIPK9.1 responded to high-pH (pH 8.5) stress, while BrrCIPK9.2 retained its ancestral function (low K⁺), thus providing further evidence of their functional divergence. These functional divergence genes facilitate turnip’s good adaptation to the extreme environment of the Tibetan Plateau. In summary, the results of this study reveal the characteristics of the duplicated BrrCIPK9 genes and provide a basis for further functional studies of BrrCBLs–BrrCIPKs in turnip. Full article

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

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11 pages, 1756 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Analysis of Exertional Rhabdomyolysis in Sickle Cell Trait Positive African Americans

by Mingqiang Ren, Nyamkhishig Sambuughin, Ognoon Mungunshukh, Daniel Baxter Edgeworth, Daniel Hupalo, Xijun Zhang, Matthew D. Wilkerson, Clifton L. Dalgard, Francis G. O’Connor and Patricia A. Deuster

Genes 2024, 15(4), 408; https://doi.org/10.3390/genes15040408 - 26 Mar 2024

Cited by 1 | Viewed by 2134

Abstract

Sickle cell trait (SCT), although generally a benign carrier state of hemoglobin S (HbAS), is a risk factor for exertional rhabdomyolysis (ERM), a rare but potentially fatal consequence of highly intense physical exercise, particularly among active-duty military personnel and high-performance athletes. The association [...] Read more.

Sickle cell trait (SCT), although generally a benign carrier state of hemoglobin S (HbAS), is a risk factor for exertional rhabdomyolysis (ERM), a rare but potentially fatal consequence of highly intense physical exercise, particularly among active-duty military personnel and high-performance athletes. The association between SCT and ERM is poorly understood. The objective of this study was to elucidate the genetic basis of ERM in an SCT-positive African American cohort. SCT-positive African Americans with a personal history of ERM (cases, n = 30) and without history of ERM (controls, n = 53) were enrolled in this study. Whole-genome sequencing was performed on DNA samples isolated from peripheral white blood cells. Participants’ demographic, behavioral, and medical history information was obtained. An additional 131 controls were extracted from SCT-positive subjects of African descent from the 1000 Genomes Project. SCT carriers with ERM were characterized by myotoxicity features, significant muscle involvement dominated by muscle weakness, and severe pain and substantial increase in serum creatine kinase, with a mean value of 50,480 U/L. A distinctive feature of the SCT individuals with ERM was exertional collapse, which was reported in 53.3% of the cases in the study cohort. An important factor for the development of ERM was the duration and frequency of strenuous physical activity in the cases compared to the controls. Whole-genome sequencing identified 79,696 protein-coding variants. Genome-wide association analysis revealed that the p.C477R, rs115958260 variant in the SLC44A3 gene was significantly associated with ERM event in SCT-positive African Americans. The study results suggest that a combination of vigorous exercise and a genetic predisposing factor is involved in ERM. Full article

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

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11 pages, 694 KiB

Open AccessEditor’s ChoiceReview

Extrachromosomal Circular DNA: An Emerging Potential Biomarker for Inflammatory Bowel Diseases?

by Valentina Petito, Federica Di Vincenzo, Lorenza Putignani, Maria T. Abreu, Birgitte Regenberg, Antonio Gasbarrini and Franco Scaldaferri

Genes 2024, 15(4), 414; https://doi.org/10.3390/genes15040414 - 26 Mar 2024

Viewed by 2529

Abstract

Inflammatory bowel disease (IBD) comprising ulcerative colitis and Crohn’s disease is a chronic immune-mediated disease which affects the gastrointestinal tract with a relapsing and remitting course, causing lifelong morbidity. IBD pathogenesis is determined by multiple factors including genetics, immune and microbial factors, and [...] Read more.

Inflammatory bowel disease (IBD) comprising ulcerative colitis and Crohn’s disease is a chronic immune-mediated disease which affects the gastrointestinal tract with a relapsing and remitting course, causing lifelong morbidity. IBD pathogenesis is determined by multiple factors including genetics, immune and microbial factors, and environmental factors. Although therapy options are expanding, remission rates are unsatisfiable, and together with the disease course, response to therapy remains unpredictable. Therefore, the identification of biomarkers that are predictive for the disease course and response to therapy is a significant challenge. Extrachromosomal circular DNA (eccDNA) fragments exist in all tissue tested so far. These fragments, ranging in length from a few hundreds of base pairs to mega base pairs, have recently gained more interest due to technological advances. Until now, eccDNA has mainly been studied in relation to cancer due to its ability to act as an amplification site for oncogenes and drug resistance genes. However, eccDNA could also play an important role in inflammation, expressed both locally in the- involved tissue and at distant sites. Here, we review the current evidence on the molecular mechanisms of eccDNA and its role in inflammation and IBD. Additionally, the potential of eccDNA as a tissue or plasma marker for disease severity and/or response to therapy is evaluated. Full article

(This article belongs to the Special Issue Genetic Biomarkers and Their Expression for Human Diseases: From the Laboratory to the Patient’s Bedside)

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14 pages, 4577 KiB

Open AccessEditor’s ChoiceArticle

Regulation of Hair Follicle Growth and Development by Different Alternative Spliceosomes of FGF5 in Rabbits

by Shaoning Sun, Bohao Zhao, Jiali Li, Xiyu Zhang, Shuyu Yao, Zhiyuan Bao, Jiawei Cai, Jie Yang, Yang Chen and Xinsheng Wu

Genes 2024, 15(4), 409; https://doi.org/10.3390/genes15040409 - 26 Mar 2024

Cited by 1 | Viewed by 1812

Abstract

This study investigated the regulatory effect of alternative spliceosomes of the fibroblast growth factor 5 (FGF5) gene on hair follicle (HF) growth and development in rabbits. The FGF5 alternative spliceosomes (called FGF5-X1, FGF5-X2, FGF5-X3) were cloned. The overexpression [...] Read more.

This study investigated the regulatory effect of alternative spliceosomes of the fibroblast growth factor 5 (FGF5) gene on hair follicle (HF) growth and development in rabbits. The FGF5 alternative spliceosomes (called FGF5-X1, FGF5-X2, FGF5-X3) were cloned. The overexpression vector and siRNA of spliceosomes were transfected into dermal papilla cells (DPCs) to analyze the regulatory effect on DPCs. The results revealed that FGF5-X2 and FGF5-X3 overexpression significantly decreased LEF1 mRNA expression (p < 0.01). FGF5-X1 overexpression significantly reduced CCND1 expression (p < 0.01). FGF5-X1 and FGF5-X2 possibly downregulated the expression level of FGF2 mRNA (p < 0.05), and FGF5-X3 significantly downregulated the expression level of FGF2 mRNA (p < 0.01). The FGF5 alternative spliceosomes significantly downregulated the BCL2 mRNA expression level in both cases (p < 0.01). FGF5-X1 and FGF5-X2 significantly increased TGFβ mRNA expression (p < 0.01). All three FGF5 alternative spliceosomes inhibited DPC proliferation. In conclusion, the expression profile of HF growth and development-related genes can be regulated by FGF5 alternative spliceosomes, inhibiting the proliferation of DPCs and has an influence on the regulation of HF growth in rabbits. This study provides insights to further investigate the mechanism of HF development in rabbits via FGF5 regulation. Full article

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

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14 pages, 2532 KiB

Open AccessEditor’s ChoiceArticle

Association of TMEM106B with Cortical APOE Gene Expression in Neurodegenerative Conditions

by Cynthia Picard, Justin Miron and Judes Poirier

Genes 2024, 15(4), 416; https://doi.org/10.3390/genes15040416 - 26 Mar 2024

Cited by 1 | Viewed by 1751

Abstract

The e4 allele of the apolipoprotein E gene is the strongest genetic risk factor for sporadic Alzheimer’s disease. Nevertheless, how APOE is regulated is still elusive. In a trans-eQTL analysis, we found a genome-wide significant association between transmembrane protein 106B (TMEM106B [...] Read more.

The e4 allele of the apolipoprotein E gene is the strongest genetic risk factor for sporadic Alzheimer’s disease. Nevertheless, how APOE is regulated is still elusive. In a trans-eQTL analysis, we found a genome-wide significant association between transmembrane protein 106B (TMEM106B) genetic variants and cortical APOE mRNA levels in human brains. The goal of this study is to determine whether TMEM106B is mis-regulated in Alzheimer’s disease or in other neurodegenerative conditions. Available genomic, transcriptomic and proteomic data from human brains were downloaded from the Mayo Clinic Brain Bank and the Religious Orders Study and Memory and Aging Project. An in-house mouse model of the hippocampal deafferentation/reinnervation was achieved via a stereotaxic lesioning surgery to the entorhinal cortex, and mRNA levels were measured using RNAseq technology. In human temporal cortices, the mean TMEM106B expression was significantly higher in Alzheimer’s disease compared to cognitively unimpaired individuals. In the mouse model, hippocampal Tmem106b reached maximum levels during the early phase of reinnervation. These results suggest an active response to tissue damage that is consistent with compensatory synaptic and terminal remodeling. Full article

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

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24 pages, 6426 KiB

Open AccessEditor’s ChoiceArticle

Myelin-Specific microRNA-23a/b Cluster Deletion Inhibits Myelination in the Central Nervous System during Postnatal Growth and Aging

by Shigeki Ishibashi, Naosuke Kamei, Yuji Tsuchikawa, Toshio Nakamae, Takayuki Akimoto, Shigeru Miyaki and Nobuo Adachi

Genes 2024, 15(4), 402; https://doi.org/10.3390/genes15040402 - 25 Mar 2024

Cited by 2 | Viewed by 1681

Abstract

Microribonucleic acids (miRNAs) comprising miR-23a/b clusters, specifically miR-23a and miR-27a, are recognized for their divergent roles in myelination within the central nervous system. However, cluster-specific miRNA functions remain controversial as miRNAs within the same cluster have been suggested to function complementarily. This study [...] Read more.

Microribonucleic acids (miRNAs) comprising miR-23a/b clusters, specifically miR-23a and miR-27a, are recognized for their divergent roles in myelination within the central nervous system. However, cluster-specific miRNA functions remain controversial as miRNAs within the same cluster have been suggested to function complementarily. This study aims to clarify the role of miR-23a/b clusters in myelination using mice with a miR-23a/b cluster deletion (KO mice), specifically in myelin expressing proteolipid protein (PLP). Inducible conditional KO mice were generated by crossing miR-23a/b cluster^flox/flox mice with PlpCre-ERT2 mice; the offspring were injected with tamoxifen at 10 days or 10 weeks of age to induce a myelin-specific miR-23a/b cluster deletion. Evaluation was performed at 10 weeks or 12 months of age and compared with control mice that were not treated with tamoxifen. KO mice exhibit impaired motor function and hypoplastic myelin sheaths in the brain and spinal cord at 10 weeks and 12 months of age. Simultaneously, significant decreases in myelin basic protein (MBP) and PLP expression occur in KO mice. The percentages of oligodendrocyte precursors and mature oligodendrocytes are consistent between the KO and control mice. However, the proportion of oligodendrocytes expressing MBP is significantly lower in KO mice. Moreover, changes in protein expression occur in KO mice, with increased leucine zipper-like transcriptional regulator 1 expression, decreased R-RAS expression, and decreased phosphorylation of extracellular signal-regulated kinases. These findings highlight the significant influence of miR-23a/b clusters on myelination during postnatal growth and aging. Full article

(This article belongs to the Special Issue Non-coding RNAs in Human Health and Disease)

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19 pages, 17490 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Identification and Expression Analysis of the Starch Synthase Gene Family in Sweet Potato and Two of Its Closely Related Species

by Zongjian Sun, Zhenqin Li, Xiongjian Lin, Zhifang Hu, Mengzhen Jiang, Binquan Tang, Zhipeng Zhao, Meng Xing, Xiaohui Yang and Hongbo Zhu

Genes 2024, 15(4), 400; https://doi.org/10.3390/genes15040400 - 25 Mar 2024

Cited by 1 | Viewed by 2023

Abstract

The starch synthase (SS) plays important roles in regulating plant growth and development and responding to adversity stresses. Although the SS family has been studied in many crops, it has not been fully identified in sweet potato and its two related species. In [...] Read more.

The starch synthase (SS) plays important roles in regulating plant growth and development and responding to adversity stresses. Although the SS family has been studied in many crops, it has not been fully identified in sweet potato and its two related species. In the present study, eight SSs were identified from Ipomoea batatas (I. batata), Ipomoea trifida (I. trifida), and Ipomoea trlioba (I. trlioba), respectively. According to the phylogenetic relationships, they were divided into five subgroups. The protein properties, chromosomal location, phylogenetic relationships, gene structure, cis-elements in the promoter, and interaction network of these proteins were also analyzed; stress expression patterns were systematically analyzed; and real-time polymerase chain reaction (qRT-PCR) analysis was performed. Ipomoea batatas starch synthase (IbSSs) were highly expressed in tuber roots, especially Ipomoea batatas starch synthase 1 (IbSS1) and Ipomoea batatas starch synthase 6 (IbSS6), which may play an important role in root development and starch biosynthesis. At the same time, the SS genes respond to potassium deficiency, hormones, cold, heat, salt, and drought stress. This study offers fresh perspectives for enhancing knowledge about the roles of SSs and potential genes to enhance productivity, starch levels, and resistance to environmental stresses in sweet potatoes. Full article

(This article belongs to the Section Bioinformatics)

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