Genes

20 pages, 17791 KiB

Open AccessEditor’s ChoiceArticle

Role of Neurocellular Endoplasmic Reticulum Stress Response in Alzheimer’s Disease and Related Dementias Risk

by Miriam Aceves, Jose Granados, Ana C. Leandro, Juan Peralta, David C. Glahn, Sarah Williams-Blangero, Joanne E. Curran, John Blangero and Satish Kumar

Genes 2024, 15(5), 569; https://doi.org/10.3390/genes15050569 - 28 Apr 2024

Cited by 2 | Viewed by 3430

Abstract

Currently, more than 55 million people around the world suffer from dementia, and Alzheimer’s Disease and Related Dementias (ADRD) accounts for nearly 60–70% of all those cases. The spread of Alzheimer’s Disease (AD) pathology and progressive neurodegeneration in the hippocampus and cerebral cortex [...] Read more.

Currently, more than 55 million people around the world suffer from dementia, and Alzheimer’s Disease and Related Dementias (ADRD) accounts for nearly 60–70% of all those cases. The spread of Alzheimer’s Disease (AD) pathology and progressive neurodegeneration in the hippocampus and cerebral cortex is strongly correlated with cognitive decline in AD patients; however, the molecular underpinning of ADRD’s causality is still unclear. Studies of postmortem AD brains and animal models of AD suggest that elevated endoplasmic reticulum (ER) stress may have a role in ADRD pathology through altered neurocellular homeostasis in brain regions associated with learning and memory. To study the ER stress-associated neurocellular response and its effects on neurocellular homeostasis and neurogenesis, we modeled an ER stress challenge using thapsigargin (TG), a specific inhibitor of sarco/endoplasmic reticulum Ca²⁺ ATPase (SERCA), in the induced pluripotent stem cell (iPSC)-derived neural stem cells (NSCs) of two individuals from our Mexican American Family Study (MAFS). High-content screening and transcriptomic analysis of the control and ER stress-challenged NSCs showed that the NSCs’ ER stress response resulted in a significant decline in NSC self-renewal and an increase in apoptosis and cellular oxidative stress. A total of 2300 genes were significantly (moderated t statistics FDR-corrected p-value ≤ 0.05 and fold change absolute ≥ 2.0) differentially expressed (DE). The pathway enrichment and gene network analysis of DE genes suggests that all three unfolded protein response (UPR) pathways, protein kinase RNA-like ER kinase (PERK), activating transcription factor-6 (ATF-6), and inositol-requiring enzyme-1 (IRE1), were significantly activated and cooperatively regulated the NSCs’ transcriptional response to ER stress. Our results show that IRE1/X-box binding protein 1 (XBP1) mediated transcriptional regulation of the E2F transcription factor 1 (E2F1) gene, and its downstream targets have a dominant role in inducing G1/S-phase cell cycle arrest in ER stress-challenged NSCs. The ER stress-challenged NSCs also showed the activation of C/EBP homologous protein (CHOP)-mediated apoptosis and the dysregulation of synaptic plasticity and neurotransmitter homeostasis-associated genes. Overall, our results suggest that the ER stress-associated attenuation of NSC self-renewal, increased apoptosis, and dysregulated synaptic plasticity and neurotransmitter homeostasis plausibly play a role in the causation of ADRD. Full article

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

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11 pages, 816 KiB

Open AccessEditor’s ChoiceArticle

Prenatal Genome-Wide Cell-Free DNA Screening: Three Years of Clinical Experience in a Hospital Prenatal Diagnostic Unit in Spain

by Laia Pedrola Vidal, Mónica Roselló Piera, Carla Martín-Grau, Juan S. Rubio Moll, Rosa Gómez Portero, Beatriz Marcos Puig, Jose V. Cervera Zamora, Ramiro Quiroga and Carmen Orellana Alonso

Genes 2024, 15(5), 568; https://doi.org/10.3390/genes15050568 - 28 Apr 2024

Viewed by 2019

Abstract

Genome-wide prenatal cell-free DNA (cfDNA) screening can be used to screen for a wide range of fetal chromosomal anomalies in pregnant patients. In this study, we describe our clinical experience with a genome-wide cfDNA assay in screening for common trisomies, sex chromosomal aneuploidies [...] Read more.

Genome-wide prenatal cell-free DNA (cfDNA) screening can be used to screen for a wide range of fetal chromosomal anomalies in pregnant patients. In this study, we describe our clinical experience with a genome-wide cfDNA assay in screening for common trisomies, sex chromosomal aneuploidies (SCAs), rare autosomal aneuploidies (RAAs), and copy-number variations (CNVs) in about 6000 patients over a three-year period at our hospital’s Prenatal Diagnostic Unit in Spain. Overall, 204 (3.3%) patients had a high-risk call, which included 76 trisomy 21, 21 trisomy 18, 7 trisomy 13, 29 SCAs, 31 RAAs, 31 CNVs, and 9 cases with multiple anomalies. The diagnostic outcomes were obtained for the high-risk cases when available, allowing for the calculation of positive predictive values (PPVs). Calculated PPVs were 95.9% for trisomy 21, 77.8% for trisomy 18, 66.7% for trisomy 13, 10.7% for RAAs, and 10.7% for CNVs. Pregnancy and birth outcomes were also collected for the majority of RAA and CNV cases. Adverse perinatal outcomes for some of these cases included preeclampsia, fetal growth restriction, preterm birth, reduced birth weight, and major congenital structural abnormalities. In conclusion, our study showed strong performance for genome-wide cfDNA screening in a large cohort of pregnancy patients in Spain. Full article

(This article belongs to the Special Issue Advance in Non-invasive Prenatal Testing: Ten Years of cfDNA-Based Screening and Diagnosis)

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18 pages, 5656 KiB

Open AccessEditor’s ChoiceArticle

Decoding Evolution of Rubioideae: Plastomes Reveal Sweet Secrets of Codon Usage, Diagnostides, and Superbarcoding

by Kamil Ciborowski, Monika Szczecińska, Mateusz Maździarz, Jakub Sawicki and Łukasz Paukszto

Genes 2024, 15(5), 562; https://doi.org/10.3390/genes15050562 - 27 Apr 2024

Cited by 1 | Viewed by 1956

Abstract

Galium genus belongs to the Rubiaceae family, which consists of approximately 14,000 species. In comparison to its well-known relatives, the plastomes of the Galium genus have not been explored so far. The plastomes of this genus have a typical, quadripartite structure, but differ [...] Read more.

Galium genus belongs to the Rubiaceae family, which consists of approximately 14,000 species. In comparison to its well-known relatives, the plastomes of the Galium genus have not been explored so far. The plastomes of this genus have a typical, quadripartite structure, but differ in gene content, since the infA gene is missing in Galium palustre and Galium trfidum. An evaluation of the effectiveness of using entire chloroplast genome sequences as superbarcodes for accurate plant species identification revealed the high potential of this method for molecular delimitation within the genus and tribe. The trnE-UUC—psbD region showed the biggest number of diagnostides (diagnostic nucleotides) which might be new potential barcodes, not only in Galium, but also in other closely related genera. Relative synonymous codon usage (RSCU) appeared to be connected with the phylogeny of the Rubiaceae family, showing that during evolution, plants started preferring specific codons over others. Full article

(This article belongs to the Special Issue The Evolutionary Genetics and Genomics of Speciation)

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12 pages, 2838 KiB

Open AccessEditor’s ChoiceReview

Roles of Nuclear Orphan Receptors TR2 and TR4 during Hematopoiesis

by Greggory Myers, Yanan Sun, Yu Wang, Hajar Benmhammed and Shuaiying Cui

Genes 2024, 15(5), 563; https://doi.org/10.3390/genes15050563 - 27 Apr 2024

Cited by 3 | Viewed by 1715

Abstract

TR2 and TR4 (NR2C1 and NR2C2, respectively) are evolutionarily conserved nuclear orphan receptors capable of binding direct repeat sequences in a stage-specific manner. Like other nuclear receptors, TR2 and TR4 possess important roles in transcriptional activation or repression with developmental stage and tissue [...] Read more.

TR2 and TR4 (NR2C1 and NR2C2, respectively) are evolutionarily conserved nuclear orphan receptors capable of binding direct repeat sequences in a stage-specific manner. Like other nuclear receptors, TR2 and TR4 possess important roles in transcriptional activation or repression with developmental stage and tissue specificity. TR2 and TR4 bind DNA and possess the ability to complex with available cofactors mediating developmental stage-specific actions in primitive and definitive erythrocytes. In erythropoiesis, TR2 and TR4 are required for erythroid development, maturation, and key erythroid transcription factor regulation. TR2 and TR4 recruit and interact with transcriptional corepressors or coactivators to elicit developmental stage-specific gene regulation during hematopoiesis. Full article

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

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16 pages, 271 KiB

Open AccessEditor’s ChoiceReview

Progress in Rice Breeding Based on Genomic Research

by Xingye Yang, Shicong Yu, Shen Yan, Hao Wang, Wei Fang, Yanqing Chen, Xiaoding Ma and Longzhi Han

Genes 2024, 15(5), 564; https://doi.org/10.3390/genes15050564 - 27 Apr 2024

Cited by 5 | Viewed by 3561

Abstract

The role of rice genomics in breeding progress is becoming increasingly important. Deeper research into the rice genome will contribute to the identification and utilization of outstanding functional genes, enriching the diversity and genetic basis of breeding materials and meeting the diverse demands [...] Read more.

The role of rice genomics in breeding progress is becoming increasingly important. Deeper research into the rice genome will contribute to the identification and utilization of outstanding functional genes, enriching the diversity and genetic basis of breeding materials and meeting the diverse demands for various improvements. Here, we review the significant contributions of rice genomics research to breeding progress over the last 25 years, discussing the profound impact of genomics on rice genome sequencing, functional gene exploration, and novel breeding methods, and we provide valuable insights for future research and breeding practices. Full article

(This article belongs to the Special Issue Genomic Studies of Plant Breeding)

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22 pages, 8084 KiB

Open AccessEditor’s ChoiceArticle

WGCNA Reveals Hub Genes and Key Gene Regulatory Pathways of the Response of Soybean to Infection by Soybean mosaic virus

by Jingping Niu, Jing Zhao, Qian Guo, Hanyue Zhang, Aiqin Yue, Jinzhong Zhao, Congcong Yin, Min Wang and Weijun Du

Genes 2024, 15(5), 566; https://doi.org/10.3390/genes15050566 - 27 Apr 2024

Cited by 5 | Viewed by 2552

Abstract

Soybean mosaic virus (SMV) is one of the main pathogens that can negatively affect soybean production and quality. To study the gene regulatory network of soybeans in response to SMV SC15, the resistant line X149 and susceptible line X97 were subjected to transcriptome [...] Read more.

Soybean mosaic virus (SMV) is one of the main pathogens that can negatively affect soybean production and quality. To study the gene regulatory network of soybeans in response to SMV SC15, the resistant line X149 and susceptible line X97 were subjected to transcriptome analysis at 0, 2, 8, 12, 24, and 48 h post-inoculation (hpi). Differential expression analysis revealed that 10,190 differentially expressed genes (DEGs) responded to SC15 infection. Weighted gene co-expression network analysis (WGCNA) was performed to identify highly related resistance gene modules; in total, eight modules, including 2256 DEGs, were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of 2256 DEGs revealed that the genes significantly clustered into resistance-related pathways, such as the plant–pathogen interaction pathway, mitogen-activated protein kinases (MAPK) signaling pathway, and plant hormone signal transduction pathway. Among these pathways, we found that the flg22, Ca²⁺, hydrogen peroxide (H₂O₂), and abscisic acid (ABA) regulatory pathways were fully covered by 36 DEGs. Among the 36 DEGs, the gene Glyma.01G225100 (protein phosphatase 2C, PP2C) in the ABA regulatory pathway, the gene Glyma.16G031900 (WRKY transcription factor 22, WRKY22) in Ca²⁺ and H₂O₂ regulatory pathways, and the gene Glyma.04G175300 (calcium-dependent protein kinase, CDPK) in Ca²⁺ regulatory pathways were highly connected hub genes. These results indicate that the resistance of X149 to SC15 may depend on the positive regulation of flg22, Ca²⁺, H₂O₂, and ABA regulatory pathways. Our study further showed that superoxide dismutase (SOD) activity, H₂O₂ content, and catalase (CAT) and peroxidase (POD) activities were significantly up-regulated in the resistant line X149 compared with those in 0 hpi. This finding indicates that the H₂O₂ regulatory pathway might be dependent on flg22- and Ca²⁺-pathway-induced ROS generation. In addition, two hub genes, Glyma.07G190100 (encoding F-box protein) and Glyma.12G185400 (encoding calmodulin-like proteins, CMLs), were also identified and they could positively regulate X149 resistance. This study provides pathways for further investigation of SMV resistance mechanisms in soybean. Full article

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

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12 pages, 252 KiB

Open AccessEditor’s ChoiceBrief Report

Examining the Effect of Genes on Depression as Mediated by Smoking and Modified by Sex

by Kirsten Voorhies, Julian Hecker, Sanghun Lee, Georg Hahn, Dmitry Prokopenko, Merry-Lynn McDonald, Alexander C. Wu, Ann Wu, John E. Hokanson, Michael H. Cho, Christoph Lange, Karin F. Hoth and Sharon M. Lutz

Genes 2024, 15(5), 565; https://doi.org/10.3390/genes15050565 - 27 Apr 2024

Viewed by 2224

Abstract

Depression is heritable, differs by sex, and has environmental risk factors such as cigarette smoking. However, the effect of single nucleotide polymorphisms (SNPs) on depression through cigarette smoking and the role of sex is unclear. In order to examine the association of SNPs [...] Read more.

Depression is heritable, differs by sex, and has environmental risk factors such as cigarette smoking. However, the effect of single nucleotide polymorphisms (SNPs) on depression through cigarette smoking and the role of sex is unclear. In order to examine the association of SNPs with depression and smoking in the UK Biobank with replication in the COPDGene study, we used counterfactual-based mediation analysis to test the indirect or mediated effect of SNPs on broad depression through the log of pack-years of cigarette smoking, adjusting for age, sex, current smoking status, and genetic ancestry (via principal components). In secondary analyses, we adjusted for age, sex, current smoking status, genetic ancestry (via principal components), income, education, and living status (urban vs. rural). In addition, we examined sex-stratified mediation models and sex-moderated mediation models. For both analyses, we adjusted for age, current smoking status, and genetic ancestry (via principal components). In the UK Biobank, rs6424532 [LOC105378800] had a statistically significant indirect effect on broad depression through the log of pack-years of cigarette smoking (p = 4.0 × 10⁻⁴) among all participants and a marginally significant indirect effect among females (p = 0.02) and males (p = 4.0 × 10⁻³). Moreover, rs10501696 [GRM5] had a marginally significant indirect effect on broad depression through the log of pack-years of cigarette smoking (p = 0.01) among all participants and a significant indirect effect among females (p = 2.2 × 10⁻³). In the secondary analyses, the sex-moderated indirect effect was marginally significant for rs10501696 [GRM5] on broad depression through the log of pack-years of cigarette smoking (p = 0.01). In the COPDGene study, the effect of an SNP (rs10501696) in GRM5 on depressive symptoms and medication was mediated by log of pack-years (p = 0.02); however, no SNPs had a sex-moderated mediated effect on depressive symptoms. In the UK Biobank, we found SNPs in two genes [LOC105378800, GRM5] with an indirect effect on broad depression through the log of pack-years of cigarette smoking. In addition, the indirect effect for GRM5 on broad depression through smoking may be moderated by sex. These results suggest that genetic regions associated with broad depression may be mediated by cigarette smoking and this relationship may be moderated by sex. Full article

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

14 pages, 885 KiB

Open AccessEditor’s ChoiceArticle

The Relationship between miR-5682 and Nutritional Status of Radiotherapy-Treated Male Laryngeal Cancer Patients

by Marcin Mazurek, Anna Brzozowska, Mirosław Maziarz, Teresa Małecka-Massalska and Tomasz Powrózek

Genes 2024, 15(5), 556; https://doi.org/10.3390/genes15050556 - 27 Apr 2024

Cited by 2 | Viewed by 1375

Abstract

Background: Nutritional deficiencies are frequently observed in patients with head and neck cancer (HNC) undergoing radiation therapy. microRNAs (miRNAs) were found to play an important role in the development of metabolic disorders throughout regulation of genes involved in inflammatory responses. This study aimed [...] Read more.

Background: Nutritional deficiencies are frequently observed in patients with head and neck cancer (HNC) undergoing radiation therapy. microRNAs (miRNAs) were found to play an important role in the development of metabolic disorders throughout regulation of genes involved in inflammatory responses. This study aimed to explore the correlation between pre-treatment miR-5682 expression and parameters reflecting nutritional deficits in laryngeal cancer (LC) patients subjected to radiotherapy (RT). Methods: Expression of miR-5682 was analyzed in plasma samples of 56 male LC individuals. Nutritional status of LC patients was assessed using anthropometric and laboratory parameters, bioelectrical impedance analysis (BIA) and clinical questionnaires. Results: A high expression of miR-5682 was associated with significantly lower values of BMI, fat mass, fat-free mass and plasma albumin at selected periods of RT course. miR-5682 allowed us to distinguish between patients classified with both SGA-C and low albumin level from other LC patients with 100% sensitivity and 69.6% specificity (AUC = 0.820; p < 0.0001). Higher expression of studied miRNA was significantly associated with shorter median overall survival (OS) in LC patients (HR = 2.26; p = 0.008). Conclusions: analysis of miR-5682 expression demonstrates a potential clinical utility in selection of LC patients suffering from nutritional deficiencies developing as a consequence of RT-based therapy. Full article

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

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12 pages, 1241 KiB

Open AccessEditor’s ChoiceReview

Genetic Mechanisms Driving Uterine Leiomyoma Pathobiology, Epidemiology, and Treatment

by Malini S. Ramaiyer, Eslam Saad, Irem Kurt and Mostafa A. Borahay

Genes 2024, 15(5), 558; https://doi.org/10.3390/genes15050558 - 27 Apr 2024

Cited by 6 | Viewed by 3852

Abstract

Uterine leiomyomas (ULs) are the most common benign tumor of the uterus. They can be associated with symptoms including abnormal uterine bleeding, pelvic pain, urinary frequency, and pregnancy complications. Despite the high prevalence of UL, its underlying pathophysiology mechanisms have historically been poorly [...] Read more.

Uterine leiomyomas (ULs) are the most common benign tumor of the uterus. They can be associated with symptoms including abnormal uterine bleeding, pelvic pain, urinary frequency, and pregnancy complications. Despite the high prevalence of UL, its underlying pathophysiology mechanisms have historically been poorly understood. Several mechanisms of pathogenesis have been suggested, implicating various genes, growth factors, cytokines, chemokines, and microRNA aberrations. The purpose of this study is to summarize the current research on the relationship of genetics with UL. Specifically, we performed a literature review of published studies to identify how genetic aberrations drive pathophysiology, epidemiology, and therapeutic approaches of UL. With regards to pathophysiology, research has identified MED12 mutations, HMGA2 overexpression, fumarate hydratase deficiency, and cytogenetic abnormalities as contributors to the development of UL. Additionally, epigenetic modifications, such as histone acetylation and DNA methylation, have been identified as contributing to UL tumorigenesis. Specifically, UL stem cells have been found to contain a unique DNA methylation pattern compared to more differentiated UL cells, suggesting that DNA methylation has a role in tumorigenesis. On a population level, genome-wide association studies (GWASs) and epidemiologic analyses have identified 23 genetic loci associated with younger age at menarche and UL growth. Additionally, various GWASs have investigated genetic loci as potential drivers of racial disparities in UL incidence. For example, decreased expression of Cytohesin 4 in African Americans has been associated with increased UL risk. Recent studies have investigated various therapeutic options, including ten-eleven translocation proteins mediating DNA methylation, adenovirus vectors for drug delivery, and “suicide gene therapy” to induce apoptosis. Overall, improved understanding of the genetic and epigenetic drivers of UL on an individual and population level can propel the discovery of novel therapeutic options. Full article

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

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13 pages, 4924 KiB

Open AccessEditor’s ChoiceArticle

Complete Mitochondrial Genome of Four Peristediidae Fish Species: Genome Characterization and Phylogenetic Analysis

by Xianhui Liao, Yijia Shih, Chenghao Jia and Tianxiang Gao

Genes 2024, 15(5), 557; https://doi.org/10.3390/genes15050557 - 27 Apr 2024

Cited by 4 | Viewed by 1817

Abstract

The systematic revision of the family Peristediidae remains an unresolved issue due to their diverse and unique morphology. Despite the popularity of using mitochondrial genome research to comprehensively understand phylogenetic relationships in fish, genetic data for peristediid fish need to be included. Therefore, [...] Read more.

The systematic revision of the family Peristediidae remains an unresolved issue due to their diverse and unique morphology. Despite the popularity of using mitochondrial genome research to comprehensively understand phylogenetic relationships in fish, genetic data for peristediid fish need to be included. Therefore, this study aims to investigate the mitochondrial genomic characteristics and intra-family phylogenetic relationships of Peristediidae by utilizing mitochondrial genome analysis. Therefore, this study aims to investigate the phylogenetic relationship of Peristediidae by utilizing mitochondrial genome analysis. The mitochondrial genome of four species of Peristediidae (Peristedion liorhynchus, Satyrichthys welchi, Satyrichthys rieffeli, and Scalicus amiscus) collected in the East China Sea was studied. The mitochondrial gene sequence lengths of four fish species were 16,533 bp, 16,526 bp, 16,527 bp, and 16,526 bp, respectively. They had the same mitochondrial structure and were all composed of 37 genes and one control region. Most PCGs used ATG as the start codon, and a few used GTG as the start codon. An incomplete stop codon (TA/T) occurred. The AT-skew and GC-skew values of 13 PCGs from four species were negative, and the GC-skew amplitude was greater than that of AT-skew. All cases of D-arm were found in tRNA-Ser (GCT). The Ka/Ks ratio analysis indicated that 13 PCGs were suffering purifying selection. Based on 12 PCGs (excluding ND6) sequences, a phylogenetic tree was constructed using Bayesian inference (BI) and maximum likelihood (ML) methods, providing a further supplement to the scientific classification of Peristediidae fish. According to the results of divergence time, the four species of fish had apparent divergence in the Early Cenozoic, which indicates that the geological events at that time caused the climax of species divergence and evolution. Full article

(This article belongs to the Special Issue DNA Taxonomy, Molecular Phylogeny and Population Genetics of Cartilaginous Fishes and Teleost Fishes)

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10 pages, 1201 KiB

Open AccessEditor’s ChoiceArticle

Optical Genome Mapping as a New Tool to Overcome Conventional Cytogenetics Limitations in Patients with Bone Marrow Failure

by June Iriondo, Ana Gómez, Josune Zubicaray, Jorge Garcia-Martinez, Lorea Abad, Carmen Matesanz, Reyes Giménez, Almudena Galán, Alejandro Sanz, Elena Sebastián, Jesús González de Pablo, Ana de la Cruz, Manuel Ramírez and Julián Sevilla

Genes 2024, 15(5), 559; https://doi.org/10.3390/genes15050559 - 27 Apr 2024

Viewed by 1640

Abstract

Cytogenetic studies are essential in the diagnosis and follow up of patients with bone marrow failure syndromes (BMFSs), but obtaining good quality results is often challenging due to hypocellularity. Optical Genome Mapping (OGM), a novel technology capable of detecting most types chromosomal structural [...] Read more.

Cytogenetic studies are essential in the diagnosis and follow up of patients with bone marrow failure syndromes (BMFSs), but obtaining good quality results is often challenging due to hypocellularity. Optical Genome Mapping (OGM), a novel technology capable of detecting most types chromosomal structural variants (SVs) at high resolution, is being increasingly used in many settings, including hematologic malignancies. Herein, we compared conventional cytogenetic techniques to OGM in 20 patients with diverse BMFSs. Twenty metaphases for the karyotype were only obtained in three subjects (15%), and no SVs were found in any of the samples. One patient with culture failure showed a gain in chromosome 1q by fluorescence in situ hybridization, which was confirmed by OGM. In contrast, OGM provided good quality results in all subjects, and SVs were detected in 14 of them (70%), mostly corresponding to cryptic submicroscopic alterations not observed by standard techniques. Therefore, OGM emerges as a powerful tool that provides complete and evaluable results in hypocellular BMFSs, reducing multiple tests into a single assay and overcoming some of the main limitations of conventional techniques. Furthermore, in addition to confirming the abnormalities detected by conventional techniques, OGM found new alterations beyond their detection limits. Full article

(This article belongs to the Special Issue Rare Neurogenetic Disorders in the Third Millennium: Diagnostic and Therapeutic Challenges)

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22 pages, 5221 KiB

Open AccessEditor’s ChoiceArticle

Exploring the Role of E6 and E7 Oncoproteins in Cervical Oncogenesis through MBD2/3-NuRD Complex Chromatin Remodeling

by Alina Fudulu, Carmen Cristina Diaconu, Iulia Virginia Iancu, Adriana Plesa, Adrian Albulescu, Marinela Bostan, Demetra Gabriela Socolov, Irina Liviana Stoian, Raluca Balan, Gabriela Anton and Anca Botezatu

Genes 2024, 15(5), 560; https://doi.org/10.3390/genes15050560 - 27 Apr 2024

Cited by 3 | Viewed by 2615

Abstract

Background: Cervical cancer is among the highest-ranking types of cancer worldwide, with human papillomavirus (HPV) as the agent driving the malignant process. One aspect of the infection’s evolution is given by epigenetic modifications, mainly DNA methylation and chromatin alteration. These processes are guided [...] Read more.

Background: Cervical cancer is among the highest-ranking types of cancer worldwide, with human papillomavirus (HPV) as the agent driving the malignant process. One aspect of the infection’s evolution is given by epigenetic modifications, mainly DNA methylation and chromatin alteration. These processes are guided by several chromatin remodeling complexes, including NuRD. The purpose of this study was to evaluate the genome-wide binding patterns of the NuRD complex components (MBD2 and MBD3) in the presence of active HPV16 E6 and E7 oncogenes and to determine the potential of identified genes through an experimental model to differentiate between cervical precursor lesions, with the aim of establishing their utility as biomarkers. Methods: The experimental model was built using the CaSki cell line and shRNA for E6 and E7 HPV16 silencing, ChIP-seq, qRT-PCR, and Western blot analyses. Selected genes’ expression was also assessed in patients. Results: Several genes have been identified to exhibit altered transcriptional activity due to the influence of HPV16 E6/E7 viral oncogenes acting through the MBD2/MBD3 NuRD complex, linking them to viral infection and cervical oncogenesis. Conclusions: The impacted genes primarily play roles in governing gene transcription, mRNA processing, and regulation of translation. Understanding these mechanisms offers valuable insights into the process of HPV-induced oncogenesis. Full article

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

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15 pages, 458 KiB

Open AccessEditor’s ChoiceReview

Sarcopenia as a Risk Factor for Alzheimer’s Disease: Genetic and Epigenetic Perspectives

by Stuart M. Raleigh and Kayleigh J. A. Orchard

Genes 2024, 15(5), 561; https://doi.org/10.3390/genes15050561 - 27 Apr 2024

Cited by 4 | Viewed by 2678

Abstract

Sarcopenia, defined as the age-associated loss of muscle mass and increased fragility with age, is increasing worldwide. The condition often precedes the development of Alzheimer’s disease, thereby decreasing the levels of mobility and physical activity in those affected. Indeed, the loss of muscle [...] Read more.

Sarcopenia, defined as the age-associated loss of muscle mass and increased fragility with age, is increasing worldwide. The condition often precedes the development of Alzheimer’s disease, thereby decreasing the levels of mobility and physical activity in those affected. Indeed, the loss of muscle mass has, in some studies, been associated with an increased risk of Alzheimer’s disease and other dementias. However, a detailed understanding of the interplay between both conditions is not available and needs to be thoroughly addressed. In the following review, we focus on several genes, specifically APOE, BDNF, ACE, FTO, and FNDC5, that have been associated with both conditions. We also discuss the epigenetic regulation of each of these genes along with non-coding RNAs (ncRNAs) that may have a role in the development of both the sarcopenic and Alzheimer’s disease phenotypes. Finally, we assert that the application of systems biology will unravel the relationship between sarcopenia and Alzheimer’s disease and believe that the prevention of muscle loss in older age will reduce the incidence of debilitating cognitive decline. Full article

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

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10 pages, 5403 KiB

Open AccessEditor’s ChoiceArticle

Whole-Genome Resequencing Revealed Selective Signatures for Growth Traits in Hu and Gangba Sheep

by Peifu Yang, Mingyu Shang, Jingjing Bao, Tianyi Liu, Jinke Xiong, Jupeng Huang, Jinghua Sun and Li Zhang

Genes 2024, 15(5), 551; https://doi.org/10.3390/genes15050551 - 26 Apr 2024

Cited by 3 | Viewed by 1622

Abstract

A genomic study was conducted to uncover the selection signatures in sheep that show extremely significant differences in growth traits under the same breed, age in months, nutrition level, and management practices. Hu sheep from Gansu Province and Gangba sheep from the Tibet [...] Read more.

A genomic study was conducted to uncover the selection signatures in sheep that show extremely significant differences in growth traits under the same breed, age in months, nutrition level, and management practices. Hu sheep from Gansu Province and Gangba sheep from the Tibet Autonomous Region in China were selected. We collected whole-genome data from 40 sheep individuals (24 Hu sheep and 16 Gangba sheep), through whole-genome sequencing. Selection signals were analyzed using parameters such as F_ST, π _ratio, and Tajima’s D. We have identified several candidate genes that have undergone strong selection, particularly those associated with growth traits. Specifically, five growth-related genes were identified in both the Hu sheep group (HDAC1, MYH7B, LCK, ACVR1, GNAI2) and the Gangba sheep group (RBBP8, ACSL3, FBXW11, PLAT, CRB1). Additionally, in a genomic region strongly selected in both the Hu and Gangba sheep groups (Chr 22: 51,425,001-51,500,000), the growth-associated gene CYP2E1 was identified, further highlighting the genetic factors influencing growth characteristics in these breeds. This study analyzes the genetic basis for significant differences in sheep phenotypes, identifies candidate genes related to sheep growth traits, lays the foundation for molecular genetic breeding in sheep, and accelerates the genetic improvement in livestock. Full article

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

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12 pages, 3039 KiB

Open AccessEditor’s ChoiceArticle

Complete Chloroplast Genome Sequence Structure and Phylogenetic Analysis of Kohlrabi (Brassica oleracea var. gongylodes L.)

by Mengliang Zhao, Yanxun Wu and Yanjing Ren

Genes 2024, 15(5), 550; https://doi.org/10.3390/genes15050550 - 26 Apr 2024

Cited by 2 | Viewed by 1558

Abstract

Kohlrabi is an important swollen-stem cabbage variety belonging to the Brassicaceae family. However, few complete chloroplast genome sequences of this genus have been reported. Here, a complete chloroplast genome with a quadripartite cycle of 153,364 bp was obtained. A total of 132 genes [...] Read more.

Kohlrabi is an important swollen-stem cabbage variety belonging to the Brassicaceae family. However, few complete chloroplast genome sequences of this genus have been reported. Here, a complete chloroplast genome with a quadripartite cycle of 153,364 bp was obtained. A total of 132 genes were identified, including 87 protein-coding genes, 37 transfer RNA genes and eight ribosomal RNA genes. The base composition analysis showed that the overall GC content was 36.36% of the complete chloroplast genome sequence. Relative synonymous codon usage frequency (RSCU) analysis showed that most codons with values greater than 1 ended with A or U, while most codons with values less than 1 ended with C or G. Thirty-five scattered repeats were identified and most of them were distributed in the large single-copy (LSC) region. A total of 290 simple sequence repeats (SSRs) were found and 188 of them were distributed in the LSC region. Phylogenetic relationship analysis showed that five Brassica oleracea subspecies were clustered into one group and the kohlrabi chloroplast genome was closely related to that of B. oleracea var. botrytis. Our results provide a basis for understanding chloroplast-dependent metabolic studies and provide new insight for understanding the polyploidization of Brassicaceae species. Full article

(This article belongs to the Special Issue Plant Plastid Genome and Phylogenetics)

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26 pages, 12138 KiB

Open AccessEditor’s ChoiceArticle

Novel Genome-Engineered H Alleles Differentially Affect Lateral Inhibition and Cell Dichotomy Processes during Bristle Organ Development

by Tanja C. Mönch, Thomas K. Smylla, Franziska Brändle, Anette Preiss and Anja C. Nagel

Genes 2024, 15(5), 552; https://doi.org/10.3390/genes15050552 - 26 Apr 2024

Viewed by 1847

Abstract

Hairless (H) encodes the major antagonist in the Notch signaling pathway, which governs cellular differentiation of various tissues in Drosophila. By binding to the Notch signal transducer Suppressor of Hairless (Su(H)), H assembles repressor complexes onto Notch target genes. Using genome engineering, [...] Read more.

Hairless (H) encodes the major antagonist in the Notch signaling pathway, which governs cellular differentiation of various tissues in Drosophila. By binding to the Notch signal transducer Suppressor of Hairless (Su(H)), H assembles repressor complexes onto Notch target genes. Using genome engineering, three new H alleles, H^FA, H^LLAA and H^WA were generated and a phenotypic series was established by several parameters, reflecting the residual H-Su(H) binding capacity. Occasionally, homozygous H^WA flies develop to adulthood. They were compared with the likewise semi-viable H^NN allele affecting H-Su(H) nuclear entry. The H homozygotes were short-lived, sterile and flightless, yet showed largely normal expression of several mitochondrial genes. Typical for H mutants, both H^WA and H^NN homozygous alleles displayed strong defects in wing venation and mechano-sensory bristle development. Strikingly, however, H^WA displayed only a loss of bristles, whereas bristle organs of H^NN flies showed a complete shaft-to-socket transformation. Apparently, the impact of H^WA is restricted to lateral inhibition, whereas that of H^NN also affects the respective cell type specification. Notably, reduction in Su(H) gene dosage only suppressed the H^NN bristle phenotype, but amplified that of H^WA. We interpret these differences as to the role of H regarding Su(H) stability and availability. Full article

(This article belongs to the Special Issue Gene Editing in Drosophila to Study Gene Function and Developmental Processes)

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12 pages, 753 KiB

Open AccessEditor’s ChoiceReview

Exploring the Role of Cell-Free Nucleic Acids and Peritoneal Dialysis: A Narrative Review

by Niccolò Morisi, Grazia Maria Virzì, Marco Ferrarini, Gaetano Alfano, Monica Zanella, Claudio Ronco and Gabriele Donati

Genes 2024, 15(5), 553; https://doi.org/10.3390/genes15050553 - 26 Apr 2024

Cited by 3 | Viewed by 2045

Abstract

Introduction: Cell-free nucleic acids (cf-NAs) represent a promising biomarker of various pathological and physiological conditions. Since its discovery in 1948, cf-NAs gained prognostic value in oncology, immunology, and other relevant fields. In peritoneal dialysis (PD), blood purification is performed by exposing the peritoneal [...] Read more.

Introduction: Cell-free nucleic acids (cf-NAs) represent a promising biomarker of various pathological and physiological conditions. Since its discovery in 1948, cf-NAs gained prognostic value in oncology, immunology, and other relevant fields. In peritoneal dialysis (PD), blood purification is performed by exposing the peritoneal membrane. Relevant sections: Complications of PD such as acute peritonitis and peritoneal membrane aging are often critical in PD patient management. In this review, we focused on bacterial DNA, cell-free DNA, mitochondrial DNA (mtDNA), microRNA (miRNA), and their potential uses as biomarkers for monitoring PD and its complications. For instance, the isolation of bacterial DNA in early acute peritonitis allows bacterial identification and subsequent therapy implementation. Cell-free DNA in peritoneal dialysis effluent (PDE) represents a marker of stress of the peritoneal membrane in both acute and chronic PD complications. Moreover, miRNA are promising hallmarks of peritoneal membrane remodeling and aging, even before its manifestation. In this scenario, with multiple cytokines involved, mtDNA could be considered equally meaningful to determine tissue inflammation. Conclusions: This review explores the relevance of cf-NAs in PD, demonstrating its promising role for both diagnosis and treatment. Further studies are necessary to implement the use of cf-NAs in PD clinical practice. Full article

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

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11 pages, 1622 KiB

Open AccessEditor’s ChoiceArticle

Exploring the Role of the MUTYH Gene in Breast, Ovarian and Endometrial Cancer

by Carla Lintas, Benedetta Canalis, Alessia Azzarà, Giovanna Sabarese, Giuseppe Perrone and Fiorella Gurrieri

Genes 2024, 15(5), 554; https://doi.org/10.3390/genes15050554 - 26 Apr 2024

Cited by 4 | Viewed by 3104

Abstract

Background: MUTYH germline monoallelic variants have been detected in a number of patients affected by breast/ovarian cancer or endometrial cancer, suggesting a potential susceptibility role, though their significance remains elusive since the disease mechanism is normally recessive. Hence, the aim of this research [...] Read more.

Background: MUTYH germline monoallelic variants have been detected in a number of patients affected by breast/ovarian cancer or endometrial cancer, suggesting a potential susceptibility role, though their significance remains elusive since the disease mechanism is normally recessive. Hence, the aim of this research was to explore the hypothesis that a second hit could have arisen in the other allele in the tumor tissue. Methods: we used Sanger sequencing and immunohistochemistry to search for a second MUTYH variant in the tumoral DNA and to assess protein expression, respectively. Results: we detected one variant of unknown significance, one variant with conflicting interpretation of pathogenicity and three benign/likely benign variants; the MUTYH protein was not detected in the tumor tissue of half of the patients, and in others, its expression was reduced. Conclusions: our results fail to demonstrate that germinal monoallelic MUTYH variants increase cancer risk through a LOH (loss of heterozygosity) mechanism in the somatic tissue; however, the absence or partial loss of the MUTYH protein in many tumors suggests its dysregulation regardless of MUTYH genetic status. Full article

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

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15 pages, 41162 KiB

Open AccessEditor’s ChoiceArticle

GhCLCc-1, a Chloride Channel Gene from Upland Cotton, Positively Regulates Salt Tolerance by Modulating the Accumulation of Chloride Ions

by Wenhao Li, Siqi Gao, Yinghao Zhao, Yuchen Wu, Xiaona Li, Jianing Li, Wei Zhu, Zongbin Ma and Wei Liu

Genes 2024, 15(5), 555; https://doi.org/10.3390/genes15050555 - 26 Apr 2024

Cited by 4 | Viewed by 1405

Abstract

The ionic toxicity induced by salinization has adverse effects on the growth and development of crops. However, researches on ionic toxicity and salt tolerance in plants have focused primarily on cations such as sodium ions (Na⁺), with very limited studies on [...] Read more.

The ionic toxicity induced by salinization has adverse effects on the growth and development of crops. However, researches on ionic toxicity and salt tolerance in plants have focused primarily on cations such as sodium ions (Na⁺), with very limited studies on chloride ions (Cl⁻). Here, we cloned the homologous genes of Arabidopsis thaliana AtCLCc, GhCLCc-1A/D, from upland cotton (Gossypium hirsutum), which were significantly induced by NaCl or KCl treatments. Subcellular localization showed that GhCLCc-1A/D were both localized to the tonoplast. Complementation of Arabidopsis atclcc mutant with GhCLCc-1 rescued its salt-sensitive phenotype. In addition, the silencing of the GhCLCc-1 gene led to an increased accumulation of Cl⁻ in the roots, stems, and leaves of cotton seedlings under salt treatments, resulting in compromised salt tolerance. And ectopic expression of the GhCLCc-1 gene in Arabidopsis reduced the accumulation of Cl⁻ in transgenic lines under salt treatments, thereby enhancing salt tolerance. These findings elucidate that GhCLCc-1 positively regulates salt tolerance by modulating Cl⁻ accumulation and could be a potential target gene for improving salt tolerance in plants. Full article

(This article belongs to the Special Issue Cotton Genes, Genetics, and Genomics)

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18 pages, 719 KiB

Open AccessEditor’s ChoiceReview

Colorectal Cancer: Genetic Underpinning and Molecular Therapeutics for Precision Medicine

by Gideon T. Dosunmu and Ardaman Shergill

Genes 2024, 15(5), 538; https://doi.org/10.3390/genes15050538 - 25 Apr 2024

Cited by 4 | Viewed by 3221

Abstract

Colorectal cancer (CRC) accounts for about 10% of all cancer cases and 9% of cancer-related deaths globally. In the United States alone, CRC represents approximately 12.6% of all cancer cases, with a mortality rate of about 8%. CRC is now the first leading [...] Read more.

Colorectal cancer (CRC) accounts for about 10% of all cancer cases and 9% of cancer-related deaths globally. In the United States alone, CRC represents approximately 12.6% of all cancer cases, with a mortality rate of about 8%. CRC is now the first leading cause of cancer death in men younger than age 50 and second in women younger than age 50. This review delves into the genetic landscape of CRC, highlighting key mutations and their implications in disease progression and treatment. We provide an overview of the current and emerging therapeutic strategies tailored to individual genomic profiles. Full article

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

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22 pages, 1376 KiB

Open AccessEditor’s ChoiceReview

Oxidative Stress Biomarkers in Male Infertility: Established Methodologies and Future Perspectives

by Filomena Mottola, Ilaria Palmieri, Maria Carannante, Angela Barretta, Shubhadeep Roychoudhury and Lucia Rocco

Genes 2024, 15(5), 539; https://doi.org/10.3390/genes15050539 - 25 Apr 2024

Cited by 8 | Viewed by 2619

Abstract

Male fertility can be affected by oxidative stress (OS), which occurs when an imbalance between the production of reactive oxygen species (ROS) and the body’s ability to neutralize them arises. OS can damage cells and influence sperm production. High levels of lipid peroxidation [...] Read more.

Male fertility can be affected by oxidative stress (OS), which occurs when an imbalance between the production of reactive oxygen species (ROS) and the body’s ability to neutralize them arises. OS can damage cells and influence sperm production. High levels of lipid peroxidation have been linked to reduced sperm motility and decreased fertilization ability. This literature review discusses the most commonly used biomarkers to measure sperm damage caused by ROS, such as the high level of OS in seminal plasma as an indicator of imbalance in antioxidant activity. The investigated biomarkers include 8-hydroxy-2-deoxyguanosine acid (8-OHdG), a marker of DNA damage caused by ROS, and F2 isoprostanoids (8-isoprostanes) produced by lipid peroxidation. Furthermore, this review focuses on recent methodologies including the NGS polymorphisms and differentially expressed gene (DEG) analysis, as well as the epigenetic mechanisms linked to ROS during spermatogenesis along with new methodologies developed to evaluate OS biomarkers. Finally, this review addresses a valuable insight into the mechanisms of male infertility provided by these advances and how they have led to new treatment possibilities. Overall, the use of biomarkers to evaluate OS in male infertility has supplied innovative diagnostic and therapeutic approaches, enhancing our understanding of male infertility mechanisms. Full article

(This article belongs to the Section Cytogenomics)

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14 pages, 4377 KiB

Open AccessEditor’s ChoiceArticle

The Satellite DNA PcH-Sat, Isolated and Characterized in the Limpet Patella caerulea (Mollusca, Gastropoda), Suggests the Origin from a Nin-SINE Transposable Element

by Agnese Petraccioli, Nicola Maio, Rosa Carotenuto, Gaetano Odierna and Fabio Maria Guarino

Genes 2024, 15(5), 541; https://doi.org/10.3390/genes15050541 - 25 Apr 2024

Viewed by 1286

Abstract

Satellite DNA (sat-DNA) was previously described as junk and selfish DNA in the cellular economy, without a clear functional role. However, during the last two decades, evidence has been accumulated about the roles of sat-DNA in different cellular functions and its probable involvement [...] Read more.

Satellite DNA (sat-DNA) was previously described as junk and selfish DNA in the cellular economy, without a clear functional role. However, during the last two decades, evidence has been accumulated about the roles of sat-DNA in different cellular functions and its probable involvement in tumorigenesis and adaptation to environmental changes. In molluscs, studies on sat-DNAs have been performed mainly on bivalve species, especially those of economic interest. Conversely, in Gastropoda (which includes about 80% of the currently described molluscs species), studies on sat-DNA have been largely neglected. In this study, we isolated and characterized a sat-DNA, here named PcH-sat, in the limpet Patella caerulea using the restriction enzyme method, particularly HaeIII. Monomeric units of PcH-sat are 179 bp long, AT-rich (58.7%), and with an identity among monomers ranging from 91.6 to 99.8%. Southern blot showed that PcH-sat is conserved in P. depressa and P. ulyssiponensis, while a smeared signal of hybridization was present in the other three investigated limpets (P. ferruginea, P. rustica and P. vulgata). Dot blot showed that PcH-sat represents about 10% of the genome of P. caerulea, 5% of that of P. depressa, and 0.3% of that of P. ulyssiponensis. FISH showed that PcH-sat was mainly localized on pericentromeric regions of chromosome pairs 2 and 4–7 of P. caerulea (2n = 18). A database search showed that PcH-sat contains a large segment (of 118 bp) showing high identity with a homologous trait of the Nin-SINE transposable element (TE) of the patellogastropod Lottia gigantea, supporting the hypothesis that TEs are involved in the rising and tandemization processes of sat-DNAs. Full article

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

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13 pages, 4076 KiB

Open AccessEditor’s ChoiceArticle

Characterization of the Apoptotic and Antimicrobial Activities of Two Initiator Caspases of Sea Cucumber Apostichopus japonicus

by Hanshuo Zhu, Zihao Yuan, Hang Xu and Li Sun

Genes 2024, 15(5), 540; https://doi.org/10.3390/genes15050540 - 25 Apr 2024

Viewed by 1477

Abstract

Caspase (CASP) is a protease family that plays a vital role in apoptosis, development, and immune response. Herein, we reported the identification and characterization of two CASPs, AjCASPX1 and AjCASPX2, from the sea cucumber Apostichopus japonicus, an important aquaculture species. AjCASPX1/2 share [...] Read more.

Caspase (CASP) is a protease family that plays a vital role in apoptosis, development, and immune response. Herein, we reported the identification and characterization of two CASPs, AjCASPX1 and AjCASPX2, from the sea cucumber Apostichopus japonicus, an important aquaculture species. AjCASPX1/2 share similar domain organizations with the vertebrate initiator caspases CASP2/9, including the CARD domain and the p20/p10 subunits with conserved functional motifs. However, compared with human CASP2/9, AjCASPX1/2 possess unique structural features in the linker region between p20 and p10. AjCASPX1, but not AjCASPX2, induced marked apoptosis of human cells by activating CASP3/7. The recombinant proteins of AjCASPX2 and the CARD domain of AjCASPX2 were able to bind to a wide range of bacteria, as well as bacterial cell wall components, and inhibit bacterial growth. AjCASPX1, when expressed in Escherichia coli, was able to kill the host bacteria. Under normal conditions, AjCASPX1 and AjCASPX2 expressions were most abundant in sea cucumber muscle and coelomocytes, respectively. After bacterial infection, both AjCASPX1 and AjCASPX2 expressions were significantly upregulated in sea cucumber tissues and cells. Together, these results indicated that AjCASPX1 and AjCASPX2 were initiator caspases with antimicrobial activity and likely functioned in apoptosis and immune defense against pathogen infection. Full article

(This article belongs to the Special Issue Genetics and Genomics in Aquatic Animals)

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13 pages, 2302 KiB

Open AccessEditor’s ChoiceArticle

Downregulation of Histone H3.3 Induces p53-Dependent Cellular Senescence in Human Diploid Fibroblasts

by Yuki Yamamoto, Ryou-u Takahashi, Masaki Kinehara, Kimiyoshi Yano, Tatsuya Kuramoto, Akira Shimamoto and Hidetoshi Tahara

Genes 2024, 15(5), 543; https://doi.org/10.3390/genes15050543 - 25 Apr 2024

Viewed by 1830

Abstract

Cellular senescence is an irreversible growth arrest that acts as a barrier to cancer initiation and progression. Histone alteration is one of the major events during replicative senescence. However, little is known about the function of H3.3 in cellular senescence. Here we found [...] Read more.

Cellular senescence is an irreversible growth arrest that acts as a barrier to cancer initiation and progression. Histone alteration is one of the major events during replicative senescence. However, little is known about the function of H3.3 in cellular senescence. Here we found that the downregulation of H3.3 induced growth suppression with senescence-like phenotypes such as senescence-associated heterochromatin foci (SAHF) and β-galactosidase (SA-β-gal) activity. Furthermore, H3.3 depletion induced senescence-like phenotypes with the p53/p21-depedent pathway. In addition, we identified miR-22-3p, tumor suppressive miRNA, as an upstream regulator of the H3F3B (H3 histone, family 3B) gene which is the histone variant H3.3 and replaces conventional H3 in active genes. Therefore, our results reveal for the first time the molecular mechanisms for cellular senescence which are regulated by H3.3 abundance. Taken together, our studies suggest that H3.3 exerts functional roles in regulating cellular senescence and is a promising target for cancer therapy. Full article

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

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22 pages, 5511 KiB

Open AccessEditor’s ChoiceArticle

Complete Chloroplast Genome of Alternanthera sessilis and Comparative Analysis with Its Congeneric Invasive Weed Alternanthera philoxeroides

by Yuanxin Wang, Xueying Zhao, Qianhui Chen, Jun Yang, Jun Hu, Dong Jia and Ruiyan Ma

Genes 2024, 15(5), 544; https://doi.org/10.3390/genes15050544 - 25 Apr 2024

Cited by 1 | Viewed by 1646

Abstract

Alternanthera sessilis is considered the closest relative to the invasive weed Alternanthera philoxeroides in China, making it an important native species for studying the invasive mechanisms and adaptations of A. philoxeroides. Chloroplasts play a crucial role in a plant’s environmental adaptation, with [...] Read more.

Alternanthera sessilis is considered the closest relative to the invasive weed Alternanthera philoxeroides in China, making it an important native species for studying the invasive mechanisms and adaptations of A. philoxeroides. Chloroplasts play a crucial role in a plant’s environmental adaptation, with their genomes being pivotal in the evolution and adaptation of both invasive and related species. However, the chloroplast genome of A. sessilis has remained unknown until now. In this study, we sequenced and assembled the complete chloroplast genome of A. sessilis using high-throughput sequencing. The A. sessilis chloroplast genome is 151,935 base pairs long, comprising two inverted repeat regions, a large single copy region, and a small single copy region. This chloroplast genome contains 128 genes, including 8 rRNA-coding genes, 37 tRNA-coding genes, 4 pseudogenes, and 83 protein-coding genes. When compared to the chloroplast genome of the invasive weed A. philoxeroides and other Amaranthaceae species, we observed significant variations in the ccsA, ycf1, and ycf2 regions in the A. sessilis chloroplast genome. Moreover, two genes, ccsA and accD, were found to be undergoing rapid evolution due to positive selection pressure. The phylogenetic trees were constructed for the Amaranthaceae family, estimating the time of independent species formation between A. philoxeroides and A. sessilis to be approximately 3.5186–8.8242 million years ago. These findings provide a foundation for understanding the population variation within invasive species among the Alternanthera genus. Full article

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

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14 pages, 3682 KiB

Open AccessEditor’s ChoiceArticle

Integrated Analysis of Transcriptome and Metabolome Reveals Differential Responses to Alternaria brassicicola Infection in Cabbage (Brassica oleracea var. capitata)

by Jinzhou Lei, Wei Zhang, Fangwei Yu, Meng Ni, Zhigang Liu, Cheng Wang, Jianbin Li, Jianghua Song and Shenyun Wang

Genes 2024, 15(5), 545; https://doi.org/10.3390/genes15050545 - 25 Apr 2024

Viewed by 1716

Abstract

Black spot, caused by Alternaria brassicicola (Ab), poses a serious threat to crucifer production, and knowledge of how plants respond to Ab infection is essential for black spot management. In the current study, combined transcriptomic and metabolic analysis was employed to [...] Read more.

Black spot, caused by Alternaria brassicicola (Ab), poses a serious threat to crucifer production, and knowledge of how plants respond to Ab infection is essential for black spot management. In the current study, combined transcriptomic and metabolic analysis was employed to investigate the response to Ab infection in two cabbage (Brassica oleracea var. capitata) genotypes, Bo257 (resistant to Ab) and Bo190 (susceptible to Ab). A total of 1100 and 7490 differentially expressed genes were identified in Bo257 (R_mock vs. R_Ab) and Bo190 (S_mock vs. S_Ab), respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that “metabolic pathways”, “biosynthesis of secondary metabolites”, and “glucosinolate biosynthesis” were the top three enriched KEGG pathways in Bo257, while “metabolic pathways”, “biosynthesis of secondary metabolites”, and “carbon metabolism” were the top three enriched KEGG pathways in Bo190. Further analysis showed that genes involved in extracellular reactive oxygen species (ROS) production, jasmonic acid signaling pathway, and indolic glucosinolate biosynthesis pathway were differentially expressed in response to Ab infection. Notably, when infected with Ab, genes involved in extracellular ROS production were largely unchanged in Bo257, whereas most of these genes were upregulated in Bo190. Metabolic profiling revealed 24 and 56 differentially accumulated metabolites in Bo257 and Bo190, respectively, with the majority being primary metabolites. Further analysis revealed that dramatic accumulation of succinate was observed in Bo257 and Bo190, which may provide energy for resistance responses against Ab infection via the tricarboxylic acid cycle pathway. Collectively, this study provides comprehensive insights into the Ab–cabbage interactions and helps uncover targets for breeding Ab-resistant varieties in cabbage. Full article

(This article belongs to the Special Issue Vegetable Genetic Breeding)

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17 pages, 1780 KiB

Open AccessEditor’s ChoiceArticle

Statistical Genetic Approaches to Investigate Genotype-by-Environment Interaction: Review and Novel Extension of Models

by Vincent P. Diego, Eron G. Manusov, Marcio Almeida, Sandra Laston, David Ortiz, John Blangero and Sarah Williams-Blangero

Genes 2024, 15(5), 547; https://doi.org/10.3390/genes15050547 - 25 Apr 2024

Cited by 3 | Viewed by 2064

Abstract

Statistical genetic models of genotype-by-environment (G×E) interaction can be divided into two general classes, one on G×E interaction in response to dichotomous environments (e.g., sex, disease-affection status, or presence/absence of an exposure) and the other in response to continuous environments (e.g., physical activity, [...] Read more.

Statistical genetic models of genotype-by-environment (G×E) interaction can be divided into two general classes, one on G×E interaction in response to dichotomous environments (e.g., sex, disease-affection status, or presence/absence of an exposure) and the other in response to continuous environments (e.g., physical activity, nutritional measurements, or continuous socioeconomic measures). Here we develop a novel model to jointly account for dichotomous and continuous environments. We develop the model in terms of a joint genotype-by-sex (for the dichotomous environment) and genotype-by-social determinants of health (SDoH; for the continuous environment). Using this model, we show how a depression variable, as measured by the Beck Depression Inventory-II survey instrument, is not only underlain by genetic effects (as has been reported elsewhere) but is also significantly determined by joint G×Sex and G×SDoH interaction effects. This model has numerous applications leading to potentially transformative research on the genetic and environmental determinants underlying complex diseases. Full article

(This article belongs to the Special Issue Statistical Genetics of Human Complex Traits)

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14 pages, 3089 KiB

Open AccessEditor’s ChoiceArticle

Non-Specific Epileptic Activity, EEG, and Brain Imaging in Loss of Function Variants in SATB1: A New Case Report and Review of the Literature

by Flavia Privitera, Stefano Pagano, Camilla Meossi, Roberta Battini, Emanuele Bartolini, Domenico Montanaro and Filippo Maria Santorelli

Genes 2024, 15(5), 548; https://doi.org/10.3390/genes15050548 - 25 Apr 2024

Viewed by 1440

Abstract

SATB1 (MIM #602075) is a relatively new gene reported only in recent years in association with neurodevelopmental disorders characterized by variable facial dysmorphisms, global developmental delay, poor or absent speech, altered electroencephalogram (EEG), and brain abnormalities on imaging. To date about thirty variants [...] Read more.

SATB1 (MIM #602075) is a relatively new gene reported only in recent years in association with neurodevelopmental disorders characterized by variable facial dysmorphisms, global developmental delay, poor or absent speech, altered electroencephalogram (EEG), and brain abnormalities on imaging. To date about thirty variants in forty-four patients/children have been described, with a heterogeneous spectrum of clinical manifestations. In the present study, we describe a new patient affected by mild intellectual disability, speech disorder, and non-specific abnormalities on EEG and neuroimaging. Family studies identified a new de novo frameshift variant c.1818delG (p.(Gln606Hisfs*101)) in SATB1. To better define genotype–phenotype associations in the different types of reported SATB1 variants, we reviewed clinical data from our patient and from the literature and compared manifestations (epileptic activity, EEG abnormalities and abnormal brain imaging) due to missense variants versus those attributable to loss-of-function/premature termination variants. Our analyses showed that the latter variants are associated with less severe, non-specific clinical features when compared with the more severe phenotypes due to missense variants. These findings provide new insights into SATB1-related disorders. Full article

(This article belongs to the Section Genetic Diagnosis)

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8 pages, 1483 KiB

Open AccessEditor’s ChoiceCase Report

Mutations in NSUN3, a Mitochondrial Methyl Transferase Gene, Cause Inherited Optic Neuropathy

by Cansu de Muijnck, Jacoline B. ten Brink, Hugoline G. de Haan, Richard J. Rodenburg, Nicole I. Wolf, Arthur A. Bergen, Camiel J. F. Boon and Maria M. van Genderen

Genes 2024, 15(5), 530; https://doi.org/10.3390/genes15050530 - 24 Apr 2024

Cited by 4 | Viewed by 1895

Abstract

Inherited optic neuropathies (IONs) are rare genetic diseases characterized by progressive visual loss due the atrophy of optic nerves. The standard diagnostic workup involving next-generation sequencing panels has a diagnostic yield of about forty percent. In the other 60% of the patients with [...] Read more.

Inherited optic neuropathies (IONs) are rare genetic diseases characterized by progressive visual loss due the atrophy of optic nerves. The standard diagnostic workup involving next-generation sequencing panels has a diagnostic yield of about forty percent. In the other 60% of the patients with a clinical diagnosis of ION, the underlying genetic variants remain unknown. In this case study, we describe a potentially new disease-associated gene, NSUN3, for IONs. The proband was a young woman with consanguineous parents. She presented with bilateral optic atrophy and nystagmus at the age of seven years. Genetic testing revealed the homozygous variant c.349_352dup p.(Ala118Glufs*45) in NSUN3, with a segregation in the family compatible with autosomal recessive inheritance. Additional functional analysis showed decreased NSUN3 mRNA levels, slightly diminished mitochondrial complex IV levels, and decreased cell respiration rates in patient fibroblasts compared to healthy controls. In conclusion, pathogenic variants in NSUN3 can cause optic neuropathy. Trio whole-exome sequencing should be considered as a diagnostic strategy in ION cases where standard diagnostic analysis does not reveal disease-causing variants. Full article

(This article belongs to the Section Neurogenomics)

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12 pages, 2663 KiB

Open AccessEditor’s ChoiceArticle

Preliminary Study on the Pathogenic Mechanism of Jujube Flower Disease in Honeybees (Apis mellifera ligustica) Based on Midgut Transcriptomics

by Yali Du, Kai Xu, Huiting Zhao, Ying Wu, Haibin Jiang, Jinming He and Yusuo Jiang

Genes 2024, 15(5), 533; https://doi.org/10.3390/genes15050533 - 24 Apr 2024

Cited by 1 | Viewed by 1239

Abstract

Honeybees are prone to poisoning, also known as jujube flower disease, after collecting nectar from jujube flowers, resulting in the tumultuous demise of foragers. The prevalence of jujube flower disease has become one of the main factors affecting the development of the jujube [...] Read more.

Honeybees are prone to poisoning, also known as jujube flower disease, after collecting nectar from jujube flowers, resulting in the tumultuous demise of foragers. The prevalence of jujube flower disease has become one of the main factors affecting the development of the jujube and beekeeping industries in Northern China. However, the pathogenic mechanisms underlying jujube flower disease in honeybees are poorly understood. Herein, we first conducted morphological observations of the midgut using HE-staining and found that jujube flower disease-affected honeybees displayed midgut damage with peritrophic membrane detachment. Jujube flower disease was found to increase the activity of chitinase and carboxylesterase (CarE) and decrease the activity of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and the content of CYP450 in the honeybee midgut. Transcriptomic data identified 119 differentially expressed genes in the midgut of diseased and healthy honeybees, including CYP6a13, CYP6a17, CYP304a1, CYP6a14, AADC, and AGXT2, which are associated with oxidoreductase activity and vitamin binding. In summary, collecting jujube flower nectar could reduce antioxidant and detoxification capacities of the honeybee midgut and, in more severe cases, damage the intestinal structure, suggesting that intestinal damage might be the main cause of honeybee death due to jujube nectar. This study provides new insights into the pathogenesis of jujube flower disease in honeybees. Full article

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

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15 pages, 7025 KiB

Open AccessEditor’s ChoiceArticle

Population Genomics of Commercial Fish Sebastes schlegelii of the Bohai and Yellow Seas (China) Using a Large SNP Panel from GBS

by Beiyan Zhu, Tianxiang Gao, Yan He, Yinquan Qu and Xiumei Zhang

Genes 2024, 15(5), 534; https://doi.org/10.3390/genes15050534 - 24 Apr 2024

Cited by 1 | Viewed by 1529

Abstract

Sebastes schlegelii is one of the most commercially important marine fish in the northwestern Pacific. However, little information about the genome-wide genetic characteristics is available for S. schlegelii individuals from the Bohai and Yellow Seas. In this study, a total of 157,778, 174,480, [...] Read more.

Sebastes schlegelii is one of the most commercially important marine fish in the northwestern Pacific. However, little information about the genome-wide genetic characteristics is available for S. schlegelii individuals from the Bohai and Yellow Seas. In this study, a total of 157,778, 174,480, and 188,756 single-nucleotide polymorphisms from Dalian (DL), Yantai (YT), and Qingdao (QD) coastal waters of China were, respectively, identified. Sixty samples (twenty samples per population) were clustered together, indicating shallow structures and close relationships with each other. The observed heterozygosity, expected heterozygosity, polymorphism information content, and nucleotide diversity ranged from 0.14316 to 0.17684, from 0.14035 to 0.17145, from 0.20672 to 0.24678, and from 7.63 × 10⁻⁶ to 8.77 × 10⁻⁶, respectively, indicating the slight difference in genetic diversity among S. schlegelii populations, and their general genetic diversity was lower compared to other marine fishes. The population divergence showed relatively low levels (from 0.01356 to 0.01678) between S. schlegelii populations. Dispersing along drifting seaweeds, as well as the ocean current that flows along the western and northern coasts of the Yellow Sea and southward along the eastern coast of China might be the major reasons for the weak genetic differentiation. These results form the basis of the population genetic characteristics of S. schlegelii based on GBS (Genotyping by Sequencing). In addition to basic population genetic information, our results provid a theoretical basis for further studies aimed at protecting and utilizing S. schlegelii resources. Full article

(This article belongs to the Special Issue DNA Taxonomy, Molecular Phylogeny and Population Genetics of Cartilaginous Fishes and Teleost Fishes)

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8 pages, 547 KiB

Open AccessEditor’s ChoiceBrief Report

Preservation of 5-Hydroxymethylcytosine Levels in LRIG1 across Genomic DNA and Cell-Free DNA in Glioma Patients

by Daša Jevšinek Skok, Luka Bolha and Nina Hauptman

Genes 2024, 15(5), 535; https://doi.org/10.3390/genes15050535 - 24 Apr 2024

Viewed by 1373

Abstract

Cell-free DNA (cfDNA) has recently emerged as a promising minimally invasive diagnostic biomarker for various cancers. In this study, our aim was to identify cfDNA biomarkers by investigating genes that displayed significant differences between glioma patients and their corresponding controls. To accomplish this, [...] Read more.

Cell-free DNA (cfDNA) has recently emerged as a promising minimally invasive diagnostic biomarker for various cancers. In this study, our aim was to identify cfDNA biomarkers by investigating genes that displayed significant differences between glioma patients and their corresponding controls. To accomplish this, we utilized publicly available data from the Gene Expression Omnibus, focusing on 5-hydroxymethylcytosine (5hmC) profiles in both cfDNA and genomic DNA (gDNA) from glioma patients and healthy individuals. The intersection of gene lists derived from these comparative analyses unveiled LRIG1 and ZNF703 as the two genes with elevated 5hmC levels in both the cfDNA of glioma patients and gDNA of glioma tissue compared to their respective controls. The gene expression data revealed both genes were upregulated in glioma tissue compared to normal brain tissue. Integration of 5hmC data revealed a strong positive correlation in the glioma tissue group between 5hmC and the gene expression of the LRIG1 gene. Furthermore, exploration using the AmiCa web tool indicated that LRIG1 gene expression was elevated compared to 17 other cancers included in the database, emphasizing its potential as a distinctive biomarker across multiple cancer types. Full article

(This article belongs to the Special Issue Genomic Diagnosis of Human Cancers)

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15 pages, 3590 KiB

Open AccessEditor’s ChoiceCase Report

Characterization of a New Variant in ARHGAP31 Probably Involved in Adams–Oliver Syndrome in a Family with a Variable Phenotypic Spectrum

by Carlo Santaniello, Alice Faversani, Luigi Corsaro, Giulia Melloni, Silvia Motta, Elena Mandorino, Davide Sacco, Sabine Stioui, Fulvio Ferrara, Davide Barteselli, Dario De Vita, Debora Manuelli and Lucy Costantino

Genes 2024, 15(5), 536; https://doi.org/10.3390/genes15050536 - 24 Apr 2024

Viewed by 1694

Abstract

Adams–Oliver syndrome is a rare inherited condition characterized by scalp defects and limb abnormalities. It is caused by variants in different genes such as ARHGAP31. Here, we used an interdisciplinary approach to study a family with lower limb anomalies. We identified a [...] Read more.

Adams–Oliver syndrome is a rare inherited condition characterized by scalp defects and limb abnormalities. It is caused by variants in different genes such as ARHGAP31. Here, we used an interdisciplinary approach to study a family with lower limb anomalies. We identified a novel variant in the ARHGAP31 gene that is predicted to result in a truncated protein with a constitutively activated catalytic site due to the loss of 688 amino acids involved in the C-terminal domain, essential for protein auto-inhibition. Pathogenic variants in ARHGAP31 exon 12, leading to a premature protein termination, are associated with Adams–Oliver syndrome. Bioinformatic analysis was useful to elucidate the impact of the identified genetic variant on protein structure. To better understand the impact of the identified variant, 3D protein models were predicted for the ARHGAP31 wild type, the newly discovered variant, and other pathogenetic alterations already reported. Our study identified a novel variant probably involved in Adams–Oliver syndrome and increased the evidence on the phenotypic variability in patients affected by this syndrome, underlining the importance of translational research, including experimental and bioinformatics analyses. This strategy represents a successful model to investigate molecular mechanisms involved in syndrome occurrence. Full article

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

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7 pages, 1040 KiB

Open AccessEditor’s ChoiceBrief Report

CD44 Expression in Clear Cell Renal Cell Carcinoma (ccRCC) Correlates with Tumor Grade and Patient Survival and Is Affected by Gene Methylation

by Anastasios D. Papanastasiou, Stavros Peroukidis, Chaido Sirinian, Elisavet Arkoumani, Dimitrios Chaniotis and Adamantia Zizi-Sermpetzoglou

Genes 2024, 15(5), 537; https://doi.org/10.3390/genes15050537 - 24 Apr 2024

Cited by 3 | Viewed by 1740

Abstract

Clear cell RCC (ccRCC) represents the most common type of kidney cancer, with surgery being the only potential curative treatment. Almost one-third of ccRCC patients relapse either locally or as cases of distant metastases. Several biomarkers have been employed in order to separate [...] Read more.

Clear cell RCC (ccRCC) represents the most common type of kidney cancer, with surgery being the only potential curative treatment. Almost one-third of ccRCC patients relapse either locally or as cases of distant metastases. Several biomarkers have been employed in order to separate ccRCC patients with better prognosis or to predict treatment outcomes, with limited results. CD44 is a membrane glycoprotein with multiple roles in normal development but also cancer. Recently, the CD44 standard isoform has been implicated in tumor progression and the metastasis cascade through microenvironment interactions. Here, through CD44 immunohistochemical staining of ccRCC patient samples and TCGA data analysis, we sought to elucidate the expression patterns (mRNA and protein) of CD44 in clear cell RCC and correlate its expression with clinicopathological parameters. We were able to show that CD44 expression presents a positive association with tumor grade and overall survival, predicting a worse patient outcome in ccRCC. In addition, our data indicate that the CD44 mRNA upregulation can be attributed to reduced gene methylation, implicating epigenetic gene regulation in ccRCC development and progression. Full article

(This article belongs to the Special Issue Genetic Markers and Liquid Biopsy for Kidney Diseases)

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8 pages, 1764 KiB

Open AccessEditor’s ChoiceCase Report

A TMEM63A Nonsense Heterozygous Variant Linked to Infantile Transient Hypomyelinating Leukodystrophy Type 19?

by Dimitra Siori, Dimitrios Vlachakis, Periklis Makrythanasis, Joanne Traeger-Synodinos, Danai Veltra, Afrodite Kampouraki and George P. Chrousos

Genes 2024, 15(5), 525; https://doi.org/10.3390/genes15050525 - 23 Apr 2024

Cited by 1 | Viewed by 2334

Abstract

Infantile onset transient hypomyelination (IOTH) is a rare form of leukodystrophy that is associated with transient motor impairment and delayed central nervous system myelination. Here, we report a case of a new mutation in the transmembrane protein 63A (TMEM63A) gene identified [...] Read more.

Infantile onset transient hypomyelination (IOTH) is a rare form of leukodystrophy that is associated with transient motor impairment and delayed central nervous system myelination. Here, we report a case of a new mutation in the transmembrane protein 63A (TMEM63A) gene identified using Whole-Exome Sequencing (WES) in an 8.5-year-old boy with clinical symptoms similar to IOTH. The patient exhibited a mild developmental delay, including hypotonia and delayed motor milestones, as well as some notable phenotypic characteristics, such as macrocephaly and macrosomia. Despite the absence of early neuroimaging, genetic testing revealed a paternally inherited variant in TMEM63A (NM_14698.3:c.220A>T;p:(Arg74*)), potentially linked to infantile transient hypomyelinating leukodystrophy type 19. Our findings in this study and the patient’s favorable clinical course underscore the potential for successful myelination even with delayed initiation and may contribute to a better understanding of the genotype–phenotype correlation in IOTH, emphasizing the importance of genetic analysis in unresolved developmental delay cases and providing critical insights for accurate diagnosis, prognosis and potential therapeutic strategies in rare leukodystrophies. Full article

(This article belongs to the Special Issue Head and Neck Genetics)

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12 pages, 1106 KiB

Open AccessEditor’s ChoiceArticle

Resolving Discrepancies in Idylla BRAF Mutational Assay Results Using Targeted Next-Generation Sequencing

by Giby V. George, Huijie Liu, Audrey N. Jajosky and Zoltán N. Oltvai

Genes 2024, 15(5), 527; https://doi.org/10.3390/genes15050527 - 23 Apr 2024

Cited by 1 | Viewed by 1565

Abstract

BRAF mutation identification is important for the diagnosis and treatment of several tumor types, both solid and hematologic. Rapid identification of BRAF mutations is required to determine eligibility for targeted BRAF inhibitor therapy. The Idylla BRAF mutation assay is a rapid, multiplex allele-specific [...] Read more.

BRAF mutation identification is important for the diagnosis and treatment of several tumor types, both solid and hematologic. Rapid identification of BRAF mutations is required to determine eligibility for targeted BRAF inhibitor therapy. The Idylla BRAF mutation assay is a rapid, multiplex allele-specific PCR test designed to detect the most common oncogenic BRAF V600 mutations in formalin-fixed paraffin-embedded (FFPE) tissue samples. Here, we describe the validation of the Idylla BRAF mutation assay in our laboratory. During routine clinical practice, we noticed cases in which BRAF V600 mutations were identified with unusual amplification curves, with three cases displaying a delayed amplification within a double amplification pattern and two false-positive calls. We therefore initiated a quality improvement effort to systematically and retrospectively evaluate next-generation sequencing (NGS)-tested cases with BRAF mutations identified within five amino acids of BRAF codon V600 and did not identify additional false-positive cases. We hypothesize that late amplification in a double amplification pattern may represent non-specific amplification, whereas cases displaying single delayed amplification curves may stem from the presence of either non-V600 variants, very low-level V600 variants, cytosine deamination artifacts, and/or non-specific amplification by an allele-specific PCR primer. Regardless, we recommend that Idylla BRAF cases with non-classical amplification curves undergo reflex NGS testing. These findings are likely relevant for other Idylla assays interrogating hotspot mutations in genes such as EGFR, IDH1/2, KRAS, and NRAS. Full article

(This article belongs to the Special Issue Precision Medicine and Genetics)

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15 pages, 8315 KiB

Open AccessEditor’s ChoiceArticle

Transcriptome Analysis on the Quality of Epimedium koreanum in Different Soil Moisture Conditions at Harvesting Stage

by Yonggang Zhang, Dantong Wang, Feng Wu, Xiangdi Huang, Xiaowei Chai and Limin Yang

Genes 2024, 15(5), 528; https://doi.org/10.3390/genes15050528 - 23 Apr 2024

Cited by 2 | Viewed by 1375

Abstract

Epimedium koreanum is a traditional Chinese tonic herb. Its main medicinal components are secondary metabolites such as flavonoids and flavonol glycosides, but the biosynthetic mechanism is still unclear. Moisture conditions are a key environmental factor affecting E. koreanum medicinal components during harvesting. Different [...] Read more.

Epimedium koreanum is a traditional Chinese tonic herb. Its main medicinal components are secondary metabolites such as flavonoids and flavonol glycosides, but the biosynthetic mechanism is still unclear. Moisture conditions are a key environmental factor affecting E. koreanum medicinal components during harvesting. Different stages of E. koreanum under natural conditions after rainfall were selected to study changes in physiological properties, herb quality, and transcriptome. Malondialdehyde (MDA) content increased significantly in the D3 stage after rainfall, and protective enzyme levels also rose. Additionally, the flavonol glycoside content was relatively high. We sequenced the transcriptomes of D1, D3, and D9 (R) and identified differentially expressed genes (DEGs) related to flavonoid synthesis. This analysis allowed us to predict the roadmap and key genes involved in flavonoid biosynthesis for E. koreanum. These results suggest that the E. koreanum quality can be enhanced by natural drought conditions in the soil after precipitation during harvest. The harvesting period of E. koreanum is optimal when soil moisture naturally dries to a relative water content of 26% after precipitation. These conditions help E. koreanum tolerate a certain level of water scarcity, resulting in increased expression of flavonoid-related genes and ultimately enhancing the quality of the herb. Full article

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

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36 pages, 8856 KiB

Open AccessEditor’s ChoiceArticle

SNP and Structural Study of the Notch Superfamily Provides Insights and Novel Pharmacological Targets against the CADASIL Syndrome and Neurodegenerative Diseases

by Louis Papageorgiou, Lefteria Papa, Eleni Papakonstantinou, Antonia Mataragka, Konstantina Dragoumani, Dimitrios Chaniotis, Apostolos Beloukas, Costas Iliopoulos, Erik Bongcam-Rudloff, George P. Chrousos, Sofia Kossida, Elias Eliopoulos and Dimitrios Vlachakis

Genes 2024, 15(5), 529; https://doi.org/10.3390/genes15050529 - 23 Apr 2024

Cited by 1 | Viewed by 2856

Abstract

The evolutionary conserved Notch signaling pathway functions as a mediator of direct cell–cell communication between neighboring cells during development. Notch plays a crucial role in various fundamental biological processes in a wide range of tissues. Accordingly, the aberrant signaling of this pathway underlies [...] Read more.

The evolutionary conserved Notch signaling pathway functions as a mediator of direct cell–cell communication between neighboring cells during development. Notch plays a crucial role in various fundamental biological processes in a wide range of tissues. Accordingly, the aberrant signaling of this pathway underlies multiple genetic pathologies such as developmental syndromes, congenital disorders, neurodegenerative diseases, and cancer. Over the last two decades, significant data have shown that the Notch signaling pathway displays a significant function in the mature brains of vertebrates and invertebrates beyond neuronal development and specification during embryonic development. Neuronal connection, synaptic plasticity, learning, and memory appear to be regulated by this pathway. Specific mutations in human Notch family proteins have been linked to several neurodegenerative diseases including Alzheimer’s disease, CADASIL, and ischemic injury. Neurodegenerative diseases are incurable disorders of the central nervous system that cause the progressive degeneration and/or death of brain nerve cells, affecting both mental function and movement (ataxia). There is currently a lot of study being conducted to better understand the molecular mechanisms by which Notch plays an essential role in the mature brain. In this study, an in silico analysis of polymorphisms and mutations in human Notch family members that lead to neurodegenerative diseases was performed in order to investigate the correlations among Notch family proteins and neurodegenerative diseases. Particular emphasis was placed on the study of mutations in the Notch3 protein and the structure analysis of the mutant Notch3 protein that leads to the manifestation of the CADASIL syndrome in order to spot possible conserved mutations and interpret the effect of these mutations in the Notch3 protein structure. Conserved mutations of cysteine residues may be candidate pharmacological targets for the potential therapy of CADASIL syndrome. Full article

(This article belongs to the Special Issue Head and Neck Genetics)

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14 pages, 4099 KiB

Open AccessEditor’s ChoiceArticle

Contradiction in Star-Allele Nomenclature of Pharmacogenes between Common Haplotypes and Rare Variants

by Se Hwan Ahn, Yoomi Park and Ju Han Kim

Genes 2024, 15(4), 521; https://doi.org/10.3390/genes15040521 - 22 Apr 2024

Viewed by 1872

Abstract

The nomenclature of star alleles has been widely used in pharmacogenomics to enhance treatment outcomes, predict drug response variability, and reduce adverse reactions. However, the discovery of numerous rare functional variants through genome sequencing introduces complexities into the star-allele system. This study aimed [...] Read more.

The nomenclature of star alleles has been widely used in pharmacogenomics to enhance treatment outcomes, predict drug response variability, and reduce adverse reactions. However, the discovery of numerous rare functional variants through genome sequencing introduces complexities into the star-allele system. This study aimed to assess the nature and impact of the rapid discovery of numerous rare functional variants in the traditional haplotype-based star-allele system. We developed a new method to construct haplogroups, representing a common ancestry structure, by iteratively excluding rare and functional variants of the 25 representative pharmacogenes using the 2504 genomes from the 1000 Genomes Project. In total, 192 haplogroups and 288 star alleles were identified, with an average of 7.68 ± 4.2 cross-ethnic haplogroups per gene. Most of the haplogroups (70.8%, 136/192) were highly aligned with their corresponding classical star alleles (VI = 1.86 ± 0.78), exhibiting higher genetic diversity than the star alleles. Approximately 41.3% (N = 119) of the star alleles in the 2504 genomes did not belong to any of the haplogroups, and most of them (91.3%, 105/116) were determined by a single variant according to the allele-definition table provided by CPIC. These functional single variants had low allele frequency (MAF < 1%), high evolutionary conservation, and variant deleteriousness, which suggests significant negative selection. It is suggested that the traditional haplotype-based naming system for pharmacogenetic star alleles now needs to be adjusted by balancing both traditional haplotyping and newly emerging variant-sequencing approaches to reduce naming complexity. Full article

(This article belongs to the Section Pharmacogenetics)

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25 pages, 7178 KiB

Open AccessEditor’s ChoiceArticle

Effects of Long-Term Cryopreservation on the Transcriptomes of Giant Grouper Sperm

by Xiaoyu Ding, Yongsheng Tian, Yishu Qiu, Pengfei Duan, Xinyi Wang, Zhentong Li, Linlin Li, Yang Liu and Linna Wang

Genes 2024, 15(4), 523; https://doi.org/10.3390/genes15040523 - 22 Apr 2024

Cited by 3 | Viewed by 1792

Abstract

The giant grouper fish (Epinephelus lanceolatus), one of the largest and rarest groupers, is a fast-growing economic fish. Grouper sperm is often used for cross-breeding with other fish and therefore sperm cryopreservation is important. However, freezing damage cannot be avoided. Herein, [...] Read more.

The giant grouper fish (Epinephelus lanceolatus), one of the largest and rarest groupers, is a fast-growing economic fish. Grouper sperm is often used for cross-breeding with other fish and therefore sperm cryopreservation is important. However, freezing damage cannot be avoided. Herein, we performed a transcriptome analysis to compare fresh and frozen sperm of the giant grouper with frozen storage times of 0, 23, 49, and 61 months. In total, 1911 differentially expressed genes (DEGs), including 91 in El-0-vs-El-23 (40 upregulated and 51 downregulated), 251 in El-0-vs-El-49 (152 upregulated and 69 downregulated), and 1569 in El-0-vs-El-61 (984 upregulated and 585 downregulated), were obtained in the giant grouper sperm. DEGs were significantly increased at 61 months of cryopreservation (p < 0.05). GO and KEGG enrichment analyses of the DEGs revealed significant enrichment in the pilus assembly, metabolic process, MAPK signaling pathway, apoptosis, and P53 signaling pathway. Time-series expression profiling of the DEGs showed that consistently upregulated modules were also significantly enriched in signaling pathways associated with apoptosis. Four genes, scarb1, odf3, exoc8, and atp5f1d, were associated with mitochondria and flagella in a weighted correlation network analysis. These genes may play an important role in the response to sperm freezing. The experimental results show that long-term cryopreservation results in freezing damage to the giant grouper sperm. This study provides rich data for studies of the mechanism underlying frozen fish sperm damage as well as a technical reference and evaluation index for the long-term cryopreservation of fish sperm. Full article

(This article belongs to the Special Issue Genetic Studies of Fish)

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21 pages, 4938 KiB

Open AccessEditor’s ChoiceArticle

Single-Nucleus Transcriptome Profiling from the Hippocampus of a PTSD Mouse Model and CBD-Treated Cohorts

by Guanbo Xie, Yihan Qin, Ning Wu, Xiao Han and Jin Li

Genes 2024, 15(4), 519; https://doi.org/10.3390/genes15040519 - 21 Apr 2024

Cited by 2 | Viewed by 2479

Abstract

Post-traumatic stress disorder (PTSD) is the most common psychiatric disorder after a catastrophic event; however, the efficacious treatment options remain insufficient. Increasing evidence suggests that cannabidiol (CBD) exhibits optimal therapeutic effects for treating PTSD. To elucidate the cell-type-specific transcriptomic pathology of PTSD and [...] Read more.

Post-traumatic stress disorder (PTSD) is the most common psychiatric disorder after a catastrophic event; however, the efficacious treatment options remain insufficient. Increasing evidence suggests that cannabidiol (CBD) exhibits optimal therapeutic effects for treating PTSD. To elucidate the cell-type-specific transcriptomic pathology of PTSD and the mechanisms of CBD against this disease, we conducted single-nucleus RNA sequencing (snRNA-seq) in the hippocampus of PTSD-modeled mice and CBD-treated cohorts. We constructed a mouse model by adding electric foot shocks following exposure to single prolonged stress (SPS+S) and tested the freezing time, anxiety-like behavior, and cognitive behavior. CBD was administrated before every behavioral test. The PTSD-modeled mice displayed behaviors resembling those of PTSD in all behavioral tests, and CBD treatment alleviated all of these PTSD-like behaviors (n = 8/group). Three mice with representative behavioral phenotypes were selected from each group for snRNA-seq 15 days after the SPS+S. We primarily focused on the excitatory neurons (ExNs) and inhibitory neurons (InNs), which accounted for 68.4% of the total cell annotations. A total of 88 differentially upregulated genes and 305 differentially downregulated genes were found in the PTSD mice, which were found to exhibit significant alterations in pathways and biological processes associated with fear response, synaptic communication, protein synthesis, oxidative phosphorylation, and oxidative stress response. A total of 63 overlapping genes in InNs were identified as key genes for CBD in the treatment of PTSD. Subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that the anti-PTSD effect of CBD was related to the regulation of protein synthesis, oxidative phosphorylation, oxidative stress response, and fear response. Furthermore, gene set enrichment analysis (GSEA) revealed that CBD also enhanced retrograde endocannabinoid signaling in ExNs, which was found to be suppressed in the PTSD group. Our research may provide a potential explanation for the pathogenesis of PTSD and facilitate the discovery of novel therapeutic targets for drug development. Moreover, it may shed light on the therapeutic mechanisms of CBD. Full article

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

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18 pages, 1355 KiB

Open AccessEditor’s ChoiceCommentary

DNA Damage, Genome Stability, and Adaptation: A Question of Chance or Necessity?

by John Herrick

Genes 2024, 15(4), 520; https://doi.org/10.3390/genes15040520 - 21 Apr 2024

Cited by 1 | Viewed by 2590

Abstract

DNA damage causes the mutations that are the principal source of genetic variation. DNA damage detection and repair mechanisms therefore play a determining role in generating the genetic diversity on which natural selection acts. Speciation, it is commonly assumed, occurs at a rate [...] Read more.

DNA damage causes the mutations that are the principal source of genetic variation. DNA damage detection and repair mechanisms therefore play a determining role in generating the genetic diversity on which natural selection acts. Speciation, it is commonly assumed, occurs at a rate set by the level of standing allelic diversity in a population. The process of speciation is driven by a combination of two evolutionary forces: genetic drift and ecological selection. Genetic drift takes place under the conditions of relaxed selection, and results in a balance between the rates of mutation and the rates of genetic substitution. These two processes, drift and selection, are necessarily mediated by a variety of mechanisms guaranteeing genome stability in any given species. One of the outstanding questions in evolutionary biology concerns the origin of the widely varying phylogenetic distribution of biodiversity across the Tree of Life and how the forces of drift and selection contribute to shaping that distribution. The following examines some of the molecular mechanisms underlying genome stability and the adaptive radiations that are associated with biodiversity and the widely varying species richness and evenness in the different eukaryotic lineages. Full article

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

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18 pages, 1238 KiB

Open AccessEditor’s ChoiceArticle

Information Provision Regarding Health-Related Direct-to-Consumer Genetic Testing for Dutch Consumers: An in-Depth Content Analysis of Sellers’ Websites

by Danny Bruins, Suzanne M. Onstwedder, Martina C. Cornel, Margreet G. E. M. Ausems, Marc H. W. van Mil and Tessel Rigter

Genes 2024, 15(4), 517; https://doi.org/10.3390/genes15040517 - 20 Apr 2024

Cited by 2 | Viewed by 2595

Abstract

Background: Previous studies have suggested that information offered by sellers of health-related direct-to-consumer genetic tests (DTC-GTs) is often incomplete, unbalanced, or too difficult to understand. The extent to which this is the case for sellers accessible to Dutch consumers has not previously [...] Read more.

Background: Previous studies have suggested that information offered by sellers of health-related direct-to-consumer genetic tests (DTC-GTs) is often incomplete, unbalanced, or too difficult to understand. The extent to which this is the case for sellers accessible to Dutch consumers has not previously been studied. Methods and Goals: The present study aimed to assess the completeness, balance, readability, and findability of informational content on a selection of websites from several health-related DTC-GT sellers accessible to Dutch consumers. An in-depth content analysis was performed based on a recently published checklist outlining key items for policy guidance regarding DTC-GT services. Results: The information provided by sellers did not equally cover all aspects relevant to health-related DTC-GT service provision. The provided information was slightly unbalanced, with benefits of health-related DTC-GT usage being overemphasized compared to its risks and limitations. The readability of the provided information was low, on average requiring college education for proper understanding. A findability analysis showed that information concerning all themes is overall relatively evenly distributed across analyzed sellers’ websites. Conclusions: Information provision by assessed health-related DTC-GT sellers is suboptimal regarding completeness, balance, and readability. To better empower potential consumers to make an informed decision regarding health-related DTC-GT usage, we advocate industry-wide enhancement of information provision. Full article

(This article belongs to the Special Issue Human Genetics: Diseases, Community, and Counseling)

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11 pages, 256 KiB

Open AccessEditor’s ChoiceArticle

Association between MCU Gene Polymorphisms with Obesity: Findings from the All of Us Research Program

by Jade Avery, Tennille Leak-Johnson and Sharon C. Francis

Genes 2024, 15(4), 512; https://doi.org/10.3390/genes15040512 - 19 Apr 2024

Cited by 1 | Viewed by 2125

Abstract

Obesity is a public health crisis, and its prevalence disproportionately affects African Americans in the United States. Dysregulation of organelle calcium homeostasis is associated with obesity. The mitochondrial calcium uniporter (MCU) complex is primarily responsible for mitochondrial calcium homeostasis. Obesity is [...] Read more.

Obesity is a public health crisis, and its prevalence disproportionately affects African Americans in the United States. Dysregulation of organelle calcium homeostasis is associated with obesity. The mitochondrial calcium uniporter (MCU) complex is primarily responsible for mitochondrial calcium homeostasis. Obesity is a multifactorial disease in which genetic underpinnings such as single-nucleotide polymorphisms (SNPs) may contribute to disease progression. The objective of this study was to identify genetic variations of MCU with anthropometric measurements and obesity in the All of Us Research Program. Methods: We used an additive genetic model to assess the association between obesity traits (body mass index (BMI), waist and hip circumference) and selected MCU SNPs in 19,325 participants (3221 normal weight and 16,104 obese). Eleven common MCU SNPs with a minor allele frequency ≥ 5% were used for analysis. Results: We observed three MCU SNPs in self-reported Black/African American (B/AA) men, and six MCU SNPs in B/AA women associated with increased risk of obesity, whereas six MCU SNPs in White men, and nine MCU SNPs in White women were protective against obesity development. Conclusions: This study found associations of MCU SNPs with obesity, providing evidence of a potential predictor of obesity susceptibility in B/AA adults. Full article

(This article belongs to the Special Issue Genetics of Obesity)

14 pages, 3118 KiB

Open AccessEditor’s ChoiceArticle

A High-Quality Assembly and Comparative Analysis of the Mitogenome of Actinidia macrosperma

by Jiangmei Gong, Jun Yang, Yan Lai, Tengfei Pan and Wenqin She

Genes 2024, 15(4), 514; https://doi.org/10.3390/genes15040514 - 19 Apr 2024

Cited by 1 | Viewed by 1757

Abstract

The mitochondrial genome (mitogenome) of Actinidia macrosperma, a traditional medicinal plant within the Actinidia genus, remains relatively understudied. This study aimed to sequence the mitogenome of A. macrosperma, determining its assembly, informational content, and developmental expression. The results revealed that the [...] Read more.

The mitochondrial genome (mitogenome) of Actinidia macrosperma, a traditional medicinal plant within the Actinidia genus, remains relatively understudied. This study aimed to sequence the mitogenome of A. macrosperma, determining its assembly, informational content, and developmental expression. The results revealed that the mitogenome of A. macrosperma is circular, spanning 752,501 bp with a GC content of 46.16%. It comprises 63 unique genes, including 39 protein-coding genes (PCGs), 23 tRNA genes, and three rRNA genes. Moreover, the mitogenome was found to contain 63 SSRs, predominantly mono-nucleotides, as well as 25 tandem repeats and 650 pairs of dispersed repeats, each with lengths equal to or greater than 60, mainly comprising forward repeats and palindromic repeats. Moreover, 53 homologous fragments were identified between the mitogenome and chloroplast genome (cp-genome), with the longest segment measuring 4296 bp. This study represents the initial report on the mitogenome of the A. macrosperma, providing crucial genetic materials for phylogenetic research within the Actinidia genus and promoting the exploitation of species genetic resources. Full article

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

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10 pages, 2078 KiB

Open AccessEditor’s ChoiceArticle

Identification of Crucial Modules and Genes Associated with Bt Gene Expression in Cotton

by Guiyuan Zhao, Zhao Geng, Jianguang Liu, Haiyan Tian, Xu Liu, Zetong An, Ning Zhao, Hanshuang Zhang, Liqiang Wu, Xingfen Wang, Yongqiang Wang and Guiyin Zhang

Genes 2024, 15(4), 515; https://doi.org/10.3390/genes15040515 - 19 Apr 2024

Cited by 1 | Viewed by 1704

Abstract

The expression of Bacillus thuringiensis (Bt) toxins in transgenic cotton confers resistance to insect pests. However, it has been demonstrated that its effectiveness varies among cotton cultivars and different tissues. In this study, we evaluated the expression of Bt protein in 28 cotton [...] Read more.

The expression of Bacillus thuringiensis (Bt) toxins in transgenic cotton confers resistance to insect pests. However, it has been demonstrated that its effectiveness varies among cotton cultivars and different tissues. In this study, we evaluated the expression of Bt protein in 28 cotton cultivars and selected 7 cultivars that differed in Bt protein expression for transcriptome analysis. Based on their Bt protein expression levels, the selected cultivars were categorized into three groups: H (high Bt protein expression), M (moderate expression), and L (low expression). In total, 342, 318, and 965 differentially expressed genes were detected in the H vs. L, M vs. L, and H vs. M comparison groups, respectively. And three modules significantly associated with Bt protein expression were identified by weighted gene co-expression network analysis. Three hub genes were selected to verify their relationships with Bt protein expression using virus-induced gene silencing (VIGS). Silencing GhM_D11G1176, encoding an MYC transcription factor, was confirmed to significantly decrease the expression of Bt protein. The present findings contribute to an improved understanding of the mechanisms that influence Bt protein expression in transgenic cotton. Full article

(This article belongs to the Special Issue Cotton Genes, Genetics, and Genomics)

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24 pages, 1974 KiB

Open AccessEditor’s ChoiceArticle

Clinical Decision Analysis of Genetic Evaluation and Testing in 1013 Intensive Care Unit Infants with Congenital Heart Defects Supports Universal Genetic Testing

by Benjamin M. Helm and Stephanie M. Ware

Genes 2024, 15(4), 505; https://doi.org/10.3390/genes15040505 - 18 Apr 2024

Cited by 5 | Viewed by 2238

Abstract

Extracardiac anomalies (ECAs) are strong predictors of genetic disorders in infants with congenital heart disease (CHD), but there are no prior studies assessing performance of ECA status as a screen for genetic diagnoses in CHD patients. This retrospective cohort study assessed this in [...] Read more.

Extracardiac anomalies (ECAs) are strong predictors of genetic disorders in infants with congenital heart disease (CHD), but there are no prior studies assessing performance of ECA status as a screen for genetic diagnoses in CHD patients. This retrospective cohort study assessed this in our comprehensive inpatient CHD genetics service focusing on neonates and infants admitted to the intensive care unit (ICU). The performance and diagnostic utility of using ECA status to screen for genetic disorders was assessed using decision curve analysis, a statistical tool to assess clinical utility, determining the threshold of phenotypic screening by ECA versus a Test-All approach. Over 24% of infants had genetic diagnoses identified (n = 244/1013), and ECA-positive status indicated a 4-fold increased risk of having a genetic disorder. However, ECA status had low–moderate screening performance based on predictive summary index, a compositive measure of positive and negative predictive values. For those with genetic diagnoses, nearly one-third (32%, 78/244) were ECA-negative but had cytogenetic and/or monogenic disorders identified by genetic testing. Thus, if the presence of multiple congenital anomalies is the phenotypic driver to initiate genetic testing, 13.4% (78/580) of infants with isolated CHD with identifiable genetic causes will be missed. Given the prevalence of genetic disorders and limited screening performance of ECA status, this analysis supports genetic testing in all CHD infants in intensive care settings rather than screening based on ECA. Full article

(This article belongs to the Special Issue Genetics, Genomics and Precision Medicine in Heart Diseases)

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17 pages, 6104 KiB

Open AccessEditor’s ChoiceArticle

Assessment of the Effect of Leonurine Hydrochloride in a Mouse Model of PCOS by Gene Expression Profiling

by Mengmeng Wang, Li Yang, Guojie Sun, Yongbin Shao, Yuran Liu, Huiying Yang, Yan Wang, Mengyuan Zhang, Yunxia Shang and Xinli Gu

Genes 2024, 15(4), 507; https://doi.org/10.3390/genes15040507 - 18 Apr 2024

Cited by 3 | Viewed by 1975

Abstract

Polycystic ovary syndrome (PCOS) is an endocrine disease commonly associated with metabolic disorders in females. Leonurine hydrochloride (Leo) plays an important role in regulating immunity, tumours, uterine smooth muscle, and ovarian function. However, the effect of Leo on PCOS has not been reported. [...] Read more.

Polycystic ovary syndrome (PCOS) is an endocrine disease commonly associated with metabolic disorders in females. Leonurine hydrochloride (Leo) plays an important role in regulating immunity, tumours, uterine smooth muscle, and ovarian function. However, the effect of Leo on PCOS has not been reported. Here, we used dehydroepiandrosterone to establish a mouse model of PCOS, and some mice were then treated with Leo by gavage. We found that Leo could improve the irregular oestros cycle of PCOS mice, reverse the significantly greater serum testosterone (T) and luteinising hormone (LH) levels, significantly reduce the follicle-stimulating hormone (FSH) level, and significantly increase the LH/FSH ratio of PCOS mice. Leo could also change the phenomenon of ovaries in PCOS mice presented with cystic follicular multiplication and a lacking corpus luteum. Transcriptome analysis identified 177 differentially expressed genes related to follicular development between the model and Leo groups. Notably, the cAMP signalling pathway, neuroactive ligand-receptor interactions, the calcium signalling pathway, the ovarian steroidogenesis pathway, and the Lhcgr, Star, Cyp11a, Hsd17b7, Camk2b, Calml4, and Phkg1 genes may be most related to improvements in hormone levels and the numbers of ovarian cystic follicles and corpora lutea in PCOS mice treated by Leo, which provides a reference for further study of the mechanism of Leo. Full article

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

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11 pages, 734 KiB

Open AccessEditor’s ChoiceArticle

Spectrum of ERCC6-Related Cockayne Syndrome (Type B): From Mild to Severe Forms

by Jacopo Sartorelli, Lorena Travaglini, Marina Macchiaiolo, Giacomo Garone, Michaela Veronika Gonfiantini, Davide Vecchio, Lorenzo Sinibaldi, Flaminia Frascarelli, Viola Ceccatelli, Sara Petrillo, Fiorella Piemonte, Gabriele Piccolo, Antonio Novelli, Daniela Longo, Stefano Pro, Adele D’Amico, Enrico Silvio Bertini and Francesco Nicita

Genes 2024, 15(4), 508; https://doi.org/10.3390/genes15040508 - 18 Apr 2024

Cited by 1 | Viewed by 2299

Abstract

(1) Background: Cockayne syndrome (CS) is an ultra-rare multisystem disorder, classically subdivided into three forms and characterized by a clinical spectrum without a clear genotype-phenotype correlation for both the two causative genes ERCC6 (CS type B) and ERCC8 (CS type A). We assessed [...] Read more.

(1) Background: Cockayne syndrome (CS) is an ultra-rare multisystem disorder, classically subdivided into three forms and characterized by a clinical spectrum without a clear genotype-phenotype correlation for both the two causative genes ERCC6 (CS type B) and ERCC8 (CS type A). We assessed this, presenting a series of patients with genetically confirmed CSB. (2) Materials and Methods: We retrospectively collected demographic, clinical, genetic, neuroimaging, and serum neurofilament light-chain (sNFL) data about CSB patients; diagnostic and severity scores were also determined. (3) Results: Data of eight ERCC6/CSB patients are presented. Four patients had CS I, three patients CS II, and one patient CS III. Various degrees of ataxia and spasticity were cardinal neurologic features, with variably combined systemic characteristics. Mean age at diagnosis was lower in the type II form, in which classic CS signs were more evident. Interestingly, sNFL determination appeared to reflect clinical classification. Two novel premature stop codon and one novel missense variants were identified. All CS I subjects harbored the p.Arg735Ter variant; the milder CS III subject carried the p.Leu764Ser missense change. (4) Conclusion: Our work confirms clinical variability also in the ERCC6/CSB type, where manifestations may range from severe involvement with prenatal or neonatal onset to normal psychomotor development followed by progressive ataxia. We propose, for the first time in CS, sNFL as a useful peripheral biomarker, with increased levels compared to currently available reference values and with the potential ability to reflect disease severity. Full article

(This article belongs to the Special Issue Study on Genotypes and Phenotypes of Neurodegenerative Diseases—2nd Edition)

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13 pages, 1907 KiB

Open AccessEditor’s ChoiceArticle

Biogeographical Ancestry Analyses Using the ForenSeq^TM DNA Signature Prep Kit and Multiple Prediction Tools

by Nina Mjølsnes Salvo, Gunn-Hege Olsen, Thomas Berg and Kirstin Janssen

Genes 2024, 15(4), 510; https://doi.org/10.3390/genes15040510 - 18 Apr 2024

Cited by 1 | Viewed by 1761

Abstract

The inference of biogeographical ancestry (BGA) can assist in police investigations of serious crime cases and help to identify missing people and victims of mass disasters. In this study, we evaluated the typing performance of 56 ancestry-informative SNPs in 177 samples using the [...] Read more.

The inference of biogeographical ancestry (BGA) can assist in police investigations of serious crime cases and help to identify missing people and victims of mass disasters. In this study, we evaluated the typing performance of 56 ancestry-informative SNPs in 177 samples using the ForenSeq™ DNA Signature Prep Kit on the MiSeq FGx system. Furthermore, we compared the prediction accuracy of the tools Universal Analysis Software v1.2 (UAS), the FROG-kb, and GenoGeographer when inferring the ancestry of 503 Europeans, 22 non-Europeans, and 5 individuals with co-ancestry. The kit was highly sensitive with complete aiSNP profiles in samples with as low as 250pg input DNA. However, in line with others, we observed low read depth and occasional drop-out in some SNPs. Therefore, we suggest not using less than the recommended 1ng of input DNA. FROG-kb and GenoGeographer accurately predicted both Europeans (99.6% and 91.8% correct, respectively) and non-Europeans (95.4% and 90.9% correct, respectively). The UAS was highly accurate when predicting Europeans (96.0% correct) but performed poorer when predicting non-Europeans (40.9% correct). None of the tools were able to correctly predict individuals with co-ancestry. Our study demonstrates that the use of multiple prediction tools will increase the prediction accuracy of BGA inference in forensic casework. Full article

(This article belongs to the Special Issue State-of-the-Art in Forensic Genetics Volume II)

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