Genes

13 pages, 855 KiB

Open AccessFeature PaperArticle

Inheritance of Resistance to Chickpea Fusarium Wilt Disease (Fusarium oxysporum f. sp. ciceris Race 2) in a Wide-Cross Cicer arietinum × Cicer reticulatum Mapping Family

by Abdulkarim Lakmes, Abdullah Jhar, Ari Sadanandom, Adrian Christopher Brennan and Abdullah Kahriman

Genes 2024, 15(6), 819; https://0-doi-org.brum.beds.ac.uk/10.3390/genes15060819 (registering DOI) - 20 Jun 2024

Abstract

Chickpea (Cicer arietinum) is a major food legume providing high quality nutrition, especially in developing regions. Chickpea wilt (Fusarium oxysporum f. sp. ciceris) causes significant annual losses. Integrated disease management of Fusarium wilt is supported by resistant varieties. Relatively [...] Read more.

Chickpea (Cicer arietinum) is a major food legume providing high quality nutrition, especially in developing regions. Chickpea wilt (Fusarium oxysporum f. sp. ciceris) causes significant annual losses. Integrated disease management of Fusarium wilt is supported by resistant varieties. Relatively few resistance genes are known so there is value in exploring genetic resources in chickpea wild relatives. This study investigates the inheritance of Fusarium wilt resistance (race 2) in recombinant inbred lines (RILs) from a cross between a cultivated susceptible chickpea variety (Gokce) and a wild resistant Cicer reticulatum line (Kayat-077). RILs, parents, resistant and susceptible tester lines were twice grown in the greenhouse with inoculation and disease symptoms scored. DNA was extracted from dried leaves and individuals were single nucleotide polymorphism (SNP) genotyped. SNPs were placed on the reference chickpea genome and quantitative trait locus (QTL) mapping was performed. Significant QTL regions were examined using PulseDB to identify candidate genes. The results showed the segregation of Fusarium wilt resistance conforming to a single gene inheritance. One significant QTL was found at the start of chromosome 8, containing 138 genes, three of which were disease-resistance candidates for chickpea breeding. Full article

(This article belongs to the Special Issue Genetics and Breeding of Legume Crops)

16 pages, 418 KiB

Open AccessArticle

Correlation Analysis of Genetic Mutations and Galectin Levels in Breast Cancer Patients

by Ella G. Markalunas, David H. Arnold, Avery T. Funkhouser, Julie C. Martin, Michael Shtutman, W. Jeffery Edenfield and Anna V. Blenda

Genes 2024, 15(6), 818; https://0-doi-org.brum.beds.ac.uk/10.3390/genes15060818 (registering DOI) - 20 Jun 2024

Abstract

Galectins are innate immune system regulators associated with disease progression in cancer. This paper aims to investigate the correlation between mutated cancer-critical genes and galectin levels in breast cancer patients to determine whether galectins and genetic profiles can be used as biomarkers for [...] Read more.

Galectins are innate immune system regulators associated with disease progression in cancer. This paper aims to investigate the correlation between mutated cancer-critical genes and galectin levels in breast cancer patients to determine whether galectins and genetic profiles can be used as biomarkers for disease and potential therapy targets. Prisma Health Cancer Institute’s Biorepository provided seventy-one breast cancer samples, including all four stages spanning the major molecular subtypes and histologies. Hotspot mutation statuses of cancer-critical genes were determined using multiplex PCR in tumor samples from the same patients by Precision Genetics and the University of South Carolina Functional Genomics Core Facility. The galectin-1, -3, and -9 levels in patients’ sera were analyzed using Enzyme-linked Immunosorbent Assay (ELISA). An analysis was performed using JMP software to compare mean and median serum galectin levels between samples with and without specific cancer-critical genes, including pooled t-test, Wilcoxon Rank Sum Test, ANOVA, and Steel Dwass Test (

α = 0.05

). Our analysis indicates that KIT mutations correlate with elevated serum levels of galectin-9 in patients with breast cancer. In patients with Luminal A subtype, FLT3 mutation correlates with lower serum galectin-1 and -9 levels and TP53 mutations correlate with higher serum galectin-3 levels. Patients with invasive ductal carcinoma had significantly higher serum galectin-3 levels than patients with ductal carcinoma in situ. Patients with both TP53 and PIK3CA mutations exhibit elevated serum galectin-3 levels, while patients with one or neither mutation show no significant difference in serum galectin-3 levels. In addition, metastatic breast cancer samples were more likely to have a KIT or PIK3CA mutation compared to primary breast cancer samples. The relationship between genetic mutations and galectin levels has the potential to identify appropriate candidates for combined therapy, targeting genetic mutations and galectins. Further understanding of the effect of genetic mutations and galectin levels on cancer progression and metastasis could aid in the search for biomarkers for breast cancer diagnosis, disease progression, and prognosis. Full article

(This article belongs to the Special Issue Breast Cancer Ecosystem: Genomic and Proteomic Profiling)

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11 pages, 2163 KiB

Open AccessArticle

Establishment and Application of a Novel Genetic Detection Panel for SNPs in Mongolian Gerbils

by Yafang Guo, Yutong Cui, Minghe Sun, Xiao Zhu, Yilang Zhang, Jing Lu, Changlong Li, Jianyi Lv, Meng Guo, Xin Liu, Zhenwen Chen, Xiaoyan Du and Xueyun Huo

Genes 2024, 15(6), 817; https://0-doi-org.brum.beds.ac.uk/10.3390/genes15060817 - 20 Jun 2024

Abstract

The Mongolian gerbil is a distinctive experimental animal in China, as its genetic qualities possess significant value in the field of medical biology research. Here, we aimed to establish an economical and efficient panel for genetic quality detection in Mongolian gerbils using single-nucleotide [...] Read more.

The Mongolian gerbil is a distinctive experimental animal in China, as its genetic qualities possess significant value in the field of medical biology research. Here, we aimed to establish an economical and efficient panel for genetic quality detection in Mongolian gerbils using single-nucleotide polymorphism (SNP) markers. To search for SNPs, we conducted whole-genome sequencing (WGS) in 40 Mongolian gerbils from outbred populations. Reliable screening criteria were established to preliminarily select SNPs with a wide genome distribution and high levels of polymorphism. Subsequently, a multiple-target regional capture detection system based on second-generation sequencing was developed for SNP genotyping. Based on the results of WGS, 219 SNPs were preliminarily selected, and they were established and optimized in a multiple-amplification system that included 206 SNP loci by genotyping three outbred populations. PopGen.32 analysis revealed that the average effective allele number, Shannon index, observed heterozygosity, expected heterozygosity, average heterozygosity, polymorphism information content, and other population genetic parameters of the Capital Medical University (CMU) gerbils were the highest, followed by those of Zhejiang gerbils and Dalian gerbils. Through scientific screening and optimization, we successfully established a novel, robust, and cost-effective genetic detection system for Mongolian gerbils by utilizing SNP markers for the first time. Full article

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

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8 pages, 459 KiB

Open AccessArticle

Extensive Contact Lens Wear Modulates Expression of miRNA-320 and miRNA-423-5p in the Human Corneal Epithelium: Possible Biomarkers of Corneal Health and Environmental Impact

by Anna M. Roszkowska, M’hammed Aguennouz, Emanuela Aragona, Romana Gargano, Giovanni William Oliverio, Leandro Inferrera and Pasquale Aragona

Genes 2024, 15(6), 816; https://0-doi-org.brum.beds.ac.uk/10.3390/genes15060816 - 20 Jun 2024

Abstract

The identification of new biomarkers of ocular diseases is nowadays of outmost importance both for early diagnosis and treatment. Epigenetics is a rapidly growing emerging area of research and its involvement in the pathophysiology of ocular disease and regulatory mechanisms is of undisputable [...] Read more.

The identification of new biomarkers of ocular diseases is nowadays of outmost importance both for early diagnosis and treatment. Epigenetics is a rapidly growing emerging area of research and its involvement in the pathophysiology of ocular disease and regulatory mechanisms is of undisputable importance for diagnostic purposes. Environmental changes may impact the ocular surface, and the knowledge of induced epigenetic changes might help to elucidate the mechanisms of ocular surface disorders. In this pilot study, we investigated the impact of extensive contact lens (CL) wearing on human corneal epithelium epigenetics. We performed ex vivo analysis of the expression of the miR-320 and miR-423-5p involved in the processes of cellular apoptosis and chronic inflammation. The human corneal epithelium was harvested from healthy patients before the photorefractive keratectomy (PRK). The patients were divided into two age- and sex-matched groups accordingly to CL wearing history with no CL wearers used as a control. The epithelium was stored frozen in dry ice at −80 °C and forwarded for miRNA extraction; afterwards, miRNA levels were detected using real-time PCR. Both miRNAs were highly expressed in CL wearers (p < 0.001), suggesting epigenetic modifications occurring in chronic ocular surface stress. These preliminary results show the relationships between selected miRNA expression and the chronic ocular surface stress associated with extensive CL use. MicroRNAs might be considered as biomarkers for the diagnosis of ocular surface conditions and the impact of environmental factors on ocular surface epigenetic. Furthermore, they might be considered as new therapeutic targets in ocular surface diseases. Full article

(This article belongs to the Collection microRNA Omnibus)

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14 pages, 8992 KiB

Open AccessArticle

Characterization and Comparative Analysis of Complete Chloroplast Genomes of Four Bromus (Poaceae, Bromeae) Species

by Shichao Li, Chunyu Tian, Haihong Hu, Yanting Yang, Huiling Ma, Qian Liu, Lemeng Liu, Zhiyong Li and Zinian Wu

Genes 2024, 15(6), 815; https://0-doi-org.brum.beds.ac.uk/10.3390/genes15060815 - 20 Jun 2024

Abstract

Bromus (Poaceae Bromeae) is a forage grass with high adaptability and ecological and economic value. Here, we sequenced Bromus ciliatus, Bromus benekenii, Bromus riparius, and Bromus rubens chloroplast genomes and compared them with four previously described species. The genome sizes [...] Read more.

Bromus (Poaceae Bromeae) is a forage grass with high adaptability and ecological and economic value. Here, we sequenced Bromus ciliatus, Bromus benekenii, Bromus riparius, and Bromus rubens chloroplast genomes and compared them with four previously described species. The genome sizes of Bromus species ranged from 136,934 bp (Bromus vulgaris) to 137,189 bp (Bromus ciliates, Bromus biebersteinii), with a typical quadripartite structure. The studied species had 129 genes, consisting of 83 protein-coding, 38 tRNA-coding, and 8 rRNA-coding genes. The highest GC content was found in the inverted repeat (IR) region (43.85–44.15%), followed by the large single-copy (LSC) region (36.25–36.65%) and the small single-copy (SSC) region (32.21–32.46%). There were 33 high-frequency codons, with those ending in A/U accounting for 90.91%. A total of 350 simple sequence repeats (SSRs) were identified, with single-nucleotide repeats being the most common (61.43%). A total of 228 forward and 141 palindromic repeats were identified. No reverse or complementary repeats were detected. The sequence identities of all sequences were very similar, especially with respect to the protein-coding and inverted repeat regions. Seven highly variable regions were detected, which could be used for molecular marker development. The constructed phylogenetic tree indicates that Bromus is a monophyletic taxon closely related to Triticum. This comparative analysis of the chloroplast genome of Bromus provides a scientific basis for species identification and phylogenetic studies. Full article

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

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10 pages, 290 KiB

Open AccessArticle

Whole-Genome Analysis of Extensively Drug-Resistant Enterobacter hormaechei Isolated from a Patient with Non-Hodgkin’s Lymphoma

by Cristina Motta Ferreira, Felipe Gomes Naveca, Guilherme Motta Antunes Ferreira, Maria de Nazaré Saunier Barbosa, Victor Costa de Souza, Franceline Oliveira Calheiros, Vander Silva Souza and William Antunes Ferreira

Genes 2024, 15(6), 814; https://0-doi-org.brum.beds.ac.uk/10.3390/genes15060814 - 20 Jun 2024

Abstract

Background: Currently, the Enterobacteriaceae species are responsible for a variety of serious infections and are already considered a global public health problem, especially in underdeveloped countries, where surveillance and monitoring programs are still scarce and limited. Analyses were performed on the complete genome [...] Read more.

Background: Currently, the Enterobacteriaceae species are responsible for a variety of serious infections and are already considered a global public health problem, especially in underdeveloped countries, where surveillance and monitoring programs are still scarce and limited. Analyses were performed on the complete genome of an extensively antibiotic-resistant strain of Enterobater hormaechei, which was isolated from a patient with non-Hodgkin’s lymphoma, who had been admitted to a hospital in the city of Manaus, Brazil. Methods: Phenotypical identification and susceptibility tests were performed in automated equipment. Total DNA extraction was performed using the PureLink genomic DNA mini-Kit. The genomic DNA library was prepared with Illumina Microbial Amplicon Prep and sequenced in the MiSeq Illumina Platform. The assembly of the whole-genome and individual analyses of specific resistance genes extracted were carried out using online tools and the Geneious Prime software. Results: The analyses identified an extensively resistant ST90 clone of E. hormaechei carrying different genes, including bla_CTX-M-15, bla_GES-2, bla_TEM-1A, bla_ACT-15, bla_OXA-1 and bla_NDM-1, [aac(3)-IIa, aac(6′)-Ian, ant(2″)-Ia], [aac(6′)-Ib-cr, (qnrB1)], dfrA25, sul1 and sul2, catB3, fosA, and qnrB, in addition to resistance to chlorhexidine, which is widely used in patient antisepsis. Conclusions: These findings highlight the need for actions to control and monitor these pathogens in the hospital environment. Full article

(This article belongs to the Special Issue Decoding the Genomic Evolution of Pathogenic Eukaryotes Through Integrated Multi-Omics Approaches)

11 pages, 1650 KiB

Open AccessArticle

Associations of Maternal Breastmilk microRNAs and Infant Obesity Status at 1 Year

by Emily Van Syoc, Molly Stegman, Rhea Sullivan, Alexandra Confair, Kaitlyn Warren and Steven D. Hicks

Genes 2024, 15(6), 813; https://0-doi-org.brum.beds.ac.uk/10.3390/genes15060813 - 20 Jun 2024

Abstract

Infant consumption of human milk (HM) is associated with a reduced risk of overweight and obesity, but the reasons for this relationship are not completely understood. There is emerging evidence that micro RNAs (miRNAs) regulate infant development and metabolism, but the associations between [...] Read more.

Infant consumption of human milk (HM) is associated with a reduced risk of overweight and obesity, but the reasons for this relationship are not completely understood. There is emerging evidence that micro RNAs (miRNAs) regulate infant development and metabolism, but the associations between HM miRNAs and infant growth remain poorly understood. We examined the relationship between HM miRNA consumption and infant obesity in 163 mother–infant dyads to determine (1) if miRNA profiles differentiate infants with obesity, and (2) if individual miRNAs accurately predicted infant obesity status at one year of age. Infant obesity was categorized as weight-for-length (WFL) Z scores or conditional weight gain (CWG) in the 95th percentile. HM miRNA profile was associated with infant age (r² = 6.4%, p = 0.001), but not maternal obesity status (r² = 1.5%, p = 0.87) or infant weight status (WFL Z-score) at birth (r² = 0.6%, p = 0.4), 1 month (r² = 0.5%, p = 0.6), or 4 months (r² = 0.8%, p = 0.2). Nine HM miRNAs were associated with either 12-month CWG or 12-month WFL Z scores. Among these 9 miRNAs, miR-224-5p remained significant in a logistic regression model that accounted for additional demographic factors (estimate = −27.57, p = 0.004). These findings suggest involvement of HM miRNAs and particularly miR-224-5p in infant growth, warranting further investigation. To our knowledge, this is the largest study of HM miRNAs and early-life obesity and contributes to the understanding of the relationship between HM miRNAs and infant growth. Full article

(This article belongs to the Special Issue RNAs in Biology)

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15 pages, 1527 KiB

Open AccessArticle

A Network of Circular RNA and MicroRNA Sequencing Provides Insights into Pigment Deposition of Changshun Blue Eggshell Chickens

by Siyu Chen, Mengqiao Zhao, Kecheng Chen, Jiaming Xu and Hua Li

Genes 2024, 15(6), 812; https://0-doi-org.brum.beds.ac.uk/10.3390/genes15060812 - 19 Jun 2024

Abstract

Eggshell color plays important biological roles and attracts the attention of both egg retailers and researchers. However, whether non-coding RNAs are involved in pigment deposition among different eggshell colors remains unknown. In this study, RNA sequencing was used to analyse the uterine gland [...] Read more.

Eggshell color plays important biological roles and attracts the attention of both egg retailers and researchers. However, whether non-coding RNAs are involved in pigment deposition among different eggshell colors remains unknown. In this study, RNA sequencing was used to analyse the uterine gland transcriptome (CircRNA and miRNA) of Changshun chicken blue-shell hens producing four different eggshell color eggs including dark blue PK(DB) and light blue (LB), dark brown and greenish (between blue and pink, DP) and pink (p). We found that miR-192-x, targeting SLC16a7, was expressed in DB, DP, and LB groups compared with the PK group, which indicates that miR-192-x may play a role in the blue eggshell color. KEGG and GO analyses showed that the “metabolic pathways” with targeted genes such BLVRA and HMOX1 were detected in dark and light blue color eggshell chickens, which confirms the different ratios of biliverdin and HO-1 involved in the deposition of blue color. As annotated by connectivity analysis, RASGRF1 and RASGRF2, belonging to the RASGRF family, are involved in the Ras signaling pathway, which plays an important role in cell growth, differentiation, metastasis and apoptosis. Our findings enrich the database of circRNA, miRNAs and genes for chicken uterine tissue, which will be useful in accelerating molecular selection for blue eggshell color layers. Full article

(This article belongs to the Special Issue Poultry Breeding and Genetics)

12 pages, 1094 KiB

Open AccessArticle

Identification and Characterization of the miRNA Transcriptome Controlling Green Pigmentation of Chicken Eggshells

by Kai Shi, Dongfeng Li, Xusheng Jiang, Yuesong Du and Minli Yu

Genes 2024, 15(6), 811; https://0-doi-org.brum.beds.ac.uk/10.3390/genes15060811 - 19 Jun 2024

Viewed by 71

Abstract

Green eggs are mainly caused by inserting an avian endogenous retrovirus (EVA-HP) fragment into the SLCO1B3 gene. Although the genotypes for this insertion allele are consistent, eggshell color (ESC) may vary after a peak laying period; light-colored eggs are undesired by consumers and [...] Read more.

Green eggs are mainly caused by inserting an avian endogenous retrovirus (EVA-HP) fragment into the SLCO1B3 gene. Although the genotypes for this insertion allele are consistent, eggshell color (ESC) may vary after a peak laying period; light-colored eggs are undesired by consumers and farmers and result in financial loss, so it is necessary to resolve this problem. miRNAs are small non-coding RNAs that exert essential functions in animal development and diseases. However, the regulatory miRNAs and detailed molecular mechanisms regulating eggshell greenness remain unclear. In the present study, we determined the genotype of green-eggshell hens through the detection of a homozygous allele insertion in the SLCO1B3 gene. The shell gland epithelium was obtained from green-eggshell hens that produced white and green shell eggs to perform transcriptome sequencing and investigate the important regulatory mechanisms that influence the ESC. Approximately 921 miRNAs were expressed in these two groups, which included 587 known miRNAs and 334 novel miRNAs, among which 44 were differentially expressed. There were 22 miRNAs that were significantly upregulated in the green and white groups, respectively, which targeted hundreds of genes, including KIT, HMOX2, and several solute carrier family genes. A Gene Ontology enrichment analysis of the target genes showed that the differentially expressed miRNA-targeted genes mainly belonged to the functional categories of homophilic cell adhesion, gland development, the Wnt signaling pathway, and epithelial tube morphogenesis. A KEGG enrichment analysis showed that the Hedgehog signaling pathway was significantly transformed in this study. The current study provides an overview of the miRNA expression profiles and the interaction between the miRNAs and their target genes. It provides valuable insights into the molecular mechanisms underlying green eggshell pigmentation, screening more effective hens to produce stable green eggs and obtaining higher economic benefits. Full article

(This article belongs to the Special Issue Poultry Genetics and Genomics—2nd Edition)

20 pages, 4966 KiB

Open AccessArticle

Multifactor Analyses of Frontal Cortex Lipids in the APP/PS1 Model of Familial Alzheimer’s Disease Reveal Anomalies in Responses to Dietary n-3 PUFA and Estrogenic Treatments

by Mario Díaz

Genes 2024, 15(6), 810; https://0-doi-org.brum.beds.ac.uk/10.3390/genes15060810 - 19 Jun 2024

Viewed by 84

Abstract

Brain lipid homeostasis is an absolute requirement for proper functionality of nerve cells and neurological performance. Current evidence demonstrates that lipid alterations are linked to neurodegenerative diseases, especially Alzheimer’s disease (AD). The complexity of the brain lipidome and its metabolic regulation has hampered [...] Read more.

Brain lipid homeostasis is an absolute requirement for proper functionality of nerve cells and neurological performance. Current evidence demonstrates that lipid alterations are linked to neurodegenerative diseases, especially Alzheimer’s disease (AD). The complexity of the brain lipidome and its metabolic regulation has hampered the identification of critical processes associated with the onset and progression of AD. While most experimental studies have focused on the effects of known factors on the development of pathological hallmarks in AD, e.g., amyloid deposition, tau protein and neurofibrillary tangles, neuroinflammation, etc., studies addressing the causative effects of lipid alterations remain largely unexplored. In the present study, we have used a multifactor approach combining diets containing different amounts of polyunsaturated fatty acids (PUFAs), estrogen availabilities, and genetic backgrounds, i.e., wild type (WT) and APP/PS1 (FAD), to analyze the lipid phenotype of the frontal cortex in middle-aged female mice. First, we observed that severe n-3 PUFA deficiency impacts the brain n-3 long-chain PUFA (LCPUFA) composition, yet it was notably mitigated by hepatic de novo synthesis. n-6 LCPUFAs, ether-linked fatty acids, and saturates were also changed by the dietary condition, but the extent of changes was dependent on the genetic background and hormonal condition. Likewise, brain cortex phospholipids were mostly modified by the genotype (FAD>WT) with nuanced effects from dietary treatment. Cholesterol (but not sterol esters) was modified by the genotype (WT>FAD) and dietary condition (higher in DHA-free conditions, especially in WT mice). However, the effects of estrogen treatment were mostly observed in relation to phospholipid remodeling in a genotype-dependent manner. Analyses of lipid-derived variables indicate that nerve cell membrane biophysics were significantly affected by the three factors, with lower membrane microviscosity (higher fluidity) values obtained for FAD animals. In conclusion, our multifactor analyses revealed that the genotype, diet, and estrogen status modulate the lipid phenotype of the frontal cortex, both as independent factors and through their interactions. Altogether, the outcomes point to potential strategies based on dietary and hormonal interventions aimed at stabilizing the brain cortex lipid composition in Alzheimer’s disease neuropathology. Full article

(This article belongs to the Special Issue Study on Genotypes and Phenotypes of Neurodegenerative Diseases (Volume II))

8 pages, 745 KiB

Open AccessArticle

Optical Genome Mapping Reveals Disruption of the RASGRF2 Gene in a Patient with Developmental Delay Carrying a De Novo Balanced Reciprocal Translocation

by Rosa Catalina Lederbogen, Sabine Hoffjan, Charlotte Thiels, Ulrike Angelika Mau-Holzmann, Sylke Singer, Maria Viktorovna Yusenko, Hoa Huu Phuc Nguyen and Wanda Maria Gerding

Genes 2024, 15(6), 809; https://0-doi-org.brum.beds.ac.uk/10.3390/genes15060809 - 19 Jun 2024

Viewed by 99

Abstract

While balanced reciprocal translocations are relatively common, they often remain clinically silent unless they lead to the disruption of functional genes. In this study, we present the case of a boy exhibiting developmental delay and mild intellectual disability. Initial karyotyping revealed a translocation [...] Read more.

While balanced reciprocal translocations are relatively common, they often remain clinically silent unless they lead to the disruption of functional genes. In this study, we present the case of a boy exhibiting developmental delay and mild intellectual disability. Initial karyotyping revealed a translocation t(5;6)(q13;q23) between chromosomes 5 and 6 with limited resolution. Optical genome mapping (OGM) enabled a more precise depiction of the breakpoint regions involved in the reciprocal translocation. While the breakpoint region on chromosome 6 did not encompass any known gene, OGM revealed the disruption of the RASGRF2 (Ras protein-specific guanine nucleotide releasing factor 2) gene on chromosome 5, implicating RASGRF2 as a potential candidate gene contributing to the observed developmental delay in the patient. Variations in RASGRF2 have so far not been reported in developmental delay, but research on the RASGRF2 gene underscores its significance in various aspects of neurodevelopment, including synaptic plasticity, signaling pathways, and behavioral responses. This study highlights the utility of OGM in identifying breakpoint regions, providing possible insights into the understanding of neurodevelopmental disorders. It also helps affected individuals in gaining more knowledge about potential causes of their conditions. Full article

(This article belongs to the Special Issue Advances of Optical Genome Mapping in Human Genetics)

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10 pages, 1000 KiB

Open AccessArticle

Up-Regulation of Non-Homologous End-Joining by MUC1

by Tadayoshi Bessho

Genes 2024, 15(6), 808; https://0-doi-org.brum.beds.ac.uk/10.3390/genes15060808 - 19 Jun 2024

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Abstract

Ionizing radiation (IR) and chemotherapy with DNA-damaging drugs such as cisplatin are vital cancer treatment options. These treatments induce double-strand breaks (DSBs) as cytotoxic DNA damage; thus, the DSB repair activity in each cancer cell significantly influences the efficacy of the treatments. Pancreatic [...] Read more.

Ionizing radiation (IR) and chemotherapy with DNA-damaging drugs such as cisplatin are vital cancer treatment options. These treatments induce double-strand breaks (DSBs) as cytotoxic DNA damage; thus, the DSB repair activity in each cancer cell significantly influences the efficacy of the treatments. Pancreatic cancers are known to be resistant to these treatments, and the overexpression of MUC1, a member of the glycoprotein mucins, is associated with IR- and chemo-resistance. Therefore, we investigated the impact of MUC1 on DSB repair. This report examined the effect of the overexpression of MUC1 on homologous recombination (HR) and non-homologous end-joining (NHEJ) using cell-based DSB repair assays. In addition, the therapeutic potential of NHEJ inhibitors including HDAC inhibitors was also studied using pancreatic cancer cell lines. The MUC1-overexpression enhances NHEJ, while partially suppressing HR. Also, MUC1-overexpressed cancer cell lines are preferentially killed by a DNA-PK inhibitor and HDAC1/2 inhibitors. Altogether, MUC1 induces metabolic changes that create an imbalance between NHEJ and HR activities, and this imbalance can be a target for selective killing by HDAC inhibitors. This is a novel mechanism of MUC1-mediated IR-resistance and will form the basis for targeting MUC1-overexpressed pancreatic cancer. Full article

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

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15 pages, 897 KiB

Open AccessReview

Beyond CAG Repeats: The Multifaceted Role of Genetics in Huntington Disease

by Marta Pengo and Ferdinando Squitieri

Genes 2024, 15(6), 807; https://0-doi-org.brum.beds.ac.uk/10.3390/genes15060807 - 19 Jun 2024

Viewed by 91

Abstract

Huntington disease (HD) is a dominantly inherited neurodegenerative disorder caused by a CAG expansion on the huntingtin (HTT) gene and is characterized by progressive motor, cognitive, and neuropsychiatric decline. Recently, new genetic factors besides CAG repeats have been implicated in the [...] Read more.

Huntington disease (HD) is a dominantly inherited neurodegenerative disorder caused by a CAG expansion on the huntingtin (HTT) gene and is characterized by progressive motor, cognitive, and neuropsychiatric decline. Recently, new genetic factors besides CAG repeats have been implicated in the disease pathogenesis. Most genetic modifiers are involved in DNA repair pathways and, as the cause of the loss of CAA interruption in the HTT gene, they exert their main influence through somatic expansion. However, this mechanism might not be the only driver of HD pathogenesis, and future studies are warranted in this field. The aim of the present review is to dissect the many faces of genetics in HD pathogenesis, from cis- and trans-acting genetic modifiers to RNA toxicity, mitochondrial DNA mutations, and epigenetics factors. Exploring genetic modifiers of HD onset and progression appears crucial to elucidate not only disease pathogenesis, but also to improve disease prediction and prevention, develop biomarkers of disease progression and response to therapies, and recognize new therapeutic opportunities. Since the same genetic mechanisms are also described in other repeat expansion diseases, their implications might encompass the whole spectrum of these disorders. Full article

(This article belongs to the Special Issue Molecular Genetics of Neurodegenerative Diseases and Neuromuscular Diseases)

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21 pages, 4673 KiB

Open AccessArticle

Leveraging Integrated RNA Sequencing to Decipher Adrenomedullin’s Protective Mechanisms in Experimental Bronchopulmonary Dysplasia

by Subarna Palit, Amrit Kumar Shrestha, Shyam Thapa, Sandra L. Grimm, Cristian Coarfa, Fabian Theis, Lukas M. Simon and Binoy Shivanna

Genes 2024, 15(6), 806; https://0-doi-org.brum.beds.ac.uk/10.3390/genes15060806 - 19 Jun 2024

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Abstract

Bronchopulmonary dysplasia (BPD) is a chronic lung disease commonly affecting premature infants, with limited therapeutic options and increased long-term consequences. Adrenomedullin (Adm), a proangiogenic peptide hormone, has been found to protect rodents against experimental BPD. This study aims to elucidate the [...] Read more.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease commonly affecting premature infants, with limited therapeutic options and increased long-term consequences. Adrenomedullin (Adm), a proangiogenic peptide hormone, has been found to protect rodents against experimental BPD. This study aims to elucidate the molecular and cellular mechanisms through which Adm influences BPD pathogenesis using a lipopolysaccharide (LPS)-induced model of experimental BPD in mice. Bulk RNA sequencing of Adm-sufficient (wild-type or Adm^+/+) and Adm-haplodeficient (Adm^+/−) mice lungs, integrated with single-cell RNA sequencing data, revealed distinct gene expression patterns and cell type alterations associated with Adm deficiency and LPS exposure. Notably, computational integration with cell atlas data revealed that Adm-haplodeficient mouse lungs exhibited gene expression signatures characteristic of increased inflammation, natural killer (NK) cell frequency, and decreased endothelial cell and type II pneumocyte frequency. Furthermore, in silico human BPD patient data analysis supported our cell type frequency finding, highlighting elevated NK cells in BPD infants. These results underscore the protective role of Adm in experimental BPD and emphasize that it is a potential therapeutic target for BPD infants with an inflammatory phenotype. Full article

(This article belongs to the Special Issue RNAs in Biology)

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1 pages, 133 KiB

Open AccessRetraction

RETRACTED: Cheng et al. Using Comorbidity Pattern Analysis to Detect Reliable Methylated Genes in Colorectal Cancer Verified by Stool DNA Test. Genes 2021, 12, 1539

by Yi-Chiao Cheng, Po-Hsien Wu, Yen-Ju Chen, Cing-Han Yang, Jhen-Li Huang, Yu-Ching Chou, Pi-Kai Chang, Chia-Cheng Wen, Shu-Wen Jao, Hsin-Hui Huang, Yi-Hsuan Tsai and Tun-Wen Pai

Genes 2024, 15(6), 805; https://0-doi-org.brum.beds.ac.uk/10.3390/genes15060805 - 19 Jun 2024

Viewed by 78

Abstract

The Genes journal retracts the article “Using Comorbidity Pattern Analysis to Detect Reliable Methylated Genes in Colorectal Cancer Verified by Stool DNA Test” [...] Full article

15 pages, 1226 KiB

Open AccessArticle

Genetic and Clinical Analyses of the KIZ-c.226C>T Variant Resulting in a Dual Mutational Mechanism

by Yogapriya Sundaresan, Antonio Rivera, Alexey Obolensky, Prakadeeswari Gopalakrishnan, Hanit Ohayon Hadad, Aya Shemesh, Samer Khateb, Maya Ross, Ron Ofri, Sharon Durst, Hadas Newman, Rina Leibu, Shiri Soudry, Dinah Zur, Tamar Ben-Yosef, Eyal Banin and Dror Sharon

Genes 2024, 15(6), 804; https://0-doi-org.brum.beds.ac.uk/10.3390/genes15060804 - 18 Jun 2024

Viewed by 327

Abstract

Retinitis pigmentosa (RP) is a heterogeneous inherited retinal disorder. Mutations in KIZ cause autosomal recessive (AR) RP. We aimed to characterize the genotype, expression pattern, and phenotype in a large cohort of KIZ cases. Sanger and whole exome sequencing were used to identify [...] Read more.

Retinitis pigmentosa (RP) is a heterogeneous inherited retinal disorder. Mutations in KIZ cause autosomal recessive (AR) RP. We aimed to characterize the genotype, expression pattern, and phenotype in a large cohort of KIZ cases. Sanger and whole exome sequencing were used to identify the KIZ variants. Medical records were reviewed and analyzed. Thirty-one patients with biallelic KIZ mutations were identified: 28 homozygous for c.226C>T (p.R76*), 2 compound heterozygous for p.R76* and c.3G>A (p.M1?), and one homozygous for c.247C>T (p.R83*). c.226C>T is a founder mutation among patients of Jewish descent. The clinical parameters were less severe in KIZ compared to DHDDS and FAM161A cases. RT-PCR analysis in fibroblast cells revealed the presence of four different transcripts in both WT and mutant samples with a lower percentage of the WT transcript in patients. Sequence analysis identified an exonic sequence enhancer (ESE) that includes the c.226 position which is affected by the mutation. KIZ mutations are an uncommon cause of IRD worldwide but are not rare among Ashkenazi Jews. Our data indicate that p.R76* affect an ESE which in turn results in the pronounced skipping of exon 3. Therefore, RNA-based therapies might show low efficacy since the mutant transcripts are spliced. Full article

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

14 pages, 869 KiB

Open AccessArticle

Associations between Radiomics and Genomics in Non-Small Cell Lung Cancer Utilizing Computed Tomography and Next-Generation Sequencing: An Exploratory Study

by Alessandro Ottaiano, Francesca Grassi, Roberto Sirica, Emanuela Genito, Giovanni Ciani, Vittorio Patanè, Riccardo Monti, Maria Paola Belfiore, Fabrizio Urraro, Mariachiara Santorsola, Alfonso Maria Ponsiglione, Marco Montella, Salvatore Cappabianca, Alfonso Reginelli, Mario Sansone, Giovanni Savarese and Roberta Grassi

Genes 2024, 15(6), 803; https://0-doi-org.brum.beds.ac.uk/10.3390/genes15060803 - 18 Jun 2024

Viewed by 221

Abstract

Background: Radiomics, an evolving paradigm in medical imaging, involves the quantitative analysis of tumor features and demonstrates promise in predicting treatment responses and outcomes. This study aims to investigate the predictive capacity of radiomics for genetic alterations in non-small cell lung cancer (NSCLC). [...] Read more.

Background: Radiomics, an evolving paradigm in medical imaging, involves the quantitative analysis of tumor features and demonstrates promise in predicting treatment responses and outcomes. This study aims to investigate the predictive capacity of radiomics for genetic alterations in non-small cell lung cancer (NSCLC). Methods: This exploratory, observational study integrated radiomic perspectives using computed tomography (CT) and genomic perspectives through next-generation sequencing (NGS) applied to liquid biopsies. Associations between radiomic features and genetic mutations were established using the Area Under the Receiver Operating Characteristic curve (AUC-ROC). Machine learning techniques, including Support Vector Machine (SVM) classification, aim to predict genetic mutations based on radiomic features. The prognostic impact of selected gene variants was assessed using Kaplan–Meier curves and Log-rank tests. Results: Sixty-six patients underwent screening, with fifty-seven being comprehensively characterized radiomically and genomically. Predominantly males (68.4%), adenocarcinoma was the prevalent histological type (73.7%). Disease staging is distributed across I/II (38.6%), III (31.6%), and IV (29.8%). Significant correlations were identified with mutations of ROS1 p.Thr145Pro (shape_Sphericity), ROS1 p.Arg167Gln (glszm_ZoneEntropy, firstorder_TotalEnergy), ROS1 p.Asp2213Asn (glszm_GrayLevelVariance, firstorder_RootMeanSquared), and ALK p.Asp1529Glu (glcm_Imc1). Patients with the ROS1 p.Thr145Pro variant demonstrated markedly shorter median survival compared to the wild-type group (9.7 months vs. not reached, p = 0.0143; HR: 5.35; 95% CI: 1.39–20.48). Conclusions: The exploration of the intersection between radiomics and cancer genetics in NSCLC is not only feasible but also holds the potential to improve genetic predictions and enhance prognostic accuracy. Full article

(This article belongs to the Special Issue Molecular Diagnostic and Prognostic Markers of Human Cancers)

10 pages, 616 KiB

Open AccessArticle

Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2 Caused by a Novel PIGA Variant Not Associated with a Skewed X-Inactivation Pattern

by Alba Gabaldon-Albero, Lourdes Cordon, Amparo Sempere, Laia Pedrola, Carla Martin-Grau, Silvestre Oltra, Sandra Monfort, Alfonso Caro-Llopis, Marta Dominguez-Martinez, Sara Hernandez-Muela, Monica Rosello, Carmen Orellana and Francisco Martinez

Genes 2024, 15(6), 802; https://0-doi-org.brum.beds.ac.uk/10.3390/genes15060802 - 18 Jun 2024

Viewed by 148

Abstract

Germline variants in the phosphatidylinositol glycan class A (PIGA) gene, which is involved in glycosylphosphatidylinositol (GPI) biosynthesis, cause multiple congenital anomalies-hypotonia-seizures syndrome 2 (MCAHS2) with X-linked recessive inheritance. The available literature has described a pattern of almost 100% X-chromosome inactivation in [...] Read more.

Germline variants in the phosphatidylinositol glycan class A (PIGA) gene, which is involved in glycosylphosphatidylinositol (GPI) biosynthesis, cause multiple congenital anomalies-hypotonia-seizures syndrome 2 (MCAHS2) with X-linked recessive inheritance. The available literature has described a pattern of almost 100% X-chromosome inactivation in mothers carrying PIGA variants. Here, we report a male infant with MCAHS2 caused by a novel PIGA variant inherited from his mother, who has a non-skewed pattern of X inactivation. Phenotypic evidence supporting the pathogenicity of the variant was obtained by flow-cytometry tests. We propose that the assessment in neutrophils of the expression of GPI-anchored proteins (GPI-APs), especially CD16, should be considered in cases with variants of unknown significance with random X-inactivation in carrier mothers in order to clarify the pathogenic role of PIGA or other gene variants linked to the synthesis of GPI-APs. Full article

(This article belongs to the Special Issue Application of Next-Generation Sequencing in Genetic Diseases Diagnosis)

14 pages, 1337 KiB

Open AccessArticle

Genome-Wide Characterization of Somatic Mutation Patterns in Cloned Dogs Reveals Implications for Neuronal Function, Tumorigenesis, and Aging

by Seung-Wan Woo, Miju Kim, Dayeon Kang, Yong-ho Choe, Seong-Ju Oh, Are-Sun You, Sung-Lim Lee and Jaemin Kim

Genes 2024, 15(6), 801; https://0-doi-org.brum.beds.ac.uk/10.3390/genes15060801 - 18 Jun 2024

Viewed by 141

Abstract

Studies on somatic mutations in cloned animals have revealed slight genetic variances between clones and their originals, but have yet to identify the precise effects of these differences within the organism. Somatic mutations contribute to aging and are implicated in tumor development and [...] Read more.

Studies on somatic mutations in cloned animals have revealed slight genetic variances between clones and their originals, but have yet to identify the precise effects of these differences within the organism. Somatic mutations contribute to aging and are implicated in tumor development and other age-related diseases. Thus, we compared whole genome sequencing data from an original dog with that of cloned dogs, identifying candidate somatic mutations that were disproportionately located within genes previously implicated in aging. The substitutional signature of cloning-specific somatic mutations mirrored the uniform distribution characteristic of the signature associated with human aging. Further analysis of genes revealed significant enrichment of traits associated with body size as well as the molecular mechanisms underlying neuronal function and tumorigenesis. Overall, the somatic mutations found in cloned dogs may indicate a conserved mechanism driving aging across species and a broad spectrum of pathway alterations. Full article

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

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19 pages, 8925 KiB

Open AccessArticle

Genome-Wide Identification of WRKY Transcription Factor Family in Chinese Rose and Response to Drought, Heat, and Salt Stress

by Xinyu Yan, Jiahui Zhao, Wei Huang, Cheng Liu, Xuan Hao, Chengye Gao, Minghua Deng and Jinfen Wen

Genes 2024, 15(6), 800; https://0-doi-org.brum.beds.ac.uk/10.3390/genes15060800 - 18 Jun 2024

Viewed by 157

Abstract

The WRKY gene family is a key transcription factor family for plant development and the stress response. However, few studies have investigated the WRKY gene family in Chinese rose (Rosa chinensis). In this study, 68 RcWRKY genes were identified from the [...] Read more.

The WRKY gene family is a key transcription factor family for plant development and the stress response. However, few studies have investigated the WRKY gene family in Chinese rose (Rosa chinensis). In this study, 68 RcWRKY genes were identified from the Chinese rose genome and classified into three primary groups and five subgroups based on the structural and phylogenetic characteristics. The analysis of the conserved domains, motifs, and gene structure revealed that the RcWRKY genes within the same group had the same exon–intron organization and composition. Chromosome mapping and gene duplication revealed that the RcWRKY genes were randomly dispersed across seven chromosomes. Fragment duplication and refined selection may have influenced the evolution of the WRKY gene family in Chinese rose. The cis-acting elements in the WRKY promoter region revealed that the RcWRKY genes contained numerous abiotic stress response elements. The results of qRT-PCR revealed that the expression of RcWRKY was tissue-specific, with high expression being observed under drought, heat, and salt stress. Notably, RcWRKY49′s expression increased more than fivefold following salt stress, indicating that it is a crucial gene mediating the salt stress response of Chinese rose. These findings shed light on the regulatory role of RcWRKY in the growth and development of Chinese rose, and they serve as a foundation for future molecular breeding programs and gene discovery. Full article

(This article belongs to the Special Issue Genetics and Breeding of Horticulture Crops)

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14 pages, 4793 KiB

Open AccessFeature PaperArticle

Blau Syndrome: Challenging Molecular Genetic Diagnostics of Autoinflammatory Disease

by Michaela Brichova, Aneta Klimova, Jarmila Heissigerova, Petra Svozilkova, Manuela Vaneckova, Pavla Dolezalova, Dana Nemcova, Marcela Michalickova, Jana Jedlickova, Lubica Dudakova and Petra Liskova

Genes 2024, 15(6), 799; https://0-doi-org.brum.beds.ac.uk/10.3390/genes15060799 - 18 Jun 2024

Viewed by 182

Abstract

The aim of this study was to describe the clinical and molecular genetic findings in seven individuals from three unrelated families with Blau syndrome. A complex ophthalmic and general health examination including diagnostic imaging was performed. The NOD2 mutational hot spot located in [...] Read more.

The aim of this study was to describe the clinical and molecular genetic findings in seven individuals from three unrelated families with Blau syndrome. A complex ophthalmic and general health examination including diagnostic imaging was performed. The NOD2 mutational hot spot located in exon 4 was Sanger sequenced in all three probands. Two individuals also underwent autoinflammatory disorder gene panel screening, and in one subject, exome sequencing was performed. Blau syndrome presenting as uveitis, skin rush or arthritis was diagnosed in four cases from three families. In two individuals from one family, only camptodactyly was noted, while another member had camptodactyly in combination with non-active uveitis and angioid streaks. One proband developed two attacks of meningoencephalitis attributed to presumed neurosarcoidosis, which is a rare finding in Blau syndrome. The probands from families 1 and 2 carried pathogenic variants in NOD2 (NM_022162.3): c.1001G>A p.(Arg334Gln) and c.1000C>T p.(Arg334Trp), respectively. In family 3, two variants of unknown significance in a heterozygous state were found: c.1412G>T p.(Arg471Leu) in NOD2 and c.928C>T p.(Arg310*) in NLRC4 (NM_001199139.1). In conclusion, Blau syndrome is a phenotypically highly variable, and there is a need to raise awareness about all clinical manifestations, including neurosarcoidosis. Variants of unknown significance pose a significant challenge regarding their contribution to etiopathogenesis of autoinflammatory diseases. Full article

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

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18 pages, 1325 KiB

Open AccessReview

Signaling Pathways Governing Cardiomyocyte Differentiation

by Isaiah K. Mensah and Humaira Gowher

Genes 2024, 15(6), 798; https://0-doi-org.brum.beds.ac.uk/10.3390/genes15060798 - 18 Jun 2024

Viewed by 326

Abstract

Cardiomyocytes are the largest cell type that make up the heart and confer beating activity to the heart. The proper differentiation of cardiomyocytes relies on the efficient transmission and perception of differentiation cues from several signaling pathways that influence cardiomyocyte-specific gene expression programs. [...] Read more.

Cardiomyocytes are the largest cell type that make up the heart and confer beating activity to the heart. The proper differentiation of cardiomyocytes relies on the efficient transmission and perception of differentiation cues from several signaling pathways that influence cardiomyocyte-specific gene expression programs. Signaling pathways also mediate intercellular communications to promote proper cardiomyocyte differentiation. We have reviewed the major signaling pathways involved in cardiomyocyte differentiation, including the BMP, Notch, sonic hedgehog, Hippo, and Wnt signaling pathways. Additionally, we highlight the differences between different cardiomyocyte cell lines and the use of these signaling pathways in the differentiation of cardiomyocytes from stem cells. Finally, we conclude by discussing open questions and current gaps in knowledge about the in vitro differentiation of cardiomyocytes and propose new avenues of research to fill those gaps. Full article

(This article belongs to the Section Epigenomics)

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12 pages, 251 KiB

Open AccessArticle

Identification of Polymorphisms in EAAT1 Glutamate Transporter Gene SLC1A3 Associated with Reduced Migraine Risk

by Cassie L. Albury, Heidi G. Sutherland, Alexis W. Y. Lam, Ngan K. Tran, Rod A. Lea, Larisa M. Haupt and Lyn R. Griffiths

Genes 2024, 15(6), 797; https://0-doi-org.brum.beds.ac.uk/10.3390/genes15060797 - 18 Jun 2024

Viewed by 213

Abstract

Dysfunction in ion channels or processes involved in maintaining ionic homeostasis is thought to lower the threshold for cortical spreading depression (CSD), and plays a role in susceptibility to associated neurological disorders, including pathogenesis of a migraine. Rare pathogenic variants in specific ion [...] Read more.

Dysfunction in ion channels or processes involved in maintaining ionic homeostasis is thought to lower the threshold for cortical spreading depression (CSD), and plays a role in susceptibility to associated neurological disorders, including pathogenesis of a migraine. Rare pathogenic variants in specific ion channels have been implicated in monogenic migraine subtypes. In this study, we further examined the channelopathic nature of a migraine through the analysis of common genetic variants in three selected ion channel or transporter genes: SLC4A4, SLC1A3, and CHRNA4. Using the Agena MassARRAY platform, 28 single-nucleotide polymorphisms (SNPs) across the three candidate genes were genotyped in a case–control cohort comprised of 182 migraine cases and 179 matched controls. Initial results identified significant associations between migraine and rs3776578 (p = 0.04) and rs16903247 (p = 0.05) genotypes within the SLC1A3 gene, which encodes the EAAT1 glutamate transporter. These SNPs were subsequently genotyped in an independent cohort of 258 migraine cases and 290 controls using a high-resolution melt assay, and association testing supported the replication of initial findings—rs3776578 (p = 0.0041) and rs16903247 (p = 0.0127). The polymorphisms are in linkage disequilibrium and localise within a putative intronic enhancer region of SLC1A3. The minor alleles of both SNPs show a protective effect on migraine risk, which may be conferred via influencing the expression of SLC1A3. Full article

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

15 pages, 2067 KiB

Open AccessArticle

Genetic Analysis of Egg Production Traits in Luhua Chickens: Insights from a Multi-Trait Animal Model and a Genome-Wide Association Study

by Qianwen Yang, Xubin Lu, Guohui Li, Huiyong Zhang, Chenghao Zhou, Jianmei Yin, Wei Han and Haiming Yang

Genes 2024, 15(6), 796; https://0-doi-org.brum.beds.ac.uk/10.3390/genes15060796 - 17 Jun 2024

Viewed by 217

Abstract

Egg production plays a pivotal role in the economic viability of hens. To analyze the genetic rules of egg production, a total of 3151 Luhua chickens were selected, the egg production traits including egg weight at first laying (Start-EW), egg weight at 43 [...] Read more.

Egg production plays a pivotal role in the economic viability of hens. To analyze the genetic rules of egg production, a total of 3151 Luhua chickens were selected, the egg production traits including egg weight at first laying (Start-EW), egg weight at 43 weeks (EW-43), egg number at 43 weeks (EN-43), and total egg number (EN-All) were recorded. Then, the effects of related factors on egg production traits were explored, using a multi-trait animal model for genetic parameter estimation and a genome-wide association study (GWAS). The results showed that body weight at first egg (BWFE), body weight at 43 weeks (BW-43), age at first egg (AFE), and seasons had significant effects on the egg production traits. Start-EW and EW-43 had moderate heritability of 0.30 and 0.21, while EN-43 and EN-All had low heritability of 0.13 and 0.16, respectively. Start-EW exhibited a robust positive correlation with EW-43, while Start-EW was negatively correlated with EN-43 and EN-All. Furthermore, gene ontology (GO) results indicated that Annexin A2 (ANXA2) and Frizzled family receptor 7 (FZD7) related to EW-43, Cyclin D1 (CCND1) and A2B adenosine receptor (ADORA2B) related to EN-All, and have been found to be mainly involved in metabolism and growth processes, and deserve more attention and further study. This study contributes to accelerating genetic progress in improving low heritability egg production traits in layers, especially in Luhua chickens. Full article

(This article belongs to the Special Issue Poultry Breeding and Genetics)

12 pages, 1217 KiB

Open AccessArticle

Genomic Characterization of Quality Wool Traits in Spanish Merino Sheep

by Gabriel Anaya, Nora Laseca, Antonio Granero, Chiraz Ziadi, Francisco Arrebola, Andrés Domingo and Antonio Molina

Genes 2024, 15(6), 795; https://0-doi-org.brum.beds.ac.uk/10.3390/genes15060795 - 17 Jun 2024

Viewed by 215

Abstract

The native Spanish Merino breed was the founder of all the other Merino and Merino-derived breeds worldwide. Despite the fact that this breed was created and improved to produce the highest quality fine wool, the global wool market crisis led to the wholescale [...] Read more.

The native Spanish Merino breed was the founder of all the other Merino and Merino-derived breeds worldwide. Despite the fact that this breed was created and improved to produce the highest quality fine wool, the global wool market crisis led to the wholescale crossing of most of the herds with breeds for meat purposes. Nevertheless, there are still some purebred animals with a high potential for producing quality wool. The objective of this study was to characterize the current wool quality of the breed and identify genes associated with these parameters. To achieve this, over 12,800 records from the most representative animals of the breed (registered in the herd book) were analyzed using the Australian OFDA 2000 system, for parameters such as fiber diameter (FD), standard deviation (SD), coefficient of variation (CV), fibers over 15 microns (>15%), staple length (SL), and comfort factor (CRV). Additionally, animals with the most extreme FD values were whole-genome sequenced using NGS. Genome-wide association studies (GWAS) determined the association of 74 variants with the different traits studied, which were located in 70 different genes. Of these genes, EDN2, COL18A1, and LRP1B, associated with fibers over 15%, and FGF12 and ADAM17, associated with SL, play a key role in hair follicle growth and development. Our study reveals the great potential for recovering this breed for fine wool production, and identifies five candidate genes whose understanding may aid in that selection process. Full article

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

13 pages, 1898 KiB

Open AccessArticle

Assessing Falling Number Stability Increases the Genomic Prediction Ability of Pre-Harvest Sprouting Resistance in Common Winter Wheat

by Theresa Albrecht, Michael Oberforster, Lorenz Hartl and Volker Mohler

Genes 2024, 15(6), 794; https://0-doi-org.brum.beds.ac.uk/10.3390/genes15060794 - 17 Jun 2024

Viewed by 202

Abstract

Pre-harvest sprouting (PHS) resistance is a complex trait, and many genes influencing the germination process of winter wheat have already been described. In the light of interannual climate variation, breeding for PHS resistance will remain mandatory for wheat breeders. Several tests and traits [...] Read more.

Pre-harvest sprouting (PHS) resistance is a complex trait, and many genes influencing the germination process of winter wheat have already been described. In the light of interannual climate variation, breeding for PHS resistance will remain mandatory for wheat breeders. Several tests and traits are used to assess PHS resistance, i.e., sprouting scores, germination index, and falling number (FN), but the variation of these traits is highly dependent on the weather conditions during field trials. Here, we present a method to assess falling number stability (FNS) employing an after-ripening period and the wetting of the kernels to improve trait variation and thus trait heritability. Different genome-based prediction scenarios within and across two subsequent seasons based on overall 400 breeding lines were applied to assess the predictive abilities of the different traits. Based on FNS, the genome-based prediction of the breeding values of wheat breeding material showed higher correlations across seasons (

r = 0.505 - 0.548

) compared to those obtained for other traits for PHS assessment (

r = 0.216 - 0.501

). By weighting PHS-associated quantitative trait loci (QTL) in the prediction model, the average predictive abilities for FNS increased from 0.585 to 0.648 within the season 2014/2015 and from 0.649 to 0.714 within the season 2015/2016. We found that markers in the Phs-A1 region on chromosome 4A had the highest effect on the predictive abilities for FNS, confirming the influence of this QTL in wheat breeding material, whereas the dwarfing genes Rht-B1 and Rht-D1 and the wheat–rye translocated chromosome T1RS.1BL exhibited effects, which are well-known, on FN per se exclusively. Full article

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

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12 pages, 2948 KiB

Open AccessArticle

Genome-Wide Identification and Expression Profiling of the α-Amylase (AMY) Gene Family in Potato

by Yudan Duan and Liping Jin

Genes 2024, 15(6), 793; https://0-doi-org.brum.beds.ac.uk/10.3390/genes15060793 - 17 Jun 2024

Viewed by 250

Abstract

Starch degradation provides energy and signaling molecules for plant growth, development, defense, and stress response. α-amylase (AMY) is one of the most important enzymes in this process. Potato tubers are rich in starch, and the hydrolysis of starch into sugar negatively [...] Read more.

Starch degradation provides energy and signaling molecules for plant growth, development, defense, and stress response. α-amylase (AMY) is one of the most important enzymes in this process. Potato tubers are rich in starch, and the hydrolysis of starch into sugar negatively impacts the frying quality of potato. Despite its importance, the AMY gene family has not been fully explored in potatoes. Here, we performed a detailed analysis of the StAMY gene family to determine its role in potato. Twenty StAMY genes were identified across the potato genome and were divided into three subgroups. The promoters of StAMY genes contained an array of cis-acting elements involved in growth and development, phytohormone signaling, and stress and defense responses. StAMY8, StAMY9, StAMY12, and StAMY20 were specifically expressed in mature tubers. Different StAMY gene family members tended to be upregulated in response to β-aminobutyric acid (BABA), Phytophthora infestans (P. infestans), benzothiadiazole (BTH), heat, salt, and drought stress. In addition, different StAMY gene family members tended to be responsive to abscisic acid (ABA), indole-3-acetic acid (IAA), gibberellic acid (GA3), and 6-benzylaminopurine (BAP) treatment. These results suggest that StAMY gene family members may be involved in starch and sugar metabolism, defense, stress response, and phytohormone signaling. The results of this study may be applicable to other starchy crops and lay a foundation for further research on the functions and regulatory mechanisms of AMY genes. Full article

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

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10 pages, 1202 KiB

Open AccessArticle

Significance of Multi-Cancer Genome Profiling Testing for Breast Cancer: A Retrospective Analysis of 3326 Cases from Japan’s National Database

by Kyoka Kawabata, Hinano Nishikubo, Saki Kanei, Rika Aoyama, Yuki Tsukada, Tomoya Sano, Daiki Imanishi, Takashi Sakuma, Koji Maruo, Yurie Yamamoto, Qiang Wang, Zhonglin Zhu, Canfeng Fan and Masakazu Yashiro

Genes 2024, 15(6), 792; https://0-doi-org.brum.beds.ac.uk/10.3390/genes15060792 - 17 Jun 2024

Viewed by 299

Abstract

Background: Breast cancer (BC) has the highest morbidity rate and the second-highest mortality rate of all cancers among women. Recently, multi-cancer genome profiling (multi-CGP) tests have become clinically available. In this study, we aimed to clarify the significance of multi-CGP testing of BC [...] Read more.

Background: Breast cancer (BC) has the highest morbidity rate and the second-highest mortality rate of all cancers among women. Recently, multi-cancer genome profiling (multi-CGP) tests have become clinically available. In this study, we aimed to clarify the significance of multi-CGP testing of BC by using the large clinical dataset from The Center for Cancer Genomics and Advanced Therapeutics (C-CAT) profiling database in Japan. Materials and Methods: A total of 3744 BC cases were extracted from the C-CAT database, which enrolled 60,250 patients between June 2019 and October 2023. Of the 3744 BC cases, a total of 3326 cases for which the C-CAT included information on ER, PR, and HER2 status were classified into four subtypes, including TNBC, HR+/HER2−, HR+/HER2+, and HR−/HER2+. Comparisons between groups were performed by the χ² test or Fisher’s exact test using EZR. Kaplan–Meier curves were created using the log-rank test. Results: Of all 3326 cases analyzed, 1114 (33.5%) were TNBC cases, HR+/HER2− accounted for 1787 cases (53.7%), HR+/HER2+ for 260 cases (7.8%), and HR−/HER2+ for 165 cases (5.0%). Genetic abnormalities were most frequently detected in TP53 (58.0%), PIK3CA (35.5%), MYC (18.7%), FGF19 (15.5%), and GATA3 (15.1%) across all BCs. The rate of TMB-High was 12.3%, and the rate of MSI-High was 0.3%, in all BC cases. Therapeutic drugs were proposed for patients with mutations in six genes: PIK3CA, ERBB2, PTEN, FGFR1, ESR1, and AKT1. The prognoses of HR+/HER2− cases were significantly (p = 0.044) better in the treated group than in the untreated group. Conclusions: These findings suggest that cancer gene panel testing is useful for HR+/HER2− cases. Full article

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

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16 pages, 5599 KiB

Open AccessArticle

by Rajech Sharkia, Abdelnaser Zalan, Amit Kessel, Wasif Al-Shareef, Hazar Zahalka, Holger Hengel, Ludger Schöls, Abdussalam Azem and Muhammad Mahajnah

Genes 2024, 15(6), 791; https://0-doi-org.brum.beds.ac.uk/10.3390/genes15060791 - 16 Jun 2024

Viewed by 230

Abstract

Mutations in the gene SCAPER (S phase Cyclin A-Associated Protein residing in the Endoplasmic Reticulum) have recently been associated with retinitis pigmentosa (RP) and intellectual disability (ID). In 2011, a possible involvement of SCAPER in human diseases was discovered for the first time [...] Read more.

Mutations in the gene SCAPER (S phase Cyclin A-Associated Protein residing in the Endoplasmic Reticulum) have recently been associated with retinitis pigmentosa (RP) and intellectual disability (ID). In 2011, a possible involvement of SCAPER in human diseases was discovered for the first time due to the identification of a homozygous mutation causing ID in an Iranian family. Later, five studies were published in 2019 that described patients with autosomal recessive syndromic retinitis pigmentosa (arRP) accompanied by ID and attention-deficit/hyperactivity disorder (ADHD). This present study describes three patients from an Arab consanguineous family in Israel with similar clinical features of the SCAPER syndrome. In addition, new manifestations of ocular symptoms, nystagmus, glaucoma, and elevator palsy, were observed. Genetic testing of the patients and both parents via whole-exome sequencing revealed the homozygous mutation c.2023–2A>G in SCAPER. Phenotypic and genotypic descriptions for all available cases described in the literature including our current three cases (37 cases) were carried out, in addition to a bioinformatics analysis for all the genetic variants that was undertaken. Our study confirms and extends the clinical manifestations of SCAPER-related disorders. Full article

(This article belongs to the Special Issue Variations of Rare Genetic Diseases)

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12 pages, 3861 KiB

Open AccessArticle

Ancient Mitochondrial Genomes Provide New Clues in the History of the Akhal-Teke Horse in China

by Siqi Zhu, Naifan Zhang, Jie Zhang, Xinyue Shao, Yaqi Guo and Dawei Cai

Genes 2024, 15(6), 790; https://0-doi-org.brum.beds.ac.uk/10.3390/genes15060790 - 15 Jun 2024

Viewed by 271

Abstract

This study analyzed ancient DNA from the remains of horses unearthed from the Shihuyao tombs. These were found to date from the Han and Tang Dynasties in Xinjiang (approximately 2200 to 1100 years ago). Two high-quality mitochondrial genomes were acquired and analyzed using [...] Read more.

This study analyzed ancient DNA from the remains of horses unearthed from the Shihuyao tombs. These were found to date from the Han and Tang Dynasties in Xinjiang (approximately 2200 to 1100 years ago). Two high-quality mitochondrial genomes were acquired and analyzed using next-generation sequencing. The genomes were split into two maternal haplogroups, B and D, according to a study that included ancient and contemporary samples from Eurasia. A close genetic affinity was observed between the horse of the Tang Dynasty and Akhal-Teke horses according to the primitive horse haplotype G1. Historical evidence suggests that the ancient Silk Road had a vital role in their dissemination. Additionally, the matrilineal history of the Akhal-Teke horse was accessed and suggested that the early domestication of the breed was for military purposes. Full article

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

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