Genes

22 pages, 4503 KiB

Open AccessEditor’s ChoiceArticle

Amplicon-Based Microbiome Profiling: From Second- to Third-Generation Sequencing for Higher Taxonomic Resolution

by Elisabetta Notario, Grazia Visci, Bruno Fosso, Carmela Gissi, Nina Tanaskovic, Maria Rescigno, Marinella Marzano and Graziano Pesole

Genes 2023, 14(8), 1567; https://doi.org/10.3390/genes14081567 - 31 Jul 2023

Cited by 18 | Viewed by 5091

Abstract

The 16S rRNA amplicon-based sequencing approach represents the most common and cost-effective strategy with great potential for microbiome profiling. The use of second-generation sequencing (NGS) technologies has led to protocols based on the amplification of one or a few hypervariable regions, impacting the [...] Read more.

The 16S rRNA amplicon-based sequencing approach represents the most common and cost-effective strategy with great potential for microbiome profiling. The use of second-generation sequencing (NGS) technologies has led to protocols based on the amplification of one or a few hypervariable regions, impacting the outcome of the analysis. Nowadays, comparative studies are necessary to assess different amplicon-based approaches, including the full-locus sequencing currently feasible thanks to third-generation sequencing (TGS) technologies. This study compared three different methods to achieve the deepest microbiome taxonomic characterization: (a) the single-region approach, (b) the multiplex approach, covering several regions of the target gene/region, both based on NGS short reads, and (c) the full-length approach, which analyzes the whole length of the target gene thanks to TGS long reads. Analyses carried out on benchmark microbiome samples, with a known taxonomic composition, highlighted a different classification performance, strongly associated with the type of hypervariable regions and the coverage of the target gene. Indeed, the full-length approach showed the greatest discriminating power, up to species level, also on complex real samples. This study supports the transition from NGS to TGS for the study of the microbiome, even if experimental and bioinformatic improvements are still necessary. Full article

(This article belongs to the Special Issue Microbiome Analysis Techniques and Discovery)

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13 pages, 4201 KiB

Open AccessEditor’s ChoiceArticle

Current Classification of Canine Muscular Dystrophies and Identification of New Variants

by G. Diane Shelton, Katie M. Minor, Steven G. Friedenberg, Jonah N. Cullen, Ling T. Guo and James R. Mickelson

Genes 2023, 14(8), 1557; https://doi.org/10.3390/genes14081557 - 29 Jul 2023

Cited by 8 | Viewed by 3268

Abstract

The spectrum of canine muscular dystrophies has rapidly grown with the recent identification of several more affected breeds and associated mutations. Defects include those in genes and protein products associated with the sarcolemma (dystrophin deficient X-linked muscular dystrophy and sarcoglycan-deficient limb–girdle muscular dystrophy) [...] Read more.

The spectrum of canine muscular dystrophies has rapidly grown with the recent identification of several more affected breeds and associated mutations. Defects include those in genes and protein products associated with the sarcolemma (dystrophin deficient X-linked muscular dystrophy and sarcoglycan-deficient limb–girdle muscular dystrophy) and with the extracellular matrix (collagen 6, laminin α2, and α-dystroglycan-deficient congenital muscular dystrophies). With the increasing application of whole genome sequencing and whole exome sequencing, the clinical and pathological spectra associated with specific neuromuscular genetic defects are constantly evolving. In this report, we provide a brief overview of the current status of gene defects reported in canine muscular dystrophies. We also report the causative mutations for novel forms of X-linked muscular dystrophy in Brittany spaniels and in a French bulldog. Full article

(This article belongs to the Special Issue Companion Animal Genetics and Genomics)

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13 pages, 4892 KiB

Open AccessEditor’s ChoiceArticle

High Atlastin 2-2 (ATL2-2) Expression Associates with Worse Prognosis in Estrogen-Receptor-Positive Breast Cancer

by Inga Reynisdottir, Adalgeir Arason, Edda S. Freysteinsdottir, Sigrun B. Kristjansdottir, Bylgja Hilmarsdottir, Gunnhildur A. Traustadottir, Oskar T. Johannsson, Bjarni A. Agnarsson and Rosa B. Barkardottir

Genes 2023, 14(8), 1559; https://doi.org/10.3390/genes14081559 - 29 Jul 2023

Cited by 2 | Viewed by 2398

Abstract

The disruption of endoplasmic reticulum (ER) homeostasis occurs in many human diseases. Atlastins (ATLs) maintain the branched network of the ER. The dysregulation of ATL2, located at ER network junctions, has been associated with cancer. ATL2 is necessary for lipid droplet formation in [...] Read more.

The disruption of endoplasmic reticulum (ER) homeostasis occurs in many human diseases. Atlastins (ATLs) maintain the branched network of the ER. The dysregulation of ATL2, located at ER network junctions, has been associated with cancer. ATL2 is necessary for lipid droplet formation in murine breast tissue. Thus, we analyzed whether ATL2 has a role in human breast cancer (BC) pathology. The expression of ATL2 variant ATL2-2 was analyzed in breast tumors from the BC cohorts of the TCGA, METABRIC, and two independent Icelandic cohorts, Cohort 1 and 2; its association with clinical, pathological, survival, and cellular pathways was explored. ATL2-2 mRNA and protein expression were higher in breast tumors than in normal tissue. ATL2-2 mRNA associated with tumor characteristics that indicate a worse prognosis. In METABRIC, high ATL2-2 mRNA levels were associated with shorter BC-specific survival (BCSS) in patients with estrogen-receptor-positive luminal breast tumors, which remained significant after correction for grade and tumor size (HR 1.334, CI 1.063–1.673). Tumors with high ATL2 mRNA showed an upregulation of hallmark pathways MYC targets v1, E2F targets, and G2M checkpoint genes. Taken together, the results suggest that high levels of ATL2-2 may support BC progression through key cancer driver pathways. Full article

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

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20 pages, 4494 KiB

Open AccessEditor’s ChoiceArticle

Mutations of BRCA1, BRCA2, and PALB2 Genes in Breast Tumor Tissue: Relationship with the Effectiveness of Neoadjuvant Chemotherapy and Disease Prognosis

by Matvey M. Tsyganov, Sofia S. Sorokovikova, Elizaveta A. Lutzkaya and Marina K. Ibragimova

Genes 2023, 14(8), 1554; https://doi.org/10.3390/genes14081554 - 28 Jul 2023

Cited by 2 | Viewed by 2260

Abstract

It has been shown that the loss of function of the BRCA1, BRCA2, and PALB2 genes due to a number of hereditary mutations or chromosomal aberrations can affect the effectiveness of chemotherapy treatment and disease prognosis in patients with various types [...] Read more.

It has been shown that the loss of function of the BRCA1, BRCA2, and PALB2 genes due to a number of hereditary mutations or chromosomal aberrations can affect the effectiveness of chemotherapy treatment and disease prognosis in patients with various types of cancer, and in particular in breast cancer. Thus, the aim of the work was to evaluate the predictive and prognostic potential of DNA copy number aberrations and mutations in the BRCA1, BRCA2, and PALB2 genes in breast tumors. Materials and Methods: The study included 66 patients with breast cancer. DNA copy number aberrations (CNA) were assessed by high-density CytoScanHD™ Array micro matrix analysis. Gene mutations were assessed by sequencing on the MiSeq™ Sequencing System using the Accel-Amplicon BRCA1, BRCA2, and PALB2 Panel. Results: It has been established that the presence of a normal copy number of PALB2 is associated with a lack of response to chemotherapy in Taxotere-containing treatment regimens (p = 0.05). In addition, the presence of a PALB2 deletion is associated with 100% metastatic survival rates (log-rank test p = 0.04). As a result of sequencing, 25 mutations were found in the BRCA1 gene, 42 mutations in BRCA2, and 27 mutations in the PALB2 gene. The effect of mutations on the effectiveness of treatment is controversial, but an effect on the survival of patients with breast cancer has been shown. So, in the presence of pathogenic mutations in the BRCA2 gene, 100% metastatic survival is observed (log-rank test p = 0.05), as well as in the elimination of PALB2 mutations during treatment (log-rank test p = 0.07). Conclusion: Currently, there is little data on the effect of chromosomal aberrations and mutations in the BRCA1/2 and PALB2 genes on the effectiveness of treatment and prognosis of the disease. At the same time, the study of these genes has great potential for testing focused on a personalized approach to the treatment of patients with breast cancer. Full article

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

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9 pages, 1324 KiB

Open AccessEditor’s ChoiceBrief Report

Rare IFT140-Associated Phenotype of Cranioectodermal Dysplasia and Features of Diagnostic Journey in Patients with Suspected Ciliopathies

by Margarita Sharova, Tatyana Markova, Maria Sumina, Marina Petukhova, Maria Bulakh, Oxana Ryzhkova, Tatyana Nagornova, Sofya Ionova, Andrey Marakhonov, Elena Dadali and Sergey Kutsev

Genes 2023, 14(8), 1553; https://doi.org/10.3390/genes14081553 - 28 Jul 2023

Cited by 2 | Viewed by 2570

Abstract

Here we present a patient with a cranioectodermal phenotype associated with pathogenic variants in the IFT140 gene. Most frequently, pathogenic variants in IFT140 correspond to the phenotype of Mainzer–Saldino syndrome. Only four patients have previously been described with this cranioectodermal phenotype and variants [...] Read more.

Here we present a patient with a cranioectodermal phenotype associated with pathogenic variants in the IFT140 gene. Most frequently, pathogenic variants in IFT140 correspond to the phenotype of Mainzer–Saldino syndrome. Only four patients have previously been described with this cranioectodermal phenotype and variants in IFT140. In comparison to other IFT140-cranioectodermal patients, our proband had similar skeletal features among with early onset end-stage renal failure that required kidney transplantation but did not have common ophthalmological features such as retinopathy, optic nerve atrophy, or nystagmus. Following exome sequencing, a splicing variant and exons 27–30 tandem duplication were suspected and further validated. The two other patients with Mainzer–Saldino syndrome that we described displayed a typical clinical picture but a special diagnostic journey. In both cases, at first only one pathogenic variant was detected following panel or exome NGS sequencing. Further WGS was performed for one of them where tandem duplication was found. Screening the third patient for the same tandem duplication was successful and revealed the presence of this duplication. Thus, we suggest that the description of the clinical feature polymorphism in a rare IFT140-cranioectodermal phenotype is extremely important for providing genetic counseling for families, as well as the formation of the correct diagnostic path for patients with a variant in IFT140. Full article

(This article belongs to the Section Genetic Diagnosis)

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23 pages, 4614 KiB

Open AccessEditor’s ChoiceArticle

Arabidopsis RAD16 Homologues Are Involved in UV Tolerance and Growth

by Linda Alrayes, Jake Stout and Dana Schroeder

Genes 2023, 14(8), 1552; https://doi.org/10.3390/genes14081552 - 28 Jul 2023

Cited by 3 | Viewed by 1679

Abstract

In plants, prolonged exposure to ultraviolet (UV) radiation causes harmful DNA lesions. Nucleotide excision repair (NER) is an important DNA repair mechanism that operates via two pathways: transcription coupled repair (TC-NER) and global genomic repair (GG-NER). In plants and mammals, TC-NER is initiated [...] Read more.

In plants, prolonged exposure to ultraviolet (UV) radiation causes harmful DNA lesions. Nucleotide excision repair (NER) is an important DNA repair mechanism that operates via two pathways: transcription coupled repair (TC-NER) and global genomic repair (GG-NER). In plants and mammals, TC-NER is initiated by the Cockayne Syndrome A and B (CSA/CSB) complex, whereas GG-NER is initiated by the Damaged DNA Binding protein 1/2 (DDB1/2) complex. In the yeast Saccharomyces cerevisiae (S. cerevisiae), GG-NER is initiated by the Radiation Sensitive 7 and 16, (RAD7/16) complex. Arabidopsis thaliana has two homologues of yeast RAD16, At1g05120 and At1g02670, which we named AtRAD16 and AtRAD16b, respectively. In this study, we characterized the roles of AtRAD16 and AtRAD16b. Arabidopsis rad16 and rad16b null mutants exhibited increased UV sensitivity. Moreover, AtRAD16 overexpression increased plant UV tolerance. Thus, AtRAD16 and AtRAD16b contribute to plant UV tolerance and growth. Additionally, we found physical interaction between AtRAD16 and AtRAD7. Thus, the Arabidopsis RAD7/16 complex is functional in plant NER. Furthermore, AtRAD16 makes a significant contribution to Arabidopsis UV tolerance compared to the DDB1/2 and the CSB pathways. This is the first time the role and interaction of DDB1/2, RAD7/16, and CSA/CSB components in a single system have been studied. Full article

(This article belongs to the Special Issue Gene Regulation of Abiotic Stress Responses in Plants)

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11 pages, 293 KiB

Open AccessEditor’s ChoiceArticle

miR-499a rs3746444 A>G Polymorphism Is Correlated with Type 2 Diabetes Mellitus and Diabetic Polyneuropathy in a Romanian Cohort: A Preliminary Study

by Emilia Burada, Maria-Magdalena Roșu, Raluca Elena Sandu, Florin Burada, Mihai Gabriel Cucu, Ioana Streață, Bianca Petre-Mandache, Gabriela Popescu-Hobeanu, Monica-Laura Cara, Anca-Maria Țucă, Elena Pinoșanu and Carmen Valeria Albu

Genes 2023, 14(8), 1543; https://doi.org/10.3390/genes14081543 - 27 Jul 2023

Cited by 2 | Viewed by 1756

Abstract

Type 2 diabetes mellitus (T2DM) is a common metabolic disorder that results from complex interactions of both environmental and genetic factors. Many single nucleotide polymorphisms (SNPs), including noncoding RNA genes, have been investigated for their association with susceptibility to T2DM and its complications, [...] Read more.

Type 2 diabetes mellitus (T2DM) is a common metabolic disorder that results from complex interactions of both environmental and genetic factors. Many single nucleotide polymorphisms (SNPs), including noncoding RNA genes, have been investigated for their association with susceptibility to T2DM and its complications, with little evidence available regarding Caucasians. The aim of the present study was to establish whether four miRNA SNPs (miR-27a rs895819 T>C, miR-146a rs2910164 G>C, miR-196a2 rs11614913 C>T, and miR-499a rs3746444 A>G) are correlated with susceptibility to T2DM and/or diabetic polyneuropathy (DPN) in a Romanian population. A total of 167 adult T2DM patients and 324 age- and sex-matched healthy controls were included in our study. miRNA SNPs were detected by real-time PCR using a TaqMan genotyping assay. A significant association with T2DM was observed only for the miR-499a rs3746444 A>G SNP in all the tested models, and the frequencies of both the miR-499a rs3746444 AG and the GG genotypes were higher in the T2DM patients compared to the controls. No correlation was observed for the miR-27a rs895819 T>C, miR-146a rs2910164 G>C, or miR-196a2 rs11614913 C>T SNPs in any genetic model. When we assessed the association of these SNPs with DPN separately, we found a positive association for the miR-499a rs3746444 SNP in both codominant and dominant models (OR 6.47, 95% CI: 1.71–24.47; OR 2.30, 95% CI: 1.23–4.29, respectively). In conclusion, this study shows that miR-499a rs3746444 A>G may influence both T2DM and DPN susceptibility, with carriers of the GG genotype and the G allele being at an increased risk in the Romanian population. Full article

(This article belongs to the Section RNA)

16 pages, 3172 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Danon Disease: Entire LAMP2 Gene Deletion with Unusual Clinical Presentation—Case Report and Review of the Literature

by Adel Shalata, Marina Bar-Shai, Yarin Hadid, Muhammad Mahroum, Hila Mintz, Zaher Eldin Shalata, Evgeny Radzishevsky, Jacob Genizi, Avraham Lorber, Tamar Ben-Yosef and Liat Yaniv

Genes 2023, 14(8), 1539; https://doi.org/10.3390/genes14081539 - 27 Jul 2023

Cited by 8 | Viewed by 3995

Abstract

Danon disease is a rare x-linked dominant multisystemic disorder with a clinical triad of severe cardiomyopathy, skeletal myopathy, and intellectual disability. It is caused by defects in the lysosome-associated membrane protein-2 (LAMP2) gene. Numerous different mutations in the LAMP2 protein have [...] Read more.

Danon disease is a rare x-linked dominant multisystemic disorder with a clinical triad of severe cardiomyopathy, skeletal myopathy, and intellectual disability. It is caused by defects in the lysosome-associated membrane protein-2 (LAMP2) gene. Numerous different mutations in the LAMP2 protein have been described. Danon disease is typically lethal by the mid-twenties in male patients due to cardiomyopathy and heart failure. Female patients usually present with milder and variable symptoms. This report describes a 42-year-old father and his 3-year-old daughter presenting with mild manifestations of the disease. The father has normal intellectual development and normal physical activity. At the age of 13, he was diagnosed with mild ventricular pre-excitation known as Wolf–Parkinson–White syndrome (WPWs), very mild and mostly asymptomatic cardiomyopathy and left ventricular hypertrophy, and at about the age of 25 presented with visual impairment due to cone–rod dystrophy. His daughter showed normal development and very mild asymptomatic electrocardiographic WPWs abnormalities with left mild ventricular hypertrophy. Genetic testing revealed an Xq24 microdeletion encompassing the entire LAMP2 gene. Relevant literature was reviewed as a reference for the etiology, diagnosis, treatment and case management. Full article

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

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12 pages, 1096 KiB

Open AccessEditor’s ChoiceReview

Esophageal Dysbiosis in Achalasia and Cancer Development: A Critical Review

by Francisco Tustumi, Vitor Pelogi Arienzo, Isabela Roskamp Sunye, Phellipe Fabbrini Santos Lucas, Bárbara Buccelli Colonno, Julia Grams Quintas, Elis Nogara Lisboa and Daniel José Szor

Genes 2023, 14(8), 1521; https://doi.org/10.3390/genes14081521 - 26 Jul 2023

Cited by 9 | Viewed by 3204

Abstract

Background: Microorganisms provide various benefits to their human hosts, including assisting with digestion, synthesizing certain vitamins, developing the gastrointestinal and immune systems, regulating metabolism, and protecting against some pathogens. However, microbial imbalances can cause tissue damage and contribute to inflammatory disorders and cancers. [...] Read more.

Background: Microorganisms provide various benefits to their human hosts, including assisting with digestion, synthesizing certain vitamins, developing the gastrointestinal and immune systems, regulating metabolism, and protecting against some pathogens. However, microbial imbalances can cause tissue damage and contribute to inflammatory disorders and cancers. Microbial dysbiosis refers to an imbalance or disruption in the normal composition and function of the microbial communities that inhabit various body parts, including the gut, oral cavity, skin, and reproductive tract. Emerging research suggests that microbial dysbiosis plays a significant role in cancer development and progression. This issue is particularly relevant in achalasia, in which food stasis, changes in endoluminal pH, and poor esophageal clearance might contribute to esophageal microbial dysbiosis. This study aimed to evaluate the association between dysbiosis and esophageal cancer development, focused on esophageal dysmotility disorders. Methods: This study is a critical review, gathering the current evidence for the association between dysbiosis and the development of esophageal cancer. Results: Studies have shown that microbiota play a role in cancer development, although the mechanisms for how they do so are not yet fully understood. One possible explanation is that microbiota alterations can lead to chronic inflammation, promoting cancer cell growth. Additionally, some bacteria produce toxins that can damage DNA and cause genomic instability, and certain bacterial products can promote tumor growth. Conclusion: Despite the close relationship between dysbiosis and cancer development in esophageal dysmotility disorders, further investigations are still needed to elucidate the precise mechanisms by which dysbiosis contributes to cancer development and to identify potential therapeutic interventions targeting the microbiota to prevent or treat cancer. Full article

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

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14 pages, 9034 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide RADseq Reveals Genetic Differentiation of Wild and Cultured Populations of Large Yellow Croaker

by Kaifen Zhang, Yongdong Zhou, Weihua Song, Lihua Jiang and Xiaojun Yan

Genes 2023, 14(7), 1508; https://doi.org/10.3390/genes14071508 - 24 Jul 2023

Cited by 5 | Viewed by 2602

Abstract

Larimichthys crocea (also known as the large yellow croaker) is one of the most economically important marine fishes in China, and research on the ecology and genetics of this species is of immense significance. In this study, we performed restriction site-associated DNA sequencing [...] Read more.

Larimichthys crocea (also known as the large yellow croaker) is one of the most economically important marine fishes in China, and research on the ecology and genetics of this species is of immense significance. In this study, we performed restriction site-associated DNA sequencing (RAD-seq) of 54 individuals collected from four sites in China to analyze the genetic structure and diversity of large yellow croaker at the genome level. It revealed that the large yellow croaker populations in the Ningde and Zhoushan coastal waters can be clearly distinguished. Different genetic diversity indices were used to analyze the genetic diversity of the large yellow croaker, which showed that there was a differentiation trend between the wild and farmed populations in Ningde. Moreover, we identified genetically differentiated genomic regions between the populations. GO gene enrichment analysis identified genes that are related to fatty acid metabolism and growth. These findings enhance our understanding of genetic differentiation and adaptation to different living environments, providing a theoretical basis for the preservation and restoration of the genetic resources of the large yellow croaker. Full article

(This article belongs to the Special Issue Bioinformatics and Population Genomics)

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24 pages, 1874 KiB

Open AccessEditor’s ChoiceReview

Epigenetic Aberrations in Major Psychiatric Diseases Related to Diet and Gut Microbiome Alterations

by Shabnam Nohesara, Hamid Mostafavi Abdolmaleky and Sam Thiagalingam

Genes 2023, 14(7), 1506; https://doi.org/10.3390/genes14071506 - 24 Jul 2023

Cited by 14 | Viewed by 4532

Abstract

Nutrition and metabolism modify epigenetic signatures like histone acetylation and DNA methylation. Histone acetylation and DNA methylation in the central nervous system (CNS) can be altered by bioactive nutrients and gut microbiome via the gut–brain axis, which in turn modulate neuronal activity and [...] Read more.

Nutrition and metabolism modify epigenetic signatures like histone acetylation and DNA methylation. Histone acetylation and DNA methylation in the central nervous system (CNS) can be altered by bioactive nutrients and gut microbiome via the gut–brain axis, which in turn modulate neuronal activity and behavior. Notably, the gut microbiome, with more than 1000 bacterial species, collectively contains almost three million functional genes whose products interact with millions of human epigenetic marks and 30,000 genes in a dynamic manner. However, genetic makeup shapes gut microbiome composition, food/nutrient metabolism, and epigenetic landscape, as well. Here, we first discuss the effect of changes in the microbial structure and composition in shaping specific epigenetic alterations in the brain and their role in the onset and progression of major mental disorders. Afterward, potential interactions among maternal diet/environmental factors, nutrition, and gastrointestinal microbiome, and their roles in accelerating or delaying the onset of severe mental illnesses via epigenetic changes will be discussed. We also provide an overview of the association between the gut microbiome, oxidative stress, and inflammation through epigenetic mechanisms. Finally, we present some underlying mechanisms involved in mediating the influence of the gut microbiome and probiotics on mental health via epigenetic modifications. Full article

(This article belongs to the Section Epigenomics)

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11 pages, 1406 KiB

Open AccessEditor’s ChoiceArticle

Evidence for Two Soybean Looper Strains in the United States with Limited Capacity for Cross-Hybridization

by Rodney N. Nagoshi, Jeffrey A. Davis, Robert L. Meagher, Fred R. Musser, Graham P. Head, Hector Portillo and Henry Teran

Genes 2023, 14(7), 1509; https://doi.org/10.3390/genes14071509 - 24 Jul 2023

Cited by 2 | Viewed by 1612

Abstract

The noctuid moth soybean looper (SBL), Chrysodeixis includens (Walker) is an economically important pest of soybeans (Glycine max (L.) Merr.) in the southeastern United States. It has characteristics that are of particular concern for pest mitigation that include a broad host range, [...] Read more.

The noctuid moth soybean looper (SBL), Chrysodeixis includens (Walker) is an economically important pest of soybeans (Glycine max (L.) Merr.) in the southeastern United States. It has characteristics that are of particular concern for pest mitigation that include a broad host range, the capacity for annual long-distance flight, and resistance in some populations to important pesticides such as pyrethroids and chitin synthesis inhibitor. The biology of SBL in the United States resembles that of the fellow noctuid fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith), a major pest of corn and several other crops. FAW exhibits a population structure in that it can be divided into two groups (host strains) that differ in their host preferences but are broadly sympatric and exhibit incomplete reproductive isolation. In this paper, strategies used to characterize the FAW strains were applied to SBL to assess the likelihood of population structure in the United States. Evidence is presented for two SBL strains that were defined phylogenetically and display differences in the proportions of a small set of genetic markers. The populations exhibit evidence of reproductive barriers sufficient to allow persistent asymmetry in the distribution of mitochondrial haplotypes. The identified molecular markers will facilitate studies characterizing the behaviors of these two populations, with relevance to pest mitigation and efforts to prevent further dispersal of the resistance traits. Full article

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

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13 pages, 1041 KiB

Open AccessEditor’s ChoiceArticle

Germline CNV Detection through Whole-Exome Sequencing (WES) Data Analysis Enhances Resolution of Rare Genetic Diseases

by Faidon-Nikolaos Tilemis, Nikolaos M. Marinakis, Danai Veltra, Maria Svingou, Kyriaki Kekou, Anastasios Mitrakos, Maria Tzetis, Konstantina Kosma, Periklis Makrythanasis, Joanne Traeger-Synodinos and Christalena Sofocleous

Genes 2023, 14(7), 1490; https://doi.org/10.3390/genes14071490 - 21 Jul 2023

Cited by 24 | Viewed by 4889

Abstract

Whole-Exome Sequencing (WES) has proven valuable in the characterization of underlying genetic defects in most rare diseases (RDs). Copy Number Variants (CNVs) were initially thought to escape detection. Recent technological advances enabled CNV calling from WES data with the use of accurate and [...] Read more.

Whole-Exome Sequencing (WES) has proven valuable in the characterization of underlying genetic defects in most rare diseases (RDs). Copy Number Variants (CNVs) were initially thought to escape detection. Recent technological advances enabled CNV calling from WES data with the use of accurate and highly sensitive bioinformatic tools. Amongst 920 patients referred for WES, 454 unresolved cases were further analysed using the ExomeDepth algorithm. CNVs were called, evaluated and categorized according to ACMG/ClinGen recommendations. Causative CNVs were identified in 40 patients, increasing the diagnostic yield of WES from 50.7% (466/920) to 55% (506/920). Twenty-two CNVs were available for validation and were all confirmed; of these, five were novel. Implementation of the ExomeDepth tool promoted effective identification of phenotype-relevant and/or novel CNVs. Among the advantages of calling CNVs from WES data, characterization of complex genotypes comprising both CNVs and SNVs minimizes cost and time to final diagnosis, while allowing differentiation between true or false homozygosity, as well as compound heterozygosity of variants in AR genes. The use of a specific algorithm for calling CNVs from WES data enables ancillary detection of different types of causative genetic variants, making WES a critical first-tier diagnostic test for patients with RDs. Full article

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

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13 pages, 1779 KiB

Open AccessEditor’s ChoiceArticle

The Effect of DNA Methylation in the Development and Progression of Chronic Kidney Disease in the General Population: An Epigenome-Wide Association Study Using the Korean Genome and Epidemiology Study Database

by Ji-Eun Kim, Min-Jee Jo, Eunjung Cho, Shin-Young Ahn, Young-Joo Kwon, Jeong-An Gim and Gang-Jee Ko

Genes 2023, 14(7), 1489; https://doi.org/10.3390/genes14071489 - 21 Jul 2023

Cited by 3 | Viewed by 2184

Abstract

Background: Although knowledge of the genetic factors influencing kidney disease is increasing, epigenetic profiles, which are associated with chronic kidney disease (CKD), have not been fully elucidated. We sought to identify the DNA methylation status of CpG sites associated with reduced kidney function [...] Read more.

Background: Although knowledge of the genetic factors influencing kidney disease is increasing, epigenetic profiles, which are associated with chronic kidney disease (CKD), have not been fully elucidated. We sought to identify the DNA methylation status of CpG sites associated with reduced kidney function and examine whether the identified CpG sites are associated with CKD development. Method: We analyzed DNA methylation patterns of 440 participants in the Korean Genome and Epidemiology Study (KoGES) with estimated glomerular filtration rates (eGFRs) ≥ 60 mL/min/1.73 m² at baseline. CKD development was defined as a decrease in the eGFR of <60 at any time during an 8-year follow-up period (“CKD prediction” analysis). In addition, among the 440 participants, 49 participants who underwent a second methylation profiling were assessed for an association between a decline in kidney function and changes in the degree of methylation of CpG sites during the 8 years (“kidney function slope” analysis). Results: In the CKD prediction analysis, methylation profiles of a total of 403,129 CpG sites were evaluated at baseline in 440 participants, and increased and decreased methylation of 268 and 189 CpG sites, respectively, were significantly correlated with the development of CKD in multivariable logistic regression. During kidney function slope analysis using follow-up methylation profiles of 49 participants, the percent methylation changes in 913 CpG sites showed a linear relationship with the percent change in eGFR during 8 years. During functional enrichment analyses for significant CpG sites found in the CKD prediction and kidney function slope analyses, we found that those CpG sites represented MAPK, PI3K/Akt, and Rap1 pathways. In addition, three CpG sites from three genes, NPHS2, CHCHD4, and AHR, were found to be significant in the CKD prediction analysis and related to a decline in kidney function. Conclusion: It is suggested that DNA methylation on specific genes is associated with the development of CKD and the deterioration of kidney function. Full article

(This article belongs to the Special Issue Epigenetics: Mechanisms in Toxicology and Disease)

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11 pages, 3141 KiB

Open AccessEditor’s ChoiceArticle

ranchSATdb: A Genome-Wide Simple Sequence Repeat (SSR) Markers Database of Livestock Species for Mutant Germplasm Characterization and Improving Farm Animal Health

by Naveen Duhan, Simardeep Kaur and Rakesh Kaundal

Genes 2023, 14(7), 1481; https://doi.org/10.3390/genes14071481 - 20 Jul 2023

Cited by 3 | Viewed by 2387

Abstract

Microsatellites, also known as simple sequence repeats (SSRs), are polymorphic loci that play an important role in genome research, animal breeding, and disease control. Ranch animals are important components of agricultural landscape. The ranch animal SSR database, ranchSATdb, is a web resource [...] Read more.

Microsatellites, also known as simple sequence repeats (SSRs), are polymorphic loci that play an important role in genome research, animal breeding, and disease control. Ranch animals are important components of agricultural landscape. The ranch animal SSR database, ranchSATdb, is a web resource which contains 15,520,263 putative SSR markers. This database provides a comprehensive tool for performing end-to-end marker selection, from SSRs prediction to generating marker primers and their cross-species feasibility, visualization of the resulting markers, and finding similarities between the genomic repeat sequences all in one place without the need to switch between other resources. The user-friendly online interface allows users to browse SSRs by genomic coordinates, repeat motif sequence, chromosome, motif type, motif frequency, and functional annotation. Users may enter their preferred flanking area around the repeat to retrieve the nucleotide sequence, they can investigate SSRs present in the genic or the genes between SSRs, they can generate custom primers, and they can also execute in silico validation of primers using electronic PCR. For customized sequences, an SSR prediction pipeline called miSATminer is also built. New species will be added to this website’s database on a regular basis throughout time. To improve animal health via genomic selection, we hope that ranchSATdb will be a useful tool for mapping quantitative trait loci (QTLs) and marker-assisted selection. The web-resource is freely accessible at https://bioinfo.usu.edu/ranchSATdb/. Full article

(This article belongs to the Special Issue Breeding and Functional Genomics in Animals)

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14 pages, 3267 KiB

Open AccessEditor’s ChoiceArticle

Comparative Analysis of the PYL Gene Family in Three Ipomoea Species and the Expression Profiling of IbPYL Genes during Abiotic Stress Response in Sweetpotato

by Lei Zhang, Weihan Song, Guosheng Xin, Mingku Zhu and Xiaoqing Meng

Genes 2023, 14(7), 1471; https://doi.org/10.3390/genes14071471 - 19 Jul 2023

Cited by 6 | Viewed by 1478

Abstract

Abscisic acid (ABA), a critical phytohormone that regulates plant development and stress response, is sensed by the ABA receptors PYR/PYL/RCAR (PYLs). The PYL genes have been widely studied in multiple plant species, while a systematic analysis of PYL genes in the genus Ipomoea [...] Read more.

Abscisic acid (ABA), a critical phytohormone that regulates plant development and stress response, is sensed by the ABA receptors PYR/PYL/RCAR (PYLs). The PYL genes have been widely studied in multiple plant species, while a systematic analysis of PYL genes in the genus Ipomoea remains unperformed. Here, a total of 13, 14, and 14 PYLs were identified in Ipomoea batatas, Ipomoea trifida, and Ipomoea triloba, respectively. Fragment duplication was speculated to play prominent roles in Ipomoea PYL gene expansions. These Ipomoea PYLs were classified into three subfamilies via phylogenetic analysis, which was supported by exon–intron structures and conserved motif analyses. Additionally, the interspecies collinearity analysis further depicted a potential evolutionary relationship between them. Moreover, qRT-PCR analysis showed that multiple IbPYLs are highly and differentially responsive to abiotic stress treatments, suggesting their potential roles in sweetpotato stress responses. Taken together, these data provide valuable insights into the PYLs in the genus Ipomoea, which may be useful for their further functional analysis of their defense against environmental changes. Full article

(This article belongs to the Special Issue Sweet Potato Genetics and Genomics)

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8 pages, 391 KiB

Open AccessEditor’s ChoiceArticle

Associations of HLA Polymorphisms with Chronic Kidney Disease in Japanese Rheumatoid Arthritis Patients

by Takashi Higuchi, Shomi Oka, Hiroshi Furukawa, Kota Shimada, Atsushi Hashimoto, Akiko Komiya, Toshihiro Matsui, Naoshi Fukui and Shigeto Tohma

Genes 2023, 14(7), 1470; https://doi.org/10.3390/genes14071470 - 19 Jul 2023

Cited by 1 | Viewed by 1959

Abstract

Objectives: The prevalence of chronic kidney disease (CKD) was reported to be higher in rheumatoid arthritis (RA) patients than in normal healthy individuals. Human leukocyte antigen (HLA) was associated with RA or CKD. Few studies on the association of HLA with [...] Read more.

Objectives: The prevalence of chronic kidney disease (CKD) was reported to be higher in rheumatoid arthritis (RA) patients than in normal healthy individuals. Human leukocyte antigen (HLA) was associated with RA or CKD. Few studies on the association of HLA with CKD in RA have been reported. Here, we investigated the association of HLA polymorphisms with CKD in Japanese RA patients. Methods: HLA-DRB1 genotyping was conducted in 351 Japanese RA patients with CKD (estimated glomerular filtration rate [eGFR] lower than 60 [mL/min/1.73 m²]) and 959 without CKD (eGFR equal to or higher than 60 [mL/min/1.73 m²]). Associations of allele carrier frequencies of DRB1 with CKD were examined in the RA patients. Results: There was an association of DRB1*13:02 with CKD in RA, but this did not achieve statistical significance (p = 0.0265, odds ratio [OR] 1.70, pc = 0.7412, 95% confidence interval [CI] 1.09–2.64). The DR6 serological group was associated with CKD in RA (p = 0.0008, OR 1.65, 95% CI 1.24–2.20). A gene-dosage effect of DR6 was not detected. Logistic regression analysis showed that the association of DR6 with CKD in RA was independent of clinical characteristics. Conclusions: The present study first revealed the independent predisposing association of DR6 with CKD in Japanese RA patients, although DR6 is known to be protective against RA. Our data suggest direct or indirect roles of HLA for the development of CKD in RA, but the mechanisms are not clear. Full article

(This article belongs to the Special Issue From Genetic to Molecular Basis of Kidney Damage)

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12 pages, 1364 KiB

Open AccessEditor’s ChoiceArticle

ERCC1 and MGMT Methylation as a Predictive Marker of Relapse and FOLFOX Response in Colorectal Cancer Patients from South Tunisia

by Dhouha Jamai, Raja Gargouri, Boulbaba Selmi and Abdelmajid Khabir

Genes 2023, 14(7), 1467; https://doi.org/10.3390/genes14071467 - 19 Jul 2023

Cited by 4 | Viewed by 1889

Abstract

Genetic and epigenetic modifications present a major cause of relapse and treatment failure in colorectal cancer. This study aims to appreciate the prognostic and predictive value of ERRC1 and MGMT methylation. We also studied the prognostic impact of the ERCC1 rs11615 polymorphism as [...] Read more.

Genetic and epigenetic modifications present a major cause of relapse and treatment failure in colorectal cancer. This study aims to appreciate the prognostic and predictive value of ERRC1 and MGMT methylation. We also studied the prognostic impact of the ERCC1 rs11615 polymorphism as well as its expression. Methylation profiles of ERCC1 and MGMT were tested by methylation-specific PCR. A polymorphism of ERCC1 was studied using PCR-RFLP and its expression was examined by immunohistochemistry. ERCC1 was methylated in 44.6% of colorectal adenocarcinoma while MGMT was methylated in 69% of cases. MGMT methylation was strongly associated with lymph node metastasis, lymph invasion, venous invasion, perineural invasion, distant metastasis and relapse. Patients with methylation of both genes were more likely to have a poor prognosis and display chemoresistance. IHC analysis revealed that ERCC1 staining was noted in 52.8% of colorectal adenocarcinoma and inversely related to distant metastasis and cancer recurrence. Kaplan Meier analysis revealed that the worst overall survival was significantly associated with ERCC1 and MGMT methylation while decreased ERCC1 expression and T/T genotype exhibited the best overall survival. The methylation of MGMT, alone or combined with ERCC1, is predictive for poor prognosis, short overall survival and chemotherapy response in colorectal cancer. Full article

(This article belongs to the Special Issue Genetics and Genomics of Colorectal Cancer and Related Diseases)

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15 pages, 4094 KiB

Open AccessEditor’s ChoiceArticle

Nutrient Metabolism Pathways Analysis and Key Candidate Genes Identification Corresponding to Cadmium Stress in Buckwheat through Multiomics Analysis

by Dengxiang Du, Hanxian Xiong, Congping Xu, Wanyong Zeng, Jinhua Li and Guoqing Dong

Genes 2023, 14(7), 1462; https://doi.org/10.3390/genes14071462 - 18 Jul 2023

Cited by 9 | Viewed by 2374

Abstract

Fagopylum tatarium (L.) Gaertn (buckwheat) can be used both as medicine and food and is also an important food crop in barren areas and has great economic value. Exploring the molecular mechanisms of the response to cadmium (Cd) stress can provide the theoretical [...] Read more.

Fagopylum tatarium (L.) Gaertn (buckwheat) can be used both as medicine and food and is also an important food crop in barren areas and has great economic value. Exploring the molecular mechanisms of the response to cadmium (Cd) stress can provide the theoretical reference for improving the buckwheat yield and quality. In this study, perennial tartary buckwheat DK19 was used as the experimental material, its key metabolic pathways in the response to Cd stress were identified and verified through transcriptomic and metabolomic data analysis. In this investigation, 1798 metabolites were identified through non-targeted metabolomic analysis containing 1091 up-regulated and 984down-regulated metabolites after treatment. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differential metabolites was significantly enriched in galactose metabolism, glycerol metabolism, phenylpropane biosynthesis, glutathione metabolism, starch and sucrose metabolism. Linkage analysis detected 11 differentially expressed genes (DEGs) in the galactose metabolism pathway, 8 candidate DEGs in the lipid metabolism pathway, and 20 candidate DEGs in the glutathione metabolism pathway. The results of our study provided useful clues for genetically improving the resistance to cadmium by analyzing the molecular mechanism of cadmium tolerance in buckwheat. Full article

(This article belongs to the Special Issue Molecular Biology of Crop Abiotic Stress Resistance)

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11 pages, 276 KiB

Open AccessEditor’s ChoiceReview

Exploring Metabolomic Patterns in Type 2 Diabetes Mellitus and Response to Glucose-Lowering Medications—Review

by Mina Shahisavandi, Kan Wang, Mohsen Ghanbari and Fariba Ahmadizar

Genes 2023, 14(7), 1464; https://doi.org/10.3390/genes14071464 - 18 Jul 2023

Cited by 16 | Viewed by 5404

Abstract

The spectrum of information related to precision medicine in diabetes generally includes clinical data, genetics, and omics-based biomarkers that can guide personalized decisions on diabetes care. Given the remarkable progress in patient risk characterization, there is particular interest in using molecular biomarkers to [...] Read more.

The spectrum of information related to precision medicine in diabetes generally includes clinical data, genetics, and omics-based biomarkers that can guide personalized decisions on diabetes care. Given the remarkable progress in patient risk characterization, there is particular interest in using molecular biomarkers to guide diabetes management. Metabolomics is an emerging molecular approach that helps better understand the etiology and promises the identification of novel biomarkers for complex diseases. Both targeted or untargeted metabolites extracted from cells, biofluids, or tissues can be investigated by established high-throughput platforms, like nuclear magnetic resonance (NMR) and mass spectrometry (MS) techniques. Metabolomics is proposed as a valuable tool in precision diabetes medicine to discover biomarkers for diagnosis, prognosis, and management of the progress of diabetes through personalized phenotyping and individualized drug-response monitoring. This review offers an overview of metabolomics knowledge as potential biomarkers in type 2 diabetes mellitus (T2D) diagnosis and the response to glucose-lowering medications. Full article

(This article belongs to the Special Issue Omics Studies of Type 2 Diabetes and Diabetes-Related Complications)

21 pages, 519 KiB

Open AccessEditor’s ChoiceReview

Association of Single Nucleotide Polymorphisms of Cytokine Genes with Depression, Schizophrenia and Bipolar Disorder

by Ekaterina V. Mikhalitskaya, Natalya M. Vyalova, Evgeny A. Ermakov, Lyudmila A. Levchuk, German G. Simutkin, Nikolay A. Bokhan and Svetlana A. Ivanova

Genes 2023, 14(7), 1460; https://doi.org/10.3390/genes14071460 - 17 Jul 2023

Cited by 16 | Viewed by 5833

Abstract

Immune gene variants are known to be associated with the risk of psychiatric disorders, their clinical manifestations, and their response to therapy. This narrative review summarizes the current literature over the past decade on the association of polymorphic variants of cytokine genes with [...] Read more.

Immune gene variants are known to be associated with the risk of psychiatric disorders, their clinical manifestations, and their response to therapy. This narrative review summarizes the current literature over the past decade on the association of polymorphic variants of cytokine genes with risk, severity, and response to treatment for severe mental disorders such as bipolar disorder, depression, and schizophrenia. A search of literature in databases was carried out using keywords related to depressive disorder, bipolar disorder, schizophrenia, inflammation, and cytokines. Gene lists were extracted from publications to identify common genes and pathways for these mental disorders. Associations between polymorphic variants of the IL1B, IL6, and TNFA genes were the most replicated and relevant in depression. Polymorphic variants of the IL1B, IL6, IL6R, IL10, IL17A, and TNFA genes have been associated with schizophrenia. Bipolar disorder has mainly been associated with polymorphic variants of the IL1B gene. Interestingly, the IL6R gene polymorphism (rs2228145) was associated with all three diseases. Some cytokine genes have also been associated with clinical presentation and response to pharmacotherapy. There is also evidence that some specific polymorphic variants may affect the expression of cytokine genes. Thus, the data from this review indicate a link between neuroinflammation and severe mental disorders. Full article

(This article belongs to the Special Issue Psychiatric and Behavioral Genetics)

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17 pages, 1961 KiB

Open AccessEditor’s ChoiceArticle

Candidate Gene Association Studies in Atopic Dermatitis in Participants of European and Asian Ancestry: A Systematic Review and Meta-Analysis

by Alexandros Pontikas, Charalabos Antonatos, Evangelos Evangelou and Yiannis Vasilopoulos

Genes 2023, 14(7), 1456; https://doi.org/10.3390/genes14071456 - 17 Jul 2023

Cited by 5 | Viewed by 5439

Abstract

Atopic dermatitis (AD) has been extensively investigated for genetic associations utilizing both candidate gene approaches and genome-wide scans. Here, we comprehensively evaluated the available literature to determine the association of candidate genes in AD to gain additional insight into the etiopathogenesis of the [...] Read more.

Atopic dermatitis (AD) has been extensively investigated for genetic associations utilizing both candidate gene approaches and genome-wide scans. Here, we comprehensively evaluated the available literature to determine the association of candidate genes in AD to gain additional insight into the etiopathogenesis of the disease. We systematically screened all studies that explored the association between polymorphisms and AD risks in cases of European and Asian ancestry and synthesized the available evidence through a random-effects meta-analysis. We identified 99 studies that met our inclusion/exclusion criteria that examined 17 candidate loci in Europeans and 14 candidate genes in Asians. We confirmed the significant associations between FLG variants in both European and Asian populations and AD risk, while synthesis of the available data revealed novel loci mapped to IL18 and TGFB1 genes in Europeans and IL12RB1 and MIF in Asians that have not yet been identified by genome-wide association studies. Our findings provide comprehensive evidence for AD risk loci in cases of both European and Asian ancestries, validating previous associations as well as revealing novel loci that could imply previously unexplored biological pathways. Full article

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

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15 pages, 3940 KiB

Open AccessEditor’s ChoiceArticle

Mn-XRN1 Has an Inhibitory Effect on Ovarian Reproduction in Macrobrachium nipponense

by Tianyong Chen, Huwei Yuan, Hui Qiao, Sufei Jiang, Wenyi Zhang, Yiwei Xiong, Hongtuo Fu and Shubo Jin

Genes 2023, 14(7), 1454; https://doi.org/10.3390/genes14071454 - 16 Jul 2023

Cited by 1 | Viewed by 1851

Abstract

XRN1 is an exoribonuclease that degrades mRNA in the cytoplasm along the 5′–3′ direction. A previous study indicated that it may be involved in the reproduction of Macrobrachium nipponense. Quantitative real-time PCR was used to detect the spatiotemporal expression pattern of Mn-XRN1 [...] Read more.

XRN1 is an exoribonuclease that degrades mRNA in the cytoplasm along the 5′–3′ direction. A previous study indicated that it may be involved in the reproduction of Macrobrachium nipponense. Quantitative real-time PCR was used to detect the spatiotemporal expression pattern of Mn-XRN1. At the tissue level, Mn-XRN1 was significantly expressed in the ovary. During development, Mn-XRN1 was significantly expressed at the CS stage of the embryo, on the 10th day post-larval and in the O2 stage of ovarian reproduction. The in situ hybridization results showed the location of Mn-XRN1 in the ovary. The expression of Mn-VASA was significantly increased after in vivo injection of Mn-XRN1 dsRNA. This suggests that Mn-XRN1 negatively regulates the expression of Mn-VASA. Furthermore, we counted the number of M. nipponense at various stages of ovarian reproduction on different days after RNAi. The results showed that ovarian development was significantly accelerated. In general, the results of the present study indicate that Mn-XRN1 has an inhibitory effect on the ovarian maturation of M. nipponense. The inhibitory effect might be through negative regulation of Mn-VASA. Full article

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

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19 pages, 1143 KiB

Open AccessEditor’s ChoiceArticle

Racial and Ethnic Disparities in Genomic Healthcare Utilization, Patient Activation, and Intrafamilial Communication of Risk among Females Tested for BRCA Variants: A Mixed Methods Study

by Sharlene Hesse-Biber, Memnun Seven, Hannah Shea, Madeline Heaney and Andrew A. Dwyer

Genes 2023, 14(7), 1450; https://doi.org/10.3390/genes14071450 - 15 Jul 2023

Cited by 10 | Viewed by 2256

Abstract

This study aimed to gain a deeper understanding of genomic healthcare utilization, patient activation, and intrafamilial risk communication among racially and ethnically diverse individuals tested for BRCA variants. We employed an explanatory, sequential, mixed-methods study guided by the Theory of Planned Behavior. Participants [...] Read more.

This study aimed to gain a deeper understanding of genomic healthcare utilization, patient activation, and intrafamilial risk communication among racially and ethnically diverse individuals tested for BRCA variants. We employed an explanatory, sequential, mixed-methods study guided by the Theory of Planned Behavior. Participants completed an online survey, including sociodemographic, medical history, and several validated instruments. A subset of participants participated in in-depth, semi-structured interviews. A total of 242 women were included in the quantitative analyses. The majority of survey participants identified as non-Hispanic white (NHW) (n = 197, 81.4%) while 45/242 (18.5%) identified as black, Indigenous, and people of color (BIPOC). The NHW participants were more likely to communicate genetic test results with healthcare providers, family, and friends than BIPOC participants (p < 0.05). BIPOC participants had lower satisfaction with testing decisions and significantly higher ratings of personal discrimination, fatalism, resilience, uncertainty, and lower patient activation scores (p < 0.05). Participants with higher education, greater satisfaction with testing decisions, and lower resilience are more likely to communicate BRCA test results with family members through the mediating effect of patient activation. Bridging disparities to ensure that genomic healthcare benefits all people may demand theory-driven, multi-level interventions targeting the individual, interpersonal, and healthcare system levels. Full article

(This article belongs to the Special Issue Advances in Genomic Nursing: Implications for Nursing Education, Practice and Research)

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13 pages, 4384 KiB

Open AccessEditor’s ChoiceArticle

Dissection of the Genetic Basis of Resistance to Stem Rot in Cultivated Peanuts (Arachis hypogaea L.) through Genome-Wide Association Study

by Liying Yan, Wanduo Song, Zhihui Wang, Dongyang Yu, Hari Sudini, Yanping Kang, Yong Lei, Dongxin Huai, Yuning Chen, Xin Wang, Qianqian Wang and Boshou Liao

Genes 2023, 14(7), 1447; https://doi.org/10.3390/genes14071447 - 14 Jul 2023

Cited by 4 | Viewed by 2168

Abstract

Peanut (Arachis hypogaea) is an important oilseed and cash crop worldwide, contributing an important source of edible oil and protein for human nutrition. However, the incidence of stem rot disease caused by Athelia rolfsii poses a major challenge to peanut cultivation, [...] Read more.

Peanut (Arachis hypogaea) is an important oilseed and cash crop worldwide, contributing an important source of edible oil and protein for human nutrition. However, the incidence of stem rot disease caused by Athelia rolfsii poses a major challenge to peanut cultivation, resulting in significant yield losses. In this study, a panel of 202 peanut accessions was evaluated for their resistance to stem rot by inoculating plants in the field with A. rolfsii-infested oat grains in three environments. The mean disease index value of each environment for accessions in subsp. fasitigiate and subsp. hypogaea showed no significant difference. Accessions from southern China displayed the lowest disease index value compared to those from other ecological regions. We used whole-genome resequencing to analyze the genotypes of the accessions and to identify significant SNPs associated with stem rot resistance through genome-wide association study (GWAS). A total of 121 significant SNPs associated with stem rot resistance in peanut were identified, with phenotypic variation explained (PVE) ranging from 12.23% to 15.51%. A total of 27 candidate genes within 100 kb upstream and downstream of 23 significant SNPs were annotated, which have functions related to recognition, signal transduction, and defense response. These significant SNPs and candidate genes provide valuable information for further validation and molecular breeding to improve stem rot resistance in peanut. Full article

(This article belongs to the Special Issue Peanut Genetics and Omics)

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15 pages, 1728 KiB

Open AccessEditor’s ChoiceReview

k-mer-Based Genome-Wide Association Studies in Plants: Advances, Challenges, and Perspectives

by Benjamin Karikari, Marc-André Lemay and François Belzile

Genes 2023, 14(7), 1439; https://doi.org/10.3390/genes14071439 - 13 Jul 2023

Cited by 10 | Viewed by 5239

Abstract

Genome-wide association studies (GWAS) have allowed the discovery of marker–trait associations in crops over recent decades. However, their power is hampered by a number of limitations, with the key one among them being an overreliance on single-nucleotide polymorphisms (SNPs) as molecular markers. Indeed, [...] Read more.

Genome-wide association studies (GWAS) have allowed the discovery of marker–trait associations in crops over recent decades. However, their power is hampered by a number of limitations, with the key one among them being an overreliance on single-nucleotide polymorphisms (SNPs) as molecular markers. Indeed, SNPs represent only one type of genetic variation and are usually derived from alignment to a single genome assembly that may be poorly representative of the population under study. To overcome this, k-mer-based GWAS approaches have recently been developed. k-mer-based GWAS provide a universal way to assess variation due to SNPs, insertions/deletions, and structural variations without having to specifically detect and genotype these variants. In addition, k-mer-based analyses can be used in species that lack a reference genome. However, the use of k-mers for GWAS presents challenges such as data size and complexity, lack of standard tools, and potential detection of false associations. Nevertheless, efforts are being made to overcome these challenges and a general analysis workflow has started to emerge. We identify the priorities for k-mer-based GWAS in years to come, notably in the development of user-friendly programs for their analysis and approaches for linking significant k-mers to sequence variation. Full article

(This article belongs to the Special Issue Genetic Mapping in Plants)

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20 pages, 6974 KiB

Open AccessEditor’s ChoiceArticle

PromGER: Promoter Prediction Based on Graph Embedding and Ensemble Learning for Eukaryotic Sequence

by Yan Wang, Shiwen Tai, Shuangquan Zhang, Nan Sheng and Xuping Xie

Genes 2023, 14(7), 1441; https://doi.org/10.3390/genes14071441 - 13 Jul 2023

Cited by 13 | Viewed by 4565

Abstract

Promoters are DNA non-coding regions around the transcription start site and are responsible for regulating the gene transcription process. Due to their key role in gene function and transcriptional activity, the prediction of promoter sequences and their core elements accurately is a crucial [...] Read more.

Promoters are DNA non-coding regions around the transcription start site and are responsible for regulating the gene transcription process. Due to their key role in gene function and transcriptional activity, the prediction of promoter sequences and their core elements accurately is a crucial research area in bioinformatics. At present, models based on machine learning and deep learning have been developed for promoter prediction. However, these models cannot mine the deeper biological information of promoter sequences and consider the complex relationship among promoter sequences. In this work, we propose a novel prediction model called PromGER to predict eukaryotic promoter sequences. For a promoter sequence, firstly, PromGER utilizes four types of feature-encoding methods to extract local information within promoter sequences. Secondly, according to the potential relationships among promoter sequences, the whole promoter sequences are constructed as a graph. Furthermore, three different scales of graph-embedding methods are applied for obtaining the global feature information more comprehensively in the graph. Finally, combining local features with global features of sequences, PromGER analyzes and predicts promoter sequences through a tree-based ensemble-learning framework. Compared with seven existing methods, PromGER improved the average specificity of 13%, accuracy of 10%, Matthew’s correlation coefficient of 16%, precision of 4%, F1 score of 6%, and AUC of 9%. Specifically, this study interpreted the PromGER by the t-distributed stochastic neighbor embedding (t-SNE) method and SHAPley Additive exPlanations (SHAP) value analysis, which demonstrates the interpretability of the model. Full article

(This article belongs to the Section Bioinformatics)

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15 pages, 2931 KiB

Open AccessEditor’s ChoiceArticle

Optimised Agrobacterium-Mediated Transformation and Application of Developmental Regulators Improve Regeneration Efficiency in Melons

by Lili Wan, Zhuanrong Wang, Xuejun Zhang, Hongxia Zeng, Jian Ren, Na Zhang, Yuhong Sun and Tang Mi

Genes 2023, 14(7), 1432; https://doi.org/10.3390/genes14071432 - 12 Jul 2023

Cited by 9 | Viewed by 3222

Abstract

Melon (Cucumis melo L.) is a protected crop in China with high economic value. Agrobacterium-mediated genetic transformation is a powerful tool to improve agronomic traits and obtain elite germplasm. However, current transformation protocols in melons are inefficient and highly genotype-dependent. To [...] Read more.

Melon (Cucumis melo L.) is a protected crop in China with high economic value. Agrobacterium-mediated genetic transformation is a powerful tool to improve agronomic traits and obtain elite germplasm. However, current transformation protocols in melons are inefficient and highly genotype-dependent. To improve transformation in melon, we tested different infiltration methods for Agrobacterium-mediated transformation. Among these methods, micro-brushing and sonication for 20 s, followed by vacuum infiltration at −1.0 kPa for 90 s, resulted in the strongest green fluorescent protein signal and increased the proportion of infected explants. We transformed melon with developmental regulatory genes AtGRF5, AtPLT5, AtBBM, AtWUS, AtWOX5, and AtWIND1 from Arabidopsis and estimated regeneration frequencies as the number of regenerating shoots/total number of inoculated explants in the selection medium. The overexpression of AtGRF5 and AtPLT5 in melon resulted in transformation efficiencies of 42.3% and 33% in ZHF and 45.6% and 32.9% in Z12, respectively, which were significantly higher than those of the control. AtGRF5 and AtPLT5 expression cassettes were added to CRISPR/Cas9 genome-editing vectors to obtain transgenic phytoene desaturase CmPDS knockout mutants. Using AtGRF5 or AtPLT5, multi-allelic mutations were observed at CmPDS target sites in recalcitrant melon genotypes. This strategy enables genotype-flexible transformation and promotes precise genome modification technologies in melons. Full article

(This article belongs to the Special Issue Biotechnology and Genetics in Fruits)

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12 pages, 1315 KiB

Open AccessEditor’s ChoiceEditorial

Non-Coding RNAs in Human Health and Diseases

by Deborah J. Good

Genes 2023, 14(7), 1429; https://doi.org/10.3390/genes14071429 - 11 Jul 2023

Cited by 20 | Viewed by 3961

Abstract

Non-coding RNAs (ncRNAs) are, arguably, the enigma of the RNA transcriptome. Even though there are more annotated ncRNAs (25,967) compared to mRNAs (19,827), we know far less about each of the genes that produce ncRNA, especially in terms of their regulation, molecular functions, [...] Read more.

Non-coding RNAs (ncRNAs) are, arguably, the enigma of the RNA transcriptome. Even though there are more annotated ncRNAs (25,967) compared to mRNAs (19,827), we know far less about each of the genes that produce ncRNA, especially in terms of their regulation, molecular functions, and interactions. Further, we are only beginning to understand the role of differential regulation or function of ncRNAs caused by genetic and epigenetic perturbations, such as single nucleotide variants (SNV), deletions, insertions, and histone/DNA modifications. The 22 papers in this Special Issue describe the emerging roles of ncRNAs in neurological, cardiovascular, immune, and hepatic systems, to name a few, as well as in diseases such as cancer, Prader–Willi Syndrome, cardiac arrhythmias, and diabetes. As we begin to understand the function and regulation of this class of RNAs, strategies targeting ncRNAs could lead to improved therapeutic interventions for some conditions. Full article

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

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17 pages, 4928 KiB

Open AccessEditor’s ChoiceArticle

Characterization and Potential Function Analysis of the SRS Gene Family in Brassica napus

by Ming Hu, Meili Xie, Xiaobo Cui, Junyan Huang, Xiaohui Cheng, Lijiang Liu, Shunping Yan, Shengyi Liu and Chaobo Tong

Genes 2023, 14(7), 1421; https://doi.org/10.3390/genes14071421 - 10 Jul 2023

Cited by 5 | Viewed by 2149

Abstract

SRS (SHI-related sequence) transcription factors play a crucial role in plant growth, development, and abiotic stress response. Although Brassica napus (B. napus) is one of the most important oil crops in the world, the role of SRS genes in B. napus ( [...] Read more.

SRS (SHI-related sequence) transcription factors play a crucial role in plant growth, development, and abiotic stress response. Although Brassica napus (B. napus) is one of the most important oil crops in the world, the role of SRS genes in B. napus (BnSRS) has not been well investigated. Therefore, we employed a bioinformatics approach to identify BnSRS genes from genomic data and investigated their characteristics, functions, and expression patterns, to gain a better understanding of how this gene family is involved in plant development and growth. The results revealed that there were 34 BnSRS gene family members in the genomic sequence of B. napus, unevenly distributed throughout the sequence. Based on the phylogenetic analysis, these BnSRS genes could be divided into four subgroups, with each group sharing comparable conserved motifs and gene structure. Analysis of the upstream promoter region showed that BnSRS genes may regulate hormone responses, biotic and abiotic stress response, growth, and development in B. napus. The protein-protein interaction analysis revealed the involvement of BnSRS genes in various biological processes and metabolic pathways. Our analysis of BnSRS gene expression showed that 23 BnSRS genes in the callus tissue exhibited a dominant expression pattern, suggesting their critical involvement in cell dedifferentiation, cell division, and tissue development. In addition, association analysis between genotype and agronomic traits revealed that BnSRS genes may be linked to some important agronomic traits in B. napus, suggesting that BnSRS genes were widely involved in the regulation of important agronomic traits (including C16.0, C18.0, C18.1, C18.2 C18.3, C20.1, C22.1, GLU, protein, TSW, and FFT). In this study, we predicted the evolutionary relationships and potential functions of BnSRS gene family members, providing a basis for the development of BnSRS gene functions which could facilitate targeted functional studies and genetic improvement for elite breeding in B. napus. Full article

(This article belongs to the Special Issue Genetics of Biotic and Abiotic Stress Response in Crops)

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13 pages, 1390 KiB

Open AccessEditor’s ChoiceReview

Genetic Risk Factors Related to Coronary Artery Disease and Role of Transforming Growth Factor Beta 1 Polymorphisms

by Damian Malinowski, Oliwia Bochniak, Katarzyna Luterek-Puszyńska, Michał Puszyński and Andrzej Pawlik

Genes 2023, 14(7), 1425; https://doi.org/10.3390/genes14071425 - 10 Jul 2023

Cited by 9 | Viewed by 5026

Abstract

Coronary artery disease (CAD) is one of the leading causes of mortality globally and has long been known to be heritable; however, the specific genetic factors involved have yet to be identified. Recent advances have started to unravel the genetic architecture of this [...] Read more.

Coronary artery disease (CAD) is one of the leading causes of mortality globally and has long been known to be heritable; however, the specific genetic factors involved have yet to be identified. Recent advances have started to unravel the genetic architecture of this disease and set high expectations about the future use of novel susceptibility variants for its prevention, diagnosis, and treatment. In the past decade, there has been major progress in this area. New tools, like common variant association studies, genome-wide association studies, meta-analyses, and genetic risk scores, allow a better understanding of the genetic risk factors driving CAD. In recent years, researchers have conducted further studies that confirmed the role of numerous genetic factors in the development of CAD. These include genes that affect lipid and carbohydrate metabolism, regulate the function of the endothelium and vascular smooth muscles, influence the coagulation system, or affect the immune system. Many CAD-associated single-nucleotide polymorphisms have been identified, although many of their functions are largely unknown. The inflammatory process that occurs in the coronary vessels is very important in the development of CAD. One important mediator of inflammation is TGFβ1. TGFβ1 plays an important role in the processes leading to CAD, such as by stimulating macrophage and fibroblast chemotaxis, as well as increasing extracellular matrix synthesis. This review discusses the genetic risk factors related to the development of CAD, with a particular focus on polymorphisms of the transforming growth factor β (TGFβ) gene and its receptor. Full article

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

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11 pages, 3453 KiB

Open AccessEditor’s ChoiceArticle

Insight into Antibiotic Synergy Combinations for Eliminating Colistin Heteroresistant Klebsiella pneumoniae

by Sahaya Glingston Rajakani, Basil Britto Xavier, Adwoa Sey, El Bounja Mariem, Christine Lammens, Herman Goossens, Youri Glupczynski and Surbhi Malhotra-Kumar

Genes 2023, 14(7), 1426; https://doi.org/10.3390/genes14071426 - 10 Jul 2023

Cited by 10 | Viewed by 2884

Abstract

Colistin heteroresistance has been identified in several bacterial species, including Escherichia coli and Klebsiella pneumoniae, and may underlie antibiotic therapy failures since it most often goes undetected by conventional antimicrobial susceptibility tests. This study utilizes population analysis profiling (PAP) and time–kill assay [...] Read more.

Colistin heteroresistance has been identified in several bacterial species, including Escherichia coli and Klebsiella pneumoniae, and may underlie antibiotic therapy failures since it most often goes undetected by conventional antimicrobial susceptibility tests. This study utilizes population analysis profiling (PAP) and time–kill assay for the detection of heteroresistance in K. pneumoniae and for evaluating the association between in vitro regrowth and heteroresistance. The mechanisms of colistin resistance and the ability of combination therapies to suppress resistance selection were also analysed. In total, 3 (18%) of the 16 colistin-susceptible strains (MIC ≤ 2 mg/L) were confirmed to be heteroresistant to colistin by PAP assay. In contrast to the colistin-susceptible control strains, all three heteroresistant strains showed regrowth when exposed to colistin after 24 h following a rapid bactericidal action. Colistin resistance in all the resistant subpopulations was due to the disruption of the mgrB gene by various insertion elements such as ISKpn14 of the IS1 family and IS903B of the IS5 family. Colistin combined with carbapenems (imipenem, meropenem), aminoglycosides (amikacin, gentamicin) or tigecycline was found to elicit in vitro synergistic effects against these colistin heteroresistant strains. Our experimental results showcase the potential of combination therapies for treatment of K. pneumoniae infections associated with colistin heteroresistance. Full article

(This article belongs to the Special Issue Mobile Genetic Elements and Microbial Multidrug Resistance)

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8 pages, 503 KiB

Open AccessEditor’s ChoiceBrief Report

Collagen Gene Variants and Anterior Cruciate Ligament Rupture in Italian Athletes: A Preliminary Report

by Myosotis Massidda, Laura Flore, Marco Scorcu, Giovanni Monteleone, Alessandra Tiloca, Massimiliano Salvi, Filippo Tocco and Carla M. Calò

Genes 2023, 14(7), 1418; https://doi.org/10.3390/genes14071418 - 9 Jul 2023

Cited by 6 | Viewed by 2112

Abstract

Several studies have investigated the role of genetics in anterior cruciate ligament (ACL) rupture, often returning conflicting results. The present pilot study aimed to analyze the association between six Single Nucleotide Polymorphisms (SNPs) (rs1800012; rs12722; rs13946; rs240736; rs970547; and rs4870723, located on the [...] Read more.

Several studies have investigated the role of genetics in anterior cruciate ligament (ACL) rupture, often returning conflicting results. The present pilot study aimed to analyze the association between six Single Nucleotide Polymorphisms (SNPs) (rs1800012; rs12722; rs13946; rs240736; rs970547; and rs4870723, located on the COL1A1, COL5A1, COL12A1, and COL14A1 genes), and ACL rupture, among Italian athletes. A hypothesis-driven association study was conducted. In total, 181 male and female athletes (n = 86 injured; n = 96 non-injured) were genotyped for the prioritized variants. All polymorphisms were genotyped using PCR RFLP, with the only exception being the rs1800012 on the COL1A1 gene, which was detected using MTPA PCR. The allele frequency distribution fell within the worldwide range. Despite the evident population variability, no selective pressure signals were recorded using PBS analysis. No significant difference was detected between the cases and controls for any of the SNPs (rs1800012; rs13946; rs240736; rs970547, and rs4870723) included in the analyses (p > 0.008, Bonferroni-adjusted for multiple comparisons). Moreover, no significant differences were found when males and females were assessed separately. Further investigations based on a larger sample size are needed, in order to draw solid conclusions for the influence between collagen genes and ACL rupture. Full article

(This article belongs to the Special Issue Genetic Basis of Sports Athletes)

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20 pages, 8689 KiB

Open AccessEditor’s ChoiceArticle

High Expression of CDCA7 in the Prognosis of Glioma and Its Relationship with Ferroptosis and Immunity

by Yunhan Wang, Yu Zhao, Zongying Zhang, Jie Zhang, Qiuyun Xu, Xiaorong Zhou and Liming Mao

Genes 2023, 14(7), 1406; https://doi.org/10.3390/genes14071406 - 6 Jul 2023

Cited by 8 | Viewed by 2529

Abstract

CDCA7 is a copy number amplification gene that promotes tumorigenesis. However, the clinical relevance and potential mechanisms of CDCA7 in glioma are unclear. CDCA7 expression level data were obtained from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases, [...] Read more.

CDCA7 is a copy number amplification gene that promotes tumorigenesis. However, the clinical relevance and potential mechanisms of CDCA7 in glioma are unclear. CDCA7 expression level data were obtained from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases, and the enriched genes and related signaling pathways were explored. Data on genes in CDCA7-related signaling pathways and nine marker genes of ferroptosis were retrieved and a protein–protein interaction (PPI) network analysis was performed. The correlation of CDCA7 to ferroptosis and tumor infiltration of 22 kinds of human immune cells and the association between CDCA7 and immune checkpoint molecules were analyzed. CDCA7 was significantly increased in gliomas in comparison to healthy tissues. Gene Ontology (GO) and gene set enrichment analysis (GSEA) revealed the impact of CDCA7 expression on multiple biological processes and signaling pathways. CDCA7 may affect ferroptosis by interacting with genes in the cell cycle pathway and P53 pathway. The increase in CDCA7 was positively correlated with multiple ferroptosis suppressor genes and genes involved in tumor-infiltrating immune cells and immune checkpoint molecules in glioma. CDCA7 can be a new prognostic factor for glioma, which is closely related to ferroptosis, tumor immune cell infiltration, and immune checkpoint. Full article

(This article belongs to the Special Issue Genotyping and Prognostic Markers in Cancers)

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17 pages, 305 KiB

Open AccessEditor’s ChoiceReview

The Current State of Charcot–Marie–Tooth Disease Treatment

by Yuji Okamoto and Hiroshi Takashima

Genes 2023, 14(7), 1391; https://doi.org/10.3390/genes14071391 - 1 Jul 2023

Cited by 22 | Viewed by 8516

Abstract

Charcot–Marie–Tooth disease (CMT) and associated neuropathies are the most predominant genetically transmitted neuromuscular conditions; however, effective pharmacological treatments have not established. The extensive genetic heterogeneity of CMT, which impacts the peripheral nerves and causes lifelong disability, presents a significant barrier to the development [...] Read more.

Charcot–Marie–Tooth disease (CMT) and associated neuropathies are the most predominant genetically transmitted neuromuscular conditions; however, effective pharmacological treatments have not established. The extensive genetic heterogeneity of CMT, which impacts the peripheral nerves and causes lifelong disability, presents a significant barrier to the development of comprehensive treatments. An estimated 100 loci within the human genome are linked to various forms of CMT and its related inherited neuropathies. This review delves into prospective therapeutic strategies used for the most frequently encountered CMT variants, namely CMT1A, CMT1B, CMTX1, and CMT2A. Compounds such as PXT3003, which are being clinically and preclinically investigated, and a broad array of therapeutic agents and their corresponding mechanisms are discussed. Furthermore, the progress in established gene therapy techniques, including gene replacement via viral vectors, exon skipping using antisense oligonucleotides, splicing modification, and gene knockdown, are appraised. Each of these gene therapies has the potential for substantial advancements in future research. Full article

(This article belongs to the Special Issue Neuromuscular Disorders: Clinical Treatment and Molecular Genetics)

15 pages, 5107 KiB

Open AccessEditor’s ChoiceArticle

Prediction of Prognosis and Chemotherapeutic Sensitivity Based on Cuproptosis-Associated lncRNAs in Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma

by Jianghong Zhou, Lili Xu, Hong Zhou, Jingjin Wang and Xiaoliang Xing

Genes 2023, 14(7), 1381; https://doi.org/10.3390/genes14071381 - 30 Jun 2023

Cited by 9 | Viewed by 2349

Abstract

Cervical cancer is the fourth most common cancer. The 5-year survival rate for metastatic cervical cancer is less than 10%. The survival time of patients with recurrent cervical cancer is approximately 13–17 months. Cuproptosis is a novel type of cell death related to [...] Read more.

Cervical cancer is the fourth most common cancer. The 5-year survival rate for metastatic cervical cancer is less than 10%. The survival time of patients with recurrent cervical cancer is approximately 13–17 months. Cuproptosis is a novel type of cell death related to mitochondrial respiration. Accumulative studies showed that long non-coding RNAs (lncRNAs) regulated cervical cancer progression. Compressive bioinformatic analysis showed that nine cuproptosis-related lncRNAs (CRLs), including C002128.2, AC002563.1, AC009237.14, AC048337.1, AC145423.1, AL117336.1, AP001542.3, ATP2A1-AS1, and LINC00426, were independently correlated with the overall survival (OS) of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) patients. The time-dependent area under curve value reached 0.716 at 1 year, 0.718 at 3 years, and 0.719 at 5 years. Notably, CESC patients in the low-risk group had increased immune cell infiltration and expression of several immune checkpoints, which indicated that they may benefit more from immune checkpoint blockade therapy. In addition, we also used the model for drug sensitivity analysis. Several drug sensitivities were more sensitive in high-risk patients and showed significant correlations with the risk models, such as Bortezomib_1191, Luminespib_1559, and Rapamycin_1084, suggesting that these drugs may be candidate clinical drugs for patients with a high risk of CESC. In summary, this study further explored the mechanism of CRLs in CESC and provided a more optimized prognostic model and some insights into chemotherapy of CESC. Full article

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

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21 pages, 6548 KiB

Open AccessEditor’s ChoiceReview

Therapeutic Targeting of RNA Splicing in Cancer

by Elizabeth A. Bonner and Stanley C. Lee

Genes 2023, 14(7), 1378; https://doi.org/10.3390/genes14071378 - 29 Jun 2023

Cited by 12 | Viewed by 7371

Abstract

RNA splicing is a key regulatory step in the proper control of gene expression. It is a highly dynamic process orchestrated by the spliceosome, a macro-molecular machinery that consists of protein and RNA components. The dysregulation of RNA splicing has been observed in [...] Read more.

RNA splicing is a key regulatory step in the proper control of gene expression. It is a highly dynamic process orchestrated by the spliceosome, a macro-molecular machinery that consists of protein and RNA components. The dysregulation of RNA splicing has been observed in many human pathologies ranging from neurodegenerative diseases to cancer. The recent identification of recurrent mutations in the core components of the spliceosome in hematologic malignancies has advanced our knowledge of how splicing alterations contribute to disease pathogenesis. This review article will discuss our current understanding of how aberrant RNA splicing regulation drives tumor initiation and progression. We will also review current therapeutic modalities and highlight emerging technologies designed to target RNA splicing for cancer treatment. Full article

(This article belongs to the Special Issue RNA Splicing in Cancer and Targeted Therapies)

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20 pages, 375 KiB

Open AccessEditor’s ChoiceReview

Clinical and Genetic Aspects of Alopecia Areata: A Cutting Edge Review

by Chih-Yi Ho, Chiu-Yen Wu, Jeff Yi-Fu Chen and Ching-Ying Wu

Genes 2023, 14(7), 1362; https://doi.org/10.3390/genes14071362 - 28 Jun 2023

Cited by 20 | Viewed by 9880

Abstract

Alopecia areata (AA) is a chronic, non-scarring, immune-mediated skin disease that affects approximately 0.5–2% of the global population. The etiology of AA is complex and involves genetic and environmental factors, with significant advancements in genetic research occurring in recent years. In addition to [...] Read more.

Alopecia areata (AA) is a chronic, non-scarring, immune-mediated skin disease that affects approximately 0.5–2% of the global population. The etiology of AA is complex and involves genetic and environmental factors, with significant advancements in genetic research occurring in recent years. In addition to well-known genes such as PTPN22, CTLA4, and IL2, which have been widely supported as being associated with AA, an increasing number of specific gene-related loci have been discovered through advances in genetic research. For instance, gene analysis of microRNAs can reveal the critical role of miRNAs in regulating gene expression, aiding in the understanding of cellular and organismal functional regulatory mechanisms. Furthermore, numerous studies have confirmed the existence of correlations between AA and other immune-related diseases. Examples include hyperthyroidism and rheumatoid arthritis. By understanding the interrelationships between AA and other immune diseases, we can further comprehend potential shared genetic foundations or pathogenic mechanisms among different diseases. Genetic research plays a crucial role in unraveling the pathogenesis of AA, as the identification of genetic variations associated with AA can assist in formulating more effective and targeted treatment strategies. Full article

(This article belongs to the Special Issue Genetics of Complex Cutaneous Disorders)

10 pages, 1983 KiB

Open AccessEditor’s ChoiceArticle

A High-Quality Chromosome-Level Genome Assembly of a Snail Cipangopaludina cathayensis (Gastropoda: Viviparidae)

by Benhe Ma, Wu Jin, Huiyun Fu, Bing Sun, Su Yang, Xueyan Ma, Haibo Wen, Xiaoping Wu, Haihua Wang and Xiaojuan Cao

Genes 2023, 14(7), 1365; https://doi.org/10.3390/genes14071365 - 28 Jun 2023

Cited by 2 | Viewed by 2942

Abstract

Cipangopaludina cathayensis (Gastropoda: Prosobranchia; Mesogastropoda; Viviparidae) is widely distributed in the freshwater habitats of China. It is an economically important snail with high edible and medicinal value. However, the genomic resources and the reference genome of this snail are lacking. In this study, [...] Read more.

Cipangopaludina cathayensis (Gastropoda: Prosobranchia; Mesogastropoda; Viviparidae) is widely distributed in the freshwater habitats of China. It is an economically important snail with high edible and medicinal value. However, the genomic resources and the reference genome of this snail are lacking. In this study, we assembled the first chromosome-level genome of C. cathayensis. The preliminary assembly genome was 1.48 Gb in size, with a contig N50 size of 93.49 Mb. The assembled sequences were anchored to nine pseudochromosomes using Hi-C data. The final genome after Hi-C correction was 1.48 Gb, with a contig N50 of 98.49 Mb and scaffold N50 of 195.21 Mb. The anchored rate of the chromosome was 99.99%. A total of 22,702 protein-coding genes were predicted. Phylogenetic analyses indicated that C. cathayensis diverged with Bellamya purificata approximately 158.10 million years ago. There were 268 expanded and 505 contracted gene families in C. cathayensis when compared with its most recent common ancestor. Five putative genes under positive selection in C. cathayensis were identified (false discovery rate <0.05). These genome data provide a valuable resource for evolutionary studies of the family Viviparidae, and for the genetic improvement of C. cathayensis. Full article

(This article belongs to the Special Issue Genetic Improvement of Aquatic Species)

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11 pages, 2055 KiB

Open AccessEditor’s ChoiceArticle

Occurrence of L1M Elements in Chromosomal Rearrangements Associated to Chronic Myeloid Leukemia (CML): Insights from Patient-Specific Breakpoints Characterization

by Alberto L’Abbate, Vittoria Moretti, Ester Pungolino, Giovanni Micheloni, Roberto Valli, Annalisa Frattini, Matteo Barcella, Francesco Acquati, Rolland A Reinbold, Lucy Costantino, Fulvio Ferrara, Alessandra Trojani, Mario Ventura, Giovanni Porta and Roberto Cairoli

Genes 2023, 14(7), 1351; https://doi.org/10.3390/genes14071351 - 27 Jun 2023

Cited by 1 | Viewed by 2431

Abstract

Chronic myeloid leukemia (CML) is a rare myeloproliferative disorder caused by the reciprocal translocation t(9;22)(q34;q11) in hematopoietic stem cells (HSCs). This chromosomal translocation results in the formation of an extra-short chromosome 22, called a Philadelphia chromosome (Ph), containing the BCR-ABL1 fusion gene responsible [...] Read more.

Chronic myeloid leukemia (CML) is a rare myeloproliferative disorder caused by the reciprocal translocation t(9;22)(q34;q11) in hematopoietic stem cells (HSCs). This chromosomal translocation results in the formation of an extra-short chromosome 22, called a Philadelphia chromosome (Ph), containing the BCR-ABL1 fusion gene responsible for the expression of a constitutively active tyrosine kinase that causes uncontrolled growth and replication of leukemic cells. Mechanisms behind the formation of this chromosomal rearrangement are not well known, even if, as observed in tumors, repetitive DNA may be involved as core elements in chromosomal rearrangements. We have participated in the explorative investigations of the PhilosoPhi34 study to evaluate residual Ph+ cells in patients with negative FISH analysis on CD34+/lin- cells with gDNA qPCR. Using targeted next-generation deep sequencing strategies, we analyzed the genomic region around the t(9;22) translocations of 82 CML patients and one CML cell line and assessed the relevance of interspersed repeat elements at breakpoints (BP). We found a statistically higher presence of LINE elements, in particular belonging to the subfamily L1M, in BP cluster regions of both chromosome 22 and 9 compared to the whole human genome. These data suggest that L1M elements could be potential drivers of t(9;22) translocation leading to the generation of the BCR-ABL1 chimeric gene and the expression of the active BCR-ABL1-controlled tyrosine kinase chimeric protein responsible for CML. Full article

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

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11 pages, 1274 KiB

Open AccessEditor’s ChoiceArticle

Polymorphism, Genetic Effect, and Association with Egg-Laying Performance of Chahua Chickens Matrix Metalloproteinases 13 Promoter

by Yanli Du, Changwei Cao, Yong Liu, Xiannian Zi, Yang He, Hongmei Shi, Jinbo Zhao, Changrong Ge and Kun Wang

Genes 2023, 14(7), 1352; https://doi.org/10.3390/genes14071352 - 27 Jun 2023

Cited by 2 | Viewed by 1511

Abstract

Matrix metalloproteinases are a group of proteases involved in the regulation of ovarian follicular development and ovulation. Among the different MMPs, MMP13 is known to play an important role in reproduction. Therefore, this study aimed to screen the molecular genetic markers of the [...] Read more.

Matrix metalloproteinases are a group of proteases involved in the regulation of ovarian follicular development and ovulation. Among the different MMPs, MMP13 is known to play an important role in reproduction. Therefore, this study aimed to screen the molecular genetic markers of the MMP13 gene that affect the egg-laying performance of Chahua chickens. Polymerase chain reaction (PCR) and sequencing were performed in the 5′ regulation region of the MMP13 gene to detect loci significantly related to the egg-laying performance of Chahua chickens. A double fluorescence reporting system, quantitative reverse transcription PCR (RT-qPCR), and Western blotting were used to study whether gene expression was regulated by identified sites, providing a theoretical basis to improve egg production in Chahua chickens. The results revealed six single nucleotide polymorphisms (SNPs; A-1887T, T-1889C, A-1890T, T-2252C, T-2329C, and C-2360A) in the promoter region of the MMP13 gene. Further analysis revealed that hens with T^-1890-C^-1889-T^-1887/T^-1890-C^-1889-T^-1887 (mutant type, MT) had an earlier age at first egg (AFE) than hens with A^-1890-T^-1889-A^-1887/A^-1890-T^-1889-A^-1887 (wild type, WT; p < 0.05). RT-qPCR showed that the relative expression level of the MMP13 gene in the ovarian tissues of individuals with the mutation was higher than that of individuals with the wild gene (p < 0.05). Western blot results confirmed higher levels of the MMP13 protein in MT ovaries compared to those in WT ovaries. Thus, this study suggests that mutation sites on the MMP13 promoter may affect gene expression. In conclusion, the MMP13 gene in Chahua chickens may be significant for egg-laying performance, and the polymorphism in its promoter region could be used as a molecular marker to improve egg-laying performance. Full article

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

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10 pages, 2170 KiB

Open AccessEditor’s ChoiceArticle

Rhabdomyosarcoma Associated with Core Myopathy/Malignant Hyperthermia: Combined Effect of Germline Variants in RYR1 and ASPSCR1 May Play a Role

by Pamela V. Andrade, Joilson M. Santos, Anne C. B. Teixeira, Vanessa F. Sogari, Michelle S. Almeida, Fabiano M. Callegari, Ana C. V. Krepischi, Acary S. B. Oliveira, Mariz Vainzof and Helga C. A. Silva

Genes 2023, 14(7), 1360; https://doi.org/10.3390/genes14071360 - 27 Jun 2023

Cited by 1 | Viewed by 2628

Abstract

Rhabdomyosarcomas have been described in association with thyroid disease, dermatomyositis, Duchenne muscular dystrophy, and in muscular dystrophy models but not in patients with ryanodine receptor-1 gene (RYR1) pathogenic variants. We described here an 18-year-old male who reported a cervical nodule. Magnetic [...] Read more.

Rhabdomyosarcomas have been described in association with thyroid disease, dermatomyositis, Duchenne muscular dystrophy, and in muscular dystrophy models but not in patients with ryanodine receptor-1 gene (RYR1) pathogenic variants. We described here an 18-year-old male who reported a cervical nodule. Magnetic resonance images revealed a mass in the ethmoidal sinus corresponding to rhabdomyosarcoma. As his father died from malignant hyperthermia (MH), an in vitro contracture test was conducted and was positive for MH susceptibility. Muscle histopathological analysis in the biopsy showed the presence of cores. Molecular analysis using NGS sequencing identified germline variants in the RYR1 and ASPSCR1 (alveolar soft part sarcoma) genes. This report expands the spectrum of diseases associated with rhabdomyosarcomas and a possible differential diagnosis of soft tissue tumors in patients with RYR1 variants. Full article

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

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15 pages, 3620 KiB

Open AccessEditor’s ChoiceArticle

Systematic Analysis of Galactinol Synthase and Raffinose Synthase Gene Families in Potato and Their Expression Patterns in Development and Abiotic Stress Responses

by Quankai Jing, Airu Chen, Zhaoyan Lv, Zhihao Dong, Lixia Wang, Xiaoke Meng, Yue Feng, Yu Wan, Chengyun Su, Yanjie Cui, Wenjuan Xu, Hualan Hou and Xiaobiao Zhu

Genes 2023, 14(7), 1344; https://doi.org/10.3390/genes14071344 - 26 Jun 2023

Cited by 15 | Viewed by 2193

Abstract

Raffinose family oligosaccharides (RFOs) are very important for plant growth, development, and abiotic stress tolerance. Galactinol synthase (GolS) and raffinose synthase (RFS) are critical enzymes involved in RFO biosynthesis. However, the whole-genome identification and stress responses of their coding genes in potato remain [...] Read more.

Raffinose family oligosaccharides (RFOs) are very important for plant growth, development, and abiotic stress tolerance. Galactinol synthase (GolS) and raffinose synthase (RFS) are critical enzymes involved in RFO biosynthesis. However, the whole-genome identification and stress responses of their coding genes in potato remain unexplored. In this study, four StGolS and nine StRFS genes were identified and classified into three and five subgroups, respectively. Remarkably, a total of two StGolS and four StRFS genes in potato were identified to form collinear pairs with those in both Arabidopsis and tomato, respectively. Subsequent analysis revealed that StGolS4 exhibited significantly high expression levels in transport-related tissues, PEG-6000, and ABA treatments, with remarkable upregulation under salt stress. Additionally, StRFS5 showed similar responses to StGolS4, but StRFS4 and StRFS8 gene expression increased significantly under salt treatment and decreased in PEG-6000 and ABA treatments. Overall, these results lay a foundation for further research on the functional characteristics and molecular mechanisms of these two gene families in response to ABA, salt, and drought stresses, and provide a theoretical foundation and new gene resources for the abiotic-stress-tolerant breeding of potato. Full article

(This article belongs to the Special Issue Physiological and Molecular Responses of Crops in Abiotic Stress Tolerance)

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19 pages, 4966 KiB

Open AccessEditor’s ChoiceArticle

Antagonistic Bacteria Bacillus velezensis VB7 Possess Nematicidal Action and Induce an Immune Response to Suppress the Infection of Root-Knot Nematode (RKN) in Tomato

by Vinothini Kamalanathan, Nakkeeran Sevugapperumal and Saranya Nallusamy

Genes 2023, 14(7), 1335; https://doi.org/10.3390/genes14071335 - 25 Jun 2023

Cited by 11 | Viewed by 2343

Abstract

Meloidogyne incognita, the root-knot nematode (RKN), a devastating plant parasitic nematode, causes considerable damage to agricultural crops worldwide. As a sedentary root parasite, it alters the root’s physiology and influences the host’s phytohormonal signaling to evade defense. The sustainable management of RKN [...] Read more.

Meloidogyne incognita, the root-knot nematode (RKN), a devastating plant parasitic nematode, causes considerable damage to agricultural crops worldwide. As a sedentary root parasite, it alters the root’s physiology and influences the host’s phytohormonal signaling to evade defense. The sustainable management of RKN remains a challenging task. Hence, we made an attempt to investigate the nematicide activity of Bacillus velezensis VB7 to trigger the innate immune response against the infection of RKN. In vitro assay, B. velezensis VB7 inhibited the hatchability of root-knot nematode eggs and juvenile mortality of M. incognita by 87.95% and 96.66%, respectively at 96 hrs. The application of B. velezensis VB7 challenged against RKN induced MAMP-triggered immunity via the expression of transcription factors/defense genes by several folds pertaining to WRKY, LOX, PAL, MYB, and PR in comparison to those RKN-inoculated and healthy control through RT-PCR. Additionally, Cytoscape analysis of defense genes indicated the coordinated expression of various other genes linked to immune response. Thus, the current study clearly demonstrated the effectiveness of B. velezensis VB7 as a potential nematicide and inducer of immune responses against RKN infestation in tomato. Full article

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

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23 pages, 2503 KiB

Open AccessEditor’s ChoiceReview

Single-Cell Analysis in the Omics Era: Technologies and Applications in Cancer

by Michele Massimino, Federica Martorana, Stefania Stella, Silvia Rita Vitale, Cristina Tomarchio, Livia Manzella and Paolo Vigneri

Genes 2023, 14(7), 1330; https://doi.org/10.3390/genes14071330 - 24 Jun 2023

Cited by 9 | Viewed by 4092

Abstract

Cancer molecular profiling obtained with conventional bulk sequencing describes average alterations obtained from the entire cellular population analyzed. In the era of precision medicine, this approach is unable to track tumor heterogeneity and cannot be exploited to unravel the biological processes behind clonal [...] Read more.

Cancer molecular profiling obtained with conventional bulk sequencing describes average alterations obtained from the entire cellular population analyzed. In the era of precision medicine, this approach is unable to track tumor heterogeneity and cannot be exploited to unravel the biological processes behind clonal evolution. In the last few years, functional single-cell omics has improved our understanding of cancer heterogeneity. This approach requires isolation and identification of single cells starting from an entire population. A cell suspension obtained by tumor tissue dissociation or hematological material can be manipulated using different techniques to separate individual cells, employed for single-cell downstream analysis. Single-cell data can then be used to analyze cell–cell diversity, thus mapping evolving cancer biological processes. Despite its unquestionable advantages, single-cell analysis produces massive amounts of data with several potential biases, stemming from cell manipulation and pre-amplification steps. To overcome these limitations, several bioinformatic approaches have been developed and explored. In this work, we provide an overview of this entire process while discussing the most recent advances in the field of functional omics at single-cell resolution. Full article

(This article belongs to the Special Issue Bioinformatic Approaches in Cancer)

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16 pages, 1877 KiB

Open AccessEditor’s ChoiceReview

Female Pattern Hair Loss: An Overview with Focus on the Genetics

by Chih-Yi Ho, Jeff Yi-Fu Chen, Wen-Li Hsu, Sebastian Yu, Wei-Chiao Chen, Szu-Hao Chiu, Hui-Ru Yang, Sheng-Yao Lin and Ching-Ying Wu

Genes 2023, 14(7), 1326; https://doi.org/10.3390/genes14071326 - 23 Jun 2023

Cited by 10 | Viewed by 20008

Abstract

Pattern hair loss can occur in both men and women, and the underlying molecular mechanisms have been continuously studied in recent years. Male androgenetic alopecia (M-AGA), also termed male pattern hair loss, is the most common type of hair loss in men. M-AGA [...] Read more.

Pattern hair loss can occur in both men and women, and the underlying molecular mechanisms have been continuously studied in recent years. Male androgenetic alopecia (M-AGA), also termed male pattern hair loss, is the most common type of hair loss in men. M-AGA is considered an androgen-dependent trait with a background of genetic predisposition. The interplay between genetic and non-genetic factors leads to the phenotype of follicular miniaturization. Although this similar pattern of phenotypic miniaturization can also be found in female pattern hair loss (FPHL), the corresponding genetic factors in M-AGA do not account for the phenotype in FPHL, indicating that there are different genes contributing to FPHL. Therefore, the role of genetic factors in FPHL is still uncertain. Understanding the genetic mechanism that causes FPHL is crucial for the future development of personalized treatment strategies. This review aims to highlight the differences in the ethnic prevalence and genetic background of FPHL, as well as the current genetic research progress in nutrition, Wnt signaling, and sex hormones related to FPHL. Full article

(This article belongs to the Special Issue Genetics of Complex Cutaneous Disorders)

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17 pages, 4556 KiB

Open AccessEditor’s ChoiceReview

Nuclear Receptor Subfamily 2 Group E Member 3 (NR2E3): Role in Retinal Development and Disease

by Maria Toms, Natasha Ward and Mariya Moosajee

Genes 2023, 14(7), 1325; https://doi.org/10.3390/genes14071325 - 23 Jun 2023

Cited by 15 | Viewed by 3942

Abstract

NR2E3 is a nuclear hormone receptor gene required for the correct development of the retinal rod photoreceptors. Expression of NR2E3 protein in rod cell precursors suppresses cone-specific gene expression and, in concert with other transcription factors including NRL, activates the expression of rod-specific [...] Read more.

NR2E3 is a nuclear hormone receptor gene required for the correct development of the retinal rod photoreceptors. Expression of NR2E3 protein in rod cell precursors suppresses cone-specific gene expression and, in concert with other transcription factors including NRL, activates the expression of rod-specific genes. Pathogenic variants involving NR2E3 cause a spectrum of retinopathies, including enhanced S-cone syndrome, Goldmann–Favre syndrome, retinitis pigmentosa, and clumped pigmentary retinal degeneration, with limited evidence of genotype–phenotype correlations. A common feature of NR2E3-related disease is an abnormally high number of cone photoreceptors that are sensitive to short wavelength light, the S-cones. This characteristic has been supported by mouse studies, which have also revealed that loss of Nr2e3 function causes photoreceptors to develop as cells that are intermediate between rods and cones. While there is currently no available cure for NR2E3-related retinopathies, there are a number of emerging therapeutic strategies under investigation, including the use of viral gene therapy and gene editing, that have shown promise for the future treatment of patients with NR2E3 variants and other inherited retinal diseases. This review provides a detailed overview of the current understanding of the role of NR2E3 in normal development and disease, and the associated clinical phenotypes, animal models, and therapeutic studies. Full article

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

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12 pages, 2286 KiB

Open AccessEditor’s ChoiceArticle

Study on the Protective Immunity Induced by Pseudotyped Baculovirus Expressing the E Protein of Tembusu Virus in Ducklings

by Zheng Ni, Tao Yun, Liu Chen, Weicheng Ye, Jionggang Hua, Yinchu Zhu, Guangqing Liu and Cun Zhang

Genes 2023, 14(7), 1316; https://doi.org/10.3390/genes14071316 - 22 Jun 2023

Cited by 1 | Viewed by 1815

Abstract

The Duck Tembusu virus (DTMUV), a pathogenic flavivirus, has been causing significant economic losses in the Chinese poultry industry since 2010. This virus can severely decrease egg production and inhibit the growth of laying ducks and ducklings. While many vaccines have been developed [...] Read more.

The Duck Tembusu virus (DTMUV), a pathogenic flavivirus, has been causing significant economic losses in the Chinese poultry industry since 2010. This virus can severely decrease egg production and inhibit the growth of laying ducks and ducklings. While many vaccines have been developed to prevent DTMUV infection, fresh outbreaks continue to occur, as few effective vaccines are available. The E glycoprotein of DTMUV is the primary target for inducing protective immunity in the natural host. Therefore, we conducted an investigation and successfully developed a recombinant baculovirus containing the DTMUV E gene. Ducklings were then vaccinated with the purified protein derived from this virus as a potential vaccine candidate. Our findings demonstrated that the E glycoprotein of DTMUV was highly expressed in Sf9 cells. The vaccination of ducklings with the recombinant baculovirus Bac-E resulted in the induction of strong humoral and cellular immune responses. Most significantly, we observed that the vaccine provided 100% protective immunity against lethal challenges with the DTMUV YY5 strain. Full article

(This article belongs to the Special Issue Molecular Genetics in Livestock Production and Disease Resistance)

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18 pages, 2172 KiB

Open AccessEditor’s ChoiceSystematic Review

The Relationship between TLR3 rs3775291 Polymorphism and Infectious Diseases: A Meta-Analysis of Case-Control Studies

by Marcos Jessé Abrahão Silva, Caroliny Soares Silva, Marcelo Cleyton da Silva Vieira, Pabllo Antonny Silva dos Santos, Cristiane Cunha Frota, Karla Valéria Batista Lima and Luana Nepomuceno Gondim Costa Lima

Genes 2023, 14(7), 1311; https://doi.org/10.3390/genes14071311 - 21 Jun 2023

Cited by 13 | Viewed by 2496

Abstract

As the host’s first line of defense against pathogens, Toll-like receptors (TLRs), such as the TLR3, are genes encoding transmembrane receptors of the same name. Depending on their expression, TLRs cause a pro- or anti-inflammatory response. The purpose of the [...] Read more.

As the host’s first line of defense against pathogens, Toll-like receptors (TLRs), such as the TLR3, are genes encoding transmembrane receptors of the same name. Depending on their expression, TLRs cause a pro- or anti-inflammatory response. The purpose of the article was to determine whether there is an association between the Toll-like receptor 3 (TLR3) rs3775291 Single Nucleotide Polymorphism—SNP and susceptibility to infections. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines and was registered in PROSPERO under the code CRD42023429533. A systematic search for relevant studies was performed using PubMed, Scopus, SciELO, Google Scholar, and Science Direct by the MeSH descriptors and the Boolean Operator “AND”: “Infections”; “TLR3”; “SNP”, between January 2005 and July 2022. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated for genotypic comparison assuming a dominant genetic model (CT + TT vs. CC). A meta-analysis of 18 studies consisting of 3118 cases and 4368 controls found a significant association for risk between the presence of the TLR3 SNP rs3775291 and infections as part of the general analysis (OR = 1.16, 95% CI = 1.04–1.28, p = 0.004). In the subgroups of continents, the SNP had a protective role in Europe for 1044 cases and 1471 controls (OR = 0.83, 95% CI = 0.70–0.99, p = 0.04); however, the Asian (for 1588 patients and 2306 controls) and American (for 486 patients and 591 controls) continents had an increase in infectious risk (OR = 1.37, 95% CI = 1.19–1.58, p < 0.001; OR = 1.42, 95% CI = 1.08–1.86, and p = 0.01, respectively). Heterogeneity between studies was detected (I² = 58%) but was explained in meta-regression by the subgroup of continents itself and publication bias was not evident. The results of the meta-analysis suggest a significant association between the TLR3 rs3775291 polymorphism and susceptibility to infections. Thus, when analyzing subgroups, the Asian and American continents showed that this SNP confers a higher risk against infections in a dominant genotypic model. Therefore, more studies are necessary to fully elucidate the role of TLR3 rs3775291 in infections. Full article

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

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15 pages, 2126 KiB

Open AccessEditor’s ChoiceArticle

Identification of Candidate QTLs and Genes for Ear Diameter by Multi-Parent Population in Maize

by Fuyan Jiang, Li Liu, Ziwei Li, Yaqi Bi, Xingfu Yin, Ruijia Guo, Jing Wang, Yudong Zhang, Ranjan Kumar Shaw and Xingming Fan

Genes 2023, 14(6), 1305; https://doi.org/10.3390/genes14061305 - 20 Jun 2023

Cited by 9 | Viewed by 2591

Abstract

Ear diameter (ED) is a critical component of grain yield (GY) in maize (Zea mays L.). Studying the genetic basis of ED in maize is of great significance in enhancing maize GY. Against this backdrop, this study was framed to (1) map [...] Read more.

Ear diameter (ED) is a critical component of grain yield (GY) in maize (Zea mays L.). Studying the genetic basis of ED in maize is of great significance in enhancing maize GY. Against this backdrop, this study was framed to (1) map the ED-related quantitative trait locus (QTL) and SNPs associated with ED; and (2) identify putative functional genes that may affect ED in maize. To accomplish this, an elite maize inbred line, Ye107, which belongs to the Reid heterotic group, was used as a common parent and crossed with seven elite inbred lines from three different heterotic groups (Suwan1, Reid, and nonReid) that exhibited abundant genetic variation in ED. This led to the construction of a multi-parent population consisting of 1215 F₇ recombinant inbred lines (F₇RILs). A genome-wide association study (GWAS) and linkage analysis were then conducted for the multi-parent population using 264,694 high-quality SNPs generated via the genotyping-by-sequencing method. Our study identified a total of 11 SNPs that were significantly associated with ED through the GWAS, and three QTLs were revealed by the linkage analysis for ED. The major QTL on chromosome 1 was co-identified in the region by the GWAS at SNP_143985532. SNP_143985532, located upstream of the Zm00001d030559 gene, encodes a callose synthase that is expressed in various tissues, with the highest expression level in the maize ear primordium. Haplotype analysis indicated that the haplotype B (allele AA) of Zm00001d030559 was positively correlated with ED. The candidate genes and SNPs identified in this study provide crucial insights for future studies on the genetic mechanism of maize ED formation, cloning of ED-related genes, and genetic improvement of ED. These results may help develop important genetic resources for enhancing maize yield through marker-assisted breeding. Full article

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

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