Genes

15 pages, 1837 KiB

Open AccessEditor’s ChoiceArticle

Trans-Activation of the Coactivator-Associated Arginine Methyltransferase 1 (Carm1) Gene by the Oncogene Product Tax of Human T-Cell Leukemia Virus Type 1

by Rahma F. Hayati, Rinka Nakajima, Yaxuan Zhou, Mashiro Shirasawa, Lin Zhao, Mariana Fikriyanti, Ritsuko Iwanaga, Andrew P. Bradford, Kenta Kurayoshi, Keigo Araki and Kiyoshi Ohtani

Genes 2024, 15(6), 698; https://doi.org/10.3390/genes15060698 - 27 May 2024

Cited by 1 | Viewed by 1882

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma. The oncogene product Tax of HTLV-I is thought to play crucial roles in leukemogenesis by promoting proliferation of the virus-infected cells through activation of growth-promoting genes. These genes [...] Read more.

Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma. The oncogene product Tax of HTLV-I is thought to play crucial roles in leukemogenesis by promoting proliferation of the virus-infected cells through activation of growth-promoting genes. These genes code for growth factors and their receptors, cytokines, cell adhesion molecules, growth signal transducers, transcription factors and cell cycle regulators. We show here that Tax activates the gene coding for coactivator-associated arginine methyltransferase 1 (CARM1), which epigenetically enhances gene expression through methylation of histones. Tax activated the Carm1 gene and increased protein expression, not only in human T-cell lines but also in normal peripheral blood lymphocytes (PHA-PBLs). Tax increased R17-methylated histone H3 on the target gene IL-2Rα, concomitant with increased expression of CARM1. Short hairpin RNA (shRNA)-mediated knockdown of CARM1 decreased Tax-mediated induction of IL-2Rα and Cyclin D2 gene expression, reduced E2F activation and inhibited cell cycle progression. Tax acted via response elements in intron 1 of the Carm1 gene, through the NF-κB pathway. These results suggest that Tax-mediated activation of the Carm1 gene contributes to leukemogenic target-gene expression and cell cycle progression, identifying the first epigenetic target gene for Tax-mediated trans-activation in cell growth promotion. Full article

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

► Show Figures

Figure 1

7 pages, 2334 KiB

Open AccessEditor’s ChoiceCase Report

HELIX Syndrome, a Claudinopathy with Relevant Dermatological Manifestations: Report of Two New Cases

by María Carmen Martínez-Romero, María Encarnación Hernández-Contreras, Juan Antonio Bafalliu-Vidal, María Barreda-Sánchez, Teresa Martínez-Menchón, Virginia Cabello-Chaves and Encarna Guillén-Navarro

Genes 2024, 15(6), 687; https://doi.org/10.3390/genes15060687 - 26 May 2024

Viewed by 1679

Abstract

HELIX syndrome (Hypohidrosis–Electrolyte disturbances–hypoLacrimia–Ichthyosis–Xerostomia) (MIM#617671) (ORPHA:528105), described in 2017, is due to an abnormal claudin 10 b protein, secondary to pathogenic CLDN10 variants. So far, only ten families have been described. We aim to describe the phenotype in the first Spanish family identified, [...] Read more.

HELIX syndrome (Hypohidrosis–Electrolyte disturbances–hypoLacrimia–Ichthyosis–Xerostomia) (MIM#617671) (ORPHA:528105), described in 2017, is due to an abnormal claudin 10 b protein, secondary to pathogenic CLDN10 variants. So far, only ten families have been described. We aim to describe the phenotype in the first Spanish family identified, highlight the skin anomalies as an important clue, and expand the genotypic spectrum. Two adult brothers from consanguineous parents with suspected ectodermal dysplasia (ED) since early childhood were re-evaluated. A comprehensive phenotypic exam and an aCGH + SNP4 × 180 K microarray followed by Sanger sequencing of the CLDN10 gene were performed. They presented hypohidrosis, xerosis, mild ichthyosis, plantar keratosis, palm hyperlinearity, alacrima, and xerostomia. In adulthood, they also developed a salt-losing nephropathy with hypokalemia and hypermagnesemia. The molecular study in both patients revealed a novel pathogenic homozygous deletion of 8 nucleotides in exon 2 of the CLDN10 gene [CLDN10 (NM_0006984.4): c.322_329delGGCTCCGA, p.Gly108fs*] leading to a premature truncation of the protein. Both parents were heterozygous carriers. Hypohidrosis, ichthyosis, and plantar keratosis associated with alacrima and xerostomia should raise suspicion for HELIX syndrome, which also includes nephropathy and electrolyte disturbances in adults. Given the potential for ED misdiagnosis in infancy, it is important to include the CLDN10 gene in a specific genodermatosis next-generation sequencing (NGS) panel to provide early diagnosis, accurate management, and genetic counseling. Full article

(This article belongs to the Special Issue Genetic Research on Monogenic Skin Disorders)

► Show Figures

Figure 1

16 pages, 438 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Gene Abnormalities and Modulated Gene Expression Associated with Radionuclide Treatment: Towards Predictive Biomarkers of Response

by Tim A. D. Smith

Genes 2024, 15(6), 688; https://doi.org/10.3390/genes15060688 - 26 May 2024

Viewed by 1480

Abstract

Molecular radiotherapy (MRT), also known as radioimmunotherapy or targeted radiotherapy, is the delivery of radionuclides to tumours by targeting receptors overexpressed on the cancer cell. Currently it is used in the treatment of a few cancer types including lymphoma, neuroendocrine, and prostate cancer. [...] Read more.

Molecular radiotherapy (MRT), also known as radioimmunotherapy or targeted radiotherapy, is the delivery of radionuclides to tumours by targeting receptors overexpressed on the cancer cell. Currently it is used in the treatment of a few cancer types including lymphoma, neuroendocrine, and prostate cancer. Recently reported outcomes demonstrating improvements in patient survival have led to an upsurge in interest in MRT particularly for the treatment of prostate cancer. Unfortunately, between 30% and 40% of patients do not respond. Further normal tissue exposure, especially kidney and salivary gland due to receptor expression, result in toxicity, including dry mouth. Predictive biomarkers to select patients who will benefit from MRT are crucial. Whilst pre-treatment imaging with imaging versions of the therapeutic agents is useful in demonstrating tumour binding and potentially organ toxicity, they do not necessarily predict patient benefit, which is dependent on tumour radiosensitivity. Transcript-based biomarkers have proven useful in tailoring external beam radiotherapy and adjuvant treatment. However, few studies have attempted to derive signatures for MRT response prediction. Here, transcriptomic studies that have identified genes associated with clinical radionuclide exposure have been reviewed. These studies will provide potential features for seeding multi-component biomarkers of MRT response. Full article

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

► Show Figures

Figure 1

16 pages, 6833 KiB

Open AccessEditor’s ChoiceArticle

Integrating Bioinformatics and Machine Learning for Genomic Prediction in Chickens

by Xiaochang Li, Xiaoman Chen, Qiulian Wang, Ning Yang and Congjiao Sun

Genes 2024, 15(6), 690; https://doi.org/10.3390/genes15060690 - 26 May 2024

Cited by 1 | Viewed by 2459

Abstract

Genomic prediction plays an increasingly important role in modern animal breeding, with predictive accuracy being a crucial aspect. The classical linear mixed model is gradually unable to accommodate the growing number of target traits and the increasingly intricate genetic regulatory patterns. Hence, novel [...] Read more.

Genomic prediction plays an increasingly important role in modern animal breeding, with predictive accuracy being a crucial aspect. The classical linear mixed model is gradually unable to accommodate the growing number of target traits and the increasingly intricate genetic regulatory patterns. Hence, novel approaches are necessary for future genomic prediction. In this study, we used an illumina 50K SNP chip to genotype 4190 egg-type female Rhode Island Red chickens. Machine learning (ML) and classical bioinformatics methods were integrated to fit genotypes with 10 economic traits in chickens. We evaluated the effectiveness of ML methods using Pearson correlation coefficients and the RMSE between predicted and actual phenotypic values and compared them with rrBLUP and BayesA. Our results indicated that ML algorithms exhibit significantly superior performance to rrBLUP and BayesA in predicting body weight and eggshell strength traits. Conversely, rrBLUP and BayesA demonstrated 2–58% higher predictive accuracy in predicting egg numbers. Additionally, the incorporation of suggestively significant SNPs obtained through the GWAS into the ML models resulted in an increase in the predictive accuracy of 0.1–27% across nearly all traits. These findings suggest the potential of combining classical bioinformatics methods with ML techniques to improve genomic prediction in the future. Full article

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

► Show Figures

Figure 1

13 pages, 2370 KiB

Open AccessEditor’s ChoiceArticle

Unlocking the Genetic Identity of Endangered Paphiopedilum Orchids: A DNA Barcoding Approach

by Małgorzata Karbarz, Dominika Szlachcikowska, Angelika Zapał and Agnieszka Leśko

Genes 2024, 15(6), 689; https://doi.org/10.3390/genes15060689 - 26 May 2024

Cited by 4 | Viewed by 1751

Abstract

Orchids of the genus Paphiopedilum, also called slippers, are among the most valued representatives of the Orchidaceae family due to their aesthetic qualities. Due to overexploitation, deforestation, and illegal trade in these plants, especially in the vegetative phase, Paphiopedilum requires special protection. This [...] Read more.

Orchids of the genus Paphiopedilum, also called slippers, are among the most valued representatives of the Orchidaceae family due to their aesthetic qualities. Due to overexploitation, deforestation, and illegal trade in these plants, especially in the vegetative phase, Paphiopedilum requires special protection. This genus is listed in Appendix I of the Convention on International Trade in Endangered Species of Wild Fauna and Flora. Their precise identification is of great importance for the preservation of genetic resources and biodiversity of the orchid family (Orchidaceae). Therefore, the main objective of the study was to investigate the usefulness of the DNA barcoding technique for the identification of endangered orchids of the genus Paphiopedilum and to determine the effectiveness of five loci: matK, rbcL, ITS2, atpF-atpH and trnH-psbA as potential molecular markers for species of this genus. Among single locus barcodes, matK was the most effective at identifying species (64%). Furthermore, matK, ITS2, matK + rbcL, and matK + trnH-psbA barcodes can be successfully used as a complementary tool to identify Paphiopedilum orchids while supporting morphological data provided by taxonomists. Full article

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

► Show Figures

Figure 1

14 pages, 1407 KiB

Open AccessEditor’s ChoiceArticle

Functional and Molecular Characterization of New SPTLC1 Missense Variants in Patients with Hereditary Sensory and Autonomic Neuropathy Type 1 (HSAN1)

by Julie Rochat, André Blavier, Séverine Ruet, Sophie Vasseur, Angela Puma, Béatrice Desnous, Victor Chan, Emilien Delmont, Shahram Attarian, Raul Juntas Morales, Isabelle Quadrio, Léo Vidoni, Nathalie Bonello-Palot and David Cheillan

Genes 2024, 15(6), 692; https://doi.org/10.3390/genes15060692 - 26 May 2024

Cited by 1 | Viewed by 1792

Abstract

Hereditary sensory and autonomic neuropathy type 1 is an autosomal dominant neuropathy caused by the SPTLC1 or SPTLC2 variants. These variants modify the preferred substrate of serine palmitoyl transferase, responsible for the first step of de novo sphingolipids synthesis, leading to accumulation of [...] Read more.

Hereditary sensory and autonomic neuropathy type 1 is an autosomal dominant neuropathy caused by the SPTLC1 or SPTLC2 variants. These variants modify the preferred substrate of serine palmitoyl transferase, responsible for the first step of de novo sphingolipids synthesis, leading to accumulation of cytotoxic deoxysphingolipids. Diagnosis of HSAN1 is based on clinical symptoms, mainly progressive loss of distal sensory keep, and genetic analysis. Aim: Identifying new SPTLC1 or SPTLC2 “gain-of-function” variants raises the question as to their pathogenicity. This work focused on characterizing six new SPTLC1 variants using in silico prediction tools, new meta-scores, 3D modeling, and functional testing to establish their pathogenicity. Methods: Variants from six patients with HSAN1 were studied. In silico, CADD and REVEL scores and the 3D modeling software MITZLI were used to characterize the pathogenic effect of the variants. Functional tests based on plasma sphingolipids quantification (total deoxysphinganine, ceramides, and dihydroceramides) were performed by tandem mass spectrometry. Results: In silico predictors did not provide very contrasting results when functional tests discriminated the different variants according to their impact on deoxysphinganine level or canonical sphingolipids synthesis. Two SPTLC1 variants were newly described as pathogenic: SPTLC1 NM_006415.4:c.998A>G and NM_006415.4:c.1015G>A. Discussion: The combination of the different tools provides arguments to establish the pathogenicity of these new variants. When available, functional testing remains the best option to establish the in vivo impact of a variant. Moreover, the comprehension of metabolic dysregulation offers opportunities to develop new therapeutic strategies for these genetic disorders. Full article

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

► Show Figures

Figure 1

17 pages, 3167 KiB

Open AccessEditor’s ChoiceArticle

Biodiversity of Demersal Fish Communities in the Cosmonaut Sea Revealed by DNA Barcoding Analyses

by Hai Li, Xing Miao, Rui Wang, Yuzhuo Liao, Yilin Wen, Ran Zhang and Longshan Lin

Genes 2024, 15(6), 691; https://doi.org/10.3390/genes15060691 - 26 May 2024

Cited by 2 | Viewed by 1444

Abstract

The Cosmonaut Sea is one of the least accessed regions in the Southern Ocean, and our knowledge about the fish biodiversity in the region is sparse. In this study, we provided a description of demersal fish diversity in the Cosmonaut Sea by analysing [...] Read more.

The Cosmonaut Sea is one of the least accessed regions in the Southern Ocean, and our knowledge about the fish biodiversity in the region is sparse. In this study, we provided a description of demersal fish diversity in the Cosmonaut Sea by analysing cytochrome oxidase I (COI) barcodes of 98 fish samples that were hauled by trawling during the 37th and 38th Chinese National Antarctic Research Expedition (CHINARE) cruises. Twenty-four species representing 19 genera and 11 families, namely, Artedidraconidae, Bathydraconidae, Bathylagidae, Channichthyidae, Liparidae, Macrouridae, Muraenolepididae, Myctophidae, Nototheniidae, Paralepididae and Zoarcidae, were discriminated and identified, which were largely identical to local fish occurrence records and the general pattern of demersal fish communities at high Antarctic shelf areas. The validity of a barcoding gap failed to be detected and confirmed across all species due to the indicative signals of two potential cryptic species. Nevertheless, DNA barcoding still demonstrated to be a very efficient and sound method for the discrimination and classification of Antarctic fishes. In the future, various sampling strategies that cover all geographic sections and depth strata of the Cosmonaut Sea are encouraged to enhance our understanding of local fish communities, within which DNA barcoding can play an important role in either molecular taxonomy or the establishment of a dedicated local reference database for eDNA metabarcoding analyses. Full article

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

► Show Figures

Figure 1

14 pages, 4224 KiB

Open AccessEditor’s ChoiceArticle

A Polygenic Risk Analysis for Identifying Ulcerative Colitis Patients with European Ancestry

by Ling Liu, Yiming Wu, Yizhou Li and Menglong Li

Genes 2024, 15(6), 684; https://doi.org/10.3390/genes15060684 - 25 May 2024

Cited by 1 | Viewed by 1479

Abstract

The incidence of ulcerative colitis (UC) has increased globally. As a complex disease, the genetic predisposition for UC could be estimated by the polygenic risk score (PRS), which aggregates the effects of a large number of genetic variants in a single quantity and [...] Read more.

The incidence of ulcerative colitis (UC) has increased globally. As a complex disease, the genetic predisposition for UC could be estimated by the polygenic risk score (PRS), which aggregates the effects of a large number of genetic variants in a single quantity and shows promise in identifying individuals at higher lifetime risk of UC. Here, based on a cohort of 2869 UC cases and 2900 controls with genotype array datasets, we used PRSice-2 to calculate PRS, and systematically analyzed factors that could affect the power of PRS, including GWAS summary statistics, population stratification, and impact of variants. After leveraging a stepwise condition analysis, we eventually established the best PRS model, achieving an AUC of 0.713. Meanwhile, samples in the top 20% of the PRS distribution had a risk of UC more than ten times higher than samples in the lowest 20% (OR = 10.435, 95% CI 8.571–12.703). Our analyses demonstrated that including population-enriched, more disease-associated SNPs and using GWAS summary statistics from similar ethnic background can improve the power of PRS. Strictly following the principle of focusing on one population in all aspects of generating PRS can be a cost-effective way to apply genotype-array-derived PRS to practical risk estimation. Full article

(This article belongs to the Special Issue Statistical Methods for Genetic Epidemiology)

► Show Figures

Figure 1

30 pages, 17832 KiB

Open AccessEditor’s ChoiceArticle

Enhancing Gene Co-Expression Network Inference for the Malaria Parasite Plasmodium falciparum

by Qi Li, Katrina A. Button-Simons, Mackenzie A. C. Sievert, Elias Chahoud, Gabriel F. Foster, Kaitlynn Meis, Michael T. Ferdig and Tijana Milenković

Genes 2024, 15(6), 685; https://doi.org/10.3390/genes15060685 - 25 May 2024

Cited by 2 | Viewed by 1692

Abstract

Background: Malaria results in more than 550,000 deaths each year due to drug resistance in the most lethal Plasmodium (P.) species P. falciparum. A full P. falciparum genome was published in 2002, yet 44.6% of its genes have unknown functions. [...] Read more.

Background: Malaria results in more than 550,000 deaths each year due to drug resistance in the most lethal Plasmodium (P.) species P. falciparum. A full P. falciparum genome was published in 2002, yet 44.6% of its genes have unknown functions. Improving the functional annotation of genes is important for identifying drug targets and understanding the evolution of drug resistance. Results: Genes function by interacting with one another. So, analyzing gene co-expression networks can enhance functional annotations and prioritize genes for wet lab validation. Earlier efforts to build gene co-expression networks in P. falciparum have been limited to a single network inference method or gaining biological understanding for only a single gene and its interacting partners. Here, we explore multiple inference methods and aim to systematically predict functional annotations for all P. falciparum genes. We evaluate each inferred network based on how well it predicts existing gene–Gene Ontology (GO) term annotations using network clustering and leave-one-out crossvalidation. We assess overlaps of the different networks’ edges (gene co-expression relationships), as well as predicted functional knowledge. The networks’ edges are overall complementary: 47–85% of all edges are unique to each network. In terms of the accuracy of predicting gene functional annotations, all networks yielded relatively high precision (as high as 87% for the network inferred using mutual information), but the highest recall reached was below 15%. All networks having low recall means that none of them capture a large amount of all existing gene–GO term annotations. In fact, their annotation predictions are highly complementary, with the largest pairwise overlap of only 27%. We provide ranked lists of inferred gene–gene interactions and predicted gene–GO term annotations for future use and wet lab validation by the malaria community. Conclusions: The different networks seem to capture different aspects of the P. falciparum biology in terms of both inferred interactions and predicted gene functional annotations. Thus, relying on a single network inference method should be avoided when possible. Supplementary data: Attached. Full article

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

► Show Figures

Figure 1

8 pages, 1581 KiB

Open AccessEditor’s ChoiceArticle

Ovine KRT81 Variants and Their Influence on Selected Wool Traits of Commercial Value

by Wenhao Li, Lingrong Bai, Huitong Zhou, Zhihe Zhang, Zhijie Ma, Guofang Wu, Yuzhu Luo, Jasmine Tanner and Jon G. H. Hickford

Genes 2024, 15(6), 681; https://doi.org/10.3390/genes15060681 - 24 May 2024

Cited by 3 | Viewed by 1182

Abstract

Keratins are the main structural protein components of wool fibres, and variation in them and their genes (KRTs) is thought to influence wool structure and characteristics. The PCR–single strand conformation polymorphism technique has been used previously to investigate genetic variation in [...] Read more.

Keratins are the main structural protein components of wool fibres, and variation in them and their genes (KRTs) is thought to influence wool structure and characteristics. The PCR–single strand conformation polymorphism technique has been used previously to investigate genetic variation in selected coding and intron regions of the type II sheep keratin gene KRT81, but no variation was identified. In this study, we used the same technique to explore the 5′ untranslated region of KRT81 and detected three sequence variants (A, B and C) that contain four single nucleotide polymorphisms. Among the 389 Merino × Southdown cross sheep investigated, variant B was linked to a reduction in clean fleece weight, while C was associated with an increase in both greasy fleece weight and clean fleece weight. No discernible effects on staple length or mean-fibre-diameter-related traits were observed. These findings suggest that variation in ovine KRT81 might influence wool growth by changing the density of wool follicles in the skin, the density of individual fibres, or the area of the skin producing fibre, as opposed to changing the rate of extrusion of fibres or their diameter. Full article

(This article belongs to the Special Issue Genetics and Breeding in Sheep and Goats)

► Show Figures

Figure 1

21 pages, 11382 KiB

Open AccessEditor’s ChoiceArticle

Gonadal Transcriptome Sequencing Analysis Reveals the Candidate Sex-Related Genes and Signaling Pathways in the East Asian Common Octopus, Octopus sinensis

by Fenghui Li, Siqing Chen, Tao Zhang, Luying Pan, Changlin Liu and Li Bian

Genes 2024, 15(6), 682; https://doi.org/10.3390/genes15060682 - 24 May 2024

Cited by 1 | Viewed by 1525

Abstract

The East Asian common octopus (Octopus sinensis) is an economically important species among cephalopods. This species exhibits a strict dioecious and allogamous reproductive strategy, along with a phenotypic sexual dimorphism, where the third right arm differentiates into hectocotylus in males. However, [...] Read more.

The East Asian common octopus (Octopus sinensis) is an economically important species among cephalopods. This species exhibits a strict dioecious and allogamous reproductive strategy, along with a phenotypic sexual dimorphism, where the third right arm differentiates into hectocotylus in males. However, our understanding of the molecular mechanisms that underlie sex determination and differentiation in this species remains limited. In the present study, we surveyed gene-expression profiles in the immature male and female gonads of O. sinensis based on the RNA-seq, and a total of 47.83 Gb of high-quality data were generated. Compared with the testis, we identified 8302 differentially expressed genes (DEGs) in the ovary, of which 4459 genes were up-regulated and 3843 genes were down-regulated. Based on the GO enrichment, many GO terms related to sex differentiation were identified, such as sex differentiation (GO: 0007548), sexual reproduction (GO: 0019953) and male sex differentiation (GO: 0046661). A KEGG classification analysis identified three conserved signaling pathways that related to sex differentiation, including the Wnt signaling pathway, TGF-β signaling pathway and Notch signaling pathway. Additionally, 21 sex-related DEGs were selected, of which 13 DEGs were male-biased, including Dmrt1, Foxn5, Foxj1, Sox30, etc., and 8 DEGs were female-biased, including Sox14, Nanos3, β-tubulin, Suh, etc. Ten DEGs were used to verify the expression patterns in the testis and ovary using the RT-qPCR method, and the results showed that the expression level shown by RT-qPCR was consistent with that from the RNA-seq, which confirmed the reliability of the transcriptome data. The results presented in this study will not only contribute to our understanding of sex-formation mechanisms in O. sinensis but also provide the foundational information for further investigating the molecular mechanisms that underline its gonadal development and facilitate the sustainable development of octopus artificial breeding. Full article

(This article belongs to the Special Issue Genetic and Genomic Studies of Marine Animals)

► Show Figures

Figure 1

14 pages, 2078 KiB

Open AccessEditor’s ChoiceReview

Current Research on Small Circular Molecules: A Comprehensive Overview on SPHINX/BMMF

by Diana Habermann, Charles M. A. P. Franz and Martin Klempt

Genes 2024, 15(6), 678; https://doi.org/10.3390/genes15060678 - 24 May 2024

Viewed by 1380

Abstract

Several years of research into the small circular DNA molecules called SPHINX and BMMF (SPHINX/BMMF) have provided information on several areas of research, medicine, microbiology and nutritional science. But there are still open questions that have not yet been addressed. Due to the [...] Read more.

Several years of research into the small circular DNA molecules called SPHINX and BMMF (SPHINX/BMMF) have provided information on several areas of research, medicine, microbiology and nutritional science. But there are still open questions that have not yet been addressed. Due to the unclear classification, evolution and sources of SPHINX/BMMF, a risk assessment is currently not possible. However, risk assessment is necessary as SPHINX/BMMF are suspected to be involved in the development of cancer and neurodegenerative diseases. In order to obtain an overview of the current state of research and to identify research gaps, a review of all the publications on this topic to date was carried out. The focus was primarily on the SPHINX/BMMF group 1 and 2 members, which is the topic of most of the research. It was discovered that the SPHINX/BMMF molecules could be integral components of mammalian cells, and are also inherited. However, their involvement in neurodegenerative and carcinogenic diseases is still unclear. Furthermore, they are probably ubiquitous in food and they resemble bacterial plasmids in parts of their DNA and protein (Rep) sequence. In addition, a connection with bacterial viruses is also suspected. Ultimately, it is still unclear whether SPHINX/BMMF have an infectious capacity and what their host or target is. Full article

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

► Show Figures

Figure 1

21 pages, 25931 KiB

Open AccessEditor’s ChoiceArticle

Neuronal Ceroid Lipofuscinosis in a Mixed-Breed Dog with a Splice Site Variant in CLN6

by Tendai Mhlanga-Mutangadura, Garrett Bullock, Sofia Cerda-Gonzalez and Martin L. Katz

Genes 2024, 15(6), 661; https://doi.org/10.3390/genes15060661 - 23 May 2024

Viewed by 2074

Abstract

A 23-month-old neutered male dog of unknown ancestry presented with a history of progressive neurological signs that included anxiety, cognitive impairment, tremors, seizure activity, ataxia, and pronounced visual impairment. The clinical signs were accompanied by global brain atrophy. Due to progression in the [...] Read more.

A 23-month-old neutered male dog of unknown ancestry presented with a history of progressive neurological signs that included anxiety, cognitive impairment, tremors, seizure activity, ataxia, and pronounced visual impairment. The clinical signs were accompanied by global brain atrophy. Due to progression in the severity of disease signs, the dog was euthanized at 26 months of age. An examination of the tissues collected at necropsy revealed dramatic intracellular accumulations of autofluorescent inclusions in the brain, retina, and cardiac muscle. The inclusions were immunopositive for subunit c of mitochondrial ATP synthase, and their ultrastructural appearances were similar to those of lysosomal storage bodies that accumulate in some neuronal ceroid lipofuscinosis (NCL) diseases. The dog also exhibited widespread neuroinflammation. Based on these findings, the dog was deemed likely to have suffered from a form of NCL. A whole genome sequence analysis of the proband’s DNA revealed a homozygous C to T substitution that altered the intron 3–exon 4 splice site of CLN6. Other mutations in CLN6 cause NCL diseases in humans and animals, including dogs. The CLN6 protein was undetectable with immunolabeling in the tissues of the proband. Based on the clinical history, fluorescence and electron-microscopy, immunohistochemistry, and molecular genetic findings, the disorder in this dog was classified as an NCL resulting from the absence of the CLN6 protein. Screening the dog’s genome for a panel of breed-specific polymorphisms indicated that its ancestry included numerous breeds, with no single breed predominating. This suggests that the CLN6 disease variant is likely to be present in other mixed-breed dogs and at least some ancestral breeds, although it is likely to be rare since other cases have not been reported to date. Full article

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

► Show Figures

Figure 1

11 pages, 2140 KiB

Open AccessEditor’s ChoiceArticle

The First Identification of Homomorphic XY Sex Chromosomes by Integrating Cytogenetic and Transcriptomic Approaches in Plestiodon elegans (Scincidae)

by Wannan Xu, Taiyue Li, Jiahui Li, Siqi Liu, Xing Yu, Min Tang, Jingxiu Dong, Jianjun Liu, Xingjiang Bu, Xingquan Xia, Huaxing Zhou and Liuwang Nie

Genes 2024, 15(6), 664; https://doi.org/10.3390/genes15060664 - 23 May 2024

Cited by 1 | Viewed by 1406

Abstract

The sex chromosomes of skinks are usually poorly differentiated and hardly distinguished by cytogenetic methods. Therefore, identifying sex chromosomes in species lacking easily recognizable heteromorphic sex chromosomes is necessary to fully understand sex chromosome diversity. In this paper, we employed cytogenetics, sex quantification [...] Read more.

The sex chromosomes of skinks are usually poorly differentiated and hardly distinguished by cytogenetic methods. Therefore, identifying sex chromosomes in species lacking easily recognizable heteromorphic sex chromosomes is necessary to fully understand sex chromosome diversity. In this paper, we employed cytogenetics, sex quantification of genes, and transcriptomic approaches to characterize the sex chromosomes in Plestiodon elegans. Cytogenetic examination of metaphases revealed a diploid number of 2n = 26, consisting of 12 macrochromosomes and 14 microchromosomes, with no significant heteromorphic chromosome pairs, speculating that the sex chromosomes may be homomorphic or poorly differentiated. The results of the sex quantification of genes showed that Calumenin (calu), COPI coat complex subunit γ 2 (copg2), and Smoothened (smo) were at half the dose in males as in females, suggesting that they are on the X chromosome. Transcriptomic data analysis from the gonads yielded the excess expression male-specific genes (n = 16), in which five PCR molecular markers were developed. Restricting the observed heterozygosity to males suggests the presence of homomorphic sex chromosomes in P. elegans, XX/XY. This is the first breakthrough in the study of the sex chromosomes of Plestiodon. Full article

(This article belongs to the Section Cytogenomics)

► Show Figures

Figure 1

12 pages, 491 KiB

Open AccessEditor’s ChoiceArticle

Prenatal Diagnosis of Cystic Fibrosis by Celocentesis

by Antonino Giambona, Margherita Vinciguerra, Filippo Leto, Filippo Cassarà, Giuseppe Marchese, Valentina Cigna, Emanuela Orlandi, Maria Elena Mugavero, Gaspare Cucinella, Aurelio Maggio, Lisa Termini, George Makrydimas, Elena D’Alcamo and Francesco Picciotto

Genes 2024, 15(6), 662; https://doi.org/10.3390/genes15060662 - 23 May 2024

Viewed by 4227

Abstract

Celocentesis is a new sampling tool for prenatal diagnosis available from 7 weeks in case of couples at risk for genetic diseases. In this study, we reported the feasibility of earlier prenatal diagnosis by celocentesis in four cases of cystic fibrosis and one [...] Read more.

Celocentesis is a new sampling tool for prenatal diagnosis available from 7 weeks in case of couples at risk for genetic diseases. In this study, we reported the feasibility of earlier prenatal diagnosis by celocentesis in four cases of cystic fibrosis and one case of cystic fibrosis and β-thalassemia co-inherited in the same fetus. Celomic fluids were aspired from the celomic cavity between 8⁺² and 9⁺³ weeks of gestation and fetal cells were picked up by micromanipulator. Maternal DNA contamination was tested and target regions of fetal DNA containing parental pathogenetic variants of CFTR and HBB genes were amplified and sequenced. Four of the five fetuses resulted as being affected by cystic fibrosis and, in all cases, the women decided to interrupt the pregnancy. In the other case, the fetus presented a healthy carrier of cystic fibrosis. The results were confirmed in three cases on placental tissue. In one case, no abortive tissue was obtained. In the last case, the woman refused the prenatal diagnosis to confirm the celocentesis data; the pregnancy is ongoing without complications. This procedure provides prenatal diagnosis of monogenic diseases at least four weeks earlier than traditional procedures, reducing the anxiety of patients and providing the option for medical termination of the affected fetus at 8–10 weeks of gestation, which is less traumatic and safer than surgical termination in the second trimester. Full article

(This article belongs to the Section Genetic Diagnosis)

► Show Figures

Figure 1

17 pages, 2487 KiB

Open AccessEditor’s ChoiceArticle

Central Roles of ZmNAC128 and ZmNAC130 in Nutrient Uptake and Storage during Maize Grain Filling

by Di Peng, Shuxing Pan, Xin Du, Erwang Chen, Junjun He and Zhiyong Zhang

Genes 2024, 15(6), 663; https://doi.org/10.3390/genes15060663 - 23 May 2024

Viewed by 1491

Abstract

Grain filling is critical for determining yield and quality, raising the question of whether central coordinators exist to facilitate the uptake and storage of various substances from maternal to filial tissues. The duplicate NAC transcription factors ZmNAC128 and ZmNAC130 could potentially serve as [...] Read more.

Grain filling is critical for determining yield and quality, raising the question of whether central coordinators exist to facilitate the uptake and storage of various substances from maternal to filial tissues. The duplicate NAC transcription factors ZmNAC128 and ZmNAC130 could potentially serve as central coordinators. By analyzing differentially expressed genes from zmnac128 zmnac130 mutants across different genetic backgrounds and growing years, we identified 243 highly and differentially expressed genes (hdEGs) as the core target genes. These 243 hdEGs were associated with storage metabolism and transporters. ZmNAC128 and ZmNAC130 play vital roles in storage metabolism, and this study revealed two additional starch metabolism-related genes, sugary enhancer1 and hexokinase1, as their direct targets. A key finding of this study was the inclusion of 17 transporter genes within the 243 hdEGs, with significant alterations in the levels of more than 10 elements/substances in mutant kernels. Among them, six out of the nine upregulated transporter genes were linked to the transport of heavy metals and metalloids (HMMs), which was consistent with the enrichment of cadmium, lead, and arsenic observed in mutant kernels. Interestingly, the levels of Mg and Zn, minerals important to biofortification efforts, were reduced in mutant kernels. In addition to their direct involvement in sugar transport, ZmNAC128 and ZmNAC130 also activate the expression of the endosperm-preferential nitrogen and phosphate transporters ZmNPF1.1 and ZmPHO1;2. This coordinated regulation limits the intake of HMMs, enhances biofortification, and facilitates the uptake and storage of essential nutrients. Full article

(This article belongs to the Special Issue Genetic Research on Maize Kernel Development )

► Show Figures

Figure 1

16 pages, 4694 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Identification and Characterization of the RWP-RK Proteins in Zanthoxylum armatum

by Xianzhe Zheng, Yanling Duan, Huifang Zheng, Hao Tang, Liumeng Zheng and Xiaobo Yu

Genes 2024, 15(6), 665; https://doi.org/10.3390/genes15060665 - 23 May 2024

Cited by 1 | Viewed by 1311

Abstract

Apomixis is a common reproductive characteristic of Zanthoxylum plants, and RWP-RKs are plant-specific transcription factors known to regulate embryonic development. However, the genome-wide analysis and function prediction of RWP-RK family genes in Z. armatum are unclear. In this study, 36 ZaRWP-RK transcription factors [...] Read more.

Apomixis is a common reproductive characteristic of Zanthoxylum plants, and RWP-RKs are plant-specific transcription factors known to regulate embryonic development. However, the genome-wide analysis and function prediction of RWP-RK family genes in Z. armatum are unclear. In this study, 36 ZaRWP-RK transcription factors were identified in the genome of Z. armatum, among which 15 genes belonged to the RKD subfamily and 21 belonged to the NLP subfamily. Duplication events of ZaRWP-RK genes were mainly segmental duplication, and synteny analysis revealed a close phylogenetic relationship between Z. armatum and Arabidopsis. The analysis of cis-elements indicated that ZaRWP-RK genes may be involved in the regulation of the embryonic development of Z. armatum by responding to plant hormones such as abscisic acid, auxin, and gibberellin. Results of a real-time PCR showed that the expression levels of most ZaRWP-RK genes were significantly increased from flowers to young fruits. Protein–protein interaction network analysis further revealed the potential roles of the ZaRWP-RK proteins in apomixis. Collectively, this study is expected to improve our understanding of ZaRWP-RK transcription factors and provide a theoretical basis for future investigations into the ZaRWP-RK genes and their regulatory mechanisms in the apomixis process of Z. armatum. Full article

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

► Show Figures

Figure 1

20 pages, 4167 KiB

Open AccessEditor’s ChoiceArticle

Transcriptomic Analyses Reveal the Effects of Walnut Kernel Cake on Adipose Deposition in Pigs

by Lei Liu, Xiaodan Shang, Li Ma, Dawei Yan, Adeyinka Abiola Adetula, Ying Bai and Xinxing Dong

Genes 2024, 15(6), 667; https://doi.org/10.3390/genes15060667 - 23 May 2024

Viewed by 1519

Abstract

With the rising cost of animal feed protein, finding affordable and effective substitutes is crucial. Walnut kernel cake, a polyphenol-, fiber-, protein- and fat-rich byproduct of walnut oil extraction, has been underexplored as a potential protein replacement in pig feed. In this study, [...] Read more.

With the rising cost of animal feed protein, finding affordable and effective substitutes is crucial. Walnut kernel cake, a polyphenol-, fiber-, protein- and fat-rich byproduct of walnut oil extraction, has been underexplored as a potential protein replacement in pig feed. In this study, we found that feeding large Diqing Tibetan pigs walnut kernel cake promoted adipose deposition and improved pork quality during pig growth. Transcriptome analysis revealed the upregulation of genes ANGPTL8, CCNP, ETV4, and TRIB3, associated with adipose deposition. Pathway analysis highlighted enrichment in adipose deposition-related pathways, including PPAR, insulin, PI3K-Akt, Wnt, and MAPK signaling. Further analysis identified DEGs (differentially expressed genes) positively correlated with adipose-related traits, such as PER2 and PTGES. Single-cell transcriptome data pointed to the specific expression of CD248 and PTGES in adipocyte progenitor/stem cells (APSCs), pivotal for adipocyte differentiation and adipose deposition regulation. This study demonstrates walnut kernel cake’s potential to substitute soybean cake in pig feed, providing high-quality protein and promoting adipose deposition. It offers insights into feed protein replacement, human functional food, fat metabolism, and related diseases, with marker genes and pathways supporting pig breeding and pork quality improvement. Full article

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

► Show Figures

Figure 1

16 pages, 8995 KiB

Open AccessEditor’s ChoiceArticle

Identification of ARF Genes and Elucidation of the Regulatory Effects of PsARF16a on the Dormancy of Tree Peony Plantlets

by Zhenzhu Fu, Xin Yuan, Yinge Zhao, Xiaohui Wang, Lin Lu, Huijuan Wang, Yanmin Li, Jie Gao, Limin Wang and Hechen Zhang

Genes 2024, 15(6), 666; https://doi.org/10.3390/genes15060666 - 23 May 2024

Cited by 1 | Viewed by 1172

Abstract

The low survival rate of transplanted plantlets, which has limited the utility of tissue-culture-based methods for the rapid propagation of tree peonies, is due to plantlet dormancy after rooting. We previously determined that the auxin response factor PsARF may be a key regulator [...] Read more.

The low survival rate of transplanted plantlets, which has limited the utility of tissue-culture-based methods for the rapid propagation of tree peonies, is due to plantlet dormancy after rooting. We previously determined that the auxin response factor PsARF may be a key regulator of tree peony dormancy. To clarify the mechanism mediating tree peony plantlet dormancy, PsARF genes were systematically identified and analyzed. Additionally, PsARF16a was transiently expressed in the leaves of tree peony plantlets to examine its regulatory effects on a downstream gene network. Nineteen PsARF genes were identified and divided into four classes. All PsARF genes encoded proteins with conserved B3 and ARF domains. The number of motifs, exons, and introns varied between PsARF genes in different classes. The overexpression of PsARF16a altered the expression of NCED, ZEP, PYL, GA2ox1, GID1, and other key genes in abscisic acid (ABA) and gibberellin (GA) signal transduction pathways, thereby promoting ABA synthesis and decreasing GA synthesis. Significant changes to the expression of some key genes contributing to starch and sugar metabolism (e.g., AMY2A, BAM3, BGLU, STP, and SUS2) may be associated with the gradual conversion of sugar into starch. This study provides important insights into PsARF functions in tree peonies. Full article

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

► Show Figures

Figure 1

16 pages, 694 KiB

Open AccessEditor’s ChoiceReview

Cardiac Remodeling and Ventricular Pacing: From Genes to Mechanics

by Onoufrios Malikides, Emmanouel Simantirakis, Evangelos Zacharis, Konstantinos Fragkiadakis, George Kochiadakis and Maria Marketou

Genes 2024, 15(6), 671; https://doi.org/10.3390/genes15060671 - 23 May 2024

Cited by 4 | Viewed by 1924

Abstract

Cardiac remodeling and ventricular pacing represent intertwined phenomena with profound implications for cardiovascular health and therapeutic interventions. This review explores the intricate relationship between cardiac remodeling and ventricular pacing, spanning from the molecular underpinnings to biomechanical alterations. Beginning with an examination of genetic [...] Read more.

Cardiac remodeling and ventricular pacing represent intertwined phenomena with profound implications for cardiovascular health and therapeutic interventions. This review explores the intricate relationship between cardiac remodeling and ventricular pacing, spanning from the molecular underpinnings to biomechanical alterations. Beginning with an examination of genetic predispositions and cellular signaling pathways, we delve into the mechanisms driving myocardial structural changes and electrical remodeling in response to pacing stimuli. Insights into the dynamic interplay between pacing strategies and adaptive or maladaptive remodeling processes are synthesized, shedding light on the clinical implications for patients with various cardiovascular pathologies. By bridging the gap between basic science discoveries and clinical translation, this review aims to provide a comprehensive understanding of cardiac remodeling in the context of ventricular pacing, paving the way for future advancements in cardiovascular care. Full article

(This article belongs to the Special Issue Cardiovascular Disease: Precision Medicine, Pharmacogenomics and Genetics)

► Show Figures

Figure 1

15 pages, 816 KiB

Open AccessEditor’s ChoiceReview

Advances in and Perspectives on Transgenic Technology and CRISPR-Cas9 Gene Editing in Broccoli

by Li Zhang, Sufang Meng, Yumei Liu, Fengqing Han, Tiemin Xu, Zhiwei Zhao and Zhansheng Li

Genes 2024, 15(6), 668; https://doi.org/10.3390/genes15060668 - 23 May 2024

Cited by 4 | Viewed by 2746

Abstract

Broccoli, a popular international Brassica oleracea crop, is an important export vegetable in China. Broccoli is not only rich in protein, vitamins, and minerals but also has anticancer and antiviral activities. Recently, an Agrobacterium-mediated transformation system has been established and optimized in [...] Read more.

Broccoli, a popular international Brassica oleracea crop, is an important export vegetable in China. Broccoli is not only rich in protein, vitamins, and minerals but also has anticancer and antiviral activities. Recently, an Agrobacterium-mediated transformation system has been established and optimized in broccoli, and transgenic transformation and CRISPR-Cas9 gene editing techniques have been applied to improve broccoli quality, postharvest shelf life, glucoraphanin accumulation, and disease and stress resistance, among other factors. The construction and application of genetic transformation technology systems have led to rapid development in broccoli worldwide, which is also good for functional gene identification of some potential traits in broccoli. This review comprehensively summarizes the progress in transgenic technology and CRISPR-Cas9 gene editing for broccoli over the past four decades. Moreover, it explores the potential for future integration of digital and smart technologies into genetic transformation processes, thus demonstrating the promise of even more sophisticated and targeted crop improvements. As the field continues to evolve, these innovations are expected to play a pivotal role in the sustainable production of broccoli and the enhancement of its nutritional and health benefits. Full article

(This article belongs to the Special Issue Molecular Genetics of Important Traits in Cruciferous Vegetables)

► Show Figures

Figure 1

17 pages, 14373 KiB

Open AccessEditor’s ChoiceArticle

C2c: Predicting Micro-C from Hi-C

by Hao Zhu, Tong Liu and Zheng Wang

Genes 2024, 15(6), 673; https://doi.org/10.3390/genes15060673 - 23 May 2024

Viewed by 2178

Abstract

Motivation: High-resolution Hi-C data, capable of detecting chromatin features below the level of Topologically Associating Domains (TADs), significantly enhance our understanding of gene regulation. Micro-C, a variant of Hi-C incorporating a micrococcal nuclease (MNase) digestion step to examine interactions between nucleosome pairs, has [...] Read more.

Motivation: High-resolution Hi-C data, capable of detecting chromatin features below the level of Topologically Associating Domains (TADs), significantly enhance our understanding of gene regulation. Micro-C, a variant of Hi-C incorporating a micrococcal nuclease (MNase) digestion step to examine interactions between nucleosome pairs, has been developed to overcome the resolution limitations of Hi-C. However, Micro-C experiments pose greater technical challenges compared to Hi-C, owing to the need for precise MNase digestion control and higher-resolution sequencing. Therefore, developing computational methods to derive Micro-C data from existing Hi-C datasets could lead to better usage of a large amount of existing Hi-C data in the scientific community and cost savings. Results: We developed C2c (“high” or upper case C to “micro” or lower case c), a computational tool based on a residual neural network to learn the mapping between Hi-C and Micro-C contact matrices and then predict Micro-C contact matrices based on Hi-C contact matrices. Our evaluation results show that the predicted Micro-C contact matrices reveal more chromatin loops than the input Hi-C contact matrices, and more of the loops detected from predicted Micro-C match the promoter–enhancer interactions. Furthermore, we found that the mutual loops from real and predicted Micro-C better match the ChIA-PET data compared to Hi-C and real Micro-C loops, and the predicted Micro-C leads to more TAD-boundaries detected compared to the Hi-C data. The website URL of C2c can be found in the Data Availability Statement. Full article

(This article belongs to the Section Bioinformatics)

► Show Figures

Figure 1

16 pages, 4300 KiB

Open AccessEditor’s ChoiceArticle

Prediction of Protein-DNA Interface Hot Spots Based on Empirical Mode Decomposition and Machine Learning

by Zirui Fang, Zixuan Li, Ming Li, Zhenyu Yue and Ke Li

Genes 2024, 15(6), 676; https://doi.org/10.3390/genes15060676 - 23 May 2024

Viewed by 1592

Abstract

Protein-DNA complex interactivity plays a crucial role in biological activities such as gene expression, modification, replication and transcription. Understanding the physiological significance of protein-DNA binding interfacial hot spots, as well as the development of computational biology, depends on the precise identification of these [...] Read more.

Protein-DNA complex interactivity plays a crucial role in biological activities such as gene expression, modification, replication and transcription. Understanding the physiological significance of protein-DNA binding interfacial hot spots, as well as the development of computational biology, depends on the precise identification of these regions. In this paper, a hot spot prediction method called EC-PDH is proposed. First, we extracted features of these hot spots’ solid solvent-accessible surface area (ASA) and secondary structure, and then the mean, variance, energy and autocorrelation function values of the first three intrinsic modal components (IMFs) of these conventional features were extracted as new features via the empirical modal decomposition algorithm (EMD). A total of 218 dimensional features were obtained. For feature selection, we used the maximum correlation minimum redundancy sequence forward selection method (mRMR-SFS) to obtain an optimal 11-dimensional-feature subset. To address the issue of data imbalance, we used the SMOTE-Tomek algorithm to balance positive and negative samples and finally used cat gradient boosting (CatBoost) to construct our hot spot prediction model for protein-DNA binding interfaces. Our method performs well on the test set, with AUC, MCC and F1 score values of 0.847, 0.543 and 0.772, respectively. After a comparative evaluation, EC-PDH outperforms the existing state-of-the-art methods in identifying hot spots. Full article

(This article belongs to the Section Bioinformatics)

► Show Figures

Figure 1

7 pages, 669 KiB

Open AccessEditor’s ChoiceCase Report

The Phenotype-Based Approach Can Solve Cold Cases: The Paradigm of Mosaic Mutations of the CREBBP Gene

by Giulia Bruna Marchetti, Donatella Milani, Livia Pisciotta, Laura Pezzoli, Paola Marchisio, Berardo Rinaldi and Maria Iascone

Genes 2024, 15(6), 654; https://doi.org/10.3390/genes15060654 - 22 May 2024

Viewed by 1549

Abstract

Rubinstein–Taybi syndrome (RTS) is a rare genetic disorder characterized by intellectual disability, facial dysmorphisms, and enlarged thumbs and halluces. Approximately 55% of RTS cases result from pathogenic variants in the CREBBP gene, with an additional 8% linked to the EP300 gene. Given the [...] Read more.

Rubinstein–Taybi syndrome (RTS) is a rare genetic disorder characterized by intellectual disability, facial dysmorphisms, and enlarged thumbs and halluces. Approximately 55% of RTS cases result from pathogenic variants in the CREBBP gene, with an additional 8% linked to the EP300 gene. Given the close relationship between these two genes and their involvement in epigenomic modulation, RTS is grouped into chromatinopathies. The extensive clinical heterogeneity observed in RTS, coupled with the growing number of disorders involving the epigenetic machinery, poses a challenge to a phenotype-based diagnostic approach for these conditions. Here, we describe the first case of a patient clinically diagnosed with RTS with a CREBBP truncating variant in mosaic form. We also review previously described cases of mosaicism in CREBBP and apply clinical diagnostic guidelines to these patients, confirming the good specificity of the consensus. Nonetheless, these reports raise questions about the potential underdiagnosis of milder cases of RTS. The application of a targeted phenotype-based approach, coupled with high-depth NGS, may enhance the diagnostic yield of whole-exome sequencing (WES) in mild and mosaic conditions. Full article

(This article belongs to the Special Issue Current Diagnostics for Rare and Ultrarare Diseases)

► Show Figures

Figure 1

10 pages, 1756 KiB

Open AccessEditor’s ChoiceArticle

Identification of FASN Gene Polymorphisms, Expression and Their Relationship with Body Size Traits in Guizhou White Goat (Capra hircus) with Different Genders

by Qingming An, Lingli Zeng, Wenying Wang, Jiangyu Yang, Jinzhu Meng, Yuanyuan Zhao and Xingchao Song

Genes 2024, 15(6), 656; https://doi.org/10.3390/genes15060656 - 22 May 2024

Cited by 1 | Viewed by 1235

Abstract

To investigate the nucleotide variation sites (SNPs) and expression differences of the fatty acid synthase gene (FASN) in Guizhou white goats, the relationship between the variation and body size traits was investigated. In this study, DNA was extracted from the blood [...] Read more.

To investigate the nucleotide variation sites (SNPs) and expression differences of the fatty acid synthase gene (FASN) in Guizhou white goats, the relationship between the variation and body size traits was investigated. In this study, DNA was extracted from the blood of 100 samples of white goats from different regions in Guizhou province, China, and the variation sites were screened using pooled sequencing by mixing DNA samples, and 242 blood samples with body size traits were used for association analysis. The allele frequency, genotype frequency, homozygosity, heterozygosity and effective gene number were calculated by using PopGene 32.0 software, the population polymorphism information content was calculated by using PIC software (Version 0.6), and the state of genetic balance of the genes was analyzed by using the chi-square test. The mRNA of FASN gene expression levels in male and female goats were investigated by using real-time fluorescence quantitative PCR (RT-qPCR). The general linear mixed model of MINTAB software (Version 16.0) was used to analyze the association between FASN gene nucleotide mutation sites and body size traits. The results showed that there was one nucleotide mutation site g.141 C/T in the target fragment of FASN gene amplification, and revealed two alleles, C and T, and three genotypes CC, CT and TT. The genotype frequencies for CC, CT and TT were 0.4308, 0.4205 and 0.1487, respectively. The allele frequencies for C and T were 0.6410 and 0.3590, respectively. The genetic homozygosity (Ho) was higher than the heterozygosity (He). The χ² test showed that the mutation site was in the Hardy–Weinberg equilibrium state (p > 0.05). The RT-qPCR results showed that the FASN gene had different expression levels in the longissimus dorsi muscle of male and female goats, and its expression was significantly higher in male goats than in female goats. The association analysis results showed that the mutation of the FASN gene had different effects on body size traits of male and female goats, and the presence of the populations of the T allele and the TT genotype recorded higher body size traits (body weight, heart girth and wither height) in female populations. Therefore, the site of the FASN gene can be used as a candidate marker for the early selection of growth traits in Guizhou white goats. Full article

(This article belongs to the Special Issue Genetics and Breeding in Sheep and Goats)

► Show Figures

Figure 1

12 pages, 4483 KiB

Open AccessEditor’s ChoiceArticle

Transcriptional Regulation Analysis Provides Insight into the Function of GSK3β Gene in Diannan Small-Ear Pig Spermatogenesis

by Xia Zhang, Guiying Zhao, Fuhua Yang, Changyao Li, Wan Lin, Hongmei Dai, Lan Zhai, Xuemin Xi, Qingting Yuan and Jinlong Huo

Genes 2024, 15(6), 655; https://doi.org/10.3390/genes15060655 - 22 May 2024

Viewed by 1742

Abstract

Glycogen synthase kinase-3β (GSK3β) not only plays a crucial role in regulating sperm maturation but also is pivotal in orchestrating the acrosome reaction. Here, we integrated single-molecule long-read and short-read sequencing to comprehensively examine GSK3β expression patterns in adult Diannan small-ear pig (DSE) [...] Read more.

Glycogen synthase kinase-3β (GSK3β) not only plays a crucial role in regulating sperm maturation but also is pivotal in orchestrating the acrosome reaction. Here, we integrated single-molecule long-read and short-read sequencing to comprehensively examine GSK3β expression patterns in adult Diannan small-ear pig (DSE) testes. We identified the most important transcript ENSSSCT00000039364 of GSK3β, obtaining its full-length coding sequence (CDS) spanning 1263 bp. Gene structure analysis located GSK3β on pig chromosome 13 with 12 exons. Protein structure analysis reflected that GSK3β consisted of 420 amino acids containing PKc-like conserved domains. Phylogenetic analysis underscored the evolutionary conservation and homology of GSK3β across different mammalian species. The evaluation of the protein interaction network, KEGG, and GO pathways implied that GSK3β interacted with 50 proteins, predominantly involved in the Wnt signaling pathway, papillomavirus infection, hippo signaling pathway, hepatocellular carcinoma, gastric cancer, colorectal cancer, breast cancer, endometrial cancer, basal cell carcinoma, and Alzheimer’s disease. Functional annotation identified that GSK3β was involved in thirteen GOs, including six molecular functions and seven biological processes. ceRNA network analysis suggested that DSE GSK3β was regulated by 11 miRNA targets. Furthermore, qPCR expression analysis across 15 tissues highlighted that GSK3β was highly expressed in the testis. Subcellular localization analysis indicated that the majority of the GSK3β protein was located in the cytoplasm of ST (swine testis) cells, with a small amount detected in the nucleus. Overall, our findings shed new light on GSK3β’s role in DSE reproduction, providing a foundation for further functional studies of GSK3β function. Full article

(This article belongs to the Topic Application of Reproductive and Genomic Biotechnologies for Livestock Breeding and Selection)

► Show Figures

Graphical abstract

26 pages, 5936 KiB

Open AccessEditor’s ChoiceArticle

Orthologs at the Base of the Olfactores Clade

by Wilfred D. Stein

Genes 2024, 15(6), 657; https://doi.org/10.3390/genes15060657 - 22 May 2024

Viewed by 1301

Abstract

Tunicate orthologs in the human genome comprise just 84 genes of the 19,872 protein-coding genes and 23 of the 16,528 non-coding genes, yet they stand at the base of the Olfactores clade, which radiated to generate thousands of tunicate and vertebrate species. What [...] Read more.

Tunicate orthologs in the human genome comprise just 84 genes of the 19,872 protein-coding genes and 23 of the 16,528 non-coding genes, yet they stand at the base of the Olfactores clade, which radiated to generate thousands of tunicate and vertebrate species. What were the powerful drivers among these genes that enabled this process? Many of these orthologs are present in gene families. We discuss the biological role of each family and the orthologs’ quantitative contribution to the family. Most important was the evolution of a second type of cadherin. This, a Type II cadherin, had the property of detaching the cell containing that cadherin from cells that expressed the Type I class. The set of such Type II cadherins could now detach and move away from their Type I neighbours, a process which would eventually evolve into the formation of the neural crest, “the fourth germ layer”, providing a wide range of possibilities for further evolutionary invention. A second important contribution were key additions to the broad development of the muscle and nerve protein and visual perception toolkits. These developments in mobility and vision provided the basis for the development of the efficient predatory capabilities of the Vertebrata. Full article

(This article belongs to the Special Issue Genomics of Evolution and Adaptation in Animals)

► Show Figures

Graphical abstract

12 pages, 1506 KiB

Open AccessEditor’s ChoiceArticle

Enhanced Learning and Memory in Patients with CRB1 Retinopathy

by Genevieve A. Wright, Ana Catalina Rodriguez-Martinez, Hanne Conn, Mar Matarin, Pamela Thompson, Anthony T. Moore, Rola Ba-Abbad, Andrew R. Webster and Mariya Moosajee

Genes 2024, 15(6), 660; https://doi.org/10.3390/genes15060660 - 22 May 2024

Cited by 1 | Viewed by 1432

Abstract

Mutations in the CRB1 gene are associated with a diverse spectrum of retinopathies with phenotypic variability causing severe visual impairment. The CRB1 gene has a role in retinal development and is expressed in the cerebral cortex and hippocampus, but its role in cognition [...] Read more.

Mutations in the CRB1 gene are associated with a diverse spectrum of retinopathies with phenotypic variability causing severe visual impairment. The CRB1 gene has a role in retinal development and is expressed in the cerebral cortex and hippocampus, but its role in cognition has not been described before. This study compares cognitive function in CRB1 retinopathy individuals with subjects with other retinopathies and the normal population. Methods: Neuropsychological tests of cognitive function were used to test individuals with CRB1 and non-CRB1 retinopathies and compare results with a standardised normative dataset. Results: CRB1 retinopathy subjects significantly outperformed those with non-CRB1 retinopathy in list learning tasks of immediate (p = 0.001) and delayed memory (p = 0.007), tests of semantic verbal fluency (p = 0.017), verbal IQ digit span subtest (p = 0.037), and estimation test of higher execution function (p = 0.020) but not in the remaining tests of cognitive function (p > 0.05). CRB1 retinopathy subjects scored significantly higher than the normal population in all areas of memory testing (p < 0.05) and overall verbal IQ tests (p = 0.0012). Non-CRB1 retinopathy subjects scored significantly higher than the normal population in story recall, verbal fluency, and overall verbal IQ tests (p = 0.0016). Conclusions: Subjects with CRB1 retinopathy may have enhanced cognitive function in areas of memory and learning. Further work is required to understand the role of CRB1 in cognition. Full article

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

► Show Figures

Figure 1

18 pages, 5716 KiB

Open AccessEditor’s ChoiceArticle

Lack of T04C9.1, the Homologue of Mammalian APPL2, Leads to Premature Ageing and Shortens Lifespan in Caenorhabditis elegans

by Zirui Li, Zhiqiang Chen, Lianghao Zhao, Jiaqi Sun, Lin Yin, Yuwei Jiang, Xiaotong Shi, Ziye Song and Lu Zhang

Genes 2024, 15(6), 659; https://doi.org/10.3390/genes15060659 - 22 May 2024

Viewed by 1400

Abstract

Ageing has been identified as an independent risk factor for various diseases; however, the physiological basis and molecular changes related to ageing are still largely unknown. Here, we show that the level of APPL2, an adaptor protein, is significantly reduced in the major [...] Read more.

Ageing has been identified as an independent risk factor for various diseases; however, the physiological basis and molecular changes related to ageing are still largely unknown. Here, we show that the level of APPL2, an adaptor protein, is significantly reduced in the major organs of aged mice. Knocking down APPL2 causes premature ageing of human umbilical vein endothelial cells (HUVECs). We find that a lack of T04C9.1, the homologue of mammalian APPL2, leads to premature ageing, slow movements, lipid deposition, decreased resistance to stresses, and shortened lifespan in Caenorhabditis elegans (C. elegans), which are associated with decreased autophagy. Activating autophagy by rapamycin or inhibition of let-363 suppresses the age-related alternations, impaired motility, and shortened lifespan of C. elegans, which are reversed by knocking down autophagy-related genes. Our work provides evidence that APPL2 and its C. elegans homologue T04C9.1 decrease with age and reveals that a lack of T04C9.1 bridges autophagy decline and ageing in C. elegans. Full article

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

► Show Figures

Figure 1

16 pages, 3122 KiB

Open AccessEditor’s ChoiceArticle

Research on the Effects of the Relationship between Agronomic Traits and Dwarfing Genes on Yield in Colored Wheat

by Wurijimusi Li, Xinmei Gao, Geqi Qi, Wurilige, Longyu Guo, Mingwei Zhang, Ying Fu, Yingjie Wang, Jingyu Wang, Ying Wang, Fengting Yang, Qianhui Gao, Yongyi Fan, Li Wen, Fengjiao Li, Xiuyan Bai, Yue Zhao, Bayarmaa Gun-Aajav and Xingjian Xu

Genes 2024, 15(6), 649; https://doi.org/10.3390/genes15060649 - 21 May 2024

Cited by 2 | Viewed by 1376

Abstract

This research focuses on 72 approved varieties of colored wheat from different provinces in China. Utilizing coefficients of variation, structural equation models, and correlation analyses, six agronomic traits of colored wheat were comprehensively evaluated, followed by further research on different dwarfing genes in [...] Read more.

This research focuses on 72 approved varieties of colored wheat from different provinces in China. Utilizing coefficients of variation, structural equation models, and correlation analyses, six agronomic traits of colored wheat were comprehensively evaluated, followed by further research on different dwarfing genes in colored wheat. Using the entropy method revealed that among the 72 colored wheat varieties, 10 were suitable for cultivation. Variety 70 was the top-performing variety, with a comprehensive index of 87.15%. In the final established structural equation model, each agronomic trait exhibited a positive direct effect on yield. Notably, plant height, spike length, and flag leaf width had significant impacts on yield, with path coefficients of 0.55, 0.40, and 0.27. Transcriptome analysis and real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) validation were used to identify three dwarfing genes controlling plant height: Rht1, Rht-D1, and Rht8. Subsequent RT-qPCR validation clustering heatmap results indicated that Rht-D1 gene expression increased with the growth of per-acre yield. Rht8 belongs to the semi-dwarf gene category and has a significant positive effect on grain yield. However, the impact of Rht1, as a dwarfing gene, on agronomic traits varies. These research findings provide crucial references for the breeding of new varieties. Full article

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

► Show Figures

Figure 1

9 pages, 1558 KiB

Open AccessEditor’s ChoiceCase Report

An Unclassified Deletion Involving the Proximal Short Arm of Chromosome 10: A New Syndrome?

by Graziano Santoro, Mariarosaria Incoronato, Edoardo Spagnoli, Ilaria Gabbiato, Simona Contini, Marta Piovan, Maurizio Ferrari, Cristina Lapucci and Daniela Zuccarello

Genes 2024, 15(6), 650; https://doi.org/10.3390/genes15060650 - 21 May 2024

Viewed by 1832

Abstract

To date, only 13 studies have described patients with large overlapping deletions of 10p11.2-p12. These individuals shared a common phenotype characterized by intellectual disability, developmental delay, distinct facial dysmorphic features, abnormal behaviour, visual impairment, cardiac malformation, and cryptorchidism in males. Molecular cytogenetic analysis [...] Read more.

To date, only 13 studies have described patients with large overlapping deletions of 10p11.2-p12. These individuals shared a common phenotype characterized by intellectual disability, developmental delay, distinct facial dysmorphic features, abnormal behaviour, visual impairment, cardiac malformation, and cryptorchidism in males. Molecular cytogenetic analysis revealed that the deletion in this chromosomal region shares a common smallest region of overlap (SRO) of 80 kb, which contains only the WAC gene (WW-domain-containing adaptor with coiled coil). In this clinical case report, we report a 5-year-old girl, born from non-consanguineous parents, with a 10p11.22p11.21 microdeletion. She presents clinical features that overlap with other patients described in the literature, such as dysmorphic traits, speech delay, and behavioural abnormalities (hyperactivity), even though the WAC gene is not involved in the microdeletion. Our results are the first to highlight that the deletion described here represents a contiguous gene syndrome that is enough to explain the distinct phenotype but partially overlaps with the previous cases reported in the literature, even though the same genes are not involved. In particular, in this study, we speculate about the role of the WAC gene that seems to be associated with normal motor development. In fact, we found that our patient is the only one described in the literature with a large deletion in the 10p11.22p11.21 region without the involvement of the WAC gene deletion, and, interestingly, the patient did not have motor delay. Full article

(This article belongs to the Special Issue Current Diagnostics for Rare and Ultrarare Diseases)

► Show Figures

Figure 1

14 pages, 3815 KiB

Open AccessEditor’s ChoiceArticle

Human-Induced Range Expansions Result in a Recent Hybrid Zone between Sister Species of Ducks

by Philip Lavretsky, Kevin J. Kraai, David Butler, James Morel, Jay A. VonBank, Joseph R. Marty, Vergie M. Musni and Daniel P. Collins

Genes 2024, 15(6), 651; https://doi.org/10.3390/genes15060651 - 21 May 2024

Cited by 1 | Viewed by 1562

Abstract

Landscapes are consistently under pressure from human-induced ecological change, often resulting in shifting species distributions. For some species, changing the geographical breadth of their niche space results in matching range shifts to regions other than those in which they are formally found. In [...] Read more.

Landscapes are consistently under pressure from human-induced ecological change, often resulting in shifting species distributions. For some species, changing the geographical breadth of their niche space results in matching range shifts to regions other than those in which they are formally found. In this study, we employ a population genomics approach to assess potential conservation issues arising from purported range expansions into the south Texas Brush Country of two sister species of ducks: mottled (Anas fulvigula) and Mexican (Anas diazi) ducks. Specifically, despite being non-migratory, both species are increasingly being recorded outside their formal ranges, with the northeastward and westward expansions of Mexican and mottled ducks, respectively, perhaps resulting in secondary contact today. We assessed genetic ancestry using thousands of autosomal loci across the ranges of both species, as well as sampled Mexican- and mottled-like ducks from across overlapping regions of south Texas. First, we confirm that both species are indeed expanding their ranges, with genetically pure Western Gulf Coast mottled ducks confirmed as far west as La Salle county, Texas, while Mexican ducks recorded across Texas counties near the USA–Mexico border. Importantly, the first confirmed Mexican × mottled duck hybrids were found in between these regions, which likely represents a recently established contact zone that is, on average, ~100 km wide. We posit that climate- and land use-associated changes, including coastal habitat degradation coupled with increases in artificial habitats in the interior regions of Texas, are facilitating these range expansions. Consequently, continued monitoring of this recent contact event can serve to understand species’ responses in the Anthropocene, but it can also be used to revise operational survey areas for mottled ducks. Full article

(This article belongs to the Special Issue Genomics of Evolution and Adaptation in Animals)

► Show Figures

Figure 1

11 pages, 1997 KiB

Open AccessEditor’s ChoiceArticle

Variability and Number of Circulating Complementary Sex Determiner (Csd) Alleles in a Breeding Population of Italian Honeybees under Controlled Mating

by Maria Grazia De Iorio, Barbara Lazzari, Licia Colli, Giulio Pagnacco and Giulietta Minozzi

Genes 2024, 15(6), 652; https://doi.org/10.3390/genes15060652 - 21 May 2024

Cited by 2 | Viewed by 1231

Abstract

In Apis mellifera, csd is the primary gene involved in sex determination: haploid hemizygous eggs develop as drones, while females develop from eggs heterozygous for the csd gene. If diploid eggs are homozygous for the csd gene, diploid drones will develop, but [...] Read more.

In Apis mellifera, csd is the primary gene involved in sex determination: haploid hemizygous eggs develop as drones, while females develop from eggs heterozygous for the csd gene. If diploid eggs are homozygous for the csd gene, diploid drones will develop, but will be eaten by worker bees before they are born. Therefore, high csd allelic diversity is a priority for colony survival and breeding. This study aims to investigate the variability of the hypervariable region (HVR) of the csd gene in bees sampled in an apiary under a selection scheme. To this end, an existing dataset of 100 whole-genome sequences was analyzed with a validated pipeline based on de novo assembly of sequences within the HVR region. In total, 102 allelic sequences were reconstructed and translated into amino acid sequences. Among these, 47 different alleles were identified, 44 of which had previously been observed, while 3 are novel alleles. The results show a high variability in the csd region in this breeding population of honeybees. Full article

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

► Show Figures

Figure 1

19 pages, 1198 KiB

Open AccessEditor’s ChoiceReview

PIWI-Interacting RNAs: A Pivotal Regulator in Neurological Development and Disease

by Xian Pan, Wang Dai, Zhenzhen Wang, Siqi Li, Tao Sun and Nan Miao

Genes 2024, 15(6), 653; https://doi.org/10.3390/genes15060653 - 21 May 2024

Cited by 2 | Viewed by 2282

Abstract

PIWI-interacting RNAs (piRNAs), a class of small non-coding RNAs (sncRNAs) with 24–32 nucleotides (nt), were initially identified in the reproductive system. Unlike microRNAs (miRNAs) or small interfering RNAs (siRNAs), piRNAs normally guide P-element-induced wimpy testis protein (PIWI) families to slice extensively complementary transposon [...] Read more.

PIWI-interacting RNAs (piRNAs), a class of small non-coding RNAs (sncRNAs) with 24–32 nucleotides (nt), were initially identified in the reproductive system. Unlike microRNAs (miRNAs) or small interfering RNAs (siRNAs), piRNAs normally guide P-element-induced wimpy testis protein (PIWI) families to slice extensively complementary transposon transcripts without the seed pairing. Numerous studies have shown that piRNAs are abundantly expressed in the brain, and many of them are aberrantly regulated in central neural system (CNS) disorders. However, the role of piRNAs in the related developmental and pathological processes is unclear. The elucidation of piRNAs/PIWI would greatly improve the understanding of CNS development and ultimately lead to novel strategies to treat neural diseases. In this review, we summarized the relevant structure, properties, and databases of piRNAs and their functional roles in neural development and degenerative disorders. We hope that future studies of these piRNAs will facilitate the development of RNA-based therapeutics for CNS disorders. Full article

(This article belongs to the Special Issue Advances in Nervous System Disorders)

► Show Figures

Figure 1

10 pages, 3509 KiB

Open AccessEditor’s ChoiceArticle

Simultaneous Detection of Common Founder Mutations Using a Cost-Effective Deep Sequencing Panel

by Sapir Shalom, Mor Hanany, Avital Eilat, Itay Chowers, Tamar Ben-Yosef, Samer Khateb, Eyal Banin and Dror Sharon

Genes 2024, 15(5), 646; https://doi.org/10.3390/genes15050646 - 20 May 2024

Cited by 1 | Viewed by 1528

Abstract

Inherited retinal diseases (IRDs) are a clinically and genetically heterogeneous group of diseases which cause visual loss due to Mendelian mutations in over 250 genes, making genetic diagnosis challenging and time-consuming. Here, we developed a new tool, CDIP (Cost-effective Deep-sequencing IRD Panel) in [...] Read more.

Inherited retinal diseases (IRDs) are a clinically and genetically heterogeneous group of diseases which cause visual loss due to Mendelian mutations in over 250 genes, making genetic diagnosis challenging and time-consuming. Here, we developed a new tool, CDIP (Cost-effective Deep-sequencing IRD Panel) in which a simultaneous sequencing of common mutations is performed. CDIP is based on simultaneous amplification of 47 amplicons harboring common mutations followed by next-generation sequencing (NGS). Following five rounds of calibration of NGS-based steps, CDIP was used in 740 IRD samples. The analysis revealed 151 mutations in 131 index cases. In 54 (7%) of these cases, CDIP identified the genetic cause of disease (the remaining were single-heterozygous recessive mutations). These include a patient that was clinically diagnosed with retinoschisis and found to be homozygous for NR2E3-c.932G>A (p.R311Q), and a patient with RP who is hemizygous for an RPGR variant, c.292C>A (p.H98N), which was not included in the analysis but is located in proximity to one of these mutations. CDIP is a cost-effective deep sequencing panel for simultaneous detection of common founder mutations. This protocol can be implemented for additional populations as well as additional inherited diseases, and mainly in populations with strong founder effects. Full article

(This article belongs to the Special Issue Feature Papers in Human Genomics and Genetic Diseases 2024)

► Show Figures

Figure 1

18 pages, 4602 KiB

Open AccessEditor’s ChoiceArticle

Metformin as an Enhancer for the Treatment of Chemoresistant CD34+ Acute Myeloid Leukemia Cells

by Indre Krastinaite, Sergej Charkavliuk, Ruta Navakauskiene and Veronika Viktorija Borutinskaite

Genes 2024, 15(5), 648; https://doi.org/10.3390/genes15050648 - 20 May 2024

Cited by 3 | Viewed by 2086

Abstract

Acute myeloid leukemia is the second most frequent type of leukemia in adults. Due to a high risk of development of chemoresistance to first-line chemotherapy, the survival rate of patients in a 5-year period is below 30%. One of the reasons is that [...] Read more.

Acute myeloid leukemia is the second most frequent type of leukemia in adults. Due to a high risk of development of chemoresistance to first-line chemotherapy, the survival rate of patients in a 5-year period is below 30%. One of the reasons is that the AML population is heterogeneous, with cell populations partly composed of very primitive CD34+CD38- hematopoietic stem/progenitor cells, which are often resistant to chemotherapy. First-line treatment with cytarabine and idarubicin fails to inhibit the proliferation of CD34+CD38- cells. In this study, we investigated Metformin’s effect with or without first-line conventional chemotherapy, or with other drugs like venetoclax and S63845, on primitive and undifferentiated CD34+ AML cells in order to explore the potential of Metformin or S63845 to serve as adjuvant therapy for AML. We found that first-line conventional chemotherapy treatment inhibited the growth of cells and arrested the cells in the S phase of the cell cycle; however, metformin affected the accumulation of cells in the G2/M phase. We observed that CD34+ KG1a cells respond better to lower doses of cytarabine or idarubicin in combination with metformin. Also, we determined that treatment with cytarabine, venetoclax, and S63845 downregulated the strong tendency of CD34+ KG1a cells to form cell aggregates in culture due to the downregulation of leukemic stem cell markers like CD34 and CD44, as well as adhesion markers. Also, we found that idarubicin slightly upregulated myeloid differentiation markers, CD11b and CD14. Treatment with cytarabine, idarubicin, venetoclax, metformin, and S63845 upregulated some cell surface markers like HLA-DR expression, and metformin upregulated CD9, CD31, and CD105 cell surface marker expression. In conclusion, we believe that metformin has the potential to be used as an adjuvant in the treatment of resistant-to-first-line-chemotherapy AML cells. Also, we believe that the results of our study will stimulate further research and the potential use of changes in the expression of cell surface markers in the development of new therapeutic strategies. Full article

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

► Show Figures

Figure 1

12 pages, 3183 KiB

Open AccessEditor’s ChoiceArticle

CHD7 Disorder—Not CHARGE Syndrome—Presenting as Isolated Cochleovestibular Dysfunction

by Jef Driesen, Helen Van Hoecke, Leen Maes, Sandra Janssens, Frederic Acke and Els De Leenheer

Genes 2024, 15(5), 643; https://doi.org/10.3390/genes15050643 - 19 May 2024

Cited by 1 | Viewed by 2099

Abstract

CHARGE syndrome, characterized by a distinct set of clinical features, has been linked primarily to mutations in the CHD7 gene. Initially defined by specific clinical criteria, including coloboma, heart defects, choanal atresia, delayed growth, and ear anomalies, CHARGE syndrome’s diagnostic spectrum has broadened [...] Read more.

CHARGE syndrome, characterized by a distinct set of clinical features, has been linked primarily to mutations in the CHD7 gene. Initially defined by specific clinical criteria, including coloboma, heart defects, choanal atresia, delayed growth, and ear anomalies, CHARGE syndrome’s diagnostic spectrum has broadened since the identification of CHD7. Variants in this gene exhibit considerable phenotypic variability, leading to the adoption of the term “CHD7 disorder” to encompass a wider range of associated symptoms. Recent research has identified CHD7 variants in individuals with isolated features such as autism spectrum disorder or gonadotropin-releasing hormone deficiency. In this study, we present three cases from two different families exhibiting audiovestibular impairment as the primary manifestation of a CHD7 variant. We discuss the expanding phenotypic variability observed in CHD7-related disorders, highlighting the importance of considering CHD7 in nonsyndromic hearing loss cases, especially when accompanied by inner ear malformations on MRI. Additionally, we underscore the necessity of genetic counseling and comprehensive clinical evaluation for individuals with CHD7 variants to ensure appropriate management of associated health concerns. Full article

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

► Show Figures

Figure 1

15 pages, 18790 KiB

Open AccessEditor’s ChoiceArticle

Whole-Transcriptome Analysis Sheds Light on the Biological Contexts of Intramuscular Fat Deposition in Ningxiang Pigs

by Zhao Jin, Hu Gao, Yawei Fu, Ruimin Ren, Xiaoxiao Deng, Yue Chen, Xiaohong Hou, Qian Wang, Gang Song, Ningyu Fan, Haiming Ma, Yulong Yin and Kang Xu

Genes 2024, 15(5), 642; https://doi.org/10.3390/genes15050642 - 19 May 2024

Cited by 1 | Viewed by 1942

Abstract

The quality of pork is significantly impacted by intramuscular fat (IMF). However, the regulatory mechanism of IMF depositions remains unclear. We performed whole-transcriptome sequencing of the longissimus dorsi muscle (IMF) from the high (5.1 ± 0.08) and low (2.9 ± 0.51) IMF groups [...] Read more.

The quality of pork is significantly impacted by intramuscular fat (IMF). However, the regulatory mechanism of IMF depositions remains unclear. We performed whole-transcriptome sequencing of the longissimus dorsi muscle (IMF) from the high (5.1 ± 0.08) and low (2.9 ± 0.51) IMF groups (%) to elucidate potential mechanisms. In summary, 285 differentially expressed genes (DEGs), 14 differentially expressed miRNAs (DEMIs), 83 differentially expressed lncRNAs (DELs), and 79 differentially expressed circRNAs (DECs) were identified. DEGs were widely associated with IMF deposition and liposome differentiation. Furthermore, competing endogenous RNA (ceRNA) regulatory networks were constructed through co-differential expression analyses, which included circRNA-miRNA-mRNA (containing 6 DEMIs, 6 DEGs, 47 DECs) and lncRNA-miRNA-mRNA (containing 6 DEMIs, 6 DEGs, 36 DELs) regulatory networks. The circRNAs sus-TRPM7_0005, sus-MTUS1_0004, the lncRNAs SMSTRG.4269.1, and MSTRG.7983.2 regulate the expression of six lipid metabolism-related target genes, including PLCB1, BAD, and GADD45G, through the binding sites of 2-4068, miR-7134-3p, and miR-190a. For instance, MSTRG.4269.1 regulates its targets PLCB1 and BAD via miRNA 2_4068. Meanwhile, sus-TRPM7_0005 controls its target LRP5 through ssc-miR-7134-3P. These findings indicate molecular regulatory networks that could potentially be applied for the marker-assisted selection of IMF to enhance pork quality. Full article

(This article belongs to the Special Issue Advances in Pig Genetic and Genomic Breeding)

► Show Figures

Figure 1

20 pages, 13287 KiB

Open AccessEditor’s ChoiceArticle

Morphological and Molecular Analysis Identified a Subspecies of Crassostrea ariakensis (Fujita, 1913) along the Coast of Asia

by Ya Chen, Cui Li, Ruijing Lu and Haiyan Wang

Genes 2024, 15(5), 644; https://doi.org/10.3390/genes15050644 - 19 May 2024

Cited by 1 | Viewed by 1385

Abstract

Crassostrea ariakensis (Fujita, 1913) is one of the most important economic and ecological oysters that is naturally distributed along the coast of Asia, separated by the Yangtze River estuary. They are usually compared as different populations, while there is no consensus on whether [...] Read more.

Crassostrea ariakensis (Fujita, 1913) is one of the most important economic and ecological oysters that is naturally distributed along the coast of Asia, separated by the Yangtze River estuary. They are usually compared as different populations, while there is no consensus on whether C. ariakensis in northern and southern areas should be considered as two species or subspecies. Here, we analyzed morphological characteristics, COI, 16s rRNA, mitogenome sequences, and species delimitation analysis (ASAP and PTP) to resolve the intraspecific taxonomic status of the C. ariakensis. Phylogenetic and ASAP analysis highlight that C. ariakensis was divided into N-type and S-type. PTP was unable to differentiate between the two types of C. ariakensis. The divergence time of N-type and S-type C. ariakinsis is estimated to be 1.6 Mya, using the relaxed uncorrelated lognormal clock method. Additionally, significant morphological differences exist between the two groups in terms of the adductor muscle scar color. Despite these differences, the COI (0.6%) and 16S rRNA (0.6%) genetic distance differences between N-type and S-type C. ariakensis has not yet reached the interspecific level. These results suggest that N-type and S-type C. ariakensis should be treated as different subspecies and renamed as C. ariakensis ariakensis subsp. nov and C. ariakensis meridioyangtzensis subsp. nov. Full article

(This article belongs to the Special Issue Genetic Evolution of Marine Shellfish—2nd Edition)

► Show Figures

Figure 1

12 pages, 1595 KiB

Open AccessEditor’s ChoiceArticle

The Landscape of Presence/Absence Variations during the Improvement of Rice

by Xia Zhou, Chenggen Qiang, Lei Chen, Dongjin Qing, Juan Huang, Jilong Li and Yinghua Pan

Genes 2024, 15(5), 645; https://doi.org/10.3390/genes15050645 - 19 May 2024

Cited by 1 | Viewed by 1871

Abstract

Rice is one of the most important staple crops in the world; therefore, the improvement of rice holds great significance for enhancing agricultural production and addressing food security challenges. Although there have been numerous studies on the role of single-nucleotide polymorphisms (SNPs) in [...] Read more.

Rice is one of the most important staple crops in the world; therefore, the improvement of rice holds great significance for enhancing agricultural production and addressing food security challenges. Although there have been numerous studies on the role of single-nucleotide polymorphisms (SNPs) in rice improvement with the development of next-generation sequencing technologies, research on the role of presence/absence variations (PAVs) in the improvement of rice is limited. In particular, there is a scarcity of studies exploring the traits and genes that may be affected by PAVs in rice. Here, we extracted PAVs utilizing resequencing data from 148 improved rice varieties distributed in Asia. We detected a total of 33,220 PAVs and found that the number of variations decreased gradually as the length of the PAVs increased. The number of PAVs was the highest on chromosome 1. Furthermore, we identified a 6 Mb hotspot region on chromosome 11 containing 1091 PAVs in which there were 29 genes related to defense responses. By conducting a genome-wide association study (GWAS) using PAV variation data and phenotypic data for five traits (flowering time, plant height, flag leaf length, flag leaf width, and panicle number) across all materials, we identified 186 significantly associated PAVs involving 20 cloned genes. A haplotype analysis and expression analysis of candidate genes revealed that important genes might be affected by PAVs, such as the flowering time gene OsSFL1 and the flag leaf width gene NAL1. Our work investigated the pattern in PAVs and explored important PAV key functional genes associated with agronomic traits. Consequently, these results provide potential and exploitable genetic resources for rice breeding. Full article

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

► Show Figures

Figure 1

10 pages, 1854 KiB

Open AccessEditor’s ChoiceArticle

Comparative Genome-Wide Alternative Splicing Analysis between Preadipocytes and Adipocytes

by Zhongyi Hou, Xin Li, Maosheng Xu, Shengbo Meng, Huifen Xu, Ming Li and Hanfang Cai

Genes 2024, 15(5), 640; https://doi.org/10.3390/genes15050640 - 18 May 2024

Viewed by 1527

Abstract

Alternative splicing is a ubiquitous regulatory mechanism in gene expression that allows a single gene to generate multiple messenger RNAs (mRNAs). Adipocyte development is regulated by many processes, and recent studies have found that splicing factors also play an important role in adipogenic [...] Read more.

Alternative splicing is a ubiquitous regulatory mechanism in gene expression that allows a single gene to generate multiple messenger RNAs (mRNAs). Adipocyte development is regulated by many processes, and recent studies have found that splicing factors also play an important role in adipogenic development. In the present study, we further investigated the differences in selective shearing during different periods of adipocyte differentiation. We identified five alternative splicing types including skipped exon, mutually exclusive exon, Alternative 5′ splice site, Alternative 3′ splice site, and Retained intron, with skipped exons being the most abundant type of selective shearing. In total, 641 differentially expressed selective shearing genes were obtained, enriched in 279 pathways, from which we selected and verified the accuracy of the sequencing results. Overall, RNA-seq revealed changes in the splicing and expression levels of these new candidate genes between precursor adipocytes and adipocytes, suggesting that they may be involved in adipocyte generation and differentiation. Full article

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

► Show Figures

Figure 1

12 pages, 4556 KiB

Open AccessEditor’s ChoiceArticle

Developmental Delay and Male-Biased Sex Ratio in esr2b Knockout Zebrafish

by Wei Peng, Yunsheng Zhang, Bolan Song, Pinhong Yang and Liangguo Liu

Genes 2024, 15(5), 636; https://doi.org/10.3390/genes15050636 - 17 May 2024

Cited by 1 | Viewed by 1554

Abstract

The estrogen receptor signaling pathway plays an important role in vertebrate embryonic development and sexual differentiation. There are four major estrogen receptors in zebrafish: esr1, esr2a, esr2b and gper. However, the specific role of different estrogen receptors in zebrafish is [...] Read more.

The estrogen receptor signaling pathway plays an important role in vertebrate embryonic development and sexual differentiation. There are four major estrogen receptors in zebrafish: esr1, esr2a, esr2b and gper. However, the specific role of different estrogen receptors in zebrafish is not clear. To investigate the role of esr2b in zebrafish development and reproduction, this study utilized TALENs technology to generate an esr2b knockout homozygous zebrafish line. The number of eggs laid by esr2b knockout female zebrafish did not differ significantly from that of wild zebrafish. The embryonic development process of wild-type and esr2b knockout zebrafish was observed, revealing a significant developmental delay in the esr2b knockout zebrafish. Additionally, mortality rates were significantly higher in esr2b knockout zebrafish than in their wild-type counterparts at 24 hpf. The reciprocal cross experiment between esr2b knockout zebrafish and wild-type zebrafish revealed that the absence of esr2b resulted in a decline in the quality of zebrafish oocytes, while having no impact on sperm cells. The knockout of esr2b also led to an abnormal sex ratio in the adult zebrafish population, with a female-to-male ratio of approximately 1:7. The quantitative PCR (qPCR) and in situ hybridization results demonstrated a significant downregulation of cyp19ab1b expression in esr2b knockout embryos compared to wild-type embryos throughout development (at 2 dpf, 3 dpf and 4 dpf). Additionally, the estrogen-mediated induction expression of cyp19ab1b was attenuated, while the estradiol-induced upregulated expression of vtg1 was disrupted. These results suggest that esr2b is involved in regulating zebrafish oocyte development and sex differentiation. Full article

(This article belongs to the Special Issue Sexual Dimorphism in Aquatic Animals)

► Show Figures

Figure 1

8 pages, 2382 KiB

Open AccessEditor’s ChoiceCase Report

Brugada Syndrome and Pulmonary Atresia with Intact Interventricular Septum: Fortuitous Finding or New Genetic Connection?

by Miguel Fogaça-da-Mata, Estefanía Martínez-Barrios, Lorenzo Jiménez-Montañés, José Cruzalegui, Fredy Chipa-Ccasani, Andrea Greco, Sergi Cesar, Núria Díez-Escuté, Patricia Cerralbo, Irene Zschaeck, Marcos Clavero Adell, Ariadna Ayerza-Casas, Daniel Palanca-Arias, Marta López, Oscar Campuzano, Josep Brugada and Georgia Sarquella-Brugada

Genes 2024, 15(5), 638; https://doi.org/10.3390/genes15050638 - 17 May 2024

Viewed by 1466

Abstract

Brugada syndrome is a rare arrhythmogenic syndrome associated mainly with pathogenic variants in the SCN5A gene. Right ventricle outflow tract fibrosis has been reported in some cases of patients diagnosed with Brugada syndrome. Pulmonary atresia with an intact ventricular septum is characterized by [...] Read more.

Brugada syndrome is a rare arrhythmogenic syndrome associated mainly with pathogenic variants in the SCN5A gene. Right ventricle outflow tract fibrosis has been reported in some cases of patients diagnosed with Brugada syndrome. Pulmonary atresia with an intact ventricular septum is characterized by the lack of a functional pulmonary valve, due to the underdevelopment of the right ventricle outflow tract. We report, for the first time, a 4-year-old boy with pulmonary atresia with an intact ventricular septum who harbored a pathogenic de novo variant in SCN5A, and the ajmaline test unmasked a type-1 Brugada pattern. We suggest that deleterious variants in the SCN5A gene could be implicated in pulmonary atresia with an intact ventricular septum embryogenesis, leading to overlapping phenotypes. Full article

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

► Show Figures

Figure 1

20 pages, 1047 KiB

Open AccessFeature PaperEditor’s ChoiceReview

KAT8 beyond Acetylation: A Survey of Its Epigenetic Regulation, Genetic Variability, and Implications for Human Health

by Lindsey Yoo, David Mendoza, Allison J. Richard and Jacqueline M. Stephens

Genes 2024, 15(5), 639; https://doi.org/10.3390/genes15050639 - 17 May 2024

Cited by 2 | Viewed by 3882

Abstract

Lysine acetyltransferase 8, also known as KAT8, is an enzyme involved in epigenetic regulation, primarily recognized for its ability to modulate histone acetylation. This review presents an overview of KAT8, emphasizing its biological functions, which impact many cellular processes and range from chromatin [...] Read more.

Lysine acetyltransferase 8, also known as KAT8, is an enzyme involved in epigenetic regulation, primarily recognized for its ability to modulate histone acetylation. This review presents an overview of KAT8, emphasizing its biological functions, which impact many cellular processes and range from chromatin remodeling to genetic and epigenetic regulation. In many model systems, KAT8’s acetylation of histone H4 lysine 16 (H4K16) is critical for chromatin structure modification, which influences gene expression, cell proliferation, differentiation, and apoptosis. Furthermore, this review summarizes the observed genetic variability within the KAT8 gene, underscoring the implications of various single nucleotide polymorphisms (SNPs) that affect its functional efficacy and are linked to diverse phenotypic outcomes, ranging from metabolic traits to neurological disorders. Advanced insights into the structural biology of KAT8 reveal its interaction with multiprotein assemblies, such as the male-specific lethal (MSL) and non-specific lethal (NSL) complexes, which regulate a wide range of transcriptional activities and developmental functions. Additionally, this review focuses on KAT8’s roles in cellular homeostasis, stem cell identity, DNA damage repair, and immune response, highlighting its potential as a therapeutic target. The implications of KAT8 in health and disease, as evidenced by recent studies, affirm its importance in cellular physiology and human pathology. Full article

(This article belongs to the Section Epigenomics)

► Show Figures

Figure 1

21 pages, 4847 KiB

Open AccessEditor’s ChoiceArticle

Inverse and Proportional Trans Modulation of Gene Expression in Human Aneuploidies

by Shuai Zhang, Ruixue Wang, Ludan Zhang, James A. Birchler and Lin Sun

Genes 2024, 15(5), 637; https://doi.org/10.3390/genes15050637 - 17 May 2024

Cited by 2 | Viewed by 1534

Abstract

Genomic imbalance in aneuploidy is often detrimental to organisms. To gain insight into the molecular basis of aneuploidies in humans, we analyzed transcriptome data from several autosomal and sex chromosome aneuploidies. The results showed that in human aneuploid cells, genes located on unvaried [...] Read more.

Genomic imbalance in aneuploidy is often detrimental to organisms. To gain insight into the molecular basis of aneuploidies in humans, we analyzed transcriptome data from several autosomal and sex chromosome aneuploidies. The results showed that in human aneuploid cells, genes located on unvaried chromosomes are inversely or proportionally trans-modulated, while a subset of genes on the varied chromosomes are compensated. Less genome-wide modulation is found for sex chromosome aneuploidy compared with autosomal aneuploidy due to X inactivation and the retention of dosage sensitive regulators on both sex chromosomes to limit the effective dosage change. We also found that lncRNA and mRNA can have different responses to aneuploidy. Furthermore, we analyzed the relationship between dosage-sensitive transcription factors and their targets, which illustrated the modulations and indicates genomic imbalance is related to stoichiometric changes in components of gene regulatory complexes.In summary, this study demonstrates the existence of trans-acting effects and compensation mechanisms in human aneuploidies and contributes to our understanding of gene expression regulation in unbalanced genomes and disease states. Full article

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

► Show Figures

Figure 1

15 pages, 4078 KiB

Open AccessEditor’s ChoiceArticle

Establishment of Parentage Identification Method for Sea Urchin Strongylocentrotus intermedius Based on SSR-seq Technology

by Xuechun Jiang, Lei Liu, Hao Guo, Peng Liu, Wenzhuo Tian, Fanjiang Ou, Jun Ding, Weijie Zhang and Yaqing Chang

Genes 2024, 15(5), 630; https://doi.org/10.3390/genes15050630 - 16 May 2024

Cited by 2 | Viewed by 1397

Abstract

To establish a parentage identification method for Strongylocentrotus intermedius, 15 microsatellite loci and simple sequence repeat sequencing (SSR-seq) technology were used to perform SSR sequencing and typing of the validation population with known pedigree information and the simulation population. Cervus v3.0 was [...] Read more.

To establish a parentage identification method for Strongylocentrotus intermedius, 15 microsatellite loci and simple sequence repeat sequencing (SSR-seq) technology were used to perform SSR sequencing and typing of the validation population with known pedigree information and the simulation population. Cervus v3.0 was used for gene frequency statistics, simulated analysis, and parentage identification analysis. The results showed that, in validation population, using 15 microsatellite loci, the highest success rate of parent pairs identification was 86%, the highest success rate of female parent identification was 93%, and the highest success rate of male parent identification was 90%. The simulated population was analyzed using 12–15 loci, and the identification rate was up to 90%. In cases where accurate parentage was not achieved, individuals could exhibit genetic similarities with 1–3 male or female parents. Individuals identified as lacking a genetic relationship can be selected as parents to prevent inbreeding. This study shows that parent pairs or single parents of most offspring can be identified successfully using these 15 selected loci. The results lay a foundation for the establishment of a parentage identification method for S. intermedius. Full article

(This article belongs to the Special Issue Genetics and Molecular Breeding in Fisheries and Aquaculture)

► Show Figures

Figure 1

15 pages, 1361 KiB

Open AccessEditor’s ChoiceArticle

Elucidating Cancer Subtypes by Using the Relationship between DNA Methylation and Gene Expression

by Muneeba Jilani, David Degras and Nurit Haspel

Genes 2024, 15(5), 631; https://doi.org/10.3390/genes15050631 - 16 May 2024

Viewed by 1986

Abstract

Advancements in the field of next generation sequencing (NGS) have generated vast amounts of data for the same set of subjects. The challenge that arises is how to combine and reconcile results from different omics studies, such as epigenome and transcriptome, to improve [...] Read more.

Advancements in the field of next generation sequencing (NGS) have generated vast amounts of data for the same set of subjects. The challenge that arises is how to combine and reconcile results from different omics studies, such as epigenome and transcriptome, to improve the classification of disease subtypes. In this study, we introduce sCClust (sparse canonical correlation analysis with clustering), a technique to combine high-dimensional omics data using sparse canonical correlation analysis (sCCA), such that the correlation between datasets is maximized. This stage is followed by clustering the integrated data in a lower-dimensional space. We apply sCClust to gene expression and DNA methylation data for three cancer genomics datasets from the Cancer Genome Atlas (TCGA) to distinguish between underlying subtypes. We evaluate the identified subtypes using Kaplan–Meier plots and hazard ratio analysis on the three types of cancer—GBM (glioblastoma multiform), lung cancer and colon cancer. Comparison with subtypes identified by both single- and multi-omics studies implies improved clinical association. We also perform pathway over-representation analysis in order to identify up-regulated and down-regulated genes as tentative drug targets. The main goal of the paper is twofold: the integration of epigenomic and transcriptomic datasets followed by elucidating subtypes in the latent space. The significance of this study lies in the enhanced categorization of cancer data, which is crucial to precision medicine. Full article

(This article belongs to the Special Issue Bioinformatics of Disease Research)

► Show Figures

Figure 1

22 pages, 3332 KiB

Open AccessEditor’s ChoiceArticle

Identification of Sex-Associated Genetic Markers in Pistacia lentiscus var. chia for Early Male Detection

by Evangelia Stavridou, Ioanna Karamichali, Evangelos Siskas, Irini Bosmali, Maslin Osanthanunkul and Panagiotis Madesis

Genes 2024, 15(5), 632; https://doi.org/10.3390/genes15050632 - 16 May 2024

Cited by 1 | Viewed by 2051

Abstract

Pistacia lentiscus var. chia is a valuable crop for its high-added-value mastic, a resin with proven pharmaceutical and cosmeceutical properties harvested from the male tree trunk. To achieve the maximum economic benefits from the cultivation of male mastic trees, it is important to [...] Read more.

Pistacia lentiscus var. chia is a valuable crop for its high-added-value mastic, a resin with proven pharmaceutical and cosmeceutical properties harvested from the male tree trunk. To achieve the maximum economic benefits from the cultivation of male mastic trees, it is important to develop early sex diagnosis molecular tools for distinguishing the sex type. Thus far, the work on sex identification has focused on Pistacia vera with promising results; however, the low transferability rates of these markers in P. lentiscus necessitates the development of species-specific sex-linked markers for P. lentiscus var. chia. To our knowledge, this is the first report regarding: (i) the development of species-specific novel transcriptome-based markers for P. lentiscus var. chia and their assessment on male, female and monoecious individuals using PCR-HRM analysis, thus, introducing a cost-effective method for sex identification with high accuracy that can be applied with minimum infrastructure, (ii) the effective sex identification in mastic tree using a combination of different sex-linked ISSR and SCAR markers with 100% accuracy, and (iii) the impact evaluation of sex type on the genetic diversity of different P. lentiscus var. chia cultivars. The results of this study are expected to provide species-specific markers for accurate sex identification that could contribute to the selection process of male mastic trees at an early stage for mass propagation systems and to facilitate future breeding efforts related to sex-linked productivity and quality of mastic resin. Full article

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

► Show Figures

Figure 1

12 pages, 830 KiB

Open AccessEditor’s ChoiceReview

Are the Head and Tail Domains of Intermediate Filaments Really Unstructured Regions?

by Konstantinos Tsilafakis and Manolis Mavroidis

Genes 2024, 15(5), 633; https://doi.org/10.3390/genes15050633 - 16 May 2024

Cited by 2 | Viewed by 1541

Abstract

Intermediate filaments (IFs) are integral components of the cytoskeleton which provide cells with tissue-specific mechanical properties and are involved in a plethora of cellular processes. Unfortunately, due to their intricate architecture, the 3D structure of the complete molecule of IFs has remained unresolved. [...] Read more.

Intermediate filaments (IFs) are integral components of the cytoskeleton which provide cells with tissue-specific mechanical properties and are involved in a plethora of cellular processes. Unfortunately, due to their intricate architecture, the 3D structure of the complete molecule of IFs has remained unresolved. Even though most of the rod domain structure has been revealed by means of crystallographic analyses, the flanked head and tail domains are still mostly unknown. Only recently have studies shed light on head or tail domains of IFs, revealing certainsecondary structures and conformational changes during IF assembly. Thus, a deeper understanding of their structure could provide insights into their function. Full article

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

► Show Figures

Figure 1

10 pages, 1347 KiB

Open AccessEditor’s ChoiceArticle

Transcriptomic Profiling of Peripheral B Cells in Antibody Positive Sjogren’s Patients Reveals Interferon Signature

by Mehrnaz Maleki-Fischbach, Kelsey Anderson and Evans R. Fernández Pérez

Genes 2024, 15(5), 628; https://doi.org/10.3390/genes15050628 - 15 May 2024

Cited by 3 | Viewed by 1808

Abstract

Background: Sjögren’s disease (SjD) is a common systemic autoimmune disease that affects mainly women. Key pathologic features include the infiltration of exocrine glands by lymphocytes and the activation of B lymphocytes with the production of autoantibodies. We aimed to analyze the transcriptome of [...] Read more.

Background: Sjögren’s disease (SjD) is a common systemic autoimmune disease that affects mainly women. Key pathologic features include the infiltration of exocrine glands by lymphocytes and the activation of B lymphocytes with the production of autoantibodies. We aimed to analyze the transcriptome of circulating B cells from patients with SJD and healthy controls to decipher the B-cell-specific contribution to SJD. Methods: RNA from peripheral blood B cells of five untreated female patients with SjD and positive ANA, positive anti-SSA (both Ro-52 and Ro-60), positive anti-SSB and positive rheumatoid-factor, and five healthy controls was subjected to whole-transcriptome sequencing. A false discovery rate of < 0.1 was applied to define differentially expressed genes (DEG). Results: RNA-sequencing identified 56 up and 23 down DEG. Hierarchal clustering showed a clear separation between the two groups. Ingenuity pathway analysis revealed that these genes may play a role in interferon signaling, chronic mycobacterial infection, and transformation to myeloproliferative disorders. Conclusions: We found upregulated expression of type-I and type-II interferon (IFN)-induced genes, as well as genes that may contribute to other concomitant conditions, including infections and a higher risk of myeloproliferative disorders. This adds insight into the autoimmune process and suggests potential targets for future functional and prognostic studies. Full article

(This article belongs to the Special Issue Autoimmune Disease Genetics Volume II)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Editor’s Choice Articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI