Genes

12 pages, 5596 KiB

Open AccessArticle

FDXR-Associated Oculopathy: Congenital Amaurosis and Early-Onset Severe Retinal Dystrophy as Common Presenting Features in a Chinese Population

by Shutong Yi, Yuxi Zheng, Zhen Yi, Yingwei Wang, Yi Jiang, Jiamin Ouyang, Shiqiang Li, Xueshan Xiao, Wenmin Sun, Panfeng Wang and Qingjiong Zhang

Genes 2023, 14(4), 952; https://doi.org/10.3390/genes14040952 - 21 Apr 2023

Cited by 2 | Viewed by 1263

Abstract

Variants in FDXR reportedly cause autosomal recessive auditory neuropathy and optic atrophy, expanding to retinal dystrophy. This study aimed to further clarify associated phenotypes. FDXR variants were selected from our in-house whole-exome sequencing dataset of 6397 families with different eye conditions. The clinical [...] Read more.

Variants in FDXR reportedly cause autosomal recessive auditory neuropathy and optic atrophy, expanding to retinal dystrophy. This study aimed to further clarify associated phenotypes. FDXR variants were selected from our in-house whole-exome sequencing dataset of 6397 families with different eye conditions. The clinical data of the identified patients were summarized. Biallelic pathogenic or likely pathogenic FDXR variants were identified in 11 unrelated patients, including 14 missense variants of which 10 were novel. Fundus observation showed complete optic disc pallor, silver wiring or severe attenuation of retinal vessels, and varying degrees of generalized retinal degeneration. Before the detection of FDXR variants, four patients were clinically diagnosed as congenital amaurosis due to the presence of nystagmus a few months after birth, while seven were diagnosed as early-onset severe retinal dystrophy due to the presence of nyctalopia and/or poor vision in early childhood. Biallelic FDXR variants are a frequent cause of congenital or early-onset severe retinal dystrophy, especially for patients with severe optic atrophy and retinal dystrophy in early childhood. Full article

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

► Show Figures

Figure 1

14 pages, 1712 KiB

Open AccessFeature PaperArticle

Assessment of Genetic Diversity in Bupleurum spp. Basing Agronomic Traits, Medicinal Components and ISSR Markers

by Yiqing Peng, Alam Nafee-Ul, Mingzhi Liu, Qiuling He and Zongsuo Liang

Genes 2023, 14(4), 951; https://doi.org/10.3390/genes14040951 - 21 Apr 2023

Cited by 1 | Viewed by 1330

Abstract

Radix bupleuri is one of the bulk medicinal materials in China and it is widely adopted in clinical applications and drug discovery. The investigation of agronomic traits, active component content and genetic diversity in diverse Radix bupleuri germplasms may provide evidence to promote [...] Read more.

Radix bupleuri is one of the bulk medicinal materials in China and it is widely adopted in clinical applications and drug discovery. The investigation of agronomic traits, active component content and genetic diversity in diverse Radix bupleuri germplasms may provide evidence to promote the selection of better strains. In this research, 13 germplasms from various sources were used to investigate the variations between different Radix bupleuri germplasms. Nine biological characteristics were noted in the field, and the levels of the two primary active ingredients were determined using high performance liquid chromatography (HPLC). Moreover, the molecular marker technique of inter-simple sequence repeat (ISSR) and the unweighted pair group method with arithmetic means (UPGMA) were employed to evaluate the molecular genetic diversity. The findings showed that there was a wide range of variation among the many varieties of Radix bupleuri, with coefficients of variation for agronomic traits and active component content ranging from 7.62% to 41.54% and 36.47% to 53.70%, respectively. Moreover, there are different degrees of relationship between the two. Since there was a significant correlation between root weight and saikosaponin content, it was possible to classify a plant based on its weight and anticipate its saikosaponin content. The 13 species were divided into four groups based on their germplasm by genetic markers-based cluster analysis. This indicated the possibility that the component content would not necessarily be related to germplasm and might easily be influenced by environmental factors. The use of ISSR marker technology made it possible to precisely identify the various Radix bupleuri provenances and its counterfeit products. There may be a way to prevent the misunderstandings caused by the appearance and composition of Chinese medicinal substances. In our study, the germplasm of Radix bupleuri that was widely circulated in the market was comprehensively evaluated in terms of agronomic traits, active components and molecular level, and identified by simple means, to provide a theoretical basis for the evaluation and screening of fine germplasms of Radix bupleuri. Full article

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

► Show Figures

Figure 1

12 pages, 2682 KiB

Open AccessArticle

The Glutathione Peroxidase Gene Family in Nitraria sibirica: Genome-Wide Identification, Classification, and Gene Expression Analysis under Stress Conditions

by Ziming Lian, Jingbo Zhang, Zhaodong Hao, Liming Zhu, Yuxin Liu, Hao Fang, Ye Lu, Xinle Li, Jisen Shi, Jinhui Chen and Tielong Cheng

Genes 2023, 14(4), 950; https://doi.org/10.3390/genes14040950 - 21 Apr 2023

Cited by 3 | Viewed by 1297

Abstract

Plant glutathione peroxidases (GPXs) are the main enzymes in the antioxidant defense system that sustain H₂O₂ homeostasis and normalize plant reaction to abiotic stress conditions. However, the genome-wide identification of the GPX gene family and its responses to environmental stresses, [...] Read more.

Plant glutathione peroxidases (GPXs) are the main enzymes in the antioxidant defense system that sustain H₂O₂ homeostasis and normalize plant reaction to abiotic stress conditions. However, the genome-wide identification of the GPX gene family and its responses to environmental stresses, especially salt stress, in Nitraria sibirica, which is a shrub that can survive in saline environments, has not yet been reported. Here, we first report the genome-wide analysis of the GPX gene family in N. sibirica, leading to a total of seven NsGPX genes that are distributed on six of the twelve chromosomes. Phylogenetic analysis showed that NsGPX genes were grouped into four major groups (Group I-IV). Three types of cis-acting elements were identified in the NsGPX promoters, mainly related to hormones and stress response. The quantitative real-time PCR (qRT-PCR) analysis indicated that NsGPX1 and NsGPX3 were significantly up-regulated in stem and leaf, while NsGPX7 transcriptionally in root in response to salt stress. The current study identified a total seven NsGPX genes in N. sibirica via genome-wide analysis, and discovered that NsGPXs may play an important role in response to salt stress. Taken together, our findings provide a basis for further functional studies of NsGPX genes, especially in regarding to the resistance to salt stress of this halophyte plant N. sibirica, eventually aid in the discovery of new methods to restore overtly saline soil. Full article

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

► Show Figures

Figure 1

20 pages, 2990 KiB

Open AccessReview

The Operon as a Conundrum of Gene Dynamics and Biochemical Constraints: What We Have Learned from Histidine Biosynthesis

by Sara Del Duca, Giulia Semenzato, Antonia Esposito, Pietro Liò and Renato Fani

Genes 2023, 14(4), 949; https://doi.org/10.3390/genes14040949 - 21 Apr 2023

Viewed by 1982

Abstract

Operons represent one of the leading strategies of gene organization in prokaryotes, having a crucial influence on the regulation of gene expression and on bacterial chromosome organization. However, there is no consensus yet on why, how, and when operons are formed and conserved, [...] Read more.

Operons represent one of the leading strategies of gene organization in prokaryotes, having a crucial influence on the regulation of gene expression and on bacterial chromosome organization. However, there is no consensus yet on why, how, and when operons are formed and conserved, and many different theories have been proposed. Histidine biosynthesis is a highly studied metabolic pathway, and many of the models suggested to explain operons origin and evolution can be applied to the histidine pathway, making this route an attractive model for the study of operon evolution. Indeed, the organization of his genes in operons can be due to a progressive clustering of biosynthetic genes during evolution, coupled with a horizontal transfer of these gene clusters. The necessity of physical interactions among the His enzymes could also have had a role in favoring gene closeness, of particular importance in extreme environmental conditions. In addition, the presence in this pathway of paralogous genes, heterodimeric enzymes and complex regulatory networks also support other operon evolution hypotheses. It is possible that histidine biosynthesis, and in general all bacterial operons, may result from a mixture of several models, being shaped by different forces and mechanisms during evolution. Full article

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

► Show Figures

Figure 1

11 pages, 2459 KiB

Open AccessBrief Report

Analysis of Viral Promoters for Transgene Expression and of the Effect of 5′-UTRs on Alternative Translational Start Sites in Chlamydomonas

by Justus Niemeyer, Laura Fischer, Frank O’Neill Aylward and Michael Schroda

Genes 2023, 14(4), 948; https://doi.org/10.3390/genes14040948 - 21 Apr 2023

Cited by 1 | Viewed by 1855

Abstract

Microalgae biotechnology has the potential to produce high quality bioproducts in a sustainable manner. Here, Chlamydomonas reinhardtii has shown great potential as a host for biotechnological exploitation. However, low expression of nuclear transgenes is still a problem and needs to be optimized. In [...] Read more.

Microalgae biotechnology has the potential to produce high quality bioproducts in a sustainable manner. Here, Chlamydomonas reinhardtii has shown great potential as a host for biotechnological exploitation. However, low expression of nuclear transgenes is still a problem and needs to be optimized. In many model organisms, viral promoters are used to drive transgene expression at high levels. However, no viruses are known to infect Chlamydomonas, and known viral promoters are not functional. Recently, two different lineages of giant viruses were identified in the genomes of Chlamydomonas reinhardtii field isolates. In this work, we tested six potentially strong promoters from these viral genomes for their ability to drive transgene expression in Chlamydomonas. We used ble, NanoLUC, and mCherry as reporter genes, and three native benchmark promoters as controls. None of the viral promoters drove expression of any reporter gene beyond background. During our study, we found that mCherry variants are produced by alternative in-frame translational start sites in Chlamydomonas. We show that this problem can be overcome by mutating the responsible methionine codons to codons for leucine and by using the 5′-UTR of βTUB2 instead of the 5′-UTRs of PSAD or RBCS2. Apparently, the βTUB2 5′-UTR promotes the use of the first start codon. This could be mediated by the formation of a stem-loop between sequences of the βTUB2 5′-UTR and sequences downstream of the first AUG in the mCherry reporter, potentially increasing the dwell time of the scanning 40S subunit on the first AUG and thus decreasing the probability of leaky scanning. Full article

(This article belongs to the Special Issue Genetic Engineering of Microalgae)

► Show Figures

Figure 1

11 pages, 31469 KiB

Open AccessCommunication

Contribution of LRP1 in Human Congenital Heart Disease Correlates with Its Roles in the Outflow Tract and Atrioventricular Cushion Development

by Angelo B. Arrigo, Wenjuan Zhu, Kylia A. Williams, Carla Guzman-Moreno, Cecilia Lo and Jiuann-Huey I. Lin

Genes 2023, 14(4), 947; https://doi.org/10.3390/genes14040947 - 21 Apr 2023

Viewed by 1519

Abstract

Due to the prevalence of congenital heart disease in the human population, determining the role of variants in congenital heart disease (CHD) can give a better understanding of the cause of the disorder. A homozygous missense mutation in the LDL receptor-related protein 1 [...] Read more.

Due to the prevalence of congenital heart disease in the human population, determining the role of variants in congenital heart disease (CHD) can give a better understanding of the cause of the disorder. A homozygous missense mutation in the LDL receptor-related protein 1 (Lrp1) in mice was shown to cause congenital heart defects, including atrioventricular septal defect (AVSD) and double outlet right ventricle (DORV). Integrative analysis of publicly available single-cell RNA sequencing (scRNA-seq) datasets and spatial transcriptomics of human and mouse hearts indicated that LRP1 is predominantly expressed in mesenchymal cells and mainly located in the developing outflow tract and atrioventricular cushion. Gene burden analysis of 1922 CHD individuals versus 2602 controls with whole-exome sequencing showed a significant excess of rare damaging LRP1 mutations in CHD (odds ratio (OR) = 2.22, p = 1.92 × 10⁻⁴), especially in conotruncal defect with OR of 2.37 (p = 1.77 × 10⁻³) and atrioventricular septal defect with OR of 3.14 (p = 0.0194). Interestingly, there is a significant relationship between those variants that have an allele frequency below 0.01% and atrioventricular septal defect, which is the phenotype observed previously in a homozygous N-ethyl-N-nitrosourea (ENU)-induced Lrp1 mutant mouse line. Full article

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

► Show Figures

Figure 1

15 pages, 3736 KiB

Open AccessArticle

Intrafollicular Retinoic Acid Signaling Is Important for Luteinizing Hormone-Induced Oocyte Meiotic Resumption

by Fupeng Wang, Yawen Tang, Yijie Cai, Ran Yang, Zongyu Wang, Xiaodong Wang, Qianying Yang, Wenjing Wang, Jianhui Tian and Lei An

Genes 2023, 14(4), 946; https://doi.org/10.3390/genes14040946 - 20 Apr 2023

Cited by 1 | Viewed by 1425

Abstract

It has been clear that retinoic acid (RA), the most active vitamin A (VA) derivative, plays a central role in governing oocyte meiosis initiation. However, it has not been functionally determined if RA participates in luteinizing hormone (LH)-induced resumption from long-lasting oocyte meiotic [...] Read more.

It has been clear that retinoic acid (RA), the most active vitamin A (VA) derivative, plays a central role in governing oocyte meiosis initiation. However, it has not been functionally determined if RA participates in luteinizing hormone (LH)-induced resumption from long-lasting oocyte meiotic arrest, which is essential for haploid oocyte formation. In the present study, using well-established in vivo and in vitro models, we identified that intrafollicular RA signaling is important for normal oocyte meiotic resumption. A mechanistic study indicated that mural granulosa cells (MGCs) are the indispensable follicular compartment for RA-prompted meiotic resumption. Moreover, retinoic acid receptor (RAR) is essential for mediating RA signaling to regulate meiotic resumption. Furthermore, we found zinc finger protein 36 (ZFP36) is the transcriptional target of RAR. Both RA signaling and epidermal growth factor (EGF) signaling were activated in MGCs in response to LH surge, and two intrafollicular signalings cooperate to induce rapid Zfp36 upregulation and Nppc mRNA decrease, which is critical to LH-induced meiotic resumption. These findings extend our understanding of the role of RA in oocyte meiosis: RA not only governs meiotic initiation but also regulates LH-induced meiotic resumption. We also emphasize the importance of LH-induced metabolic changes in MGCs in this process. Full article

(This article belongs to the Special Issue Genetic Regulation of Animal Reproduction)

► Show Figures

Figure 1

14 pages, 6456 KiB

Open AccessArticle

RNA-Sequencing Characterization of lncRNA and mRNA Functions in Septic Pig Liver Injury

by Jing Zhang, Zhihui Xue, Qingbo Zhao, Keke Zhang, Ao Zhou, Liangyu Shi and Yulan Liu

Genes 2023, 14(4), 945; https://doi.org/10.3390/genes14040945 - 20 Apr 2023

Viewed by 1500

Abstract

We assessed differentially expressed (DE) mRNAs and lncRNAs in the liver of septic pigs to explore the key factors regulating lipopolysaccharide (LPS)-induced liver injury. We identified 543 DE lncRNAs and 3642 DE mRNAs responsive to LPS. Functional enrichment analysis revealed the DE mRNAs [...] Read more.

We assessed differentially expressed (DE) mRNAs and lncRNAs in the liver of septic pigs to explore the key factors regulating lipopolysaccharide (LPS)-induced liver injury. We identified 543 DE lncRNAs and 3642 DE mRNAs responsive to LPS. Functional enrichment analysis revealed the DE mRNAs were involved in liver metabolism and other pathways related to inflammation and apoptosis. We also found significantly upregulated endoplasmic reticulum stress (ERS)-associated genes, including the receptor protein kinase receptor-like endoplasmic reticulum kinase (PERK), the eukaryotic translation initiation factor 2α (EIF2S1), the transcription factor C/EBP homologous protein (CHOP), and activating transcription factor 4 (ATF4). In addition, we predicted 247 differentially expressed target genes (DETG) of DE lncRNAs. The analysis of protein-protein interactions (PPI) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway detected key DETGs that are involved in metabolic pathways, such as N-Acetylgalactosaminyltransferase 2 (GALNT2), argininosuccinate synthetase 1 (ASS1), and fructose 1,6-bisphosphatase 1 (FBP1). LNC_003307 was the most abundant DE lncRNA in the pig liver, with a marked upregulation of >10-fold after LPS stimulation. We identified three transcripts for this gene using the rapid amplification of the cDNA ends (RACE) technique and obtained the shortest transcript sequence. This gene likely derives from the nicotinamide N-methyltransferase (NNMT) gene in pigs. According to the identified DETGs of LNC_003307, we hypothesize that this gene regulates inflammation and endoplasmic reticulum stress in LPS-induced liver damage in pigs. This study provides a transcriptomic reference for further understanding of the regulatory mechanisms underlying septic hepatic injury. Full article

(This article belongs to the Special Issue Genetic Analyses of Immune Genes in Human and Animals)

► Show Figures

Figure 1

15 pages, 3809 KiB

Open AccessArticle

SPAG9 Expression Predicts Good Prognosis in Patients with Clear-Cell Renal Cell Carcinoma: A Bioinformatics Analysis with Experimental Validation

by Liwen Qiao, Lu Zhang and Huiming Wang

Genes 2023, 14(4), 944; https://doi.org/10.3390/genes14040944 - 20 Apr 2023

Cited by 1 | Viewed by 1491

Abstract

Clear-cell renal cell carcinoma (ccRCC) is the most common and aggressive type of renal-cell carcinoma (RCC). Sperm-associated antigen 9 (SPAG9) has been reported to promote the progression of a variety of tumors and is thus a potential prognostic marker. This study [...] Read more.

Clear-cell renal cell carcinoma (ccRCC) is the most common and aggressive type of renal-cell carcinoma (RCC). Sperm-associated antigen 9 (SPAG9) has been reported to promote the progression of a variety of tumors and is thus a potential prognostic marker. This study combined a bioinformatics analysis with an experimental validation, exploring the prognostic value of SPAG9 expression in ccRCC patients and the possible underlying mechanisms. The SPAG9 expression was associated with a poor prognosis in pan-cancer patients, but with a good prognosis and slow tumor progression in ccRCC patients. To explore the underlying mechanism, we investigated the roles of SPAG9 in ccRCC and bladder urothelial carcinoma (BLCA). The latter was chosen for comparison with ccRCC to represent the tumor types in which SPAG9 expression suggests a poor prognosis. The overexpression of SPAG9 increased the expression of autophagy-related genes in 786-O cells but not in HTB-9 cells, and SPAG9 expression was significantly correlated with a weaker inflammatory response in ccRCC but not in BLCA. Through an integrated bioinformatics analysis, we screened out seven key genes (AKT3, MAPK8, PIK3CA, PIK3R3, SOS1, SOS2, and STAT5B) in this study. The correlation between SPAG9 expression and ccRCC prognosis depends on the expression of key genes. Since most of the key genes were PI3K-AKT-pathway members, we used the PI3K agonist 740Y-P to stimulate the 786-O cells, to mimic the effect of key-gene overexpression. Compared with the Ov-SPAG9 786-O cells, the 740Y-P further increased the expression of autophagy-related genes by more than twofold. Moreover, we constructed a nomogram based on SPAG9/key genes and other clinical features, which was proven to have some predictive value. Our study found that SPAG9 expression predicted opposite clinical outcomes in pan-cancer and ccRCC patients, and we speculated that SPAG9 suppresses tumor progression by promoting autophagy and inhibiting inflammatory responses in ccRCC. We further found that some genes might cooperate with SPAG9 to promote autophagy, and that these were highly expressed in the tumor stroma and could be represented by key genes. The SPAG9-based nomogram can help to estimate the long-term prognosis of ccRCC patients, indicating that SPAG9 is a potential prognostic marker for ccRCC. Full article

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

► Show Figures

Figure 1

14 pages, 10168 KiB

Open AccessArticle

Gene Losses and Homology of the Chloroplast Genomes of Taxillus and Phacellaria Species

by Liwei Wu, Panhui Fan, Jianguo Zhou, Yonghua Li, Zhichao Xu, Yulin Lin, Yu Wang, Jingyuan Song and Hui Yao

Genes 2023, 14(4), 943; https://doi.org/10.3390/genes14040943 - 19 Apr 2023

Cited by 4 | Viewed by 1380

Abstract

Research on the chloroplast genome of parasitic plants is limited. In particular, the homology between the chloroplast genomes of parasitic and hyperparasitic plants has not been reported yet. In this study, three chloroplast genomes of Taxillus (Taxillus chinensis, Taxillus delavayi, [...] Read more.

Research on the chloroplast genome of parasitic plants is limited. In particular, the homology between the chloroplast genomes of parasitic and hyperparasitic plants has not been reported yet. In this study, three chloroplast genomes of Taxillus (Taxillus chinensis, Taxillus delavayi, and Taxillus thibetensis) and one chloroplast genome of Phacellaria (Phacellaria rigidula) were sequenced and analyzed, among which T. chinensis is the host of P. rigidula. The chloroplast genomes of the four species were 119,941–138,492 bp in length. Compared with the chloroplast genome of the autotrophic plant Nicotiana tabacum, all of the ndh genes, three ribosomal protein genes, three tRNA genes and the infA gene were lost in the three Taxillus species. Meanwhile, in P. rigidula, the trnV-UAC gene and the ycf15 gene were lost, and only one ndh gene (ndhB) existed. The results of homology analysis showed that the homology between P. rigidula and its host T. chinensis was low, indicating that P. rigidula grows on its host T. chinensis but they do not share the chloroplast genome. In addition, horizontal gene transfer was not found between P. rigidula and its host T. chinensis. Several candidate highly variable regions in the chloroplast genomes of Taxillus and Phacellaria species were selected for species identification study. Phylogenetic analysis revealed that the species of Taxillus and Scurrula were closely related and supported that Scurrula and Taxillus should be treated as congeneric, while species in Phacellaria had a close relationship with that in Viscum. Full article

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

► Show Figures

Figure 1

9 pages, 2055 KiB

Open AccessArticle

PMIDigest: Interactive Review of Large Collections of PubMed Entries to Distill Relevant Information

by Jorge Novoa, Mónica Chagoyen, Carlos Benito, F. Javier Moreno and Florencio Pazos

Genes 2023, 14(4), 942; https://doi.org/10.3390/genes14040942 - 19 Apr 2023

Cited by 2 | Viewed by 1361

Abstract

Scientific knowledge is being accumulated in the biomedical literature at an unprecedented pace. The most widely used database with biomedicine-related article abstracts, PubMed, currently contains more than 36 million entries. Users performing searches in this database for a subject of interest face thousands [...] Read more.

Scientific knowledge is being accumulated in the biomedical literature at an unprecedented pace. The most widely used database with biomedicine-related article abstracts, PubMed, currently contains more than 36 million entries. Users performing searches in this database for a subject of interest face thousands of entries (articles) that are difficult to process manually. In this work, we present an interactive tool for automatically digesting large sets of PubMed articles: PMIDigest (PubMed IDs digester). The system allows for classification/sorting of articles according to different criteria, including the type of article and different citation-related figures. It also calculates the distribution of MeSH (medical subject headings) terms for categories of interest, providing in a picture of the themes addressed in the set. These MeSH terms are highlighted in the article abstracts in different colors depending on the category. An interactive representation of the interarticle citation network is also presented in order to easily locate article “clusters” related to particular subjects, as well as their corresponding “hub” articles. In addition to PubMed articles, the system can also process a set of Scopus or Web of Science entries. In summary, with this system, the user can have a “bird’s eye view” of a large set of articles and their main thematic tendencies and obtain additional information not evident in a plain list of abstracts. Full article

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

► Show Figures

Figure 1

23 pages, 3375 KiB

Open AccessReview

The Genetics of Fitness Reorganization during the Transition to Multicellularity: The Volvocine regA-like Family as a Model

by Zachariah I. Grochau-Wright, Aurora M. Nedelcu and Richard E. Michod

Genes 2023, 14(4), 941; https://doi.org/10.3390/genes14040941 - 19 Apr 2023

Viewed by 1612

Abstract

The evolutionary transition from single-celled to multicellular individuality requires organismal fitness to shift from the cell level to a cell group. This reorganization of fitness occurs by re-allocating the two components of fitness, survival and reproduction, between two specialized cell types in the [...] Read more.

The evolutionary transition from single-celled to multicellular individuality requires organismal fitness to shift from the cell level to a cell group. This reorganization of fitness occurs by re-allocating the two components of fitness, survival and reproduction, between two specialized cell types in the multicellular group: soma and germ, respectively. How does the genetic basis for such fitness reorganization evolve? One possible mechanism is the co-option of life history genes present in the unicellular ancestors of a multicellular lineage. For instance, single-celled organisms must regulate their investment in survival and reproduction in response to environmental changes, particularly decreasing reproduction to ensure survival under stress. Such stress response life history genes can provide the genetic basis for the evolution of cellular differentiation in multicellular lineages. The regA-like gene family in the volvocine green algal lineage provides an excellent model system to study how this co-option can occur. We discuss the origin and evolution of the volvocine regA-like gene family, including regA—the gene that controls somatic cell development in the model organism Volvox carteri. We hypothesize that the co-option of life history trade-off genes is a general mechanism involved in the transition to multicellular individuality, making volvocine algae and the regA-like family a useful template for similar investigations in other lineages. Full article

(This article belongs to the Special Issue The Genetics and Evolution of Multicellularity)

► Show Figures

Figure 1

27 pages, 3925 KiB

Open AccessArticle

Genome-Wide Identification and Gene Expression Analysis of Sweet Cherry Aquaporins (Prunus avium L.) under Abiotic Stresses

by Ariel Salvatierra, Patricio Mateluna, Guillermo Toro, Simón Solís and Paula Pimentel

Genes 2023, 14(4), 940; https://doi.org/10.3390/genes14040940 - 19 Apr 2023

Cited by 1 | Viewed by 1724

Abstract

Aquaporins (AQPs) are integral transmembrane proteins well known as channels involved in the mobilization of water, small uncharged molecules and gases. In this work, the main objective was to carry out a comprehensive study of AQP encoding genes in Prunus avium (cv. Mazzard [...] Read more.

Aquaporins (AQPs) are integral transmembrane proteins well known as channels involved in the mobilization of water, small uncharged molecules and gases. In this work, the main objective was to carry out a comprehensive study of AQP encoding genes in Prunus avium (cv. Mazzard F12/1) on a genome-wide scale and describe their transcriptional behaviors in organs and in response to different abiotic stresses. A total of 28 non-redundant AQP genes were identified in Prunus spp. Genomes, which were phylogenetically grouped into five subfamilies (seven PIPs, eight NIPs, eight TIPs, three SIPs and two XIPs). Bioinformatic analyses revealed a high synteny and remarkable conservation of structural features among orthologs of different Prunus genomes. Several cis-acting regulatory elements (CREs) related to stress regulation were detected (ARE, WRE3, WUN, STRE, LTR, MBS, DRE, AT-rich and TC-rich). The above could be accounting for the expression variations associated with plant organs and, especially, each abiotic stress analyzed. Gene expressions of different PruavAQPs were shown to be preferentially associated with different stresses. PruavXIP2;1 and PruavXIP1;1 were up-regulated in roots at 6 h and 72 h of hypoxia, and in PruavXIP2;1 a slight induction of expression was also detected in leaves. Drought treatment strongly down-regulated PruavTIP4;1 but only in roots. Salt stress exhibited little or no variation in roots, except for PruavNIP4;1 and PruavNIP7;1, which showed remarkable gene repression and induction, respectively. Interestingly, PruavNIP4;1, the AQP most expressed in cherry roots subjected to cold temperatures, also showed this pattern in roots under high salinity. Similarly, PruavNIP4;2 consistently was up-regulated at 72 h of heat and drought treatments. From our evidence is possible to propose candidate genes for the development of molecular markers for selection processes in breeding programs for rootstocks and/or varieties of cherry. Full article

(This article belongs to the Special Issue Genome-Wide Identifications: Recent Trends in Genomic Studies)

► Show Figures

Figure 1

18 pages, 3218 KiB

Open AccessArticle

Genome-Wide Identification of the KNOX Gene Family in Japanese Apricot (Prunus mume Sieb. et Zucc.) and Functional Characterization of PmKNAT2 Genes

by Yang Bai, Ting Shi, Xiao Huang, Pengyu Zhou, Kenneth Omondi Ouma, Zhaojun Ni, Feng Gao, Wei Tan, Chengdong Ma, Yufan Ma and Zhihong Gao

Genes 2023, 14(4), 939; https://doi.org/10.3390/genes14040939 - 18 Apr 2023

Viewed by 1318

Abstract

The Knotted1-like Homeobox gene is crucial for plant morphological development and growth. Physicochemical characteristics, phylogenetic relationships, chromosomal localization, cis-acting elements, and tissue-specific expression patterns of the 11 PmKNOX genes found in the Japanese apricot genome in this study were examined. Proteins of 11 [...] Read more.

The Knotted1-like Homeobox gene is crucial for plant morphological development and growth. Physicochemical characteristics, phylogenetic relationships, chromosomal localization, cis-acting elements, and tissue-specific expression patterns of the 11 PmKNOX genes found in the Japanese apricot genome in this study were examined. Proteins of 11 PmKNOX were soluble proteins with isoelectric points between 4.29 and 6.53, molecular masses between 15.732 and 44.011 kDa, and amino acid counts between 140 and 430. The identified PmKNOX gene family was split into three subfamilies by jointly constructing the phylogenetic tree of KNOX proteins in Japanese apricot and Arabidopsis thaliana. Combined outcomes of the analyzed conserved motifs and gene structures of the 11 PmKNOX genes from the same subfamily displayed comparable gene structure and motif patterns. The 11 PmKNOX members were distributed across six chromosomes, while two sets of PmKNOX genes were found to be collinear. Analysis of the 2000 bp promoter upstream of the coding region of the PmKNOX gene revealed that most PmKNOX genes might be involved in the physiological metabolism, growth and development processes of plants. The PmKNOX gene expression profile revealed that these genes were expressed at varying levels in different tissues, and most of them were linked to the meristems of leaf and flower buds, suggesting that PmKNOX may be involved in plants’ apical meristems. In Arabidopsis thaliana, functional validation of PmKNAT2a and PmKNAT2b revealed that these two genes might be involved in regulating leaf and stem development. In addition to laying the groundwork for future research on the function of these genes, understanding the evolutionary relationships between members of the PmKNOX gene family provides opportunities for future breeding in Japanese apricots. Full article

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

► Show Figures

Figure 1

15 pages, 1942 KiB

Open AccessReview

Polycomb-like Proteins in Gene Regulation and Cancer

by Sabrina Fischer and Robert Liefke

Genes 2023, 14(4), 938; https://doi.org/10.3390/genes14040938 - 18 Apr 2023

Cited by 4 | Viewed by 2281

Abstract

Polycomb-like proteins (PCLs) are a crucial group of proteins associated with the Polycomb repressive complex 2 (PRC2) and are responsible for setting up the PRC2.1 subcomplex. In the vertebrate system, three homologous PCLs exist: PHF1 (PCL1), MTF2 (PCL2), and PHF19 (PCL3). Although the [...] Read more.

Polycomb-like proteins (PCLs) are a crucial group of proteins associated with the Polycomb repressive complex 2 (PRC2) and are responsible for setting up the PRC2.1 subcomplex. In the vertebrate system, three homologous PCLs exist: PHF1 (PCL1), MTF2 (PCL2), and PHF19 (PCL3). Although the PCLs share a similar domain composition, they differ significantly in their primary sequence. PCLs play a critical role in targeting PRC2.1 to its genomic targets and regulating the functionality of PRC2. However, they also have PRC2-independent functions. In addition to their physiological roles, their dysregulation has been associated with various human cancers. In this review, we summarize the current understanding of the molecular mechanisms of the PCLs and how alterations in their functionality contribute to cancer development. We particularly highlight the nonoverlapping and partially opposing roles of the three PCLs in human cancer. Our review provides important insights into the biological significance of the PCLs and their potential as therapeutic targets for cancer treatment. Full article

(This article belongs to the Special Issue Molecular Mechanisms of the Polycomb Repressive Complex 2 (PRC2) and Its Role in Human Cancer)

► Show Figures

Figure 1

12 pages, 1060 KiB

Open AccessArticle

Comprehensive Genetic Analysis of Druze Provides Insights into Carrier Screening

by Eden Avnat, Guy Shapira, Shelly Shoval, Ifat Israel-Elgali, Anna Alkelai, Alan R. Shuldiner, Claudia Gonzaga-Jauregui, Jamal Zidan, Taiseer Maray, Noam Shomron and Eitan Friedman

Genes 2023, 14(4), 937; https://doi.org/10.3390/genes14040937 - 18 Apr 2023

Cited by 1 | Viewed by 1536

Abstract

Background: Druze individuals, like many genetically homogeneous and isolated populations, harbor recurring pathogenic variants (PV) in autosomal recessive (AR) disorders. Methods: Variant calling of whole-genome sequencing (WGS) of 40 Druze from the Human Genome Diversity Project (HGDP) was performed (HGDP-cohort). Additionally, we performed [...] Read more.

Background: Druze individuals, like many genetically homogeneous and isolated populations, harbor recurring pathogenic variants (PV) in autosomal recessive (AR) disorders. Methods: Variant calling of whole-genome sequencing (WGS) of 40 Druze from the Human Genome Diversity Project (HGDP) was performed (HGDP-cohort). Additionally, we performed whole exome sequencing (WES) of 118 Druze individuals: 38 trios and 2 couples, representing geographically distinct clans (WES-cohort). Rates of validated PV were compared with rates in worldwide and Middle Eastern populations, from the gnomAD and dbSNP datasets. Results: Overall, 34 PVs were identified: 30 PVs in genes underlying AR disorders, 3 additional PVs were associated with autosomal dominant (AD) disorders, and 1 PV with X-linked-dominant inherited disorder in the WES cohort. Conclusions: The newly identified PVs associated with AR conditions should be considered for incorporation into prenatal-screening options offered to Druze individuals after an extension and validation of the results in a larger study. Full article

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

► Show Figures

Figure 1

15 pages, 17686 KiB

Open AccessArticle

Unraveling the Dysbiosis of Vaginal Microbiome to Understand Cervical Cancer Disease Etiology—An Explainable AI Approach

by Karthik Sekaran, Rinku Polachirakkal Varghese, Mohanraj Gopikrishnan, Alsamman M. Alsamman, Achraf El Allali, Hatem Zayed and George Priya Doss C

Genes 2023, 14(4), 936; https://doi.org/10.3390/genes14040936 - 18 Apr 2023

Cited by 1 | Viewed by 1913

Abstract

Microbial Dysbiosis is associated with the etiology and pathogenesis of diseases. The studies on the vaginal microbiome in cervical cancer are essential to discern the cause and effect of the condition. The present study characterizes the microbial pathogenesis involved in developing cervical cancer. [...] Read more.

Microbial Dysbiosis is associated with the etiology and pathogenesis of diseases. The studies on the vaginal microbiome in cervical cancer are essential to discern the cause and effect of the condition. The present study characterizes the microbial pathogenesis involved in developing cervical cancer. Relative species abundance assessment identified Firmicutes, Actinobacteria, and Proteobacteria dominating the phylum level. A significant increase in Lactobacillus iners and Prevotella timonensis at the species level revealed its pathogenic influence on cervical cancer progression. The diversity, richness, and dominance analysis divulges a substantial decline in cervical cancer compared to control samples. The β diversity index proves the homogeneity in the subgroups’ microbial composition. The association between enriched Lactobacillus iners at the species level, Lactobacillus, Pseudomonas, and Enterococcus genera with cervical cancer is identified by Linear discriminant analysis Effect Size (LEfSe) prediction. The functional enrichment corroborates the microbial disease association with pathogenic infections such as aerobic vaginitis, bacterial vaginosis, and chlamydia. The dataset is trained and validated with repeated k-fold cross-validation technique using a random forest algorithm to determine the discriminative pattern from the samples. SHapley Additive exPlanations (SHAP), a game theoretic approach, is employed to analyze the results predicted by the model. Interestingly, SHAP identified that the increase in Ralstonia has a higher probability of predicting the sample as cervical cancer. New evidential microbiomes identified in the experiment confirm the presence of pathogenic microbiomes in cervical cancer vaginal samples and their mutuality with microbial imbalance. Full article

(This article belongs to the Special Issue Bioinformatics of Sequencing Data: A Machine Learning Approach)

► Show Figures

Figure 1

15 pages, 2012 KiB

Open AccessArticle

Mitochondrial Heteroplasmy and PCR Amplification Bias Lead to Wrong Species Delimitation with High Confidence in the South American and Antarctic Marine Bivalve Aequiyoldia eightsii Species Complex

by Mariano Martínez, Lars Harms, Doris Abele and Christoph Held

Genes 2023, 14(4), 935; https://doi.org/10.3390/genes14040935 - 18 Apr 2023

Cited by 2 | Viewed by 1159

Abstract

The species delimitation of the marine bivalve species complex Aequiyoldia eightsii in South America and Antarctica is complicated by mitochondrial heteroplasmy and amplification bias in molecular barcoding. In this study, we compare different data sources (mitochondrial cytochrome c oxidase subunit I (COI [...] Read more.

The species delimitation of the marine bivalve species complex Aequiyoldia eightsii in South America and Antarctica is complicated by mitochondrial heteroplasmy and amplification bias in molecular barcoding. In this study, we compare different data sources (mitochondrial cytochrome c oxidase subunit I (COI) sequences; nuclear and mitochondrial SNPs). Whilst all the data suggest that populations on either side of the Drake Passage belong to different species, the picture is less clear within Antarctic populations, which harbor three distinct mitochondrial lineages (p-dist ≈ 6%) that coexist in populations and in a subset of individuals with heteroplasmy. Standard barcoding procedures lead to amplification bias favoring either haplotype unpredictably and thus overestimate the species richness with high confidence. However, nuclear SNPs show no differentiation akin to the trans-Drake comparison, suggesting that the Antarctic populations represent a single species. Their distinct haplotypes likely evolved during periods of temporary allopatry, whereas recombination eroded similar differentiation patterns in the nuclear genome after secondary contact. Our study highlights the importance of using multiple data sources and careful quality control measures to avoid bias and increase the accuracy of molecular species delimitation. We recommend an active search for mitochondrial heteroplasmy and haplotype-specific primers for amplification in DNA-barcoding studies. Full article

(This article belongs to the Special Issue Polar Genomics)

► Show Figures

Figure 1

12 pages, 3685 KiB

Open AccessArticle

Functional Analysis of a Novel, Non-Canonical RPGR Splice Variant Causing X-Linked Retinitis Pigmentosa

by Samuel Koller, Tim Beltraminelli, Jordi Maggi, Agnès Wlodarczyk, Silke Feil, Luzy Baehr, Christina Gerth-Kahlert, Moreno Menghini and Wolfgang Berger

Genes 2023, 14(4), 934; https://doi.org/10.3390/genes14040934 - 18 Apr 2023

Cited by 1 | Viewed by 1673

Abstract

X-linked retinitis pigmentosa (XLRP) caused by mutations in the RPGR gene is one of the most severe forms of RP due to its early onset and intractable progression. Most cases have been associated with genetic variants within the purine-rich exon ORF15 region of [...] Read more.

X-linked retinitis pigmentosa (XLRP) caused by mutations in the RPGR gene is one of the most severe forms of RP due to its early onset and intractable progression. Most cases have been associated with genetic variants within the purine-rich exon ORF15 region of this gene. RPGR retinal gene therapy is currently being investigated in several clinical trials. Therefore, it is crucial to report and functionally characterize (all novel) potentially pathogenic DNA sequence variants. Whole-exome sequencing (WES) was performed for the index patient. The splicing effects of a non-canonical splice variant were tested on cDNA from whole blood and a minigene assay. WES revealed a rare, non-canonical splice site variant predicted to disrupt the wildtype splice acceptor and create a novel acceptor site 8 nucleotides upstream of RPGR exon 12. Reverse-transcription PCR analyses confirmed the disruption of the correct splicing pattern, leading to the insertion of eight additional nucleotides in the variant transcript. Transcript analyses with minigene assays and cDNA from peripheral blood are useful tools for the characterization of splicing defects due to variants in the RPGR and may increase the diagnostic yield in RP. The functional analysis of non-canonical splice variants is required to classify those variants as pathogenic according to the ACMG’s criteria. Full article

(This article belongs to the Special Issue Genetics in Inherited Retinal Diseases)

► Show Figures

Figure 1

42 pages, 3406 KiB

Open AccessEditor’s ChoiceReview

The Hexosamine Biosynthesis Pathway: Regulation and Function

by Alysta Paneque, Harvey Fortus, Julia Zheng, Guy Werlen and Estela Jacinto

Genes 2023, 14(4), 933; https://doi.org/10.3390/genes14040933 - 18 Apr 2023

Cited by 24 | Viewed by 6150

Abstract

The hexosamine biosynthesis pathway (HBP) produces uridine diphosphate-N-acetyl glucosamine, UDP-GlcNAc, which is a key metabolite that is used for N- or O-linked glycosylation, a co- or post-translational modification, respectively, that modulates protein activity and expression. The production of hexosamines [...] Read more.

The hexosamine biosynthesis pathway (HBP) produces uridine diphosphate-N-acetyl glucosamine, UDP-GlcNAc, which is a key metabolite that is used for N- or O-linked glycosylation, a co- or post-translational modification, respectively, that modulates protein activity and expression. The production of hexosamines can occur via de novo or salvage mechanisms that are catalyzed by metabolic enzymes. Nutrients including glutamine, glucose, acetyl-CoA, and UTP are utilized by the HBP. Together with availability of these nutrients, signaling molecules that respond to environmental signals, such as mTOR, AMPK, and stress-regulated transcription factors, modulate the HBP. This review discusses the regulation of GFAT, the key enzyme of the de novo HBP, as well as other metabolic enzymes that catalyze the reactions to produce UDP-GlcNAc. We also examine the contribution of the salvage mechanisms in the HBP and how dietary supplementation of the salvage metabolites glucosamine and N-acetylglucosamine could reprogram metabolism and have therapeutic potential. We elaborate on how UDP-GlcNAc is utilized for N-glycosylation of membrane and secretory proteins and how the HBP is reprogrammed during nutrient fluctuations to maintain proteostasis. We also consider how O-GlcNAcylation is coupled to nutrient availability and how this modification modulates cell signaling. We summarize how deregulation of protein N-glycosylation and O-GlcNAcylation can lead to diseases including cancer, diabetes, immunodeficiencies, and congenital disorders of glycosylation. We review the current pharmacological strategies to inhibit GFAT and other enzymes involved in the HBP or glycosylation and how engineered prodrugs could have better therapeutic efficacy for the treatment of diseases related to HBP deregulation. Full article

(This article belongs to the Special Issue Signaling and Gene Regulation in Metabolism)

► Show Figures

Figure 1

19 pages, 7429 KiB

Open AccessArticle

How to Choose? Comparing Different Methods to Count Wolf Packs in a Protected Area of the Northern Apennines

by Arianna Dissegna, Martino Rota, Simone Basile, Giuseppe Fusco, Marco Mencucci, Nadia Cappai, Marco Galaverni, Elena Fabbri, Edoardo Velli and Romolo Caniglia

Genes 2023, 14(4), 932; https://doi.org/10.3390/genes14040932 - 18 Apr 2023

Viewed by 2017

Abstract

Despite a natural rewilding process that caused wolf populations in Europe to increase and expand in the last years, human–wolf conflicts still persist, threatening the long-term wolf presence in both anthropic and natural areas. Conservation management strategies should be carefully designed on updated [...] Read more.

Despite a natural rewilding process that caused wolf populations in Europe to increase and expand in the last years, human–wolf conflicts still persist, threatening the long-term wolf presence in both anthropic and natural areas. Conservation management strategies should be carefully designed on updated population data and planned on a wide scale. Unfortunately, reliable ecological data are difficult and expensive to obtain and often hardly comparable through time or among different areas, especially because of different sampling designs. In order to assess the performance of different methods to estimate wolf (Canis lupus L.) abundance and distribution in southern Europe, we simultaneously applied three techniques: wolf howling, camera trapping and non-invasive genetic sampling in a protected area of the northern Apennines. We aimed at counting the minimum number of packs during a single wolf biological year and evaluating the pros and cons for each technique, comparing results obtained from different combinations of these three methods and testing how sampling effort may affect results. We found that packs’ identifications could be hardly comparable if methods were separately used with a low sampling effort: wolf howling identified nine, camera trapping 12 and non-invasive genetic sampling eight packs. However, increased sampling efforts produced more consistent and comparable results across all used methods, although results from different sampling designs should be carefully compared. The integration of the three techniques yielded the highest number of detected packs, 13, although with the highest effort and cost. A common standardised sampling strategy should be a priority approach to studying elusive large carnivores, such as the wolf, allowing for the comparison of key population parameters and developing shared and effective conservation management plans. Full article

(This article belongs to the Special Issue Genetics and the Canines: From Evolution to Conservation)

► Show Figures

Figure 1

13 pages, 4784 KiB

Open AccessCase Report

Specific Deoxyceramide Species Correlate with Expression of Macular Telangiectasia Type 2 (MacTel2) in a SPTLC2 Carrier HSAN1 Family

by Lindsey M. Q. Wilson, Sadaf Saba, Jun Li, Lev Prasov and Jason M. L. Miller

Genes 2023, 14(4), 931; https://doi.org/10.3390/genes14040931 - 18 Apr 2023

Viewed by 1659

Abstract

Hereditary sensory and autonomic neuropathy type 1 (HSAN1/HSN1) is a peripheral neuropathy most commonly associated with pathogenic variants in the serine palmitoyltransferase complex (SPTLC1, SPTLC2) genes, which are responsible for sphingolipid biosynthesis. Recent reports have shown that some HSAN1 patients also develop macular [...] Read more.

Hereditary sensory and autonomic neuropathy type 1 (HSAN1/HSN1) is a peripheral neuropathy most commonly associated with pathogenic variants in the serine palmitoyltransferase complex (SPTLC1, SPTLC2) genes, which are responsible for sphingolipid biosynthesis. Recent reports have shown that some HSAN1 patients also develop macular telangiectasia type 2 (MacTel2), a retinal neurodegeneration with an enigmatic pathogenesis and complex heritability. Here, we report a novel association of a SPTLC2 c.529A>G p.(Asn177Asp) variant with MacTel2 in a single member of a family that otherwise has multiple members afflicted with HSAN1. We provide correlative data to suggest that the variable penetrance of the HSAN1/MacTel2-overlap phenotype in the proband may be explained by levels of certain deoxyceramide species, which are aberrant intermediates of sphingolipid metabolism. We provide detailed retinal imaging of the proband and his HSAN1+/MacTel2- brothers and suggest mechanisms by which deoxyceramide levels may induce retinal degeneration. This is the first report of HSAN1 vs. HSAN1/MacTel2 overlap patients to comprehensively profile sphingolipid intermediates. The biochemical data here may help shed light on the pathoetiology and molecular mechanisms of MacTel2. Full article

(This article belongs to the Special Issue Genetics of Eye Development and Disease)

► Show Figures

Figure 1

10 pages, 773 KiB

Open AccessCase Report

Young Onset Alzheimer’s Disease Associated with C9ORF72 Hexanucleotide Expansion: Further Evidence for a Still Unsolved Association

by Giulia Vinceti, Chiara Gallingani, Elisabetta Zucchi, Ilaria Martinelli, Giulia Gianferrari, Cecilia Simonini, Roberta Bedin, Annalisa Chiari, Giovanna Zamboni and Jessica Mandrioli

Genes 2023, 14(4), 930; https://doi.org/10.3390/genes14040930 - 17 Apr 2023

Cited by 2 | Viewed by 1623

Abstract

Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are recognized as part of a disease continuum (FTD-ALS spectrum), in which the most common genetic cause is chromosome 9 open reading frame 72 (C9ORF72) gene hexanucleotide repeat expansion. The clinical phenotype of [...] Read more.

Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are recognized as part of a disease continuum (FTD-ALS spectrum), in which the most common genetic cause is chromosome 9 open reading frame 72 (C9ORF72) gene hexanucleotide repeat expansion. The clinical phenotype of patients carrying this expansion varies widely and includes diseases beyond the FTD-ALS spectrum. Although a few cases of patients with C9ORF72 expansion and a clinical or biomarker-supported diagnosis of Alzheimer’s disease (AD) have been described, they have been considered too sparse to establish a definite association between the C9ORF72 expansion and AD pathology. Here, we describe a C9ORF72 family with pleomorphic phenotypical expressions: a 54-year-old woman showing cognitive impairment and behavioral disturbances with both neuroimaging and cerebrospinal fluid (CSF) biomarkers consistent with AD pathology, her 49-year-old brother with typical FTD-ALS, and their 63-year-old mother with the behavioral variant of FTD and CSF biomarkers suggestive of AD pathology. The young onset of disease in all three family members and their different phenotypes and biomarker profiles make the simple co-occurrence of different diseases an extremely unlikely explanation. Our report adds to previous findings and may contribute to further expanding the spectrum of diseases associated with C9ORF72 expansion. Full article

(This article belongs to the Special Issue Research Strategies to Unveil the Genetic and Molecular Basis of ALS)

► Show Figures

Figure 1

18 pages, 4003 KiB

Open AccessArticle

The Complete Chloroplast Genomes of Gynostemma Reveal the Phylogenetic Relationships of Species within the Genus

by Jiaxia Gan, Ying Li, Deying Tang, Baolin Guo, Doudou Li, Feng Cao, Chao Sun, Liying Yu and Zhuyun Yan

Genes 2023, 14(4), 929; https://doi.org/10.3390/genes14040929 - 17 Apr 2023

Cited by 2 | Viewed by 1494

Abstract

Gynostemma is an important medicinal and food plant of the Cucurbitaceae family. The phylogenetic position of the genus Gynostemma in the Cucurbitaceae family has been determined by morphology and phylogenetics, but the evolutionary relationships within the genus Gynostemma remain to be explored. The [...] Read more.

Gynostemma is an important medicinal and food plant of the Cucurbitaceae family. The phylogenetic position of the genus Gynostemma in the Cucurbitaceae family has been determined by morphology and phylogenetics, but the evolutionary relationships within the genus Gynostemma remain to be explored. The chloroplast genomes of seven species of the genus Gynostemma were sequenced and annotated, of which the genomes of Gynostemma simplicifolium, Gynostemma guangxiense and Gynostemma laxum were sequenced and annotated for the first time. The chloroplast genomes ranged from 157,419 bp (Gynostemma compressum) to 157,840 bp (G. simplicifolium) in length, including 133 identical genes: 87 protein-coding genes, 37 tRNA genes, eight rRNA genes and one pseudogene. Phylogenetic analysis showed that the genus Gynostemma is divided into three primary taxonomic clusters, which differs from the traditional morphological classification of the genus Gynostemma into the subgenus Gynostemma and Trirostellum. The highly variable regions of atpH-atpL, rpl32-trnL, and ccsA-ndhD, the repeat unilts of AAG/CTT and ATC/ATG in simple sequence repeats (SSRs) and the length of overlapping regions between rps19 and inverted repeats(IRb) and between ycf1 and small single-copy (SSC) were found to be consistent with the phylogeny. Observations of fruit morphology of the genus Gynostemma revealed that transitional state species have independent morphological characteristics, such as oblate fruit and inferior ovaries. In conclusion, both molecular and morphological results showed consistency with those of phylogenetic analysis. Full article

(This article belongs to the Special Issue Advances in Chloroplast Genomics and Proteostasis)

► Show Figures

Figure 1

13 pages, 2784 KiB

Open AccessArticle

Insight into the Natural History of Pathogenic Variant c.919-2A>G in the SLC26A4 Gene Involved in Hearing Loss: The Evidence for Its Common Origin in Southern Siberia (Russia)

by Valeriia Yu. Danilchenko, Marina V. Zytsar, Ekaterina A. Maslova, Konstantin E. Orishchenko and Olga L. Posukh

Genes 2023, 14(4), 928; https://doi.org/10.3390/genes14040928 - 17 Apr 2023

Viewed by 1346

Abstract

Pathogenic variants in the SLC26A4 gene leading to nonsyndromic recessive deafness (DFNB4), or Pendred syndrome, are some of the most common causes of hearing loss worldwide. Earlier, we found a high proportion of SLC26A4-related hearing loss with prevailing pathogenic variant c.919-2A>G (69.3% [...] Read more.

Pathogenic variants in the SLC26A4 gene leading to nonsyndromic recessive deafness (DFNB4), or Pendred syndrome, are some of the most common causes of hearing loss worldwide. Earlier, we found a high proportion of SLC26A4-related hearing loss with prevailing pathogenic variant c.919-2A>G (69.3% among all mutated SLC26A4 alleles that have been identified) in Tuvinian patients belonging to the indigenous Turkic-speaking Siberian people living in the Tyva Republic (Southern Siberia, Russia), which implies a founder effect in the accumulation of c.919-2A>G in Tuvinians. To evaluate a possible common origin of c.919-2A>G, we genotyped polymorphic STR and SNP markers, intragenic and flanking SLC26A4, in patients homozygous for c.919-2A>G and in healthy controls. The common STR and SNP haplotypes carrying c.919-2A>G were revealed, which convincingly indicates the origin of c.919-2A>G from a single ancestor, supporting a crucial role of the founder effect in the c.919-2A>G prevalence in Tuvinians. Comparison analysis with previously published data revealed the identity of the small SNP haplotype (~4.5 kb) in Tuvinian and Han Chinese carriers of c.919-2A>G, which suggests their common origin from founder chromosomes. We assume that c.919-2A>G could have originated in the geographically close territories of China or Tuva and subsequently spread to other regions of Asia. In addition, the time intervals of the c.919-2A>G occurrence in Tuvinians were roughly estimated. Full article

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

► Show Figures

Figure 1

18 pages, 2177 KiB

Open AccessArticle

Optimizing Sparse Testing for Genomic Prediction of Plant Breeding Crops

by Osval A. Montesinos-López, Carolina Saint Pierre, Salvador A. Gezan, Alison R. Bentley, Brandon A. Mosqueda-González, Abelardo Montesinos-López, Fred van Eeuwijk, Yoseph Beyene, Manje Gowda, Keith Gardner, Guillermo S. Gerard, Leonardo Crespo-Herrera and José Crossa

Genes 2023, 14(4), 927; https://doi.org/10.3390/genes14040927 - 17 Apr 2023

Cited by 2 | Viewed by 2075

Abstract

While sparse testing methods have been proposed by researchers to improve the efficiency of genomic selection (GS) in breeding programs, there are several factors that can hinder this. In this research, we evaluated four methods (M1–M4) for sparse testing allocation of lines to [...] Read more.

While sparse testing methods have been proposed by researchers to improve the efficiency of genomic selection (GS) in breeding programs, there are several factors that can hinder this. In this research, we evaluated four methods (M1–M4) for sparse testing allocation of lines to environments under multi-environmental trails for genomic prediction of unobserved lines. The sparse testing methods described in this study are applied in a two-stage analysis to build the genomic training and testing sets in a strategy that allows each location or environment to evaluate only a subset of all genotypes rather than all of them. To ensure a valid implementation, the sparse testing methods presented here require BLUEs (or BLUPs) of the lines to be computed at the first stage using an appropriate experimental design and statistical analyses in each location (or environment). The evaluation of the four cultivar allocation methods to environments of the second stage was done with four data sets (two large and two small) under a multi-trait and uni-trait framework. We found that the multi-trait model produced better genomic prediction (GP) accuracy than the uni-trait model and that methods M3 and M4 were slightly better than methods M1 and M2 for the allocation of lines to environments. Some of the most important findings, however, were that even under a scenario where we used a training-testing relation of 15–85%, the prediction accuracy of the four methods barely decreased. This indicates that genomic sparse testing methods for data sets under these scenarios can save considerable operational and financial resources with only a small loss in precision, which can be shown in our cost-benefit analysis. Full article

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

► Show Figures

Figure 1

3 pages, 170 KiB

Open AccessEditorial

Editorial for the Genetics of Muscular Dystrophies from the Pathogenesis to Gene Therapy Special Issue

by Luisa Politano and Filippo M. Santorelli

Genes 2023, 14(4), 926; https://doi.org/10.3390/genes14040926 - 17 Apr 2023

Viewed by 967

Abstract

Muscular dystrophies (MDs) make up a clinically and genetically heterogeneous group of skeletal muscle diseases with progressive muscle weakness and atrophy [...] Full article

(This article belongs to the Special Issue Genetics of Muscular Dystrophies from Pathogenesis to Gene Therapy)

18 pages, 5283 KiB

Open AccessArticle

Genome-Wide Identification, Characterization, and Expression of TCP Genes Family in Orchardgrass

by Cheng Wang, Guangyan Feng, Xiaoheng Xu, Linkai Huang, Gang Nie, Dandan Li and Xinquan Zhang

Genes 2023, 14(4), 925; https://doi.org/10.3390/genes14040925 - 16 Apr 2023

Cited by 2 | Viewed by 1336

Abstract

Plant-specific TCP transcription factors regulate several plant growth and development processes. Nevertheless, little information is available about the TCP family in orchardgrass (Dactylis glomerata L.). This study identified 22 DgTCP transcription factors in orchardgrass and determined their structure, phylogeny, and expression in [...] Read more.

Plant-specific TCP transcription factors regulate several plant growth and development processes. Nevertheless, little information is available about the TCP family in orchardgrass (Dactylis glomerata L.). This study identified 22 DgTCP transcription factors in orchardgrass and determined their structure, phylogeny, and expression in different tissues and developmental stages. The phylogenetic tree classified the DgTCP gene family into two main subfamilies, including class I and II supported by the exon–intron structure and conserved motifs. The DgTCP promoter regions contained various cis-elements associated with hormones, growth and development, and stress responses, including MBS (drought inducibility), circadian (circadian rhythms), and TCA-element (salicylic acid responsiveness). Moreover, DgTCP9 possibly regulates tillering and flowering time. Additionally, several stress treatments upregulated DgTCP1, DgTCP2, DgTCP6, DgTCP12, and DgTCP17, indicting their potential effects regarding regulating responses to the respective stress. This research offers a valuable basis for further studies of the TCP gene family in other Gramineae and reveals new ideas for increasing gene utilization. Full article

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

► Show Figures

Figure 1

17 pages, 2372 KiB

Open AccessArticle

Saudi Community-Based Screening Study on Genetic Variants in β-Cell Dysfunction and Its Role in Women with Gestational Diabetes Mellitus

by Amal F. Alshammary, Malak Mohammed Al-Hakeem and Imran Ali Khan

Genes 2023, 14(4), 924; https://doi.org/10.3390/genes14040924 - 16 Apr 2023

Cited by 4 | Viewed by 1592

Abstract

Background: Diabetes (hyperglycemia) is defined as a multifactorial metabolic disorder in which insulin resistance and defects in pancreatic β-cell dysfunction are two major pathophysiologic abnormalities that underpin towards gestational diabetes mellitus (GDM). TCF7L2, KCNQ1, and KCNJ11 genes are connected to the [...] Read more.

Background: Diabetes (hyperglycemia) is defined as a multifactorial metabolic disorder in which insulin resistance and defects in pancreatic β-cell dysfunction are two major pathophysiologic abnormalities that underpin towards gestational diabetes mellitus (GDM). TCF7L2, KCNQ1, and KCNJ11 genes are connected to the mechanism of β-cell dysfunction. The purpose of this study was to investigate the genes associated with β-cell dysfunction and their genetic roles in the rs7903146, rs2237892, and rs5219 variants in Saudi women diagnosed with type 2 diabetes mellitus and GDM. Materials and Methods: In this case-control study, 100 women with GDM and 100 healthy volunteers (non-GDM) were recruited. Genotyping was performed using polymerase chain reaction (PCR), followed by restriction fragment length analysis. Validation was performed using Sanger sequencing. Statistical analyses were performed using multiple software packages. Results: Clinical studies showed a β-cell dysfunction positive association in women with GDM when compared to non-GDM women (p < 0.05). Both rs7903146 (CT vs. CC: OR-2.12 [95%CI: 1.13–3.96]; p = 0.01 & T vs. C: (OR-2.03 [95%CI: 1.32–3.11]; p = 0.001) and rs5219 SNPs (AG vs. AA: OR-3.37 [95%CI: 1.63–6.95]; p = 0.0006 & G vs. A: OR-3.03 [95%CI: 1.66–5.52]; p = 0.0001) showed a positive association with genotype and allele frequencies in women with GDM. ANOVA analysis confirmed that weight (p = 0.02), BMI (p = 0.01), and PPBG (p = 0.003) were associated with rs7903146 and BMI (p = 0.03) was associated with rs2237892 SNPs. Conclusions: This study confirms that the SNPs rs7903146 (TCF7L2) and rs5219 (KCNJ11) are strongly associated with GDM in the Saudi population. Future studies should address the limitations of this study. Full article

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

► Show Figures

Graphical abstract

21 pages, 40744 KiB

Open AccessArticle

Genome-Wide Identification and Bioinformatics Analyses of Host Defense Peptides Snakin/GASA in Mangrove Plants

by Chenjing Shang, Ting Ye, Qiao Zhou, Pengyu Chen, Xiangyu Li, Wenyi Li, Si Chen, Zhangli Hu and Wei Zhang

Genes 2023, 14(4), 923; https://doi.org/10.3390/genes14040923 - 16 Apr 2023

Cited by 7 | Viewed by 1497

Abstract

Host defense peptides (HDPs) are components of plant defensive barriers that resist microbial infection. Members of the Snakin/GASA protein family in plants have functions of regulating plant growth, defense, and bacteriostasis. Most mangrove plants grow in coastal zones. In order to survive in [...] Read more.

Host defense peptides (HDPs) are components of plant defensive barriers that resist microbial infection. Members of the Snakin/GASA protein family in plants have functions of regulating plant growth, defense, and bacteriostasis. Most mangrove plants grow in coastal zones. In order to survive in harsh environments, mangrove plants have evolved complex adaptations against microbes. In this study, Snakin/GASA family members were identified and analyzed in the genomes of three mangrove species. Twenty-seven, thirteen, and nine candidate Snakin/GASA family members were found in Avicennia marina, Kandelia obovata, and Aegiceras corniculatum, respectively. These Snakin/GASA family members were identified and categorized into three subfamilies via phylogenetic analysis. The genes coding for the Snakin/GASA family members were unevenly distributed on chromosomes. Collinearity and conservative motif analyses showed that the Snakin/GASA family members in K. obovata and A. corniculatum underwent multiple gene duplication events. Snakin/GASA family member expression in normal leaves and leaves infected with pathogenic microorganisms of the three mangrove species was verified using real-time quantitative polymerase chain reaction. The expression of KoGASA3 and 4, AcGASA5 and 10, and AmGASA1, 4, 5, 15, 18, and 23 increased after microbial infection. This study provides a research basis for the verification of HDPs from mangrove plants and suggests directions for the development and utilization of marine biological antimicrobial peptides. Full article

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

► Show Figures

Figure 1

Journal Menu

Journal Browser

Genes, Volume 14, Issue 4 (April 2023) – 179 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI