Genes

20 pages, 2990 KiB

Open AccessEditor’s ChoiceReview

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

Cited by 3 | Viewed by 4697

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)

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12 pages, 5596 KiB

Open AccessEditor’s ChoiceArticle

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 9 | Viewed by 2285

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)

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15 pages, 3736 KiB

Open AccessEditor’s ChoiceArticle

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 4 | Viewed by 2398

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)

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27 pages, 3925 KiB

Open AccessEditor’s ChoiceArticle

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 7 | Viewed by 3204

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)

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9 pages, 2055 KiB

Open AccessEditor’s ChoiceArticle

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 9 | Viewed by 2850

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)

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14 pages, 10168 KiB

Open AccessEditor’s ChoiceArticle

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 9 | Viewed by 2500

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)

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15 pages, 17686 KiB

Open AccessEditor’s ChoiceArticle

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 9 | Viewed by 3569

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)

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12 pages, 1060 KiB

Open AccessEditor’s ChoiceArticle

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 2792

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)

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15 pages, 1942 KiB

Open AccessEditor’s ChoiceReview

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 9 | Viewed by 4078

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)

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18 pages, 2177 KiB

Open AccessEditor’s ChoiceArticle

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 11 | Viewed by 3789

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)

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14 pages, 5790 KiB

Open AccessEditor’s ChoiceArticle

Deep-Learning-Based Hepatic Ploidy Quantification Using H&E Histopathology Images

by Zhuoyu Wen, Yu-Hsuan Lin, Shidan Wang, Naoto Fujiwara, Ruichen Rong, Kevin W. Jin, Donghan M. Yang, Bo Yao, Shengjie Yang, Tao Wang, Yang Xie, Yujin Hoshida, Hao Zhu and Guanghua Xiao

Genes 2023, 14(4), 921; https://doi.org/10.3390/genes14040921 - 16 Apr 2023

Cited by 4 | Viewed by 3299

Abstract

Polyploidy, the duplication of the entire genome within a single cell, is a significant characteristic of cells in many tissues, including the liver. The quantification of hepatic ploidy typically relies on flow cytometry and immunofluorescence (IF) imaging, which are not widely available in [...] Read more.

Polyploidy, the duplication of the entire genome within a single cell, is a significant characteristic of cells in many tissues, including the liver. The quantification of hepatic ploidy typically relies on flow cytometry and immunofluorescence (IF) imaging, which are not widely available in clinical settings due to high financial and time costs. To improve accessibility for clinical samples, we developed a computational algorithm to quantify hepatic ploidy using hematoxylin-eosin (H&E) histopathology images, which are commonly obtained during routine clinical practice. Our algorithm uses a deep learning model to first segment and classify different types of cell nuclei in H&E images. It then determines cellular ploidy based on the relative distance between identified hepatocyte nuclei and determines nuclear ploidy using a fitted Gaussian mixture model. The algorithm can establish the total number of hepatocytes and their detailed ploidy information in a region of interest (ROI) on H&E images. This is the first successful attempt to automate ploidy analysis on H&E images. Our algorithm is expected to serve as an important tool for studying the role of polyploidy in human liver disease. Full article

(This article belongs to the Special Issue Feature Papers in Technologies and Resources for Genetics 2023)

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17 pages, 2152 KiB

Open AccessEditor’s ChoiceArticle

Clinical and Genetic Characteristics of Hypophosphatasia in Chinese Adults

by Xiang Li, Na Ren, Ziyuan Wang, Ya Wang, Yunqiu Hu, Weiwei Hu, Jiemei Gu, Wei Hong, Zhenlin Zhang and Chun Wang

Genes 2023, 14(4), 922; https://doi.org/10.3390/genes14040922 - 16 Apr 2023

Cited by 4 | Viewed by 3407

Abstract

Hypophosphatasia (HPP) is an inherited disease caused by ALPL mutation, resulting in decreased alkaline phosphatase (ALP) activity and damage to bone and tooth mineralization. The clinical symptoms of adult HPP are variable, making diagnosis challenging. This study aims to clarify the clinical and [...] Read more.

Hypophosphatasia (HPP) is an inherited disease caused by ALPL mutation, resulting in decreased alkaline phosphatase (ALP) activity and damage to bone and tooth mineralization. The clinical symptoms of adult HPP are variable, making diagnosis challenging. This study aims to clarify the clinical and genetic characteristics of HPP in Chinese adults. There were 19 patients, including 1 with childhood-onset and 18 with adult-onset HPP. The median age was 62 (32–74) years and 16 female patients were involved. Common symptoms included musculoskeletal symptoms (12/19), dental problems (8/19), fractures (7/19), and fatigue (6/19). Nine patients (47.4%) were misdiagnosed with osteoporosis and six received anti-resorptive treatment. The average serum ALP level was 29.1 (14–53) U/L and 94.7% (18/19) of patients had ALP levels below 40 U/L. Genetic analysis found 14 ALPL mutations, including three novel mutations—c.511C>G (p.His171Ala), c.782C>A (p.Pro261Gln), and 1399A>G (p.Met467Val). The symptoms of two patients with compound heterozygous mutations were more severe than those with heterozygous mutations. Our study summarized the clinical characteristics of adult HPP patients in the Chinese population, expanded the spectrum of pathogenic mutations, and deepened clinicians’ understanding of this neglected disease. Full article

(This article belongs to the Special Issue Genetic Research in Metabolic Diseases)

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17 pages, 2372 KiB

Open AccessEditor’s ChoiceArticle

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 12 | Viewed by 2664

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)

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18 pages, 5283 KiB

Open AccessEditor’s ChoiceArticle

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 11 | Viewed by 2331

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)

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21 pages, 40744 KiB

Open AccessEditor’s ChoiceArticle

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 11 | Viewed by 2793

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)

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17 pages, 1243 KiB

Open AccessEditor’s ChoiceArticle

Interaction between KLOTHO-VS Heterozygosity and APOE ε4 Allele Predicts Rate of Cognitive Decline in Late-Onset Alzheimer’s Disease

by Xi Richard Chen, Yongzhao Shao, Martin J. Sadowski and on behalf of the Alzheimer’s Disease Neuroimaging Initiative

Genes 2023, 14(4), 917; https://doi.org/10.3390/genes14040917 - 15 Apr 2023

Cited by 2 | Viewed by 3255

Abstract

KLOTHO-VS heterozygosity (KL-VS^het+) promotes longevity and protects against cognitive decline in aging. To determine whether KL-VS^het+ mitigates Alzheimer’s disease (AD) progression, we used longitudinal linear-mixed models to compare the rate of change in multiple cognitive measures [...] Read more.

KLOTHO-VS heterozygosity (KL-VS^het+) promotes longevity and protects against cognitive decline in aging. To determine whether KL-VS^het+ mitigates Alzheimer’s disease (AD) progression, we used longitudinal linear-mixed models to compare the rate of change in multiple cognitive measures in AD patients stratified by APOE ε4 carrier status. We aggregated data on 665 participants (208 KL-VS^het−/ε4−, 307 KL-VS^het−/ε4+, 66 KL-VS^het+/ε4−, and 84 KL-VS^het+/ε4+) from two prospective cohorts, the National Alzheimer’s Coordinating Center and the Alzheimer’s Disease Neuroimaging Initiative. All participants were initially diagnosed with mild cognitive impairment, later developed AD dementia during the study, and had at least three subsequent visits. KL-VS^het+ conferred slower cognitive decline in ε4 non-carriers (+0.287 MMSE points/year, p = 0.001; −0.104 CDR-SB points/year, p = 0.026; −0.042 ADCOMS points/year, p < 0.001) but not in ε4 carriers who generally had faster rates of decline than non-carriers. Stratified analyses showed that the protective effect of KL-VS^het+ was particularly prominent in male participants, those who were older than the median baseline age of 76 years, or those who had an education level of at least 16 years. For the first time, our study provides evidence that KL-VS^het+ status has a protective effect on AD progression and interacts with the ε4 allele. Full article

(This article belongs to the Special Issue Molecular Biomarkers in Alzheimer’s Disease)

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15 pages, 3467 KiB

Open AccessEditor’s ChoiceArticle

The Potential Regulation of A-to-I RNA Editing on Genes in Parkinson’s Disease

by Sijia Wu, Qiuping Xue, Xinyu Qin, Xiaoming Wu, Pora Kim, Jacqueline Chyr, Xiaobo Zhou and Liyu Huang

Genes 2023, 14(4), 919; https://doi.org/10.3390/genes14040919 - 15 Apr 2023

Cited by 3 | Viewed by 2607

Abstract

Parkinson’s disease (PD) is characterized by dopaminergic neurodegeneration and an abnormal accumulation of α-synuclein aggregates. A number of genetic factors have been shown to increase the risk of PD. Exploring the underlying molecular mechanisms that mediate PD’s transcriptomic diversity can help us understand [...] Read more.

Parkinson’s disease (PD) is characterized by dopaminergic neurodegeneration and an abnormal accumulation of α-synuclein aggregates. A number of genetic factors have been shown to increase the risk of PD. Exploring the underlying molecular mechanisms that mediate PD’s transcriptomic diversity can help us understand neurodegenerative pathogenesis. In this study, we identified 9897 A-to-I RNA editing events associated with 6286 genes across 372 PD patients. Of them, 72 RNA editing events altered miRNA binding sites and this may directly affect miRNA regulations of their host genes. However, RNA editing effects on the miRNA regulation of genes are more complex. They can (1) abolish existing miRNA binding sites, which allows miRNAs to regulate other genes; (2) create new miRNA binding sites that may sequester miRNAs from regulating other genes; or (3) occur in the miRNA seed regions and change their targets. The first two processes are also referred to as miRNA competitive binding. In our study, we found 8 RNA editing events that may alter the expression of 1146 other genes via miRNA competition. We also found one RNA editing event that modified a miRNA seed region, which was predicted to disturb the regulation of four genes. Considering the PD-related functions of the affected genes, 25 A-to-I RNA editing biomarkers for PD are proposed, including the 3 editing events in the EIF2AK2, APOL6, and miR-4477b seed regions. These biomarkers may alter the miRNA regulation of 133 PD-related genes. All these analyses reveal the potential mechanisms and regulations of RNA editing in PD pathogenesis. Full article

(This article belongs to the Special Issue Transcriptomics and Bioinformatics in Precision Medicine)

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15 pages, 3359 KiB

Open AccessEditor’s ChoiceArticle

Identification of the Function of the Pathogenesis-Related Protein GmPR1L in the Resistance of Soybean to Cercospora sojina Hara

by Yeyao Du, Nooral Amin, Naveed Ahmad, Hanzhu Zhang, Ye Zhang, Yang Song, Sujie Fan and Piwu Wang

Genes 2023, 14(4), 920; https://doi.org/10.3390/genes14040920 - 15 Apr 2023

Cited by 9 | Viewed by 2263

Abstract

Pathogenesis-related proteins, often used as molecular markers of disease resistance in plants, can enable plants to obtain systemic resistance. In this study, a gene encoding a pathogenesis-related protein was identified via RNA-seq sequencing analysis performed at different stages of soybean seedling development. Because [...] Read more.

Pathogenesis-related proteins, often used as molecular markers of disease resistance in plants, can enable plants to obtain systemic resistance. In this study, a gene encoding a pathogenesis-related protein was identified via RNA-seq sequencing analysis performed at different stages of soybean seedling development. Because the gene sequence showed the highest similarity with PR1L sequence in soybean, the gene was named GmPR1-9-like (GmPR1L). GmPR1L was either overexpressed or silenced in soybean seedlings through Agrobacterium-mediated transformation to examine the resistance of soybean to infection caused by Cercospora sojina Hara. The results revealed that GmPR1L-overexpressing soybean plants had a smaller lesion area and improved resistance to C. sojina infection, whereas GmPR1L-silenced plants had low resistance to C. sojina infection. Fluorescent real-time PCR indicated that overexpression of GmPR1L induced the expression of genes such as WRKY, PR9, and PR14, which are more likely to be co-expressed during C. sojina infection. Furthermore, the activities of SOD, POD, CAT, and PAL were significantly increased in GmPR1L-overexpressing soybean plants after seven days of infection. The resistance of the GmPR1L-overexpressing lines OEA1 and OEA2 to C. sojina infection was significantly increased from a neutral level in wild-type plants to a moderate level. These findings predominantly reveal the positive role of GmPR1L in inducing resistance to C. sojina infection in soybean, which may facilitate the production of improved disease-resistant soybean cultivars in the future. Full article

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

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18 pages, 1152 KiB

Open AccessEditor’s ChoiceReview

Understanding HAT1: A Comprehensive Review of Noncanonical Roles and Connection with Disease

by Miguel A. Ortega, Diego De Leon-Oliva, Cielo Garcia-Montero, Oscar Fraile-Martinez, Diego Liviu Boaru, María del Val Toledo Lobo, Ignacio García-Tuñón, Mar Royuela, Natalio García-Honduvilla, Julia Bujan, Luis G. Guijarro, Melchor Alvarez-Mon and Miguel Ángel Alvarez-Mon

Genes 2023, 14(4), 915; https://doi.org/10.3390/genes14040915 - 14 Apr 2023

Cited by 11 | Viewed by 4455

Abstract

Histone acetylation plays a vital role in organizing chromatin, regulating gene expression and controlling the cell cycle. The first histone acetyltransferase to be identified was histone acetyltransferase 1 (HAT1), but it remains one of the least understood acetyltransferases. HAT1 catalyzes the acetylation of [...] Read more.

Histone acetylation plays a vital role in organizing chromatin, regulating gene expression and controlling the cell cycle. The first histone acetyltransferase to be identified was histone acetyltransferase 1 (HAT1), but it remains one of the least understood acetyltransferases. HAT1 catalyzes the acetylation of newly synthesized H4 and, to a lesser extent, H2A in the cytoplasm. However, 20 min after assembly, histones lose acetylation marks. Moreover, new noncanonical functions have been described for HAT1, revealing its complexity and complicating the understanding of its functions. Recently discovered roles include facilitating the translocation of the H3H4 dimer into the nucleus, increasing the stability of the DNA replication fork, replication-coupled chromatin assembly, coordination of histone production, DNA damage repair, telomeric silencing, epigenetic regulation of nuclear lamina-associated heterochromatin, regulation of the NF-κB response, succinyl transferase activity and mitochondrial protein acetylation. In addition, the functions and expression levels of HAT1 have been linked to many diseases, such as many types of cancer, viral infections (hepatitis B virus, human immunodeficiency virus and viperin synthesis) and inflammatory diseases (chronic obstructive pulmonary disease, atherosclerosis and ischemic stroke). The collective data reveal that HAT1 is a promising therapeutic target, and novel therapeutic approaches, such as RNA interference and the use of aptamers, bisubstrate inhibitors and small-molecule inhibitors, are being evaluated at the preclinical level. Full article

(This article belongs to the Special Issue Epigenetic Regulation of Cell Fate)

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14 pages, 2367 KiB

Open AccessEditor’s ChoiceArticle

Identification of Differentially Expressed Genes and Molecular Pathways Involved in Osteoclastogenesis Using RNA-seq

by Sarah Rashid, Scott G. Wilson, Kun Zhu, John P. Walsh, Jiake Xu and Benjamin H. Mullin

Genes 2023, 14(4), 916; https://doi.org/10.3390/genes14040916 - 14 Apr 2023

Cited by 14 | Viewed by 3800

Abstract

Osteoporosis is a disease that is characterised by reduced bone mineral density (BMD) and can be exacerbated by the excessive bone resorption of osteoclasts (OCs). Bioinformatic methods, including functional enrichment and network analysis, can provide information about the underlying molecular mechanisms that participate [...] Read more.

Osteoporosis is a disease that is characterised by reduced bone mineral density (BMD) and can be exacerbated by the excessive bone resorption of osteoclasts (OCs). Bioinformatic methods, including functional enrichment and network analysis, can provide information about the underlying molecular mechanisms that participate in the progression of osteoporosis. In this study, we harvested human OC-like cells differentiated in culture and their precursor peripheral blood mononuclear cells (PBMCs) and characterised the transcriptome of the two cell types using RNA-sequencing in order to identify differentially expressed genes. Differential gene expression analysis was performed in RStudio using the edgeR package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to identify enriched GO terms and signalling pathways, with inter-connected regions characterised using protein–protein interaction analysis. In this study, we identified 3201 differentially expressed genes using a 5% false discovery rate; 1834 genes were upregulated, whereas 1367 genes were downregulated. We confirmed a significant upregulation of several well-established OC genes including CTSK, DCSTAMP, ACP5, MMP9, ITGB3, and ATP6V0D2. The GO analysis suggested that upregulated genes are involved in cell division, cell migration, and cell adhesion, while the KEGG pathway analysis highlighted oxidative phosphorylation, glycolysis and gluconeogenesis, lysosome, and focal adhesion pathways. This study provides new information about changes in gene expression and highlights key biological pathways involved in osteoclastogenesis. Full article

(This article belongs to the Section Bioinformatics)

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19 pages, 4742 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

The Complete Mitochondrial Genome of Mytilisepta virgata (Mollusca: Bivalvia), Novel Gene Rearrangements, and the Phylogenetic Relationships of Mytilidae

by Minhui Xu, Zhongqi Gu, Ji Huang, Baoying Guo, Lihua Jiang, Kaida Xu, Yingying Ye and Jiji Li

Genes 2023, 14(4), 910; https://doi.org/10.3390/genes14040910 - 13 Apr 2023

Cited by 11 | Viewed by 2948

Abstract

The circular mitochondrial genome of Mytilisepta virgata spans 14,713 bp, which contains 13 protein-coding genes (PCGs), 2 ribosomal RNA genes, and 22 transfer RNA genes. Analysis of the 13 PCGs reveals that the mitochondrial gene arrangement of Mytilisepta is relatively conserved at the [...] Read more.

The circular mitochondrial genome of Mytilisepta virgata spans 14,713 bp, which contains 13 protein-coding genes (PCGs), 2 ribosomal RNA genes, and 22 transfer RNA genes. Analysis of the 13 PCGs reveals that the mitochondrial gene arrangement of Mytilisepta is relatively conserved at the genus level. The location of the atp8 gene in Mytilisepta keenae differs from that of other species. However, compared with the putative molluscan ancestral gene order, M. virgata exhibits a high level of rearrangement. We constructed phylogenetic trees based on concatenated 12 PCGs from Mytilidae. As a result, we found that M. virgata is in the same clade as other Mytilisepta spp. The result of estimated divergence times revealed that M. virgata and M. keenae diverged around the early Paleogene period, although the oldest Mytilisepta fossil was from the late or upper Eocene period. Our results provide robust statistical evidence for a sister-group relationship within Mytilida. The findings not only confirm previous results, but also provide valuable insights into the evolutionary history of Mytilidae. Full article

(This article belongs to the Special Issue Mitochondrial DNA Replication and Transcription)

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15 pages, 4217 KiB

Open AccessEditor’s ChoiceArticle

The Effect of Fetal Bovine Acellular Dermal Matrix Seeded with Wharton’s Jelly Mesenchymal Stem Cells for Healing Full-Thickness Skin Wounds

by Reyhaneh Nassiri Mansour, Elham Hasanzadeh, Mozhgan Abasi, Mazaher Gholipourmalekabadi, Amir Mellati and Seyed Ehsan Enderami

Genes 2023, 14(4), 909; https://doi.org/10.3390/genes14040909 - 13 Apr 2023

Cited by 7 | Viewed by 2891

Abstract

The treatment of full-thickness skin wounds is a problem in the clinical setting, as they do not heal spontaneously. Extensive pain at the donor site and a lack of skin grafts limit autogenic and allogeneic skin graft availability. We evaluated fetal bovine acellular [...] Read more.

The treatment of full-thickness skin wounds is a problem in the clinical setting, as they do not heal spontaneously. Extensive pain at the donor site and a lack of skin grafts limit autogenic and allogeneic skin graft availability. We evaluated fetal bovine acellular dermal matrix (FADM) in combination with human Wharton’s jelly mesenchymal stem cells (hWJ-MSCs) to heal full-thickness skin wounds. FADM was prepared from a 6-month-old trauma-aborted fetus. WJ-MSCs were derived from a human umbilical cord and seeded on the FADM. Rat models of full-thickness wounds were created and divided into three groups: control (no treatment), FADM, and FADM-WJMSCs groups. Wound treatment was evaluated microscopically and histologically on days 7, 14, and 21 post-surgery. The prepared FADM was porous and decellularized with a normal range of residual DNA. WJ-MSCs were seeded and proliferated on FADM effectively. The highest wound closure rate was observed in the FADM-WJMSC group on days 7 and 14 post-surgery. Furthermore, this group had fewer inflammatory cells than other groups. Finally, in this study, we observed that, without using the differential cell culture media of fibroblasts, the xenogeneic hWJSCs in combination with FADM could promote an increased rate of full-thickness skin wound closure with less inflammation. Full article

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

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19 pages, 1348 KiB

Open AccessEditor’s ChoiceReview

The Potential Biological Roles of Circular RNAs in the Immune Systems of Insects to Pathogen Invasion

by Muhammad Nadeem Abbas, Saima Kausar, Isma Gul, Jisheng Li, Huijuan Yu, Mengyao Dong and Hongjuan Cui

Genes 2023, 14(4), 895; https://doi.org/10.3390/genes14040895 - 12 Apr 2023

Cited by 8 | Viewed by 3171

Abstract

Circular RNAs (circRNAs) are a newly discovered class of endogenously expressed non-coding RNAs (ncRNAs). They are highly stable, covalently closed molecules that frequently exhibit tissue-specific expression in eukaryotes. A small number of circRNAs are abundant and have been remarkably conserved throughout evolution. Numerous [...] Read more.

Circular RNAs (circRNAs) are a newly discovered class of endogenously expressed non-coding RNAs (ncRNAs). They are highly stable, covalently closed molecules that frequently exhibit tissue-specific expression in eukaryotes. A small number of circRNAs are abundant and have been remarkably conserved throughout evolution. Numerous circRNAs are known to play important biological roles by acting as microRNAs (miRNAs) or protein inhibitors (‘sponges’), by regulating the function of proteins, or by being translated themselves. CircRNAs have distinct cellular functions due to structural and production differences from mRNAs. Recent advances highlight the importance of characterizing circRNAs and their targets in a variety of insect species in order to fully understand how they contribute to the immune responses of these insects. Here, we focus on the recent advances in our understanding of the biogenesis of circRNAs, regulation of their abundance, and biological roles, such as serving as templates for translation and in the regulation of signaling pathways. We also discuss the emerging roles of circRNAs in regulating immune responses to various microbial pathogens. Furthermore, we describe the functions of circRNAs encoded by microbial pathogens that play in their hosts. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Insect Immune Responses)

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19 pages, 1231 KiB

Open AccessEditor’s ChoiceReview

Epigenetic Alterations of Brain Non-Neuronal Cells in Major Mental Diseases

by Hamid Mostafavi Abdolmaleky, Marian Martin, Jin-Rong Zhou and Sam Thiagalingam

Genes 2023, 14(4), 896; https://doi.org/10.3390/genes14040896 - 12 Apr 2023

Cited by 16 | Viewed by 5074

Abstract

The tissue-specific expression and epigenetic dysregulation of many genes in cells derived from the postmortem brains of patients have been reported to provide a fundamental biological framework for major mental diseases such as autism, schizophrenia, bipolar disorder, and major depression. However, until recently, [...] Read more.

The tissue-specific expression and epigenetic dysregulation of many genes in cells derived from the postmortem brains of patients have been reported to provide a fundamental biological framework for major mental diseases such as autism, schizophrenia, bipolar disorder, and major depression. However, until recently, the impact of non-neuronal brain cells, which arises due to cell-type-specific alterations, has not been adequately scrutinized; this is because of the absence of techniques that directly evaluate their functionality. With the emergence of single-cell technologies, such as RNA sequencing (RNA-seq) and other novel techniques, various studies have now started to uncover the cell-type-specific expression and DNA methylation regulation of many genes (e.g., TREM2, MECP2, SLC1A2, TGFB2, NTRK2, S100B, KCNJ10, and HMGB1, and several complement genes such as C1q, C3, C3R, and C4) in the non-neuronal brain cells involved in the pathogenesis of mental diseases. Additionally, several lines of experimental evidence indicate that inflammation and inflammation-induced oxidative stress, as well as many insidious/latent infectious elements including the gut microbiome, alter the expression status and the epigenetic landscapes of brain non-neuronal cells. Here, we present supporting evidence highlighting the importance of the contribution of the brain’s non-neuronal cells (in particular, microglia and different types of astrocytes) in the pathogenesis of mental diseases. Furthermore, we also address the potential impacts of the gut microbiome in the dysfunction of enteric and brain glia, as well as astrocytes, which, in turn, may affect neuronal functions in mental disorders. Finally, we present evidence that supports that microbiota transplantations from the affected individuals or mice provoke the corresponding disease-like behavior in the recipient mice, while specific bacterial species may have beneficial effects. Full article

(This article belongs to the Section Epigenomics)

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11 pages, 2649 KiB

Open AccessEditor’s ChoiceArticle

Biotransformation of High Concentrations of Ginsenoside Substrate into Compound K by β-glycosidase from Sulfolobus solfataricus

by Pan Wang, Congcong Tang, Yannan Liu, Jing Yang and Daidi Fan

Genes 2023, 14(4), 897; https://doi.org/10.3390/genes14040897 - 12 Apr 2023

Cited by 10 | Viewed by 2664

Abstract

The rare ginsenoside Compound K (CK) is an attractive ingredient in traditional medicines, cosmetics, and the food industry because of its various biological activities. However, it does not exist in nature. The commonly used method for the production of CK is enzymatic conversion. [...] Read more.

The rare ginsenoside Compound K (CK) is an attractive ingredient in traditional medicines, cosmetics, and the food industry because of its various biological activities. However, it does not exist in nature. The commonly used method for the production of CK is enzymatic conversion. In order to further improve the catalytic efficiency and increase the CK content, a thermostable β-glycosidase from Sulfolobus solfataricus was successfully expressed in Pichia pastoris and secreted into fermentation broth. The recombinant SS-bgly in the supernatant showed enzyme activity of 93.96 U/mg at 120 h when using pNPG as substrate. The biotransformation conditions were optimized at pH 6.0 and 80 °C, and its activity was significantly enhanced in the presence of 3 mM Li⁺. When the substrate concentration was 10 mg/mL, the recombinant SS-bgly completely converted the ginsenoside substrate to CK with a productivity of 507.06 μM/h. Moreover, the recombinant SS-bgly exhibited extraordinary tolerance against high substrate concentrations. When the ginsenoside substrate concentration was increased to 30 mg/mL, the conversion could still reach 82.5% with a productivity of 314.07 μM/h. Thus, the high temperature tolerance, resistance to a variety of metals, and strong substrate tolerance make the recombinant SS-bgly expressed in P. pastoris a potential candidate for the industrial production of the rare ginsenoside CK. Full article

(This article belongs to the Special Issue Microbial Genome Engineering and Synthetic Biology)

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3 pages, 186 KiB

Open AccessEditor’s ChoiceEditorial

Special Issue “DNA Replication/Repair, and the DNA Damage Response in Human Disease”

by Dong Zhang, Kristin A. Eckert and Marietta Y. W. T. Lee

Genes 2023, 14(4), 893; https://doi.org/10.3390/genes14040893 - 11 Apr 2023

Cited by 1 | Viewed by 2349

Abstract

Mutations of numerous genes involved in DNA replication, DNA repair, and DNA damage response (DDR) pathways lead to a variety of human diseases, including aging and cancer [...] Full article

(This article belongs to the Special Issue DNA Replication/Repair, and the DNA Damage Response in Human Disease)

16 pages, 326 KiB

Open AccessEditor’s ChoiceArticle

Molecular and Sociodemographic Colorectal Cancer Disparities in Latinos Living in Puerto Rico

by Julyann Perez-Mayoral, Maria Gonzalez-Pons, Hilmaris Centeno-Girona, Ingrid M. Montes-Rodríguez, Marievelisse Soto-Salgado, Belisa Suárez, Natalia Rodríguez, Giancarlo Colón, Javier Sevilla, Daphne Jorge, Xavier Llor, Rosa M. Xicola, Doris H. Toro, Luis Tous-López, Marla Torres-Torres, José S. Reyes, Nicolas López-Acevedo, Ajay Goel, Segundo Rodríguez-Quilichini and Marcia Cruz-Correa

Genes 2023, 14(4), 894; https://doi.org/10.3390/genes14040894 - 11 Apr 2023

Cited by 5 | Viewed by 2983

Abstract

Background: The incidence of sporadic colorectal cancer (CRC) among individuals <50 years (early-onset CRC) has been increasing in the United States (U.S.) and Puerto Rico. CRC is currently the leading cause of cancer death among Hispanic men and women living in Puerto Rico [...] Read more.

Background: The incidence of sporadic colorectal cancer (CRC) among individuals <50 years (early-onset CRC) has been increasing in the United States (U.S.) and Puerto Rico. CRC is currently the leading cause of cancer death among Hispanic men and women living in Puerto Rico (PRH). The objective of this study was to characterize the molecular markers and clinicopathologic features of colorectal tumors from PRH to better understand the molecular pathways leading to CRC in this Hispanic subpopulation. Methods: Microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS and BRAF mutation status were analyzed. Sociodemographic and clinicopathological characteristics were evaluated using Chi-squared and Fisher’s exact tests. Results: Of the 718 tumors analyzed, 34.2% (n = 245) were early-onset CRC, and 51.7% were males. Among the tumors with molecular data available (n = 192), 3.2% had MSI, 9.7% had BRAF, and 31.9% had KRAS mutations. The most common KRAS mutations observed were G12D (26.6%) and G13D (20.0%); G12C was present in 4.4% of tumors. A higher percentage of Amerindian admixture was significantly associated with early-onset CRC. Conclusions: The differences observed in the prevalence of the molecular markers among PRH tumors compared to other racial/ethnic groups suggest a distinct molecular carcinogenic pathway among Hispanics. Additional studies are warranted. Full article

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

12 pages, 5298 KiB

Open AccessEditor’s ChoiceArticle

A Multi-Tissue Gene Expression Atlas of Water Buffalo (Bubalus bubalis) Reveals Transcriptome Conservation between Buffalo and Cattle

by Jingfang Si, Dongmei Dai, Kun Li, Lingzhao Fang and Yi Zhang

Genes 2023, 14(4), 890; https://doi.org/10.3390/genes14040890 - 10 Apr 2023

Cited by 8 | Viewed by 2850

Abstract

We generated 73 transcriptomic data of water buffalo, which were integrated with publicly available data in this species, yielding a large dataset of 355 samples representing 20 major tissue categories. We established a multi-tissue gene expression atlas of water buffalo. Furthermore, by comparing [...] Read more.

We generated 73 transcriptomic data of water buffalo, which were integrated with publicly available data in this species, yielding a large dataset of 355 samples representing 20 major tissue categories. We established a multi-tissue gene expression atlas of water buffalo. Furthermore, by comparing them with 4866 cattle transcriptomic data from the cattle genotype–tissue expression atlas (CattleGTEx), we found that the transcriptomes of the two species exhibited conservation in their overall gene expression patterns, tissue-specific gene expression and house-keeping gene expression. We further identified conserved and divergent expression genes between the two species, with the largest number of differentially expressed genes found in the skin, which may be related to structural and functional differences in the skin of the two species. This work provides a source of functional annotation of the buffalo genome and lays the foundations for future genetic and evolutionary studies in water buffalo. Full article

(This article belongs to the Special Issue Co-evolution of Mobilome and Genome)

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12 pages, 1726 KiB

Open AccessEditor’s ChoiceCase Report

Rare 15q21.1q22.31 Duplication Due to a Familial Chromosomal Insertion and Diagnostic Investigation in a Carrier of Balanced Chromosomal Rearrangement and Intellectual Disability

by Carolina Gama Nascimento, Joana Rosa Marques Prota, Ilária Cristina Sgardioli, Samira Spineli-Silva, Nilma Lúcia Viguetti Campos, Vera Lúcia Gil-da-Silva-Lopes and Társis Paiva Vieira

Genes 2023, 14(4), 885; https://doi.org/10.3390/genes14040885 - 9 Apr 2023

Viewed by 3077

Abstract

Insertions are rare balanced chromosomal rearrangements with an increased risk of imbalances for the offspring. Moreover, balanced rearrangements in individuals with abnormal phenotypes may be associated to the phenotype by different mechanisms. This study describes a three-generation family with a rare chromosomal insertion. [...] Read more.

Insertions are rare balanced chromosomal rearrangements with an increased risk of imbalances for the offspring. Moreover, balanced rearrangements in individuals with abnormal phenotypes may be associated to the phenotype by different mechanisms. This study describes a three-generation family with a rare chromosomal insertion. G-banded karyotype, chromosomal microarray analysis (CMA), whole-exome sequencing (WES), and low-pass whole-genome sequencing (WGS) were performed. Six individuals had the balanced insertion [ins(9;15)(q33;q21.1q22.31)] and three individuals had the derivative chromosome 9 [der(9)ins(9;15)(q33;q21.1q22.31)]. The three subjects with unbalanced rearrangement showed similar clinical features, including intellectual disability, short stature, and facial dysmorphisms. CMA of these individuals revealed a duplication of 19.3 Mb at 15q21.1q22.31. A subject with balanced rearrangement presented with microcephaly, severe intellectual disability, absent speech, motor stereotypy, and ataxia. CMA of this patient did not reveal pathogenic copy number variations and low-pass WGS showed a disruption of the RABGAP1 gene at the 9q33 breakpoint. This gene has been recently associated with a recessive disorder, which is not compatible with the mode of inheritance in this patient. WES revealed an 88 bp deletion in the MECP2 gene, consistent with Rett syndrome. This study describes the clinical features associated with the rare 15q21.1–q22.31 duplication and reinforces that searching for other genetic causes is warranted for individuals with inherited balanced chromosomal rearrangements and abnormal phenotypes. Full article

(This article belongs to the Special Issue Advances in Clinical Cytogenetics)

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8 pages, 479 KiB

Open AccessEditor’s ChoiceCase Report

SATB2-Associated Syndrome Due to a c.715C>T:p(Arg239*) Variant in Adulthood: Natural History and Literature Review

by Matheus de Mello Copelli, Eleonore Pairet, Milena Atique-Tacla, Társis Paiva Vieira, Simone Appenzeller, Raphaël Helaers, Miikka Vikkula and Vera Lúcia Gil-da-Silva-Lopes

Genes 2023, 14(4), 882; https://doi.org/10.3390/genes14040882 - 8 Apr 2023

Cited by 2 | Viewed by 4254

Abstract

SATB2-associated syndrome (SAS) is a rare condition, and it is characterized by severe developmental delay/intellectual disability, especially severe speech delay/or absence, craniofacial abnormalities, and behavioral problems. Most of the published reports are limited to children, with little information about the natural history [...] Read more.

SATB2-associated syndrome (SAS) is a rare condition, and it is characterized by severe developmental delay/intellectual disability, especially severe speech delay/or absence, craniofacial abnormalities, and behavioral problems. Most of the published reports are limited to children, with little information about the natural history of the disease and the possible novel signs and symptoms or behavioral changes in adulthood. We describe the management and follow-up of a 25-year-old male with SAS due to a de novo heterozygous nonsense variant SATB2:c.715C>T:p.(Arg239*) identified by whole-exome sequencing and review the literature. The case herein described contributes to a better characterization of the natural history of this genetic condition and in addition to the genotype–phenotype correlation of the SATB2:c.715C>T:p.(Arg239*) variant in SAS, highlights some particularities of its management. Full article

(This article belongs to the Special Issue Genetic Disorders with Developmental Delay and Intellectual Disability)

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16 pages, 5144 KiB

Open AccessEditor’s ChoiceArticle

Complete Mitochondrial Genome of Piophila casei (Diptera: Piophilidae): Genome Description and Phylogenetic Implications

by Shenghui Bi, Yanfei Song, Linggao Liu, Jing Wan, Ying Zhou, Qiujin Zhu and Jianfeng Liu

Genes 2023, 14(4), 883; https://doi.org/10.3390/genes14040883 - 8 Apr 2023

Cited by 13 | Viewed by 2616

Abstract

Piophila casei is a flesh-feeding Diptera insect that adversely affects foodstuffs, such as dry-cured ham and cheese, and decaying human and animal carcasses. However, the unknown mitochondrial genome of P. casei can provide information on its genetic structure and phylogenetic position, which is [...] Read more.

Piophila casei is a flesh-feeding Diptera insect that adversely affects foodstuffs, such as dry-cured ham and cheese, and decaying human and animal carcasses. However, the unknown mitochondrial genome of P. casei can provide information on its genetic structure and phylogenetic position, which is of great significance to the research on its prevention and control. Therefore, we sequenced, annotated, and analyzed the previously unknown complete mitochondrial genome of P. casei. The complete mt genome of P. casei is a typical circular DNA, 15,785 bp in length, with a high A + T content of 76.6%. It contains 13 protein-coding genes (PCG), 2 ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and 1 control region. Phylogenetic analysis of 25 Diptera species was conducted using Bayesian and maximum likelihood methods, and their divergence times were inferred. The comparison of the mt genomes from two morphologically similar insects P. casei and Piophila megastigmata indicates a divergence time of 7.28 MYA between these species. The study provides a reference for understanding the forensic medicine, taxonomy, and genetics of P. casei. Full article

(This article belongs to the Special Issue Genetics, Phylogeny, and Evolution of Insects)

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12 pages, 1337 KiB

Open AccessEditor’s ChoiceArticle

Leri–Weill Dyschondrosteosis Caused by a Leaky Homozygous SHOX Splice-Site Variant

by Julia Vodopiutz, Lisa-Maria Steurer, Florentina Haufler, Franco Laccone, Dorota Garczarczyk-Asim, Matthias Hilkenmeier, Philipp Steinbauer and Andreas R. Janecke

Genes 2023, 14(4), 877; https://doi.org/10.3390/genes14040877 - 7 Apr 2023

Cited by 2 | Viewed by 2389

Abstract

SHOX deficiency is a common genetic cause of short stature of variable degree. SHOX haploinsufficiency causes Leri–Weill dyschondrosteosis (LWD) as well as nonspecific short stature. SHOX haploinsufficiency is known to result from heterozygous loss-of-function variants with pseudo-autosomal dominant inheritance, while biallelic SHOX loss-of-function [...] Read more.

SHOX deficiency is a common genetic cause of short stature of variable degree. SHOX haploinsufficiency causes Leri–Weill dyschondrosteosis (LWD) as well as nonspecific short stature. SHOX haploinsufficiency is known to result from heterozygous loss-of-function variants with pseudo-autosomal dominant inheritance, while biallelic SHOX loss-of-function variants cause the more severe skeletal dysplasia, Langer mesomelic dyschondrosteosis (LMD). Here we report for the first time the pseudo-autosomal recessive inheritance of LWD in two siblings caused by a novel homozygous non-canonical, leaky splice-site variant in intron 3 of SHOX: c.544+5G>C. Transcript analyses in patient-derived fibroblasts showed homozygous patients to produce approximately equal amounts of normally spliced mRNA and mRNA with the abnormal retention of intron 3 and containing a premature stop codon (p.Val183Glyfs*31). The aberrant transcript was shown to undergo nonsense-mediated mRNA decay, and thus resulting in SHOX haploinsufficiency in the homozygous patient. Six healthy relatives who are of normal height are heterozygous for this variant and fibroblasts from a heterozygote for the c.544+5G>C variant produced wild-type transcript amounts comparable to healthy control. The unique situation reported here highlights the fact that the dosage of SHOX determines the clinical phenotype rather than the Mendelian inheritance pattern of SHOX variants. This study extends the molecular and inheritance spectrum of SHOX deficiency disorder and highlights the importance of functional testing of SHOX variants of unknown significance in order to allow appropriate counseling and precision medicine for each family individual. Full article

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

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16 pages, 1399 KiB

Open AccessEditor’s ChoiceArticle

Evidence of Association between CTLA-4 Gene Polymorphisms and Colorectal Cancers in Saudi Patients

by Nouf Al-Harbi, Maha-Hamadien Abdulla, Mansoor-Ali Vaali-Mohammed, Thamer Bin Traiki, Mohammed Alswayyed, Omar Al-Obeed, Islem Abid, Suliman Al-Omar and Lamjed Mansour

Genes 2023, 14(4), 874; https://doi.org/10.3390/genes14040874 - 6 Apr 2023

Cited by 9 | Viewed by 2921

Abstract

Cytotoxic T lymphocyte antigen-4 (CTLA-4) has been identified as an immunosuppressive molecule involved in the negative regulation of T cells. It is highly expressed in several types of autoimmune diseases and cancers including colorectal cancer (CRC). (1) Objective: To explore the association between [...] Read more.

Cytotoxic T lymphocyte antigen-4 (CTLA-4) has been identified as an immunosuppressive molecule involved in the negative regulation of T cells. It is highly expressed in several types of autoimmune diseases and cancers including colorectal cancer (CRC). (1) Objective: To explore the association between CTLA-4 single nucleotide polymorphisms (SNP) and risk to (CRC) in the Saudi population. (2) Methods: In this case-control study, 100 patients with CRC and 100 matched healthy controls were genotyped for three CTLA-4 SNPs: rs11571317 (−658C > T), rs231775 (+49A > G) and rs3087243 (CT60 G > A), using TaqMan assay method. Associations were evaluated using odds ratios (ORs) and 95% confidence intervals (95% CIs) for five inheritance models (co-dominant, dominant, recessive, over-dominant and log-additive). Furthermore, CTLA-4 expression levels were evaluated using quantitative real-time PCR (Q-RT-PCR) in colon cancer and adjacent colon tissues. (3) Results: Our result showed a significant association of the G allele (OR = 2.337, p < 0.0001) and GG genotype of the missense SNP +49A > G with increased risk of developing CRC in codominant (OR = 8.93, p < 0.0001) and recessive (OR = 16.32, p < 0.0001) models. Inversely, the AG genotype was significantly associated with decreased risk to CRC in the codominant model (OR = 0.23, p < 0.0001). In addition, the CT60 G > A polymorphism exhibited a strong association with a high risk of developing CRC for the AA genotype in codominant (OR = 3.323, p = 0.0053) and in allele models (OR = 1.816, p = 0.005). No significant association was found between −658C > T and CRC. The haplotype analysis showed that the G-A-G haplotype of the rs11571317, rs231775 and rs3087243 was associated with high risk for CRC (OR = 57.66; p < 0.001). The CTLA-4 mRNA gene expression was found significantly higher in tumors compared to normal adjacent colon samples (p < 0.001). (4) Conclusions: Our findings support an association between the CTLA-4 rs231775 (+49A > G) and rs3087243 (CT60 G > A) polymorphisms and CRC risk in the Saudi population. Further validation in a larger cohort size is needed prior to utilizing these SNPs as a potential screening marker in the Saudi population. Full article

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

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13 pages, 680 KiB

Open AccessEditor’s ChoiceArticle

Occurrence of High-Risk Clonal Lineages ST58, ST69, ST224, and ST410 among Extended-Spectrum β-Lactamase-Producing Escherichia coli Isolated from Healthy Free-Range Chickens (Gallus gallus domesticus) in a Rural Region in Tunisia

by Saloua Benlabidi, Anis Raddaoui, Sana Lengliz, Sarah Cheriet, Paul Hynds, Wafa Achour, Taoufik Ghrairi and Mohamed Salah Abbassi

Genes 2023, 14(4), 875; https://doi.org/10.3390/genes14040875 - 6 Apr 2023

Cited by 11 | Viewed by 2878

Abstract

Antimicrobial-resistant Escherichia coli isolates have emerged in various ecologic compartments and evolved to spread globally. We sought to (1.) investigate the occurrence of ESBL-producing E. coli (ESBL-Ec) in feces from free-range chickens in a rural region and (2.) characterize the genetic background of [...] Read more.

Antimicrobial-resistant Escherichia coli isolates have emerged in various ecologic compartments and evolved to spread globally. We sought to (1.) investigate the occurrence of ESBL-producing E. coli (ESBL-Ec) in feces from free-range chickens in a rural region and (2.) characterize the genetic background of antimicrobial resistance and the genetic relatedness of collected isolates. Ninety-five feces swabs from free-range chickens associated with two households (House 1/House 2) in a rural region in northern Tunisia were collected. Samples were screened to recover ESBL-Ec, and collected isolates were characterized for phenotype/genotype of antimicrobial resistance, integrons, and molecular typing (pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST)). Overall, 47 ESBL-Ec were identified, with the following genes detected: 35 bla_CTX-M-1, 5 bla_CTX-M-55, 5 bla_CTX-M-15, 1 bla_SHV-2, and 1 bla_SHV-12. Resistance to fluoroquinolones, tetracycline, sulfonamides, and colistin was encoded by aac(6′)-Ib-cr (n = 21), qnrB (n = 1), and qnrS (n = 2); tetA (n = 17)/tetB (n = 26); sul1 (n = 29)/sul2 (n = 18); and mcr-2 (n = 2) genes, respectively. PFGE and MLST identified genetic homogeneity of isolates in House 1; however, isolates from House 2 were heterogeneous. Notably, among nine identified sequence types, ST58, ST69, ST224, and ST410 belong to pandemic high-risk clonal lineages associated with extrapathogenic E. coli. Minor clones belonging to ST410 and ST471 were shared by chickens from both households. The virulence genes fyuA, fimH, papGIII, and iutA were detected in 35, 47, 17, and 23 isolates, respectively. Findings indicate a high occurrence of ESBL-Ec in free-range chickens and highlight the occurrence of pandemic zoonotic clones. Full article

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

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18 pages, 4359 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Identification and Expression Analysis of the SHI-Related Sequence Family in Cassava

by Huling Huang, Jiming Song, Yating Feng, Linling Zheng, Yinhua Chen and Kai Luo

Genes 2023, 14(4), 870; https://doi.org/10.3390/genes14040870 - 5 Apr 2023

Cited by 9 | Viewed by 3516

Abstract

The SHORT INTERNODES (SHI)-related sequences (SRS) are plant-specific transcription factors that have been quantitatively characterized during plant growth, regeneration, and stress responses. However, the genome-wide discovery of SRS family genes and their involvement in abiotic stress-related activities in cassava have [...] Read more.

The SHORT INTERNODES (SHI)-related sequences (SRS) are plant-specific transcription factors that have been quantitatively characterized during plant growth, regeneration, and stress responses. However, the genome-wide discovery of SRS family genes and their involvement in abiotic stress-related activities in cassava have not been documented. A genome-wide search strategy was used to identify eight family members of the SRS gene family in cassava (Manihot esculenta Crantz). Based on their evolutionary linkages, all MeSRS genes featured homologous RING-like zinc finger and IXGH domains. Genetic architecture and conserved motif analysis validated the categorization of MeSRS genes into four groups. Eight pairs of segmental duplications were detected, resulting in an increase in the number of MeSRS genes. Orthologous studies of SRS genes among cassava and three different plant species (Arabidopsis thaliana, Oryza sativa, and Populus trichocarpa) provided important insights into the probable history of the MeSRS gene family. The functionality of MeSRS genes was elucidated through the prediction of protein–protein interaction networks and cis-acting domains. RNA-seq data demonstrated tissue/organ expression selectivity and preference of the MeSRS genes. Furthermore, qRT-PCR investigation of MeSRS gene expression after exposure to salicylic acid (SA) and methyl jasmonate (MeJA) hormone treatments, as well as salt (NaCl) and osmotic (polyethylene glycol, PEG) stresses, showed their stress-responsive patterns. This genome-wide characterization and identification of the evolutionary relationships and expression profiles of the cassava MeSRS family genes will be helpful for further research into this gene family and its function in stress response. It may also assist future agricultural efforts to increase the stress tolerance of cassava. Full article

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

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18 pages, 3800 KiB

Open AccessEditor’s ChoiceArticle

An MPS-Based 50plex Microhaplotype Assay for Forensic DNA Analysis

by Ranran Zhang, Jiaming Xue, Mengyu Tan, Dezhi Chen, Yuanyuan Xiao, Guihong Liu, Yazi Zheng, Qiushuo Wu, Miao Liao, Meili Lv, Shengqiu Qu and Weibo Liang

Genes 2023, 14(4), 865; https://doi.org/10.3390/genes14040865 - 4 Apr 2023

Cited by 8 | Viewed by 3084

Abstract

Microhaplotypes (MHs) are widely accepted as powerful markers in forensic studies. They have the advantage of both short tandem repeats (STRs) and single nucleotide polymorphisms (SNPs), with no stutter and amplification bias, short fragments and amplicons, low mutation and recombination rates, and high [...] Read more.

Microhaplotypes (MHs) are widely accepted as powerful markers in forensic studies. They have the advantage of both short tandem repeats (STRs) and single nucleotide polymorphisms (SNPs), with no stutter and amplification bias, short fragments and amplicons, low mutation and recombination rates, and high polymorphisms. In this study, we constructed a panel of 50 MHs that are distributed on 21 chromosomes and analyzed them using the Multiseq multiple polymerase chain reaction (multi-PCR) targeted capture sequencing protocol based on the massively parallel sequencing (MPS) platform. The sizes of markers and amplicons ranged between 11–81 bp and 123–198 bp, respectively. The sensitivity was 0.25 ng, and the calling results were consistent with Sanger sequencing and the Integrative Genomics Viewer (IGV). It showed measurable polymorphism among sequenced 137 Southwest Chinese Han individuals. No significant deviations in the Hardy–Weinberg equilibrium (HWE) and linkage disequilibrium (LD) were found at all MHs after Bonferroni correction. Furthermore, the specificity was 1:40 for simulated two-person mixtures, and the detection rates of highly degraded single samples and mixtures were 100% and 93–100%, respectively. Moreover, animal DNA testing was incomplete and low depth. Overall, our MPS-based 50-plex MH panel is a powerful forensic tool that provides a strong supplement and enhancement for some existing panels. Full article

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

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17 pages, 2051 KiB

Open AccessEditor’s ChoiceArticle

Leishmania infantum (JPCM5) Transcriptome, Gene Models and Resources for an Active Curation of Gene Annotations

by Esther Camacho, Sandra González-de la Fuente, Jose Carlos Solana, Laura Tabera, Fernando Carrasco-Ramiro, Begoña Aguado and Jose M. Requena

Genes 2023, 14(4), 866; https://doi.org/10.3390/genes14040866 - 4 Apr 2023

Cited by 3 | Viewed by 2643

Abstract

Leishmania infantum is one of the causative agents of visceral leishmaniases, the most severe form of leishmaniasis. An improved assembly for the L. infantum genome was published five years ago, yet delineation of its transcriptome remained to be accomplished. In this work, the [...] Read more.

Leishmania infantum is one of the causative agents of visceral leishmaniases, the most severe form of leishmaniasis. An improved assembly for the L. infantum genome was published five years ago, yet delineation of its transcriptome remained to be accomplished. In this work, the transcriptome annotation was attained by a combination of both short and long RNA-seq reads. The good agreement between the results derived from both methodologies confirmed that transcript assembly based on Illumina RNA-seq and further delimitation according to the positions of spliced leader (SAS) and poly-A (PAS) addition sites is an adequate strategy to annotate the transcriptomes of Leishmania, a procedure previously used for transcriptome annotation in other Leishmania species and related trypanosomatids. These analyses also confirmed that the Leishmania transcripts boundaries are relatively slippery, showing extensive heterogeneity at the 5′- and 3′-ends. However, the use of RNA-seq reads derived from the PacBio technology (referred to as Iso-Seq) allowed the authors to uncover some complex transcription patterns occurring at particular loci that would be unnoticed by the use of short RNA-seq reads alone. Thus, Iso-Seq analysis provided evidence that transcript processing at particular loci would be more dynamic than expected. Another noticeable finding was the observation of a case of allelic heterozygosity based on the existence of chimeric Iso-Seq reads that might be generated by an event of intrachromosomal recombination. In addition, we are providing the L. infantum gene models, including both UTRs and CDS regions, that would be helpful for undertaking whole-genome expression studies. Moreover, we have built the foundations of a communal database for the active curation of both gene/transcript models and functional annotations for genes and proteins. Full article

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

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12 pages, 10682 KiB

Open AccessEditor’s ChoiceArticle

High-Quality Assembly and Comparative Analysis of Actinidia latifolia and A. valvata Mitogenomes

by Wangmei Ren, Liying Wang, Guangcheng Feng, Cheng Tao, Yongsheng Liu and Jun Yang

Genes 2023, 14(4), 863; https://doi.org/10.3390/genes14040863 - 3 Apr 2023

Cited by 7 | Viewed by 2211

Abstract

Kiwifruit (Actinidia) has been recently domesticated as a horticultural crop with remarkably economic and nutritional value. In this study, by combining sequence datasets from Oxford Nanopore long-reads and Illumina short-reads, we de novo assembled two mitogenomes of Actinidia latifolia and A. [...] Read more.

Kiwifruit (Actinidia) has been recently domesticated as a horticultural crop with remarkably economic and nutritional value. In this study, by combining sequence datasets from Oxford Nanopore long-reads and Illumina short-reads, we de novo assembled two mitogenomes of Actinidia latifolia and A. valvata, respectively. The results indicated that the A. latifolia mitogenome has a single, circular, 825,163 bp molecule while the A. valvata mitogenome possesses two distinct circular molecules, 781,709 and 301,558 bp, respectively. We characterized the genome structure, repeated sequences, DNA transfers, and dN/dS selections. The phylogenetic analyses showed that A. valvata and A. arguta, or A. latifolia and A. eriantha, were clustered together, respectively. This study provides valuable sequence resources for evolutionary study and molecular breeding in kiwifruit. Full article

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

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11 pages, 1011 KiB

Open AccessEditor’s ChoiceArticle

The Evolution of Mitochondrial Genomes between Two Cymbidium Sister Species: Dozens of Circular Chromosomes and the Maintenance and Deterioration of Genome Synteny

by Xiaoling Li, Mengqing Zhe, Yiwei Huang, Weishu Fan, Junbo Yang and Andan Zhu

Genes 2023, 14(4), 864; https://doi.org/10.3390/genes14040864 - 3 Apr 2023

Cited by 8 | Viewed by 3022

Abstract

Plant mitochondrial genomes (mitogenomes) exhibit fluid genome architectures, which could lead to the rapid erosion of genome synteny over a short evolutionary time scale. Among the species-rich orchid family, the leafy Cymbidium lancifolium and leafless Cymbidium macrorhizon are sister species with remarkable differences [...] Read more.

Plant mitochondrial genomes (mitogenomes) exhibit fluid genome architectures, which could lead to the rapid erosion of genome synteny over a short evolutionary time scale. Among the species-rich orchid family, the leafy Cymbidium lancifolium and leafless Cymbidium macrorhizon are sister species with remarkable differences in morphology and nutritional physiology. Although our understanding of the evolution of mitochondria is incomplete, these sister taxa are ideal for examining this subject. In this study, the complete mitogenomes of C. lancifolium and C. macrorhizon, totaling 704,244 bp and 650,751 bp, respectively, were assembled. In the 2 mitogenomes, 38 protein-coding genes, 18 cis- and 6 trans-spliced introns, and approximately 611 Kb of homologous sequences are identical; overall, they have 99.4% genome-wide similarity. Slight variations in the mitogenomes of C. lancifolium and C. macrorhizon in repeat content (21.0 Kb and 21.6 Kb, respectively) and mitochondrial DNA of plastid origin (MIPT; 38.2 Kb and 37.5 Kb, respectively) were observed. The mitogenome architectures of C. lancifolium and C. macrorhizon are complex and comprise 23 and 22 mini-circular chromosomes, respectively. Pairwise comparisons indicate that the two mitogenomes are largely syntenic, and the disparity in chromosome numbers is likely due to repeat-mediated rearrangements among different chromosomes. Notably, approximately 93.2 Kb C. lancifolium mitochondrial sequences lack any homology in the C. macrorhizon mitogenome, indicating frequent DNA gains and losses, which accounts mainly for the size variation. Our findings provide unique insights into mitogenome evolution in leafy and leafless plants of sister species and shed light on mitogenome dynamics during the transition from mixotrophy to mycoheterotrophy. Full article

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

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13 pages, 4692 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Association Study on Reproductive Traits Using Imputation-Based Whole-Genome Sequence Data in Yorkshire Pigs

by Jingchun Sun, Jinhong Xiao, Yifan Jiang, Yaxin Wang, Minghao Cao, Jialin Wei, Taiyong Yu, Xiangdong Ding and Gongshe Yang

Genes 2023, 14(4), 861; https://doi.org/10.3390/genes14040861 - 2 Apr 2023

Cited by 9 | Viewed by 3557

Abstract

Reproductive traits have a key impact on production efficiency in the pig industry. It is necessary to identify the genetic structure of potential genes that influence reproductive traits. In this study, a genome-wide association study (GWAS) based on chip and imputed data of [...] Read more.

Reproductive traits have a key impact on production efficiency in the pig industry. It is necessary to identify the genetic structure of potential genes that influence reproductive traits. In this study, a genome-wide association study (GWAS) based on chip and imputed data of five reproductive traits, namely, total number born (TNB), number born alive (NBA), litter birth weight (LBW), gestation length (GL), and number of weaned (NW), was performed in Yorkshire pigs. In total, 272 of 2844 pigs with reproductive records were genotyped using KPS Porcine Breeding SNP Chips, and then chip data were imputed to sequencing data using two online software programs: the Pig Haplotype Reference Panel (PHARP v2) and Swine Imputation Server (SWIM 1.0). After quality control, we performed GWAS based on chip data and the two different imputation databases by using fixed and random model circulating probability unification (FarmCPU) models. We discovered 71 genome-wide significant SNPs and 25 potential candidate genes (e.g., SMAD4, RPS6KA2, CAMK2A, NDST1, and ADCY5). Functional enrichment analysis revealed that these genes are mainly enriched in the calcium signaling pathway, ovarian steroidogenesis, and GnRH signaling pathways. In conclusion, our results help to clarify the genetic basis of porcine reproductive traits and provide molecular markers for genomic selection in pig breeding. Full article

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

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13 pages, 4343 KiB

Open AccessEditor’s ChoiceArticle

Molecular Characterization of the Acyl-CoA-Binding Protein Genes Reveals Their Significant Roles in Oil Accumulation and Abiotic Stress Response in Cotton

by Yizhen Chen, Mingchuan Fu, Hao Li, Liguo Wang, Renzhong Liu and Zhanji Liu

Genes 2023, 14(4), 859; https://doi.org/10.3390/genes14040859 - 1 Apr 2023

Cited by 3 | Viewed by 1906

Abstract

Members of the acyl-CoA-binding protein (ACBP) gene family play vital roles in diverse processes related to lipid metabolism, growth and development, and environmental response. Plant ACBP genes have been well-studied in a variety of species including Arabidopsis, soybean, rice and maize. However, the [...] Read more.

Members of the acyl-CoA-binding protein (ACBP) gene family play vital roles in diverse processes related to lipid metabolism, growth and development, and environmental response. Plant ACBP genes have been well-studied in a variety of species including Arabidopsis, soybean, rice and maize. However, the identification and functions of ACBP genes in cotton remain to be elucidated. In this study, a total of 11 GaACBP, 12 GrACBP, 20 GbACBP, and 19 GhACBP genes were identified in the genomes of Gossypium arboreum, Gossypium raimondii, Gossypium babardense, and Gossypium hirsutum, respectively, and grouped into four clades. Forty-nine duplicated gene pairs were identified in Gossypium ACBP genes, and almost all of which have undergone purifying selection during the long evolutionary process. In addition, expression analyses showed that most of the GhACBP genes were highly expressed in the developing embryos. Furthermore, GhACBP1 and GhACBP2 were induced by salt and drought stress based on a real-time quantitative PCR (RT-qPCR) assay, indicating that these genes may play an important role in salt- and drought-stress tolerance. This study will provide a basic resource for further functional analysis of the ACBP gene family in cotton. Full article

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

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22 pages, 2001 KiB

Open AccessEditor’s ChoiceArticle

Genomic Regions Associated with Milk Composition and Fertility Traits in Spring-Calved Dairy Cows in New Zealand

by J. M. D. R. Jayawardana, Nicolas Lopez-Villalobos, Lorna R. McNaughton and Rebecca E. Hickson

Genes 2023, 14(4), 860; https://doi.org/10.3390/genes14040860 - 1 Apr 2023

Cited by 10 | Viewed by 3620

Abstract

The objective of this study was to identify genomic regions and genes that are associated with the milk composition and fertility traits of spring-calved dairy cows in New Zealand. Phenotypic data from the 2014–2015 and 2021–2022 calving seasons in two Massey University dairy [...] Read more.

The objective of this study was to identify genomic regions and genes that are associated with the milk composition and fertility traits of spring-calved dairy cows in New Zealand. Phenotypic data from the 2014–2015 and 2021–2022 calving seasons in two Massey University dairy herds were used. We identified 73 SNPs that were significantly associated with 58 potential candidate genes for milk composition and fertility traits. Four SNPs on chromosome 14 were highly significant for both fat and protein percentages, and the associated genes were DGAT1, SLC52A2, CPSF1, and MROH1. For fertility traits, significant associations were detected for intervals from the start of mating to first service, the start of mating to conception, first service to conception, calving to first service, and 6-wk submission, 6-wk in-calf, conception to first service in the first 3 weeks of the breeding season, and not in calf and 6-wk calving rates. Gene Ontology revealed 10 candidate genes (KCNH5, HS6ST3, GLS, ENSBTAG00000051479, STAT1, STAT4, GPD2, SH3PXD2A, EVA1C, and ARMH3) that were significantly associated with fertility traits. The biological functions of these genes are related to reducing the metabolic stress of cows and increasing insulin secretion during the mating period, early embryonic development, foetal growth, and maternal lipid metabolism during the pregnancy period. Full article

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

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15 pages, 4754 KiB

Open AccessEditor’s ChoiceArticle

Stable Isotope Tracing Reveals an Altered Fate of Glucose in N-Acetyltransferase 1 Knockout Breast Cancer Cells

by James T. F. Wise, Xinmin Yin, Xipeng Ma, Xiang Zhang and David W. Hein

Genes 2023, 14(4), 843; https://doi.org/10.3390/genes14040843 - 31 Mar 2023

Cited by 2 | Viewed by 2677

Abstract

Breast cancer is one of the leading causes of cancer death. Recent studies found that arylamine N-acetyltransferase 1 (NAT1) is frequently upregulated in breast cancer, further suggesting NAT1 could be a potential therapeutic target for breast cancer. Previous publications have established that [...] Read more.

Breast cancer is one of the leading causes of cancer death. Recent studies found that arylamine N-acetyltransferase 1 (NAT1) is frequently upregulated in breast cancer, further suggesting NAT1 could be a potential therapeutic target for breast cancer. Previous publications have established that NAT1 knockout (KO) in breast cancer cell lines leads to growth reduction both in vitro and in vivo and metabolic changes. These reports suggest that NAT1 contributes to the energy metabolism of breast cancer cells. Proteomic analysis and non-targeted metabolomics suggested that NAT1 KO may change the fate of glucose as it relates to the TCA/KREB cycle of the mitochondria of breast cancer cells. In this current study, we used [U-¹³C]-glucose stable isotope resolved metabolomics to determine the effect of NAT1 KO on the metabolic profile of MDA-MB-231 breast cancer cells. We incubated breast cancer cells (MDA-MB-231 cells) and NAT1 Crispr KO cells (KO#2 and KO#5) with [U-¹³C]-glucose for 24 h. Tracer incubation polar metabolites from the cells were extracted and analyzed by 2DLC-MS, and metabolite differences were compared between the parental and NAT1 KO cells. Differences consistent between the two KO cells were considered changes due to the loss of NAT1. The data revealed decreases in the ¹³C enrichment of TCA/Krebs cycle intermediates in NAT1 KO cells compared to the MDA-MB-231 cells. Specifically, ¹³C-labeled citrate, isocitrate, a-ketoglutarate, fumarate, and malate were all decreased in NAT1 KO cells. We also detected increased ¹³C-labeled L-lactate levels in the NAT1 KO cells and decreased ¹³C enrichment in some nucleotides. Pathway analysis showed that arginine biosynthesis, alanine, aspartate and glutamate metabolism, and the TCA cycle were most affected. These data provide additional evidence supporting the impacts of NAT1 knockout on cellular energy metabolism. The data suggest that NAT1 expression is important for the proper functioning of mitochondria and the flux of glucose through the TCA/Krebs cycle in breast cancer cells. The metabolism changes in the fate of glucose in NAT1 KO breast cancer cells offer more insight into the role of NAT1 in energy metabolism and the growth of breast cancer cells. These data provide additional evidence that NAT1 may be a useful therapeutic target for breast cancer. Full article

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

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15 pages, 12498 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Comprehensive Transcriptome Analysis of Responses during Cold Stress in Wheat (Triticum aestivum L.)

by Lei Li, Chenglin Han, Jinwei Yang, Zhiqiang Tian, Ruyun Jiang, Fei Yang, Kemeng Jiao, Menglei Qi, Lili Liu, Baozhu Zhang, Jishan Niu, Yumei Jiang, Yongchun Li and Jun Yin

Genes 2023, 14(4), 844; https://doi.org/10.3390/genes14040844 - 31 Mar 2023

Cited by 13 | Viewed by 3819

Abstract

Wheat production is often impacted by pre-winter freezing damage and cold spells in later spring. To study the influences of cold stress on wheat seedlings, unstressed Jing 841 was sampled once at the seedling stage, followed by 4 °C stress treatment for 30 [...] Read more.

Wheat production is often impacted by pre-winter freezing damage and cold spells in later spring. To study the influences of cold stress on wheat seedlings, unstressed Jing 841 was sampled once at the seedling stage, followed by 4 °C stress treatment for 30 days and once every 10 days. A total of 12,926 differentially expressed genes (DEGs) were identified from the transcriptome. K-means cluster analysis found a group of genes related to the glutamate metabolism pathway, and many genes belonging to the bHLH, MYB, NAC, WRKY, and ERF transcription factor families were highly expressed. Starch and sucrose metabolism, glutathione metabolism, and plant hormone signal transduction pathways were found. Weighted Gene Co-Expression Network Analysis (WGCNA) identified several key genes involved in the development of seedlings under cold stress. The cluster tree diagram showed seven different modules marked with different colors. The blue module had the highest correlation coefficient for the samples treated with cold stress for 30 days, and most genes in this module were rich in glutathione metabolism (ko00480). A total of eight DEGs were validated using quantitative real-time PCR. Overall, this study provides new insights into the physiological metabolic pathways and gene changes in a cold stress transcriptome, and it has a potential significance for improving freezing tolerance in wheat. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Plant Stress Responses)

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21 pages, 5897 KiB

Open AccessEditor’s ChoiceArticle

Sequencing of the Pituitary Transcriptome after GnRH Treatment Uncovers the Involvement of lncRNA-m23b/miR-23b-3p/CAMK2D in FSH Synthesis and Secretion

by Tian Wang, Guokun Zhao, Song Yu, Yi Zheng, Haixiang Guo, Haoqi Wang, Peisen Zhao, Wenyin Xie, Wenzhi Ren and Bao Yuan

Genes 2023, 14(4), 846; https://doi.org/10.3390/genes14040846 - 31 Mar 2023

Cited by 2 | Viewed by 2277

Abstract

The pituitary gland is a key participant in the hypothalamic–pituitary–gonadal axis, as it secretes a variety of hormones and plays an important role in mammalian reproduction. Gonadotrophin-releasing hormone(GnRH) signaling molecules can bind to GnRH receptors on the surfaces of adenohypophysis gonadotropin cells and [...] Read more.

The pituitary gland is a key participant in the hypothalamic–pituitary–gonadal axis, as it secretes a variety of hormones and plays an important role in mammalian reproduction. Gonadotrophin-releasing hormone(GnRH) signaling molecules can bind to GnRH receptors on the surfaces of adenohypophysis gonadotropin cells and regulate the expression of follicle-stimulating hormone(FSH) and luteinizing hormone(LH) through various pathways. An increasing number of studies have shown that noncoding RNAs mediate the regulation of GnRH signaling molecules in the adenohypophysis. However, the expression changes and underlying mechanisms of genes and noncoding RNAs in the adenohypophysis under the action of GnRH remain unclear. In the present study, we performed RNA sequencing (RNA-seq) of the rat adenohypophysis before and after GnRH treatment to identify differentially expressed mRNAs, lncRNAs, and miRNAs. We found 385 mRNAs, 704 lncRNAs, and 20 miRNAs that were significantly differentially expressed in the rat adenohypophysis. Then, we used a software to predict the regulatory roles of lncRNAs as molecular sponges that compete with mRNAs to bind miRNAs, and construct a GnRH-mediated ceRNA regulatory network. Finally, we enriched the differentially expressed mRNAs, lncRNA target genes, and ceRNA regulatory networks to analyze their potential roles. Based on the sequencing results, we verified that GnRH could affect FSH synthesis and secretion by promoting the competitive binding of lncRNA-m23b to miR-23b-3p to regulate the expression of Calcium/Calmodulin Dependent Protein Kinase II Delta(CAMK2D). Our findings provide strong data to support exploration of the physiological processes in the rat adenohypophysis under the action of GnRH. Furthermore, our profile of lncRNA expression in the rat adenohypophysis provides a theoretical basis for research on the roles of lncRNAs in the adenohypophysis. Full article

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

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10 pages, 2654 KiB

Open AccessEditor’s ChoiceCase Report

A Complex Intrachromosomal Rearrangement Disrupting IRF6 in a Family with Popliteal Pterygium and Van der Woude Syndromes

by Alya A. Al-Kurbi, Elbay Aliyev, Sana AlSa’afin, Waleed Aamer, Sasirekha Palaniswamy, Aljazi Al-Maraghi, Houda Kilani, Ammira Al-Shabeeb Akil, Mitchell A. Stotland and Khalid A. Fakhro

Genes 2023, 14(4), 849; https://doi.org/10.3390/genes14040849 - 31 Mar 2023

Cited by 2 | Viewed by 4401

Abstract

Clefts of the lip and/or palate (CL/P) are considered the most common form of congenital anomalies occurring either in isolation or in association with other clinical features. Van der woude syndrome (VWS) is associated with about 2% of all CL/P cases and is [...] Read more.

Clefts of the lip and/or palate (CL/P) are considered the most common form of congenital anomalies occurring either in isolation or in association with other clinical features. Van der woude syndrome (VWS) is associated with about 2% of all CL/P cases and is further characterized by having lower lip pits. Popliteal pterygium syndrome (PPS) is a more severe form of VWS, normally characterized by orofacial clefts, lower lip pits, skin webbing, skeletal anomalies and syndactyly of toes and fingers. Both syndromes are inherited in an autosomal dominant manner, usually caused by heterozygous mutations in the Interferon Regulatory Factor 6 (IRF6) gene. Here we report the case of a two-generation family where the index presented with popliteal pterygium syndrome while both the father and sister had clinical features of van der woude syndrome, but without any point mutations detected by re-sequencing of known gene panels or microarray testing. Using whole genome sequencing (WGS) followed by local de novo assembly, we discover and validate a copy-neutral, 429 kb complex intra-chromosomal rearrangement in the long arm of chromosome 1, disrupting the IRF6 gene. This variant is copy-neutral, novel against publicly available databases, and segregates in the family in an autosomal dominant pattern. This finding suggests that missing heritability in rare diseases may be due to complex genomic rearrangements that can be resolved by WGS and de novo assembly, helping deliver answers to patients where no genetic etiology was identified by other means. Full article

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

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21 pages, 3345 KiB

Open AccessEditor’s ChoiceReview

The CRISPR/Cas System: A Customizable Toolbox for Molecular Detection

by Yuxuan He, Wei Yan, Likun Long, Liming Dong, Yue Ma, Congcong Li, Yanbo Xie, Na Liu, Zhenjuan Xing, Wei Xia and Feiwu Li

Genes 2023, 14(4), 850; https://doi.org/10.3390/genes14040850 - 31 Mar 2023

Cited by 27 | Viewed by 6466

Abstract

Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated proteins (Cas) are promising molecular diagnostic tools for rapidly and precisely elucidating the structure and function of genomes due to their high specificity, programmability, and multi-system compatibility in nucleic acid recognition. Multiple parameters [...] Read more.

Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated proteins (Cas) are promising molecular diagnostic tools for rapidly and precisely elucidating the structure and function of genomes due to their high specificity, programmability, and multi-system compatibility in nucleic acid recognition. Multiple parameters limit the ability of a CRISPR/Cas system to detect DNA or RNA. Consequently, it must be used in conjunction with other nucleic acid amplification techniques or signal detection techniques, and the reaction components and reaction conditions should be modified and optimized to maximize the detection performance of the CRISPR/Cas system against various targets. As the field continues to develop, CRISPR/Cas systems have the potential to become an ultra-sensitive, convenient, and accurate biosensing platform for the detection of specific target sequences. The design of a molecular detection platform employing the CRISPR/Cas system is asserted on three primary strategies: (1) Performance optimization of the CRISPR/Cas system; (2) enhancement of the detection signal and its interpretation; and (3) compatibility with multiple reaction systems. This article focuses on the molecular characteristics and application value of the CRISPR/Cas system and reviews recent research progress and development direction from the perspectives of principle, performance, and method development challenges to provide a theoretical foundation for the development and application of the CRISPR/CAS system in molecular detection technology. Full article

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

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15 pages, 1856 KiB

Open AccessEditor’s ChoiceArticle

Phenotypes and Genotypes in Patients with SMC1A-Related Developmental and Epileptic Encephalopathy

by Xiuhua L. Bozarth, Jonathan Lopez, He Fang, Jacqueline Lee-Eng, Zhijun Duan and Xinxian Deng

Genes 2023, 14(4), 852; https://doi.org/10.3390/genes14040852 - 31 Mar 2023

Cited by 15 | Viewed by 3684

Abstract

The X-linked SMC1A gene encodes a core subunit of the cohesin complex that plays a pivotal role in genome organization and gene regulation. Pathogenic variants in SMC1A are often dominant-negative and cause Cornelia de Lange syndrome (CdLS) with growth retardation and typical facial [...] Read more.

The X-linked SMC1A gene encodes a core subunit of the cohesin complex that plays a pivotal role in genome organization and gene regulation. Pathogenic variants in SMC1A are often dominant-negative and cause Cornelia de Lange syndrome (CdLS) with growth retardation and typical facial features; however, rare SMC1A variants cause a developmental and epileptic encephalopathy (DEE) with intractable early-onset epilepsy that is absent in CdLS. Unlike the male-to-female ratio of 1:2 in those with CdLS associated with dominant-negative SMC1A variants, SMC1A-DEE loss-of-function (LOF) variants are found exclusively in females due to presumed lethality in males. It is unclear how different SMC1A variants cause CdLS or DEE. Here, we report on phenotypes and genotypes of three females with DEE and de novo SMC1A variants, including a novel splice-site variant. We also summarize 41 known SMC1A-DEE variants to characterize common and patient-specific features. Interestingly, compared to 33 LOFs detected throughout the gene, 7/8 non-LOFs are specifically located in the N/C-terminal ATPase head or the central hinge domain, both of which are predicted to affect cohesin assembly, thus mimicking LOFs. Along with the characterization of X-chromosome inactivation (XCI) and SMC1A transcription, these variants strongly suggest that a differential SMC1A dosage effect of SMC1A-DEE variants is closely associated with the manifestation of DEE phenotypes. Full article

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

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11 pages, 2305 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Association Study Reveals the Genetic Basis of Duck Plumage Colors

by Xinye Zhang, Tao Zhu, Liang Wang, Xueze Lv, Weifang Yang, Changqing Qu, Haiying Li, Huie Wang, Zhonghua Ning and Lujiang Qu

Genes 2023, 14(4), 856; https://doi.org/10.3390/genes14040856 - 31 Mar 2023

Cited by 12 | Viewed by 5546

Abstract

Plumage color is an artificially and naturally selected trait in domestic ducks. Black, white, and spotty are the main feather colors in domestic ducks. Previous studies have shown that black plumage color is caused by MC1R, and white plumage color is caused [...] Read more.

Plumage color is an artificially and naturally selected trait in domestic ducks. Black, white, and spotty are the main feather colors in domestic ducks. Previous studies have shown that black plumage color is caused by MC1R, and white plumage color is caused by MITF. We performed a genome-wide association study (GWAS) to identify candidate genes associated with white, black, and spotty plumage in ducks. Two non-synonymous SNPs in MC1R (c.52G>A and c.376G>A) were significantly related to duck black plumage, and three SNPs in MITF (chr13:15411658A>G, chr13:15412570T>C and chr13:15412592C>G) were associated with white plumage. Additionally, we also identified the epistatic interactions between causing loci. Some ducks with white plumage carry the c.52G>A and c.376G>A in MC1R, which also compensated for black and spotty plumage color phenotypes, suggesting that MC1R and MITF have an epistatic effect. The MITF locus was supposed to be an upstream gene to MC1R underlying the white, black, and spotty colors. Although the specific mechanism remains to be further clarified, these findings support the importance of epistasis in plumage color variation in ducks. Full article

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

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11 pages, 1442 KiB

Open AccessEditor’s ChoiceCommunication

Retinal Phenotyping of a Murine Model of Lafora Disease

by Ajoy Vincent, Kashif Ahmed, Rowaida Hussein, Zorana Berberovic, Anupreet Tumber, Xiaochu Zhao and Berge A. Minassian

Genes 2023, 14(4), 854; https://doi.org/10.3390/genes14040854 - 31 Mar 2023

Cited by 1 | Viewed by 2484

Abstract

Lafora disease (LD) is a progressive neurologic disorder caused by biallelic pathogenic variants in EPM2A or EPM2B, leading to tissue accumulation of polyglucosan aggregates termed Lafora bodies (LBs). This study aimed to characterize the retinal phenotype in Epm2a^−/− mice by examining [...] Read more.

Lafora disease (LD) is a progressive neurologic disorder caused by biallelic pathogenic variants in EPM2A or EPM2B, leading to tissue accumulation of polyglucosan aggregates termed Lafora bodies (LBs). This study aimed to characterize the retinal phenotype in Epm2a^−/− mice by examining knockout (KO; Epm2a^−/−) and control (WT) littermates at two time points (10 and 14 months, respectively). In vivo exams included electroretinogram (ERG) testing, optical coherence tomography (OCT) and retinal photography. Ex vivo retinal testing included Periodic acid Schiff Diastase (PASD) staining, followed by imaging to assess and quantify LB deposition. There was no significant difference in any dark-adapted or light-adapted ERG parameters between KO and WT mice. The total retinal thickness was comparable between the groups and the retinal appearance was normal in both groups. On PASD staining, LBs were observed in KO mice within the inner and outer plexiform layers and in the inner nuclear layer. The average number of LBs within the inner plexiform layer in KO mice were 1743 ± 533 and 2615 ± 915 per mm², at 10 and 14 months, respectively. This is the first study to characterize the retinal phenotype in an Epm2a^−/− mouse model, demonstrating significant LB deposition in the bipolar cell nuclear layer and its synapses. This finding may be used to monitor the efficacy of experimental treatments in mouse models. Full article

(This article belongs to the Topic Animal Models of Human Disease)

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