Genes

18 pages, 14513 KiB

Open AccessArticle

Gene Conversion Explains Elevated Diversity in the Immunity Modulating APL1 Gene of the Malaria Vector Anopheles funestus

by Jack Hearn, Jacob M. Riveron, Helen Irving, Gareth D. Weedall and Charles S. Wondji

Genes 2022, 13(6), 1102; https://doi.org/10.3390/genes13061102 - 20 Jun 2022

Cited by 1 | Viewed by 2204

Abstract

Leucine-rich repeat proteins and antimicrobial peptides are the key components of the innate immune response to Plasmodium and other microbial pathogens in Anopheles mosquitoes. The APL1 gene of the malaria vector Anopheles funestus has exceptional levels of non-synonymous polymorphism across the range of [...] Read more.

Leucine-rich repeat proteins and antimicrobial peptides are the key components of the innate immune response to Plasmodium and other microbial pathogens in Anopheles mosquitoes. The APL1 gene of the malaria vector Anopheles funestus has exceptional levels of non-synonymous polymorphism across the range of An. funestus, with an average π_n of 0.027 versus a genome-wide average of 0.002, and π_n is consistently high in populations across Africa. Elevated APL1 diversity was consistent between the independent pooled-template and target-enrichment datasets, however no link between APL1 diversity and insecticide resistance was observed. Although lacking the diversity of APL1, two further mosquito innate-immunity genes of the gambicin anti-microbial peptide family had π_n/π_s ratios greater than one, possibly driven by either positive or balancing selection. The cecropin antimicrobial peptides were expressed much more highly than other anti-microbial peptide genes, a result discordant with current models of anti-microbial peptide activity. The observed APL1 diversity likely results from gene conversion between paralogues, as evidenced by shared polymorphisms, overlapping read mappings, and recombination events among paralogues. In conclusion, we hypothesize that higher gene expression of APL1 than its paralogues is correlated with a more open chromatin formation, which enhances gene conversion and elevated diversity at this locus. Full article

(This article belongs to the Special Issue Adaptive Evolution of Insects)

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16 pages, 996 KiB

Open AccessFeature PaperReview

Synthetic Lethality Targeting Polθ

by Małgorzata Drzewiecka, Gabriela Barszczewska-Pietraszek, Piotr Czarny, Tomasz Skorski and Tomasz Śliwiński

Genes 2022, 13(6), 1101; https://doi.org/10.3390/genes13061101 - 20 Jun 2022

Cited by 12 | Viewed by 4758

Abstract

Research studies regarding synthetic lethality (SL) in human cells are primarily motivated by the potential of this phenomenon to be an effective, but at the same time, safe to the patient’s anti-cancer chemotherapy. Among the factors that are targets for the induction of [...] Read more.

Research studies regarding synthetic lethality (SL) in human cells are primarily motivated by the potential of this phenomenon to be an effective, but at the same time, safe to the patient’s anti-cancer chemotherapy. Among the factors that are targets for the induction of the synthetic lethality effect, those involved in DNA repair seem to be the most relevant. Specifically, when mutation in one of the canonical DNA double-strand break (DSB) repair pathways occurs, which is a frequent event in cancer cells, the alternative pathways may be a promising target for the elimination of abnormal cells. Currently, inhibiting RAD52 and/or PARP1 in the tumor cells that are deficient in the canonical repair pathways has been the potential target for inducing the effect of synthetic lethality. Unfortunately, the development of resistance to commonly used PARP1 inhibitors (PARPi) represents the greatest obstacle to working out a successful treatment protocol. DNA polymerase theta (Polθ), encoded by the POLQ gene, plays a key role in an alternative DSB repair pathway—theta-mediated end joining (TMEJ). Thus, it is a promising target in the treatment of tumors harboring deficiencies in homologous recombination repair (HRR), where its inhibition can induce SL. In this review, the authors discuss the current state of knowledge on Polθ as a potential target for synthetic lethality-based anticancer therapies. Full article

(This article belongs to the Special Issue Signaling Pathway of Cancer)

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15 pages, 3980 KiB

Open AccessArticle

The Sweetpotato Voltage-Gated K⁺ Channel β Subunit, KIbB1, Positively Regulates Low-K⁺ and High-Salinity Tolerance by Maintaining Ion Homeostasis

by Hong Zhu, Xue Yang, Qiyan Li, Jiayu Guo, Tao Ma, Shuyan Liu, Shunyu Lin, Yuanyuan Zhou, Chunmei Zhao, Jingshan Wang and Jiongming Sui

Genes 2022, 13(6), 1100; https://doi.org/10.3390/genes13061100 - 20 Jun 2022

Cited by 4 | Viewed by 1980

Abstract

Voltage-gated K⁺ channel β subunits act as a structural component of K_in channels in different species. The β subunits are not essential to the channel activity but confer different properties through binding the T1 domain or the C-terminal of α subunits. [...] Read more.

Voltage-gated K⁺ channel β subunits act as a structural component of K_in channels in different species. The β subunits are not essential to the channel activity but confer different properties through binding the T1 domain or the C-terminal of α subunits. Here, we studied the physiological function of a novel gene, KIbB1, encoding a voltage-gated K⁺ channel β subunit in sweetpotato. The transcriptional level of this gene was significantly higher in the low-K⁺-tolerant line than that in the low-K⁺-sensitive line under K⁺ deficiency conditions. In Arabidopsis, KIbB1 positively regulated low-K⁺ tolerance through regulating K⁺ uptake and translocation. Under high-salinity stress, the growth conditions of transgenic lines were obviously better than wild typr (WT). Enzymatic and non-enzymatic reactive oxygen species (ROS) scavenging were activated in transgenic plants. Accordingly, the malondialdehyde (MDA) content and the accumulation of ROS such as H₂O₂ and O²⁻ were lower in transgenic lines under salt stress. It was also found that the overexpression of KIbB1 enhanced K⁺ uptake, but the translocation from root to shoot was not affected under salt stress. This demonstrates that KIbB1 acted as a positive regulator in high-salinity stress resistance through regulating Na⁺ and K⁺ uptake to maintain K⁺/Na⁺ homeostasis. These results collectively suggest that the mechanisms of KIbB1 in regulating K⁺ were somewhat different between low-K⁺ and high-salinity conditions. Full article

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

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27 pages, 448 KiB

Open AccessReview

Psychosis in Parkinson’s Disease: A Lesson from Genetics

by Efthalia Angelopoulou, Anastasia Bougea, Sokratis G. Papageorgiou and Chiara Villa

Genes 2022, 13(6), 1099; https://doi.org/10.3390/genes13061099 - 20 Jun 2022

Cited by 11 | Viewed by 4073

Abstract

Psychosis in Parkinson’s disease (PDP) represents a common and debilitating condition that complicates Parkinson’s disease (PD), mainly in the later stages. The spectrum of psychotic symptoms are heterogeneous, ranging from minor phenomena of mild illusions, passage hallucinations and sense of presence to severe [...] Read more.

Psychosis in Parkinson’s disease (PDP) represents a common and debilitating condition that complicates Parkinson’s disease (PD), mainly in the later stages. The spectrum of psychotic symptoms are heterogeneous, ranging from minor phenomena of mild illusions, passage hallucinations and sense of presence to severe psychosis consisting of visual hallucinations (and rarely, auditory and tactile or gustatory) and paranoid delusions. PDP is associated with increased caregiver stress, poorer quality of life for patients and carers, reduced survival and risk of institutionalization with a significant burden on the healthcare system. Although several risk factors for PDP development have been identified, such as aging, sleep disturbances, long history of PD, cognitive impairment, depression and visual disorders, the pathophysiology of psychosis in PD is complex and still insufficiently clarified. Additionally, several drugs used to treat PD can aggravate or even precipitate PDP. Herein, we reviewed and critically analyzed recent studies exploring the genetic architecture of psychosis in PD in order to further understand the pathophysiology of PDP, the risk factors as well as the most suitable therapeutic strategies. Full article

(This article belongs to the Special Issue Genetic Basis Underlying Neuropsychiatric Disorders)

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11 pages, 591 KiB

Open AccessArticle

Identifying Rare Genetic Variants of Immune Mediators as Risk Factors for Autism Spectrum Disorder

by Chunquan Cai, Zhaoqing Yin, Aiping Liu, Hui Wang, Shujuan Zeng, Zhangxing Wang, Huixian Qiu, Shijun Li, Jiaxiu Zhou and Mingbang Wang

Genes 2022, 13(6), 1098; https://doi.org/10.3390/genes13061098 - 20 Jun 2022

Cited by 7 | Viewed by 2842

Abstract

Autism spectrum disorder (ASD) affects more than 1% of children, and there is no viable pharmacotherapeutic agent to treat the core symptoms of ASD. Studies have shown that children with ASD show changes in their levels of immune response molecules. Our previous studies [...] Read more.

Autism spectrum disorder (ASD) affects more than 1% of children, and there is no viable pharmacotherapeutic agent to treat the core symptoms of ASD. Studies have shown that children with ASD show changes in their levels of immune response molecules. Our previous studies have shown that ASD is more common in children with folate receptor autoantibodies. We also found that children with ASD have abnormal gut immune function, which was characterized by a significant increase in the content of immunoglobulin A and an increase in gut-microbiota-associated epitope diversity. These studies suggest that the immune mechanism plays an important role in the occurrence of ASD. The present study aims to systematically assess gene mutations in immune mediators in patients with ASD. We collected genetic samples from 72 children with ASD (2–12 years old) and 107 healthy controls without ASD (20–78 years old). We used our previously-designed immune gene panel, which can capture cytokine and receptor genes, the coding regions of MHC genes, and genes of innate immunity. Target region sequencing (500×) and bioinformatics analytical methods were used to identify variants in immune response genes associated with patients with ASD. A total of 4 rare variants were found to be associated with ASD, including HLA-B: p.A93G, HLA-DQB1: p.S229N, LILRB2: p.R322H, and LILRB2: c.956-4C>T. These variants were present in 44.44% (32/72) of the ASD patients and were detected in 3.74% (4/107) of the healthy controls. We expect these genetic variants will serve as new targets for the clinical genetic assessment of ASD, and our findings suggest that immune abnormalities in children with ASD may have a genetic basis. Full article

(This article belongs to the Special Issue Bioinformatics and Genetics of Human Diseases)

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8 pages, 275 KiB

Open AccessArticle

Integrated Analysis of Tissue-Specific Gene Expression in Diabetes by Tensor Decomposition Can Identify Possible Associated Diseases

by Y-H. Taguchi and Turki Turki

Genes 2022, 13(6), 1097; https://doi.org/10.3390/genes13061097 - 20 Jun 2022

Cited by 1 | Viewed by 1942

Abstract

In the field of gene expression analysis, methods of integrating multiple gene expression profiles are still being developed and the existing methods have scope for improvement. The previously proposed tensor decomposition-based unsupervised feature extraction method was improved by introducing standard deviation optimization. The [...] Read more.

In the field of gene expression analysis, methods of integrating multiple gene expression profiles are still being developed and the existing methods have scope for improvement. The previously proposed tensor decomposition-based unsupervised feature extraction method was improved by introducing standard deviation optimization. The improved method was applied to perform an integrated analysis of three tissue-specific gene expression profiles (namely, adipose, muscle, and liver) for diabetes mellitus, and the results showed that it can detect diseases that are associated with diabetes (e.g., neurodegenerative diseases) but that cannot be predicted by individual tissue expression analyses using state-of-the-art methods. Although the selected genes differed from those identified by the individual tissue analyses, the selected genes are known to be expressed in all three tissues. Thus, compared with individual tissue analyses, an integrated analysis can provide more in-depth data and identify additional factors, namely, the association with other diseases. Full article

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

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21 pages, 3700 KiB

Open AccessArticle

Comparative Transcriptome Analysis of Organ-Specific Adaptive Responses to Hypoxia Provides Insights to Human Diseases

by Kuo-Sheng Hung, Shiow-Yi Chen, Pang-Hung Hsu, Bo-An Lin, Chin-Hua Hu, Cing-Han Yang, Tun-Wen Pai, Wen-Shyong Tzou and Hsin-Yu Chung

Genes 2022, 13(6), 1096; https://doi.org/10.3390/genes13061096 - 19 Jun 2022

Cited by 3 | Viewed by 3076

Abstract

The common carp is a hypoxia-tolerant fish, and the understanding of its ability to live in low-oxygen environments has been applied to human health issues such as cancer and neuron degeneration. Here, we investigated differential gene expression changes during hypoxia in five common [...] Read more.

The common carp is a hypoxia-tolerant fish, and the understanding of its ability to live in low-oxygen environments has been applied to human health issues such as cancer and neuron degeneration. Here, we investigated differential gene expression changes during hypoxia in five common carp organs including the brain, the gill, the head kidney, the liver, and the intestine. Based on RNA sequencing, gene expression changes under hypoxic conditions were detected in over 1800 genes in common carp. The analysis of these genes further revealed that all five organs had high expression-specific properties. According to the results of the GO and KEGG, the pathways involved in the adaptation to hypoxia provided information on responses specific to each organ in low oxygen, such as glucose metabolism and energy usage, cholesterol synthesis, cell cycle, circadian rhythm, and dopamine activation. DisGeNET analysis showed that some human diseases such as cancer, diabetes, epilepsy, metabolism diseases, and social ability disorders were related to hypoxia-regulated genes. Our results suggested that common carp undergo various gene regulations in different organs under hypoxic conditions, and integrative bioinformatics may provide some potential targets for advancing disease research. Full article

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

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14 pages, 5056 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Association Studies Reveal Candidate Genes Related to Stem Diameter in Cucumber (Cucumis sativus L.)

by Yingying Yang, Shaoyun Dong, Han Miao, Xiaoping Liu, Zhuonan Dai, Xiangsheng Li, Xingfang Gu and Shengping Zhang

Genes 2022, 13(6), 1095; https://doi.org/10.3390/genes13061095 - 19 Jun 2022

Cited by 6 | Viewed by 2396

Abstract

The stem diameter, an important agronomic trait, affects cucumber growth and yield. However, no genes responsible for cucumber stem diameter have been identified yet. In this study, the stem diameter of 88 cucumber core germplasms were measured in spring 2020, autumn 2020 and [...] Read more.

The stem diameter, an important agronomic trait, affects cucumber growth and yield. However, no genes responsible for cucumber stem diameter have been identified yet. In this study, the stem diameter of 88 cucumber core germplasms were measured in spring 2020, autumn 2020 and autumn 2021, and a genome-wide association study (GWAS) was carried out based on the gene sequence and stem diameter of core germplasms. A total of eight loci (gSD1.1, gSD2.1, gSD3.1, gSD3.2, gSD4.1, gSD5.1, gSD5.2, and gSD6.1) significantly associated with cucumber stem diameter were detected. Of these, five loci (gSD1.1, gSD2.1, gSD3.1, gSD5.2, and gSD6.1) were repeatedly detected in two or more seasons and were considered as robust and reliable loci. Based on the linkage disequilibrium sequences of the associated SNP loci, 37 genes were selected. By further investigating the five loci via analyzing Arabidopsis homologous genes and gene haplotypes, five genes (CsaV3_1G028310, CsaV3_2G006960, CsaV3_3G009560, CsaV3_5G031320, and CsaV3_6G031260) showed variations in amino acid sequence between thick stem lines and thin stem lines. Expression pattern analyses of these genes also showed a significant difference between thick stem and thin stem lines. This study laid the foundation for gene cloning and molecular mechanism study of cucumber stem development. Full article

(This article belongs to the Special Issue Cucumber Genetics and Breeding - a Themed Issue in Memory of Academician Feng Hou (1928 - 2020))

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23 pages, 9090 KiB

Open AccessArticle

Integrated Analysis of a Ferroptosis-Related LncRNA Signature for Evaluating the Prognosis of Patients with Colorectal Cancer

by Shaohua Xu, Yanjie Zhou, Junyun Luo, Su Chen, Jiahui Xie, Hui Liu, Yirong Wang and Zhaoyong Li

Genes 2022, 13(6), 1094; https://doi.org/10.3390/genes13061094 - 19 Jun 2022

Cited by 11 | Viewed by 3227

Abstract

LncRNAs have been well known for their multiple functions in the tumorigenesis, development, and relapse of colorectal cancer (CRC). Accumulating studies demonstrated that the expression of lncRNAs can be regulated by ferroptosis, a biological process that has been revealed to suppress CRC progression. [...] Read more.

LncRNAs have been well known for their multiple functions in the tumorigenesis, development, and relapse of colorectal cancer (CRC). Accumulating studies demonstrated that the expression of lncRNAs can be regulated by ferroptosis, a biological process that has been revealed to suppress CRC progression. However, the functions and clinical implications of ferroptosis-associated lncRNAs in CRC remain largely unknown. We, herein, aim to construct a prognostic signature with ferroptosis-related lncRNAs for the prognostic estimation of CRC patients. Firstly, we identified the lncRNAs related to ferroptosis based on the RNA-Seq data of CRC from the TCGA database. The univariate and multivariate Cox analyses were then performed to establish a prognostic signature composed of eight ferroptosis-related lncRNAs (AL161729.4, AC010973.2, CCDC144NL-AS1, AC009549.1, LINC01857, AP003555.1, AC099850.3, and AC008494.3). Furthermore, we divided the CRC patients into high- and low-risk groups based on the signature and found the overall survival (OS) of patients in the high-risk group was significantly shorter than that in the low-risk group (p = 3.31 × 10⁻¹¹). Moreover, the patients in the high-risk groups had shorter recurrence-free survival (RFS) (p = 6.5 × 10⁻³) and disease-free survival (DFS) (p = 4.27 × 10⁻⁴), as well as higher tumor recurrence rate. Additionally, we found that the oncogenic pathways were enriched in the high-risk group, whereas the ferroptosis pathway that probably repressed CRC development was enriched in the low-risk group. In summary, our signature may provide a theoretical foundation for not only accurate judgment for prognosis but also evaluation for recurrence and metastasis in CRC patients. Full article

(This article belongs to the Special Issue The Role of RNA Processing and Metabolism in Tumors)

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13 pages, 1521 KiB

Open AccessCommunication

Exploring the Potential of Symmetric Exon Deletion to Treat Non-Ischemic Dilated Cardiomyopathy by Removing Frameshift Mutations in TTN

by Ignacio Rodriguez-Polo and Rüdiger Behr

Genes 2022, 13(6), 1093; https://doi.org/10.3390/genes13061093 - 19 Jun 2022

Cited by 2 | Viewed by 3379

Abstract

Non-ischemic dilated cardiomyopathy (DCM) is one of the most frequent pathologies requiring cardiac transplants. Even though the etiology of this disease is complex, frameshift mutations in the giant sarcomeric protein Titin could explain up to 25% of the familial and 18% of the [...] Read more.

Non-ischemic dilated cardiomyopathy (DCM) is one of the most frequent pathologies requiring cardiac transplants. Even though the etiology of this disease is complex, frameshift mutations in the giant sarcomeric protein Titin could explain up to 25% of the familial and 18% of the sporadic cases of DCM. Many studies have shown the potential of genome editing using CRISPR/Cas9 to correct truncating mutations in sarcomeric proteins and have established the grounds for myoediting. However, these therapies are still in an immature state, with only few studies showing an efficient treatment of cardiac diseases. This publication hypothesizes that the Titin (TTN)-specific gene structure allows the application of myoediting approaches in a broad range of locations to reframe TTNtvvariants and to treat DCM patients. Additionally, to pave the way for the generation of efficient myoediting approaches for DCM, we screened and selected promising target locations in TTN. We conceptually explored the deletion of symmetric exons as a therapeutic approach to restore TTN’s reading frame in cases of frameshift mutations. We identified a set of 94 potential candidate exons of TTN that we consider particularly suitable for this therapeutic deletion. With this study, we aim to contribute to the development of new therapies to efficiently treat titinopathies and other diseases caused by mutations in genes encoding proteins with modular structures, e.g., Obscurin. Full article

(This article belongs to the Section Technologies and Resources for Genetics)

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26 pages, 5245 KiB

Open AccessArticle

Co-Expression Analysis Reveals Differential Expression of Homologous Genes Associated with Specific Terpenoid Biosynthesis in Rehmannia glutinosa

by Ji-Nam Kang, Jong-Won Han, So-Hee Yang and Si-Myung Lee

Genes 2022, 13(6), 1092; https://doi.org/10.3390/genes13061092 - 19 Jun 2022

Cited by 3 | Viewed by 2606

Abstract

Terpenoids are naturally occurring compounds involved in respiration, photosynthesis, membrane fluidity, and pathogen interactions and are classified according to the structure of their carbon skeleton. Although most terpenoids possess pharmacological activity, knowledge about terpenoid metabolism in medicinal plants is insufficient. Rehmannia glutinosa ( [...] Read more.

Terpenoids are naturally occurring compounds involved in respiration, photosynthesis, membrane fluidity, and pathogen interactions and are classified according to the structure of their carbon skeleton. Although most terpenoids possess pharmacological activity, knowledge about terpenoid metabolism in medicinal plants is insufficient. Rehmannia glutinosa (R. glutinosa) is a traditional herb that is widely used in East Asia and has been reported to contain various terpenoids. In this study, we performed a comprehensive transcriptome analysis of terpenoid metabolism in R. glutinosa using two RNA sequencing platforms: Illumina and PacBio. The results show that the sterol, saponin, iridoid, and carotenoid pathways are active in R. glutinosa. Sterol and saponin biosynthesis were mevalonate pathway dependent, whereas iridoid and carotenoid biosynthesis were methylerythritol 4-phosphate pathway dependent. In addition, we found that the homologous genes of key enzymes involved in terpenoid metabolism were expressed differentially and that the differential expression of these genes was associated with specific terpenoid biosynthesis. The different expression of homologous genes encoding acetyl-CoA acetyltransferase, 3-hydroxy-3-methylglutaryl-CoA reductase, mevalonate kinase, mevalonate diphosphate decarboxylase, farnesyl pyrophosphate synthase, squalene synthase, and squalene epoxidase was associated with sterol and saponin biosynthesis. Homologous genes encoding 1-deoxy-D-xylulose 5-phosphate synthase were also differentially expressed and were associated with carotenoid and iridoid biosynthesis. These results suggest that the biosynthesis of specific terpenoids can be regulated by the homologous of key enzymes involved in plant terpenoid metabolism. Full article

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

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19 pages, 4897 KiB

Open AccessArticle

Screening of Differentially Expressed Genes and miRNAs in Hypothalamus and Pituitary Gland of Sheep under Different Photoperiods

by Qingqing Liu, Ran Di, Chunhuan Ren, Xiaoyun He, Xiangyu Wang, Qing Xia, Mingxing Chu and Zijun Zhang

Genes 2022, 13(6), 1091; https://doi.org/10.3390/genes13061091 - 19 Jun 2022

Cited by 4 | Viewed by 2779

Abstract

The reproduction of sheep is affected by many factors such as light, nutrition and genetics. The Hypothalamic-pituitary-gonadal (HPG) axis is an important pathway for sheep reproduction, and changes in HPG axis-related gene expression can affect sheep reproduction. In this study, a model of [...] Read more.

The reproduction of sheep is affected by many factors such as light, nutrition and genetics. The Hypothalamic-pituitary-gonadal (HPG) axis is an important pathway for sheep reproduction, and changes in HPG axis-related gene expression can affect sheep reproduction. In this study, a model of bilateral ovarian removal and estrogen supplementation (OVX + E₂) was applied to screen differentially expressed genes and miRNAs under different photoperiods using whole transcriptome sequencing and reveal the regulatory effects of the photoperiod on the upstream tissues of the HPG axis in sheep. Whole transcriptome sequencing was performed in ewe hypothalamus (HYP) and distal pituitary (PD) tissues under short photoperiod 21st day (SP21) and long photoperiod 21st day (LP21). Compared to the short photoperiod, a total of 1813 differential genes (up-regulation 966 and down-regulation 847) and 145 differential miRNAs (up-regulation 73 and down-regulation 72) were identified in the hypothalamus of long photoperiod group. Similarly, 2492 differential genes (up-regulation 1829 and down-regulation 663) and 59 differential miRNAs (up-regulation 49 and down-regulation 10) were identified in the pituitary of long photoperiod group. Subsequently, GO and KEGG enrichment analysis revealed that the differential genes and target genes of differential miRNA were enriched in GnRH, Wnt, ErbB and circadian rhythm pathways associated with reproduction. Combined with sequence complementation and gene expression correlation analysis, several miRNA-mRNA target combinations (e.g., LHB regulated by novel-414) were obtained. Taken together, these results will help to understand the regulatory effect of the photoperiod on the upstream tissues of HPG in sheep. Full article

(This article belongs to the Special Issue Gene Regulation of Development and Reproduction in Mammals)

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15 pages, 2921 KiB

Open AccessArticle

paPAML: An Improved Computational Tool to Explore Selection Pressure on Protein-Coding Sequences

by Raphael Steffen, Lynn Ogoniak, Norbert Grundmann, Anna Pawluchin, Oliver Soehnlein and Jürgen Schmitz

Genes 2022, 13(6), 1090; https://doi.org/10.3390/genes13061090 - 18 Jun 2022

Cited by 2 | Viewed by 4812

Abstract

Evolution is change over time. Although neutral changes promoted by drift effects are most reliable for phylogenetic reconstructions, selection-relevant changes are of only limited use to reconstruct phylogenies. On the other hand, comparative analyses of neutral and selected changes of protein-coding DNA sequences [...] Read more.

Evolution is change over time. Although neutral changes promoted by drift effects are most reliable for phylogenetic reconstructions, selection-relevant changes are of only limited use to reconstruct phylogenies. On the other hand, comparative analyses of neutral and selected changes of protein-coding DNA sequences (CDS) retrospectively tell us about episodic constrained, relaxed, and adaptive incidences. The ratio of sites with nonsynonymous (amino acid altering) versus synonymous (not altering) mutations directly measures selection pressure and can be analysed by using the Phylogenetic Analysis by Maximum Likelihood (PAML) software package. We developed a CDS extractor for compiling protein-coding sequences (CDS-extractor) and parallel PAML (paPAML) to simplify, amplify, and accelerate selection analyses via parallel processing, including detection of negatively selected sites. paPAML compiles results of site, branch-site, and branch models and detects site-specific negative selection with the output of a codon list labelling significance values. The tool simplifies selection analyses for casual and inexperienced users and accelerates computing speeds up to the number of allocated computer threads. We then applied paPAML to examine the evolutionary impact on a new GINS Complex Subunit 3 exon, and neutrophil-associated as well as lysin and apolipoprotein genes. Compared with codeml (PAML version 4.9j) and HyPhy (HyPhy FEL version 2.5.26), all paPAML test runs performed with 10 computing threads led to identical selection pressure results, whereas the total selection analysis via paPAML, including all model comparisons, was about 3 to 5 times faster than the longest running codeml model and about 7 to 15 times faster than the entire processing time of these codeml runs. Full article

(This article belongs to the Special Issue Mobile Elements in Phylogenomic Reconstructions)

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12 pages, 3296 KiB

Open AccessReview

Dominant Stickler Syndrome

by Zack Soh, Allan J. Richards, Annie McNinch, Philip Alexander, Howard Martin and Martin P. Snead

Genes 2022, 13(6), 1089; https://doi.org/10.3390/genes13061089 - 18 Jun 2022

Cited by 16 | Viewed by 5474

Abstract

The Stickler syndromes are a group of genetic connective tissue disorders associated with an increased risk of rhegmatogenous retinal detachment, deafness, cleft palate, and premature arthritis. This review article focuses on the molecular genetics of the autosomal dominant forms of the disease. Pathogenic [...] Read more.

The Stickler syndromes are a group of genetic connective tissue disorders associated with an increased risk of rhegmatogenous retinal detachment, deafness, cleft palate, and premature arthritis. This review article focuses on the molecular genetics of the autosomal dominant forms of the disease. Pathogenic variants in COL2A1 causing Stickler syndrome usually result in haploinsufficiency of the protein, whereas pathogenic variants of type XI collagen more usually exert dominant negative effects. The severity of the disease phenotype is thus dependent on the location and nature of the mutation, as well as the normal developmental role of the respective protein. Full article

(This article belongs to the Special Issue Genetics in Stickler Syndrome)

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10 pages, 753 KiB

Open AccessEditor’s ChoiceArticle

Toxoplasma gondii Seropositivity Interacts with Catechol-O-methyltransferase Val105/158Met Variation Increasing the Risk of Schizophrenia

by Paula Rovira, Blanca Gutiérrez, Antonio Sorlózano-Puerto, José Gutiérrez-Fernández, Esther Molina, Margarita Rivera, Rafael Martínez-Leal, Inmaculada Ibanez-Casas, María Victoria Martín-Laguna, Araceli Rosa, Francisco Torres-González and Jorge A. Cervilla

Genes 2022, 13(6), 1088; https://doi.org/10.3390/genes13061088 - 18 Jun 2022

Cited by 6 | Viewed by 2938

Abstract

Schizophrenia is a heterogeneous and severe psychotic disorder. Epidemiological findings have suggested that the exposure to infectious agents such as Toxoplasma gondii (T. gondii) is associated with an increased risk for schizophrenia. On the other hand, there is evidence involving the [...] Read more.

Schizophrenia is a heterogeneous and severe psychotic disorder. Epidemiological findings have suggested that the exposure to infectious agents such as Toxoplasma gondii (T. gondii) is associated with an increased risk for schizophrenia. On the other hand, there is evidence involving the catechol-O-methyltransferase (COMT) Val105/158Met polymorphism in the aetiology of schizophrenia since it alters the dopamine metabolism. A case–control study of 141 patients and 142 controls was conducted to analyse the polymorphism, the prevalence of anti-T. gondii IgG, and their interaction on the risk for schizophrenia. IgG were detected by ELISA, and genotyping was performed with TaqMan Real-Time PCR. Although no association was found between any COMT genotype and schizophrenia, we found a significant association between T. gondii seropositivity and the disorder (χ² = 11.71; p-value < 0.001). Furthermore, the risk for schizophrenia conferred by T. gondii was modified by the COMT genotype, with those who had been exposed to the infection showing a different risk compared to that of nonexposed ones depending on the COMT genotype (χ² for the interaction = 7.28, p-value = 0.007). This study provides evidence that the COMT genotype modifies the risk for schizophrenia conferred by T. gondii infection, with it being higher in those individuals with the Met/Met phenotype, intermediate in heterozygous, and lower in those with the Val/Val phenotype. Full article

(This article belongs to the Special Issue Advances in Genetics of Psychiatric Disorders)

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17 pages, 9746 KiB

Open AccessArticle

Characterization of Immune-Based Molecular Subtypes and Prognostic Model in Prostate Adenocarcinoma

by Li Guo, Yihao Kang, Daoliang Xia, Yujie Ren, Xueni Yang, Yangyang Xiang, Lihua Tang, Dekang Ren, Jiafeng Yu, Jun Wang and Tingming Liang

Genes 2022, 13(6), 1087; https://doi.org/10.3390/genes13061087 - 18 Jun 2022

Viewed by 2428

Abstract

Prostate adenocarcinoma (PRAD), also named prostate cancer, the most common visceral malignancy, is diagnosed in male individuals. Herein, in order to obtain immune-based subtypes, we performed an integrative analysis to characterize molecular subtypes based on immune-related genes, and further discuss the potential features [...] Read more.

Prostate adenocarcinoma (PRAD), also named prostate cancer, the most common visceral malignancy, is diagnosed in male individuals. Herein, in order to obtain immune-based subtypes, we performed an integrative analysis to characterize molecular subtypes based on immune-related genes, and further discuss the potential features and differences between identified subtypes. Simultaneously, we also construct an immune-based risk model to assess cancer prognosis. Our findings showed that the two subtypes, C1 and C2, could be characterized, and the two subtypes showed different characteristics that could clearly describe the heterogeneity of immune microenvironments. The C2 subtype presented a better survival rate than that in the C1 subtype. Further, we constructed an immune-based prognostic model based on four screened abnormally expressed genes, and they were selected as predictors of the robust prognostic model (AUC = 0.968). Our studies provide reference for characterization of molecular subtypes and immunotherapeutic agents against prostate cancer, and the developed robust and useful immune-based prognostic model can contribute to cancer prognosis and provide reference for the individualized treatment plan and health resource utilization. These findings further promote the development and application of precision medicine in prostate cancer. Full article

(This article belongs to the Topic Big Data in Healthcare, Bioinformatics and Precision Medicine)

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16 pages, 1511 KiB

Open AccessArticle

SSR-Based Molecular Identification and Population Structure Analysis for Forage Pea (Pisum sativum var. arvense L.) Landraces

by Kamil Haliloglu, Aras Turkoglu, Mustafa Tan and Peter Poczai

Genes 2022, 13(6), 1086; https://doi.org/10.3390/genes13061086 - 18 Jun 2022

Cited by 9 | Viewed by 2876

Abstract

Plant genetic diversity has a significant role in providing traits that can help meet future challenges, such as the need to adapt crops to changing climatic conditions or outbreaks of disease. Our aim in this study was to evaluate the diversity of 61 [...] Read more.

Plant genetic diversity has a significant role in providing traits that can help meet future challenges, such as the need to adapt crops to changing climatic conditions or outbreaks of disease. Our aim in this study was to evaluate the diversity of 61 forage pea specimens (P. sativum ssp. arvense L.) collected from the northeastern Anatolia region of Turkey using 28 simple sequence repeat (SSR) markers. These primers generated a total of 82 polymorphic bands. The number of observed alleles (Na) per primer varied from 2 to 4 with a mean of 2.89 alleles/locus. The mean value of expected heterozygosity (Exp-Het = 0.50) was higher than the mean value of observed heterozygosity (Obs-Het = 0.22). The mean of polymorphic information content (PIC) was 0.41 with a range of 0.03–0.70. The mean number of effective alleles (Ne) was found to be 2.15, Nei’s expected heterozygosity (H) 0.49, and Shannon’s information index (I) 0.81. Cluster analysis through the unweighted pair-group mean average (UPGMA) method revealed that 61 forage pea landraces were divided into three main clusters. Genetic dissimilarity between the genotypes, calculated with the use of NTSYS-pc software, varied between 0.10 (G30 and G34) and 0.66 (G1 and G32). Principal coordinate analysis (PCoA) revealed that three principal coordinates explained 51.54% of the total variation. Moreover, population structure analysis showed that all genotypes formed three sub-populations. Expected heterozygosity values varied between 0.2669 (the first sub-population) and 0.3223 (third sub-population), with an average value of 0.2924. Average population differentiation measurement (Fst) was identified as 0.2351 for the first sub-population, 0.3838 for the second sub-population, and 0.2506 for the third sub-population. In general, current results suggest that SSR markers could be constantly used to illuminate the genetic diversity of forage pea landraces and can potentially be incorporated into future studies that examine the diversity within a larger collection of forage pea genotypes from diverse regions. Full article

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

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11 pages, 429 KiB

Open AccessArticle

Prevalence of Pathogenic Germline BRCA1/2 Variants and Their Association with Clinical Characteristics in Patients with Epithelial Ovarian Cancer in a Rural Area of Japan

by Akiko Abe, Issei Imoto, Shoichiro Tange, Masato Nishimura and Takeshi Iwasa

Genes 2022, 13(6), 1085; https://doi.org/10.3390/genes13061085 - 18 Jun 2022

Cited by 1 | Viewed by 2706

Abstract

The prevalence of germline BRCA1 or BRCA2 pathogenic variants (gBRCA1/2-PV) in patients with primary epithelial ovarian cancer (OC) in a rural area of Japan and their association with clinical characteristics, including treatment response and survival outcome, were investigated. A total of [...] Read more.

The prevalence of germline BRCA1 or BRCA2 pathogenic variants (gBRCA1/2-PV) in patients with primary epithelial ovarian cancer (OC) in a rural area of Japan and their association with clinical characteristics, including treatment response and survival outcome, were investigated. A total of 123 unbiased patients with OC were tested for gBRCA1 and gBRCA2 using next-generation sequencing-based targeted amplicon sequencing. Clinical characteristics of OC patients with and without gBRCA1/2 status were compared. The overall prevalence of gBRCA1/2-PV was 15.4% (19 cases), with gBRCA2-PV (10.5%, 13 cases) being more common than gBRCA1-PV (4.9%, 6 cases). Among the observed gBRCA1/2-PV, several novel variants were included, suggesting that gBRCA1/2-PV unique to the local area exist. gBRCA1/2-PV was significantly more prevalent in OC patients at an older age, with high-grade serous carcinoma, with advanced-stage tumors, and with a family history of breast cancer or hereditary breast and ovarian cancer syndrome (HBOC)-associated cancers. Patients with advanced-stage OC with gBRCA1/2-PV showed a significantly lower recurrence rate and tended to have better progression-free and overall survival than those with wild-type gBRCA1/2. Genetic testing for gBRCA1/2 status in all OC patients is useful not only for diagnosing HBOC in patients and their relatives to assess the risk of HBOC-associated cancers, but also to estimate therapy response and outcomes in patients. Full article

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

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11 pages, 1627 KiB

Open AccessArticle

Identification of the Core Promoter and Variants Regulating Chicken CCKAR Expression

by Zhepeng Wang, Angus M. A. Reid, Peter W. Wilson and Ian C. Dunn

Genes 2022, 13(6), 1083; https://doi.org/10.3390/genes13061083 - 18 Jun 2022

Cited by 2 | Viewed by 1946

Abstract

Decreased expression of chicken cholecystokinin A receptor (CCKAR) attenuates satiety, which contributes to increased food intake and growth for modern broilers. The study aims to define the core promoter of CCKAR, and to identify variants associated with expression activity. A [...] Read more.

Decreased expression of chicken cholecystokinin A receptor (CCKAR) attenuates satiety, which contributes to increased food intake and growth for modern broilers. The study aims to define the core promoter of CCKAR, and to identify variants associated with expression activity. A 21 kb region around the CCKAR was re-sequenced to detect sequence variants. A series of 5′-deleted promoter plasmids were constructed to define the core promoter of CCKAR. The effects of sequence variants located in promoter (PSNP) and conserved (CSNP) regions on promoter activity were analyzed by comparing luciferase activity between haplotypes. A total of 182 variants were found in the 21 kb region. There were no large structural variants around CCKAR. pNL−328/+183, the one with the shortest insertion, showed the highest activity among the six promoter constructs, implying that the key cis elements regulating CCKAR expression are mainly distributed 328 bp upstream. We detected significant activity differences between high- and low-growth associated haplotypes in four of the six promoter constructs. The high-growth haplotypes of constructs pNL−1646/+183, pNL−799/+183 and pNL−528/+183 showed lower activities than the low-growth haplotypes, which is consistent with decreased expression of CCKAR in high-growth chickens. Lower expression of the high-growth allele was also detected for the CSNP5-containing construct. The data suggest that the core promoter of CCKAR is located the 328 bp region upstream from the transcription start site. Lower expression activities shown by the high-growth haplotypes in the reporter assay suggest that CSNP5 and variants located between 328 bp and 1646 bp upstream form a promising molecular basis for decreased expression of CCKAR and increased growth in chickens. Full article

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

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10 pages, 1629 KiB

Open AccessArticle

Strategy to Estimate Sample Sizes to Justify the Association between MMP1 SNP and Osteoarthritis

by Chung-Cheng Kao, Hsiang-En Hsu, Jen-Chieh Lai, Hsiang-Cheng Chen, Su-Wen Chuang and Meng-Chang Lee

Genes 2022, 13(6), 1084; https://doi.org/10.3390/genes13061084 - 17 Jun 2022

Cited by 4 | Viewed by 2050

Abstract

Background: the impact of knee osteoarthritis (OA) poses a formidable challenge to older adults. Studies have reported that genetic factors, such as MMP1, are one of important risk factors for knee OA. Although the relationship between the genetic polymorphism of MMP1 rs1799750 [...] Read more.

Background: the impact of knee osteoarthritis (OA) poses a formidable challenge to older adults. Studies have reported that genetic factors, such as MMP1, are one of important risk factors for knee OA. Although the relationship between the genetic polymorphism of MMP1 rs1799750 and the risk of knee OA has been explored, conclusions have been nonunanimous and pending due to research sample sizes, one of determinants in studying genetic polymorphisms associated with disease. Objective: to establish a model to assess whether the genetic polymorphism of MMP1 rs1799750 is associated with knee OA based on an estimation of sample sizes. Methods: samples were collected from a case–control and meta-analysis study. In the case–control study, patients who underwent knee X-ray examinations based on the Kellgren–Lawrence Grading System (KL) as diagnostic criteria were recruited at the Health Examination Center of the Tri-Service General Hospital from 2015 to 2019. Gene sequencing was conducted using iPLEX Gold. Those with unsuccessful gene sequencing were excluded. Finally, there were 569 patients in the knee OA group (KL ≥ 2) and 534 participants in the control group (KL < 2). In the meta-analysis, we used the databases PubMed, EMBASE, and Cochrane to search for studies on the relationship between MMP1 rs1799750 and knee OA. Next, we adopted the trial sequential analysis (TSA) method to assess whether sample sizes were sufficient or not to determine the risk of the genetic polymorphism of MMP1 rs1799750 on knee OA in Caucasians and Asians. Results: in Caucasians, the MMP1 rs1799750 was not significantly associated with knee OA with an odds ratios (OR) of 1.10 (95% confidence interval, CI: 0.45–2.68). Some extra 8559 samples were needed to conclude this relationship in Caucasians by the TSA model. In Asians, neither our case–control study results (n = 1103) nor a combination of samples from the case–control and meta-analysis results showed an association between MMP1 rs1799750 and knee OA. The OR (95% CI) was 1.10 (0.81–1.49) in a combination of Asian samples. Some extra 5517 samples were needed to justify this relationship in Asians by the TSA model. Conclusions: this research shows that an extra 8559 and 5517 samples are needed in Caucasians and Asians, respectively, in order to justify the association between MMP1 rs1799750 and knee OA. Full article

(This article belongs to the Special Issue Genetic Risks and Molecular Epidemiology of Osteoarthritis)

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14 pages, 4854 KiB

Open AccessEditor’s ChoiceArticle

Tubulin TUBB4B Is Involved in Spermatogonia Proliferation and Cell Cycle Processes

by Meiying Feng, Kai Wang, Shuying Fu, Hengxi Wei, Xiaokun Mu, Li Li and Shouquan Zhang

Genes 2022, 13(6), 1082; https://doi.org/10.3390/genes13061082 - 17 Jun 2022

Cited by 5 | Viewed by 2911

Abstract

Tubb4b (tubulin β-4b chain) is essential for cell growth and development as a microtubule network protein. Previous studies have shown that TUBB4B affects mouse pronucleus migration, but the gene function has yet to be elucidated. To study TUBB4B-related functions in mouse reproductive development, [...] Read more.

Tubb4b (tubulin β-4b chain) is essential for cell growth and development as a microtubule network protein. Previous studies have shown that TUBB4B affects mouse pronucleus migration, but the gene function has yet to be elucidated. To study TUBB4B-related functions in mouse reproductive development, we designed a single sgRNA in chromosome 2 and generated a knockout spermatogonia cell line of the β-tubulin isoform Tubb4b by the CRISPR/Cas9 system. Tubb4b-KO spermatogonia recognized abnormal lysosomal membranes and cell morphology defects. Compared to control mouse spermatogonia, the proliferation rate was significantly slower and cycling stagnated in the G1/0 population. Although spermatogonia lacking TUBB4B have abnormal divisions, they are not lethal. We detected the mRNA levels of the cell-regulating cyclins CyclinsD1, CyclinsE, Cdk2, Cdk4, P21, Skp2 and the cell growth factors C/EBP α, C/EBP β, and G-CSF in the spermatogonia of Tubb4b-KO and found that the expressions of CyclinsD1, Skp2 and cell growth factors were significantly reduced. Further analysis revealed that 675 genes were expressed differently after Tubb4b deletion and were enriched in negative regulation of cell population proliferation (GO:0008285), negative regulation of cell cycle G2/M phase transition (GO:1902750), and positive regulation of cell death (GO: 0010942). We also found that there is a common gene Cdkn1a (P21) in these three GO pathways related to cell proliferation and cell cycle, and both quantitative analysis and transcriptome sequencing results showed that the expression of this gene was up-regulated in Tubb4b knockout cells. This implies that Tubb4b may be involved in the division of spermatogonia with multiple cell cycle regulatory proteins. Overall, these data indicate that Tubb4b has a specific role in regulating spermatogonia proliferation and cell cycle. Full article

(This article belongs to the Special Issue Studies on Developmental Genetic Programs of Animal Early Embryogenesis)

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15 pages, 970 KiB

Open AccessReview

Network-Based Methods for Approaching Human Pathologies from a Phenotypic Point of View

by Juan A. G. Ranea, James Perkins, Mónica Chagoyen, Elena Díaz-Santiago and Florencio Pazos

Genes 2022, 13(6), 1081; https://doi.org/10.3390/genes13061081 - 17 Jun 2022

Cited by 4 | Viewed by 3081

Abstract

Network and systemic approaches to studying human pathologies are helping us to gain insight into the molecular mechanisms of and potential therapeutic interventions for human diseases, especially for complex diseases where large numbers of genes are involved. The complex human pathological landscape is [...] Read more.

Network and systemic approaches to studying human pathologies are helping us to gain insight into the molecular mechanisms of and potential therapeutic interventions for human diseases, especially for complex diseases where large numbers of genes are involved. The complex human pathological landscape is traditionally partitioned into discrete “diseases”; however, that partition is sometimes problematic, as diseases are highly heterogeneous and can differ greatly from one patient to another. Moreover, for many pathological states, the set of symptoms (phenotypes) manifested by the patient is not enough to diagnose a particular disease. On the contrary, phenotypes, by definition, are directly observable and can be closer to the molecular basis of the pathology. These clinical phenotypes are also important for personalised medicine, as they can help stratify patients and design personalised interventions. For these reasons, network and systemic approaches to pathologies are gradually incorporating phenotypic information. This review covers the current landscape of phenotype-centred network approaches to study different aspects of human diseases. Full article

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

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17 pages, 3481 KiB

Open AccessArticle

Transcriptome and Differentially Expressed Gene Profiles in Mycelium, Primordium and Fruiting Body Development in Stropharia rugosoannulata

by Haibo Hao, Jinjing Zhang, Qian Wang, Jianchun Huang, Jiaxiang Juan, Benke Kuai, Zhiyong Feng and Hui Chen

Genes 2022, 13(6), 1080; https://doi.org/10.3390/genes13061080 - 17 Jun 2022

Cited by 8 | Viewed by 3192

Abstract

Stropharia rugosoannulata uses straw as a growth substrate during artificial cultivation and has been widely promoted in China. However, its fruiting body formation and development processes have not been elucidated. In this study, the developmental transcriptomes were analyzed at three stages: the mycelium [...] Read more.

Stropharia rugosoannulata uses straw as a growth substrate during artificial cultivation and has been widely promoted in China. However, its fruiting body formation and development processes have not been elucidated. In this study, the developmental transcriptomes were analyzed at three stages: the mycelium (G-S), primordium (P-S) and fruiting body (M-F) stages. A total of 9690 differentially expressed genes (DEGs) were identified in the different developmental stages. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that these DEGs were involved mainly in hydrolase activity, structural molecule activity and oxidoreductase activity as well as xenobiotic biodegradation and metabolism and energy metabolism pathways. We further found that the higher expression of most carbohydrate enzyme (i.e., GH, CE, CBM, AA and PL) genes in the hyphal (i.e., G-S) stage was related mainly to substrate degradation, while the upregulation of glycosyltransferase (GT) gene expression in the P-S and M-F stages may be related to cell wall synthesis. In addition, we found that CO₂-sensing-related genes (i.e., CA-2, CA-3, PKA-1 and PKA-2) were upregulated in the P-S and M-F stages, heat shock protein genes (HSP60 and HSP90) were significantly downregulated in the P-S stage and upregulated in the M-F stage and the transcription factors (i.e., steA, MYB, nosA, HAP1, and GATA-4/5/6) involved in growth and development were significantly upregulated in the P-S stage. These results suggest that environmental factors (i.e., CO₂ and temperature) and transcription factors may play a key role in primordium formation. In short, this study provides new insights into the study of stimulating primordia formation affecting the development of fruiting bodies of S. rugosoannulata. Full article

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

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6 pages, 228 KiB

Open AccessArticle

Investigation of Dombrock Blood Group Alleles and Genotypes among Saudi Blood Donors in Southwestern Saudi Arabia

by Amr J. Halawani, Abdullah S. Mansor, Hamza M. Assaggaf, Hibah A. Almasmoum, Hisham I. Abu-Tawil, Khalaf F. Alsharif, Gasim Dobie and Mahmoud M. Habibullah

Genes 2022, 13(6), 1079; https://doi.org/10.3390/genes13061079 - 17 Jun 2022

Cited by 1 | Viewed by 2781

Abstract

The Dombrock (DO) blood group system has two primary antigens, Do^a and Do^b, which can cause delayed hemolytic transfusion reactions. The paucity of specific monospecific antibodies can hamper the typing based on these antigens. Thus, blood group genotyping (BGG) was [...] Read more.

The Dombrock (DO) blood group system has two primary antigens, Do^a and Do^b, which can cause delayed hemolytic transfusion reactions. The paucity of specific monospecific antibodies can hamper the typing based on these antigens. Thus, blood group genotyping (BGG) was investigated as a possible solution. Sequence-specific primers were designed to target a single nucleotide polymorphism (rs11276) on the ART4 gene encoding the DO*A and DO*B alleles. Blood samples (n = 150) from randomly selected volunteer donors were used. DNA was extracted and resulting PCR products were purified and sequenced. The allelic frequencies of DO*A and DO*B were (n = 122, 40.67%) and (n = 178, 59.33%), respectively. The distributions of DO genotypes were as follows: DO*A/DO*A (n = 20), 13.33%; DO*B/DO*B (n = 48), 32.00%; and DO*A/DO*B (n = 82), 54.67%. In conclusion, this study reports on the allelic frequencies of DO*A and DO*B of the DO blood group system in Jazan Province, Kingdom of Saudi Arabia. Furthermore, this study reports on the prevalence of each genotype, of which DO*A/DO*B was the most abundant. This study contributes significantly to build the current blood donor database in Southwestern Saudi Arabia. Moreover, it may assist in providing safe blood to polytransfused patients and reduce the risk of the red cell alloimmunization. Full article

(This article belongs to the Special Issue Genetics of Human Blood Group Antigens)

15 pages, 5132 KiB

Open AccessArticle

Antioxidant Activity of Phenolic Extraction from Different Sweetpotato (Ipomoea batatas (L.) Lam.) Blades and Comparative Transcriptome Analysis Reveals Differentially Expressed Genes of Phenolic Metabolism in Two Genotypes

by Peitao Chen, Hairong Ran, Jiaxin Li, Jikai Zong, Qingqing Luo, Tengfei Zhao, Zhihua Liao, Yueli Tang and Yufan Fu

Genes 2022, 13(6), 1078; https://doi.org/10.3390/genes13061078 - 16 Jun 2022

Cited by 8 | Viewed by 2556

Abstract

Sweetpotato (Ipomoea batatas (L.) Lam.), which has a complex genome, is one of the most important storage root crops in the world. Sweetpotato blades are considered as a potential source of natural antioxidants owing to their high phenolic content with powerful free [...] Read more.

Sweetpotato (Ipomoea batatas (L.) Lam.), which has a complex genome, is one of the most important storage root crops in the world. Sweetpotato blades are considered as a potential source of natural antioxidants owing to their high phenolic content with powerful free radical scavenging ability. The molecular mechanism of phenolic metabolism in sweetpotato blades has been seldom reported thus far. In this work, 23 sweetpotato genotypes were used for the analysis of their antioxidant activity, total polyphenol content (TPC) and total flavonoid content (TFC). ‘Shangshu19’ and ‘Wan1314-6’ were used for RNA-seq. The results showed that antioxidant activity, TPC and TFC of 23 genotypes had significant difference. There was a significant positive correlation between TPC, TFC and antioxidant activity. The RNA-seq analysis results of two genotypes, ‘Shangshu19’ and ‘Wan1314-6’, which had significant differences in antioxidant activity, TPC and TFC, showed that there were 7810 differentially expressed genes (DEGs) between the two genotypes. Phenylpropanoid biosynthesis was the main differential pathway, and upregulated genes were mainly annotated to chlorogenic acid, flavonoid and lignin biosynthesis pathways. Our results establish a theoretical and practical basis for sweetpotato breeding with antioxidant activity and phenolics in the blades and provide a theoretical basis for the study of phenolic metabolism engineering in sweetpotato blade. Full article

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

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15 pages, 2715 KiB

Open AccessEditor’s ChoiceArticle

Vasa Is a Potential Germ Cell Marker in Leopard Coral Grouper (Plectropomus leopardus)

by Mingyi Wang, Hui Ding, Shaoxuan Wu, Mengya Wang, Cun Wei, Bo Wang, Zhenmin Bao and Jingjie Hu

Genes 2022, 13(6), 1077; https://doi.org/10.3390/genes13061077 - 16 Jun 2022

Cited by 5 | Viewed by 2645

Abstract

Vasa (Ddx4, DEAD box polypeptide 4), an extremely specific marker of germ cells in vivo, is an ATP-dependent RNA helicase that plays an essential role in germ cell development and gametogenesis. However, the expression and function information about this gene in [...] Read more.

Vasa (Ddx4, DEAD box polypeptide 4), an extremely specific marker of germ cells in vivo, is an ATP-dependent RNA helicase that plays an essential role in germ cell development and gametogenesis. However, the expression and function information about this gene in groupers remains lacking. Here, vasa homolog termed Plvasa was isolated and identified Plvasa as a putative germ cell marker in the leopard coral grouper, (Plectropomus leopardus). Results indicated that Plvasa contained 17 exons in the genomic sequence and 9 conserved motifs of the DEAD-box protein by sequence analysis. The sequence comparison, phylogenetic analyses and synteny analyses showed that Plvasa was homologous with other teleosts. Additionally, the expression of Plvasa was significantly higher in gonads than in other tissues in adult individuals (p < 0.05). Further, the distribution of Plvasa revealed that it was only expressed in the germ cells, such as spermatids, germline stem cells and oocytes at different stages, and could not be detected in the somatic cells of gonads. The current study verified that the Plvasa gene is a valuable molecular marker of germ cells in leopard coral grouper, which potentially plays an important role in investigating the genesis and development of teleost germ cells. Full article

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

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15 pages, 1276 KiB

Open AccessFeature PaperArticle

Genetic Profile of Patients with Limb-Girdle Muscle Weakness in the Chilean Population

by Mathieu Cerino, Patricio González-Hormazábal, Mario Abaji, Sebastien Courrier, Francesca Puppo, Yves Mathieu, Alejandra Trangulao, Nicholas Earle, Claudia Castiglioni, Jorge Díaz, Mario Campero, Ricardo Hughes, Carmen Vargas, Rocío Cortés, Karin Kleinsteuber, Ignacio Acosta, J. Andoni Urtizberea, Nicolas Lévy, Marc Bartoli, Martin Krahn, Lilian Jara, Pablo Caviedes, Svetlana Gorokhova and Jorge A. Bevilacqua Show full author list Hide full author list

Genes 2022, 13(6), 1076; https://doi.org/10.3390/genes13061076 - 16 Jun 2022

Cited by 5 | Viewed by 3007

Abstract

Hereditary myopathies are a group of genetically determined muscle disorders comprising more than 300 entities. In Chile, there are no specific registries of the distinct forms of these myopathies. We now report the genetic findings of a series of Chilean patients presenting with [...] Read more.

Hereditary myopathies are a group of genetically determined muscle disorders comprising more than 300 entities. In Chile, there are no specific registries of the distinct forms of these myopathies. We now report the genetic findings of a series of Chilean patients presenting with limb-girdle muscle weakness of unknown etiology. Eighty-two patients were explored using high-throughput sequencing approaches with neuromuscular gene panels, establishing a definite genetic diagnosis in 49 patients (59.8%) and a highly probable genetic diagnosis in eight additional cases (9.8%). The most frequent causative genes identified were DYSF and CAPN3, accounting for 22% and 8.5% of the cases, respectively, followed by DMD (4.9%) and RYR1 (4.9%). The remaining 17 causative genes were present in one or two cases only. Twelve novel variants were identified. Five patients (6.1%) carried a variant of uncertain significance in genes partially matching the clinical phenotype. Twenty patients (24.4%) did not carry a pathogenic or likely pathogenic variant in the phenotypically related genes, including five patients (6.1%) presenting an autoimmune neuromuscular disorder. The relative frequency of the different forms of myopathy in Chile is like that of other series reported from different regions of the world with perhaps a relatively higher incidence of dysferlinopathy. Full article

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

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15 pages, 2695 KiB

Open AccessArticle

Identification of Putative SNP Markers Associated with Resistance to Egyptian Loose Smut Race(s) in Spring Barley

by Kamal A. M. Abo-Elyousr, Amira M. I. Mourad, P. Stephen Baenziger, Abdelaal H. A. Shehata, Peter E. Eckstein, Aaron D. Beattie and Ahmed Sallam

Genes 2022, 13(6), 1075; https://doi.org/10.3390/genes13061075 - 16 Jun 2022

Cited by 6 | Viewed by 2684

Abstract

Loose smut (LS) disease is a serious problem that affects barley yield. Breeding of resistant cultivars and identifying new genes controlling LS has received very little attention. Therefore, it is important to understand the genetic basis of LS control in order to genetically [...] Read more.

Loose smut (LS) disease is a serious problem that affects barley yield. Breeding of resistant cultivars and identifying new genes controlling LS has received very little attention. Therefore, it is important to understand the genetic basis of LS control in order to genetically improve LS resistance. To address this challenge, a set of 57 highly diverse barley genotypes were inoculated with Egyptian loose smut race(s) and the infected seeds/plants were evaluated in two growing seasons. Loose smut resistance (%) was scored on each genotype. High genetic variation was found among all tested genotypes indicating considerable differences in LS resistance that can be used for breeding. The broad-sense heritability (H²) of LS (0.95) was found. Moreover, genotyping-by-sequencing (GBS) was performed on all genotypes and generated in 16,966 SNP markers which were used for genetic association analysis using single-marker analysis. The analysis identified 27 significant SNPs distributed across all seven chromosomes that were associated with LS resistance. One SNP (S6_17854595) was located within the HORVU6Hr1G010050 gene model that encodes a protein kinase domain-containing protein (similar to the Un8 LS resistance gene, which contains two kinase domains). A TaqMan marker (0751D06 F6/R6) for the Un8 gene was tested in the diverse collection. The results indicated that none of the Egyptian genotypes had the Un8 gene. The result of this study provided new information on the genetic control of LS resistance. Moreover, good resistance genotypes were identified and can be used for breeding cultivars with improved resistance to Egyptian LS. Full article

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

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16 pages, 3488 KiB

Open AccessArticle

First Report of Complete Mitochondrial Genome in the Tribes Coomaniellini and Dicercini (Coleoptera: Buprestidae) and Phylogenetic Implications

by Xuyan Huang, Bo Chen, Zhonghua Wei and Aimin Shi

Genes 2022, 13(6), 1074; https://doi.org/10.3390/genes13061074 - 16 Jun 2022

Cited by 11 | Viewed by 2235

Abstract

The complete mitochondrial genomes (mitogenomes) of the tribes Coomaniellini and Dicercini were sequenced and described in this study, including Coomaniella copipes (16,196 bp), Coomaniella dentata (16,179 bp), and Dicerca corrugata (16,276 bp). These complete mitogenomes are very similar in length and encoded 37 [...] Read more.

The complete mitochondrial genomes (mitogenomes) of the tribes Coomaniellini and Dicercini were sequenced and described in this study, including Coomaniella copipes (16,196 bp), Coomaniella dentata (16,179 bp), and Dicerca corrugata (16,276 bp). These complete mitogenomes are very similar in length and encoded 37 typical mitochondrial genes, including 22 transfer RNA genes (tRNAs), 2 ribosomal RNA genes (rRNAs) and 13 protein-coding genes (PCGs). Most of PCGs had typical ATN start codons and terminated with TAR. Among these mitogenomes, Leu2 (L2), Ile (I), Ser2 (S2), and Phe (F) were the four most frequently encoded amino acids. Moreover, phylogenetic analyses were performed based on three kinds of nucleotide matrixes (13 PCGs, 2 rRNAs, and 13 PCGs + 2 rRNAs) among the available sequenced species of the family Buprestidae using Bayesian inference and Maximum-likelihood methods. The results showed that a Chrysochroninae species interspersed in Buprestinae, and Coomaniellini is more closely related to Dicercini than Melanophilini. Moreover, the clade of Buprestidae was well separated from outgroups and the monophyly of Agrilinae is confirmed again. Our whole mitogenome phylogenetic results support that the genus Dicerca can be transferred from Chrysochroinae to Buprestinae; whether Dicercini can be completely transferred remains to be further verified after enriching samples. Our results have produced new complete mitogenomic data, which will provide information for future phylogenetic and taxonomic research. Full article

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

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11 pages, 2868 KiB

Open AccessArticle

Robust Prediction of Prognosis and Immunotherapy Response for Bladder Cancer through Machine Learning Algorithm

by Shanshan Hu, Shengying Gu, Shuowen Wang, Chendong Qi, Chenyang Shi, Fengdan Qian and Guorong Fan

Genes 2022, 13(6), 1073; https://doi.org/10.3390/genes13061073 - 16 Jun 2022

Cited by 3 | Viewed by 2630

Abstract

The important roles of machine learning and ferroptosis in bladder cancer (BCa) are still poorly understood. In this study, a comprehensive analysis of 19 ferroptosis-related genes (FRGs) was performed in 1322 patients with BCa from four independent patient cohorts and a pan-cancer cohort [...] Read more.

The important roles of machine learning and ferroptosis in bladder cancer (BCa) are still poorly understood. In this study, a comprehensive analysis of 19 ferroptosis-related genes (FRGs) was performed in 1322 patients with BCa from four independent patient cohorts and a pan-cancer cohort of 9824 patients. Twelve FRGs were selected through machine learning algorithm to construct the prognosis model. Significantly differential survival outcomes (hazard ratio (HR) = 2.09, 95% confidence interval (CI): 1.55–2.82, p < 0.0001) were observed between patients with high and low ferroptosis scores in the TCGA cohort, which was also verified in the E-MTAB-4321 cohort (HR = 4.71, 95% CI: 1.58–14.03, p < 0.0001), the GSE31684 cohort (HR = 1.76, 95% CI: 1.08–2.87, p = 0.02), and the pan-cancer cohort (HR = 1.15, 95% CI: 1.07–1.24, p < 0.0001). Tumor immunity-related pathways, including the IL-17 signaling pathway and JAK-STAT signaling pathway, were found to be associated with the ferroptosis score in BCa through a functional enrichment analysis. Further verification in the IMvigor210 cohort revealed the BCa patients with high ferroptosis scores tended to have worse survival outcome after receiving tumor immunotherapy. Significantly different ferroptosis scores could also be found between BCa patients with different reactions to treatment with immune checkpoint inhibitors. Full article

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

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Genes, Volume 13, Issue 6 (June 2022) – 168 articles

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