Genes

14 pages, 2161 KiB

Open AccessEditor’s ChoiceArticle

Identification of LncRNAs and Functional Analysis of ceRNA Related to Fatty Acid Synthesis during Flax Seed Development

by Xinsen Yang, Caiyue Liu, Qiaoling Tang, Tianbao Zhang, Limin Wang, Lida Han, Jianping Zhang and Xinwu Pei

Genes 2023, 14(5), 967; https://doi.org/10.3390/genes14050967 - 24 Apr 2023

Cited by 3 | Viewed by 1854

Abstract

Flax is a flowering plant cultivated for its oil and contains various unsaturated fatty acids. Linseed oil is known as the “deep-sea fish oil” of plants, and is beneficial to brain and blood lipids, among other positive effects. Long non-coding RNAs (lncRNAs) play [...] Read more.

Flax is a flowering plant cultivated for its oil and contains various unsaturated fatty acids. Linseed oil is known as the “deep-sea fish oil” of plants, and is beneficial to brain and blood lipids, among other positive effects. Long non-coding RNAs (lncRNAs) play an important role in plant growth and development. There are not many studies assessing how lncRNAs are related to the fatty acid synthesis of flax. The relative oil contents of the seeds of the variety Heiya NO.14 (for fiber) and the variety Macbeth (for oil) were determined at 5 day, 10 day, 20 day, and 30 day after flowering. We found that 10–20 day is an important period for ALA accumulation in the Macbeth variety. The strand-specific transcriptome data were analyzed at these four time points, and a series of lncRNAs related to flax seed development were screened. A competing endogenous RNA (ceRNA) network was constructed and the accuracy of the network was verified using qRT-PCR. MSTRG.20631.1 could act with miR156 on the same target, squamosa promoter-binding-like protein (SPL), to influence fatty acid biosynthesis through a gluconeogenesis-related pathway during flax seed development. This study provides a theoretical basis for future studies assessing the potential functions of lncRNAs during seed development. Full article

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

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14 pages, 637 KiB

Open AccessEditor’s ChoiceArticle

Prognostic Values of Gene Copy Number Alterations in Prostate Cancer

by Abdulaziz Alfahed, Henry Okuchukwu Ebili, Nasser Eissa Almoammar, Glowi Alasiri, Osama A. AlKhamees, Jehad A. Aldali, Ayoub Al Othaim, Zaki H. Hakami, Abdulhadi M. Abdulwahed and Hisham Ali Waggiallah

Genes 2023, 14(5), 956; https://doi.org/10.3390/genes14050956 - 22 Apr 2023

Cited by 7 | Viewed by 3050

Abstract

Whilst risk prediction for individual prostate cancer (PCa) cases is of a high priority, the current risk stratification indices for PCa management have severe limitations. This study aimed to identify gene copy number alterations (CNAs) with prognostic values and to determine if any [...] Read more.

Whilst risk prediction for individual prostate cancer (PCa) cases is of a high priority, the current risk stratification indices for PCa management have severe limitations. This study aimed to identify gene copy number alterations (CNAs) with prognostic values and to determine if any combination of gene CNAs could have risk stratification potentials. Clinical and genomic data of 500 PCa cases from the Cancer Genome Atlas stable were retrieved from the Genomic Data Commons and cBioPortal databases. The CNA statuses of a total of 52 genetic markers, including 21 novel markers and 31 previously identified potential prognostic markers, were tested for prognostic significance. The CNA statuses of a total of 51/52 genetic markers were significantly associated with advanced disease at an odds ratio threshold of ≥1.5 or ≤0.667. Moreover, a Kaplan–Meier test identified 27/52 marker CNAs which correlated with disease progression. A Cox Regression analysis showed that the amplification of MIR602 and deletions of MIR602, ZNF267, MROH1, PARP8, and HCN1 correlated with a progression-free survival independent of the disease stage and Gleason prognostic group grade. Furthermore, a binary logistic regression analysis identified twenty-two panels of markers with risk stratification potentials. The best model of 7/52 genetic CNAs, which included the SPOP alteration, SPP1 alteration, CCND1 amplification, PTEN deletion, CDKN1B deletion, PARP8 deletion, and NKX3.1 deletion, stratified the PCa cases into a localised and advanced disease with an accuracy of 70.0%, sensitivity of 85.4%, specificity of 44.9%, positive predictive value of 71.67%, and negative predictive value of 65.35%. This study validated prognostic gene level CNAs identified in previous studies, as well as identified new genetic markers with CNAs that could potentially impact risk stratification in PCa. Full article

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

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12 pages, 1531 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Japanese Flounder pol-miR-155 Is Involved in Edwardsiella tarda Infection via ATG3

by Zhanwei Zhang and Xiaolu Guan

Genes 2023, 14(5), 958; https://doi.org/10.3390/genes14050958 - 22 Apr 2023

Cited by 5 | Viewed by 2011

Abstract

MicroRNAs (miRNAs) are small RNA molecules that function in the post-transcriptionally regulation of the expression of diverse genes, including those involved in immune defense. Edwardsiella tarda can infect a broad range of hosts and cause severe disease in aquatic species, including Japanese flounder [...] Read more.

MicroRNAs (miRNAs) are small RNA molecules that function in the post-transcriptionally regulation of the expression of diverse genes, including those involved in immune defense. Edwardsiella tarda can infect a broad range of hosts and cause severe disease in aquatic species, including Japanese flounder (Paralichthys olivaceus). In this study, we examined the regulation mechanism of a flounder miRNA, pol-miR-155, during the infection of E. tarda. Pol-miR-155 was identified to target flounder ATG3. Overexpression of pol-miR-155 or knockdown of ATG3 expression suppressed autophagy and promoted the intracellular replication of E. tarda in flounder cells. Overexpression of pol-miR-155 activated the NF-κB signaling pathway and further promoted the expression of downstream immune related genes of interleukin (IL)-6 and IL-8. These results unraveled the regulatory effect of pol-miR-155 in autophagy and in E. tarda infection. Full article

(This article belongs to the Special Issue Advances in Genes and Genomics of Aquatic Animals and Pathogens)

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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 4655

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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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 2378

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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42 pages, 3406 KiB

Open AccessEditor’s ChoiceReview

The Hexosamine Biosynthesis Pathway: Regulation and Function

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

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

Cited by 84 | Viewed by 15355

Abstract

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

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

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

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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 2749

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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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 3268

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, 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 3205

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 2589

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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23 pages, 2815 KiB

Open AccessEditor’s ChoiceArticle

Whole Mitochondrial Genome Detection and Analysis of Two- to Four-Generation Maternal Pedigrees Using a New Massively Parallel Sequencing Panel

by Dan Peng, Jiaojiao Geng, Jingyi Yang, Jiajun Liu, Nana Wang, Riga Wu and Hongyu Sun

Genes 2023, 14(4), 912; https://doi.org/10.3390/genes14040912 - 14 Apr 2023

Cited by 7 | Viewed by 2653

Abstract

Mitochondrial DNA (mtDNA) is an effective genetic marker in forensic practice, especially for aged bones and hair shafts. Detection of the whole mitochondrial genome (mtGenome) using traditional Sanger-type sequencing is laborious and time-consuming. Additionally, its ability to distinguish point heteroplasmy (PHP) and length [...] Read more.

Mitochondrial DNA (mtDNA) is an effective genetic marker in forensic practice, especially for aged bones and hair shafts. Detection of the whole mitochondrial genome (mtGenome) using traditional Sanger-type sequencing is laborious and time-consuming. Additionally, its ability to distinguish point heteroplasmy (PHP) and length heteroplasmy (LHP) is limited. The application of massively parallel sequencing in mtDNA detection helps researchers to study the mtGenome in-depth. The ForenSeq mtDNA Whole Genome Kit, which contains a total of 245 short amplicons, is one of the multiplex library preparation kits for the mtGenome. We used this system to detect the mtGenome in the blood samples and hair shafts of thirty-three individuals from eight two-generation pedigrees, one three-generation pedigree, and one four-generation pedigree. High-quality sequencing results were obtained. Ten unique mtGenome haplotypes were observed in the mothers from the ten pedigrees. A total of 26 PHPs were observed using the interpretation threshold of 6%. Eleven types of LHPs in six regions were evaluated in detail. When considering homoplasmic variants only, consistent mtGenome haplotypes were observed between the twice-sequenced libraries and between the blood and hair shafts from the same individual and among maternal relatives in the pedigrees. Four inherited PHPs were observed, and the remainder were de novo/disappearing PHPs in the pedigrees. Our results demonstrate the effective capability of the ForenSeq mtDNA Whole Genome Kit to generate the complete mtGenome in blood and hair shafts, as well as the complexity of mtDNA haplotype comparisons between different types of maternal relatives when heteroplasmy is considered. Full article

(This article belongs to the Special Issue Advances in Forensic Molecular Genetics)

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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 2328

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 2959

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, 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 3046

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 4209

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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27 pages, 13999 KiB

Open AccessEditor’s ChoiceArticle

Chromosome-Level Genome Assembly of the Blue Mussel Mytilus chilensis Reveals Molecular Signatures Facing the Marine Environment

by Cristian Gallardo-Escárate, Valentina Valenzuela-Muñoz, Gustavo Nuñez-Acuña, Diego Valenzuela-Miranda, Fabian J. Tapia, Marco Yévenes, Gonzalo Gajardo, Jorge E. Toro, Pablo A. Oyarzún, Gloria Arriagada, Beatriz Novoa, Antonio Figueras, Steven Roberts and Marco Gerdol

Genes 2023, 14(4), 876; https://doi.org/10.3390/genes14040876 - 7 Apr 2023

Cited by 17 | Viewed by 4799

Abstract

The blue mussel Mytilus chilensis is an endemic and key socioeconomic species inhabiting the southern coast of Chile. This bivalve species supports a booming aquaculture industry, which entirely relies on artificially collected seeds from natural beds that are translocated to diverse physical–chemical ocean [...] Read more.

The blue mussel Mytilus chilensis is an endemic and key socioeconomic species inhabiting the southern coast of Chile. This bivalve species supports a booming aquaculture industry, which entirely relies on artificially collected seeds from natural beds that are translocated to diverse physical–chemical ocean farming conditions. Furthermore, mussel production is threatened by a broad range of microorganisms, pollution, and environmental stressors that eventually impact its survival and growth. Herein, understanding the genomic basis of the local adaption is pivotal to developing sustainable shellfish aquaculture. We present a high-quality reference genome of M. chilensis, which is the first chromosome-level genome for a Mytilidae member in South America. The assembled genome size was 1.93 Gb, with a contig N50 of 134 Mb. Through Hi-C proximity ligation, 11,868 contigs were clustered, ordered, and assembled into 14 chromosomes in congruence with the karyological evidence. The M. chilensis genome comprises 34,530 genes and 4795 non-coding RNAs. A total of 57% of the genome contains repetitive sequences with predominancy of LTR-retrotransposons and unknown elements. Comparative genome analysis of M. chilensis and M. coruscus was conducted, revealing genic rearrangements distributed into the whole genome. Notably, transposable Steamer-like elements associated with horizontal transmissible cancer were explored in reference genomes, suggesting putative relationships at the chromosome level in Bivalvia. Genome expression analysis was also conducted, showing putative genomic differences between two ecologically different mussel populations. The evidence suggests that local genome adaptation and physiological plasticity can be analyzed to develop sustainable mussel production. The genome of M. chilensis provides pivotal molecular knowledge for the Mytilus complex. Full article

(This article belongs to the Special Issue Genetics and Genomics in Aquatic Animals)

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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 2374

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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34 pages, 2226 KiB

Open AccessEditor’s ChoiceReview

An Update of Epigenetic Drugs for the Treatment of Cancers and Brain Diseases: A Comprehensive Review

by Zahra Sahafnejad, Shahin Ramazi and Abdollah Allahverdi

Genes 2023, 14(4), 873; https://doi.org/10.3390/genes14040873 - 6 Apr 2023

Cited by 50 | Viewed by 7893

Abstract

Epigenetics has long been recognized as a significant field in biology and is defined as the investigation of any alteration in gene expression patterns that is not attributed to changes in the DNA sequences. Epigenetic marks, including histone modifications, non-coding RNAs, and DNA [...] Read more.

Epigenetics has long been recognized as a significant field in biology and is defined as the investigation of any alteration in gene expression patterns that is not attributed to changes in the DNA sequences. Epigenetic marks, including histone modifications, non-coding RNAs, and DNA methylation, play crucial roles in gene regulation. Numerous studies in humans have been carried out on single-nucleotide resolution of DNA methylation, the CpG island, new histone modifications, and genome-wide nucleosome positioning. These studies indicate that epigenetic mutations and aberrant placement of these epigenetic marks play a critical role in causing the disease. Consequently, significant development has occurred in biomedical research in identifying epigenetic mechanisms, their interactions, and changes in health and disease conditions. The purpose of this review article is to provide comprehensive information about the different types of diseases caused by alterations in epigenetic factors such as DNA methylation and histone acetylation or methylation. Recent studies reported that epigenetics could influence the evolution of human cancer via aberrant methylation of gene promoter regions, which is associated with reduced gene function. Furthermore, DNA methyltransferases (DNMTs) in the DNA methylation process as well as histone acetyltransferases (HATs)/histone deacetylases (HDACs) and histone methyltransferases (HMTs)/demethylases (HDMs) in histone modifications play important roles both in the catalysis and inhibition of target gene transcription and in many other DNA processes such as repair, replication, and recombination. Dysfunction in these enzymes leads to epigenetic disorders and, as a result, various diseases such as cancers and brain diseases. Consequently, the knowledge of how to modify aberrant DNA methylation as well as aberrant histone acetylation or methylation via inhibitors by using epigenetic drugs can be a suitable therapeutic approach for a number of diseases. Using the synergistic effects of DNA methylation and histone modification inhibitors, it is hoped that many epigenetic defects will be treated in the future. Numerous studies have demonstrated a link between epigenetic marks and their effects on brain and cancer diseases. Designing appropriate drugs could provide novel strategies for the management of these diseases in the near future. Full article

(This article belongs to the Special Issue Epigenetics in Brain Development and Neurodevelopmental Disorders)

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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 2622

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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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 1896

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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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 2609

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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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 2262

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 4370

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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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 2459

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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15 pages, 3298 KiB

Open AccessEditor’s ChoiceArticle

Chronic Stress Alters Hippocampal Renin-Angiotensin-Aldosterone System Component Expression in an Aged Rat Model of Wolfram Syndrome

by Marite Punapart, Riin Reimets, Kadri Seppa, Silvia Kirillov, Nayana Gaur, Kattri-Liis Eskla, Toomas Jagomäe, Eero Vasar and Mario Plaas

Genes 2023, 14(4), 827; https://doi.org/10.3390/genes14040827 - 30 Mar 2023

Cited by 2 | Viewed by 2891

Abstract

Biallelic mutations in the gene encoding WFS1 underlie the development of Wolfram syndrome (WS), a rare neurodegenerative disorder with no available cure. We have previously shown that Wfs1 deficiency can impair the functioning of the renin-angiotensin-aldosterone system (RAAS). The expression of two key [...] Read more.

Biallelic mutations in the gene encoding WFS1 underlie the development of Wolfram syndrome (WS), a rare neurodegenerative disorder with no available cure. We have previously shown that Wfs1 deficiency can impair the functioning of the renin-angiotensin-aldosterone system (RAAS). The expression of two key receptors, angiotensin II receptor type 2 (Agtr2) and bradykinin receptor B1 (Bdkrb1), was downregulated both in vitro and in vivo across multiple organs in a rat model of WS. Here, we show that the expression of key RAAS components is also dysregulated in neural tissue from aged WS rats and that these alterations are not normalized by pharmacological treatments (liraglutide (LIR), 7,8-dihydroxyflavone (7,8-DHF) or their combination). We found that the expression of angiotensin II receptor type 1a (Agtr1a), angiotensin II receptor type 1b (Agtr1b), Agtr2 and Bdkrb1 was significantly downregulated in the hippocampus of WS animals that experienced chronic experimental stress. Treatment-naïve WS rats displayed different gene expression patterns, underscoring the effect of prolonged experiment-induced stress. Altogether, we posit that Wfs1 deficiency disturbs RAAS functioning under chronic stressful conditions, thereby exacerbating neurodegeneration in WS. Full article

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

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13 pages, 2893 KiB

Open AccessEditor’s ChoiceArticle

SODD Promotes Lung Cancer Tumorigenesis by Activating the PDK1/AKT and RAF/MEK/ERK Signaling

by Fan Bao, Su An, Yang Yang and Tian-Rui Xu

Genes 2023, 14(4), 829; https://doi.org/10.3390/genes14040829 - 30 Mar 2023

Cited by 3 | Viewed by 2504

Abstract

Background: The Bcl2-associated athanogene4 (BAG4/SODD) protein could be identified as a tumor marker for several malignancies and plays a major role in the occurrence, development, and drug resistance of tumors. However, the role of Silencer of death domains (SODD) in lung carcinogenesis is [...] Read more.

Background: The Bcl2-associated athanogene4 (BAG4/SODD) protein could be identified as a tumor marker for several malignancies and plays a major role in the occurrence, development, and drug resistance of tumors. However, the role of Silencer of death domains (SODD) in lung carcinogenesis is still elusive. Objective: To illuminate the effect of SODD on the proliferation, migration, invasion, and apoptosis of lung cancer cells and tumor growth in vivo and explore the corresponding mechanism. Methods: The expression of SODD in tumor and normal tissues was determined and compared via western blot. SODD gene knockout lung cancer cells (H1299 cells) were established through a CRISPR/Cas9 gene deleting system, and a transient SODD overexpression of H1299 cells was also constructed. Then, cell proliferation and invasion were assessed through colony formation and cell counting kit-8 assays, transwell migration assays, and wound healing assays. Cell drug sensitivity is also analyzed by Cell Counting Kit-8 assay. The flow cytometer was used to perform cell circle and apoptosis analysis. The interaction of SODD and RAF-1 was confirmed by co-immunoprecipitation, and the phosphorylated level of Phosphatidylinositol 3-kinase (PI3K), Serine/threonine-protein kinase (AKT), Rapidly accelerated fibrosarcoma (RAF)-1,and extracellular signal regulated kinase (ERK) in cells was examined by western blot to evaluate the activation of PI3K/PDK1/AKT and RAF/MEK/ERK pathways. In vivo, Xenograft tumor assay of SODD knockout H1299 cells was used to evaluate further the role of SODD on the proliferation of H1299 cells. Results: SODD binds to RAF-1 and is over-expressed in lung tissues, and promotes the proliferation, migration, invasion, and drug sensitivity of H1299 cells. The reduced cells in the S phase and increased cells arrested in the G2/M phase were found in SODD knockout H1299 cells, and more cells got apoptosis. The expression of 3-phosphoinositide-dependent protein kinase 1(PDK1) protein in SODD knockout H1299 cells decreases distinctively, and the phosphorylated level of AKT, RAF-1, and ERK-1 kinase in SODD knockout H1299 cells is also less than that in normal H1299 cells. In contrast, SODD overexpression significantly increases the phosphorylation of AKT. In vivo, SODD promotes the tumorigenicity of H1299 cells in nude mice. Conclusions: SODD is overexpressed in lung tissues and plays a considerable role in the development and progression of lung cancer by regulating the PI3K/PDK1/AKT and RAF/MEK/ERK pathways. Full article

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

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16 pages, 788 KiB

Open AccessEditor’s ChoiceArticle

Rare Coding Variants in Patients with Non-Syndromic Vestibular Dysfunction

by Angelo Augusto M. Sumalde, Melissa A. Scholes, Olivia A. Kalmanson, Elizabeth A. Terhune, Lidia Frejo, Cambria I. Wethey, Pablo Roman-Naranjo, Patrick M. Carry, Samuel P. Gubbels, Jose A. Lopez-Escamez, Nancy Hadley-Miller and Regie Lyn P. Santos-Cortez

Genes 2023, 14(4), 831; https://doi.org/10.3390/genes14040831 - 30 Mar 2023

Cited by 3 | Viewed by 3253

Abstract

Vertigo due to vestibular dysfunction is rare in children. The elucidation of its etiology will improve clinical management and the quality of life of patients. Genes for vestibular dysfunction were previously identified in patients with both hearing loss and vertigo. This study aimed [...] Read more.

Vertigo due to vestibular dysfunction is rare in children. The elucidation of its etiology will improve clinical management and the quality of life of patients. Genes for vestibular dysfunction were previously identified in patients with both hearing loss and vertigo. This study aimed to identify rare, coding variants in children with peripheral vertigo but no hearing loss, and in patients with potentially overlapping phenotypes, namely, Meniere’s disease or idiopathic scoliosis. Rare variants were selected from the exome sequence data of 5 American children with vertigo, 226 Spanish patients with Meniere’s disease, and 38 European–American probands with scoliosis. In children with vertigo, 17 variants were found in 15 genes involved in migraine, musculoskeletal phenotypes, and vestibular development. Three genes, OTOP1, HMX3, and LAMA2, have knockout mouse models for vestibular dysfunction. Moreover, HMX3 and LAMA2 were expressed in human vestibular tissues. Rare variants within ECM1, OTOP1, and OTOP2 were each identified in three adult patients with Meniere’s disease. Additionally, an OTOP1 variant was identified in 11 adolescents with lateral semicircular canal asymmetry, 10 of whom have scoliosis. We hypothesize that peripheral vestibular dysfunction in children may be due to multiple rare variants within genes that are involved in the inner ear structure, migraine, and musculoskeletal disease. Full article

(This article belongs to the Special Issue Feature Papers in Human Genomics and Genetic Diseases 2023)

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32 pages, 1390 KiB

Open AccessEditor’s ChoiceArticle

Gene Association Analysis of Quantitative Trait Based on Functional Linear Regression Model with Local Sparse Estimator

by Jingyu Wang, Fujie Zhou, Cheng Li, Ning Yin, Huiming Liu, Binxian Zhuang, Qingyu Huang and Yongxian Wen

Genes 2023, 14(4), 834; https://doi.org/10.3390/genes14040834 - 30 Mar 2023

Cited by 1 | Viewed by 1787

Abstract

Functional linear regression models have been widely used in the gene association analysis of complex traits. These models retain all the genetic information in the data and take full advantage of spatial information in genetic variation data, which leads to brilliant detection power. [...] Read more.

Functional linear regression models have been widely used in the gene association analysis of complex traits. These models retain all the genetic information in the data and take full advantage of spatial information in genetic variation data, which leads to brilliant detection power. However, the significant association signals identified by the high-power methods are not all the real causal SNPs, because it is easy to regard noise information as significant association signals, leading to a false association. In this paper, a method based on the sparse functional data association test (SFDAT) of gene region association analysis is developed based on a functional linear regression model with local sparse estimation. The evaluation indicators CSR and DL are defined to evaluate the feasibility and performance of the proposed method with other indicators. Simulation studies show that: (1) SFDAT performs well under both linkage equilibrium and linkage disequilibrium simulation; (2) SFDAT performs successfully for gene regions (including common variants, low-frequency variants, rare variants and mix variants); (3) With power and type I error rates comparable to OLS and Smooth, SFDAT has a better ability to handle the zero regions. The Oryza sativa data set is analyzed by SFDAT. It is shown that SFDAT can better perform gene association analysis and eliminate the false positive of gene localization. This study showed that SFDAT can lower the interference caused by noise while maintaining high power. SFDAT provides a new method for the association analysis between gene regions and phenotypic quantitative traits. Full article

(This article belongs to the Section Bioinformatics)

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15 pages, 6799 KiB

Open AccessEditor’s ChoiceArticle

vwa1 Knockout in Zebrafish Causes Abnormal Craniofacial Chondrogenesis by Regulating FGF Pathway

by Xiaomin Niu, Fuyu Zhang, Lu Ping, Yibei Wang, Bo Zhang, Jian Wang and Xiaowei Chen

Genes 2023, 14(4), 838; https://doi.org/10.3390/genes14040838 - 30 Mar 2023

Cited by 10 | Viewed by 2885

Abstract

Hemifacial microsomia (HFM), a rare disorder of first- and second-pharyngeal arch development, has been linked to a point mutation in VWA1 (von Willebrand factor A domain containing 1), encoding the protein WARP in a five-generation pedigree. However, how the VWA1 mutation relates to [...] Read more.

Hemifacial microsomia (HFM), a rare disorder of first- and second-pharyngeal arch development, has been linked to a point mutation in VWA1 (von Willebrand factor A domain containing 1), encoding the protein WARP in a five-generation pedigree. However, how the VWA1 mutation relates to the pathogenesis of HFM is largely unknown. Here, we sought to elucidate the effects of the VWA1 mutation at the molecular level by generating a vwa1-knockout zebrafish line using CRISPR/Cas9. Mutants and crispants showed cartilage dysmorphologies, including hypoplastic Meckel’s cartilage and palatoquadrate cartilage, malformed ceratohyal with widened angle, and deformed or absent ceratobranchial cartilages. Chondrocytes exhibited a smaller size and aspect ratio and were aligned irregularly. In situ hybridization and RT-qPCR showed a decrease in barx1 and col2a1a expression, indicating abnormal cranial neural crest cell (CNCC) condensation and differentiation. CNCC proliferation and survival were also impaired in the mutants. Expression of FGF pathway components, including fgf8a, fgfr1, fgfr2, fgfr3, fgfr4, and runx2a, was decreased, implying a role for VWA1 in regulating FGF signaling. Our results demonstrate that VWA1 is essential for zebrafish chondrogenesis through effects on condensation, differentiation, proliferation, and apoptosis of CNCCs, and likely impacts chondrogenesis through regulation of the FGF pathway. Full article

(This article belongs to the Special Issue Zebrafish Models for Human Genetic Disease Studies)

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12 pages, 1854 KiB

Open AccessEditor’s ChoiceArticle

Whole Genome Sequencing Provides Information on the Genomic Architecture and Diversity of Cultivated Gilthead Seabream (Sparus aurata) Broodstock Nuclei

by Francesca Bertolini, Anisa Ribani, Fabrizio Capoccioni, Luca Buttazzoni, Samuele Bovo, Giuseppina Schiavo, Massimo Caggiano, Max F. Rothschild and Luca Fontanesi

Genes 2023, 14(4), 839; https://doi.org/10.3390/genes14040839 - 30 Mar 2023

Cited by 1 | Viewed by 2765

Abstract

The gilthead seabream (Sparus aurata) is a species of relevance for the Mediterranean aquaculture industry. Despite the advancement of genetic tools for the species, breeding programs still do not often include genomics. In this study, we designed a genomic strategy to [...] Read more.

The gilthead seabream (Sparus aurata) is a species of relevance for the Mediterranean aquaculture industry. Despite the advancement of genetic tools for the species, breeding programs still do not often include genomics. In this study, we designed a genomic strategy to identify signatures of selection and genomic regions of high differentiation among populations of farmed fish stocks. A comparative DNA pooling sequencing approach was applied to identify signatures of selection in gilthead seabream from the same hatchery and from different nuclei that had not been subjected to genetic selection. Identified genomic regions were further investigated to detect SNPs with predicted high impact. The analyses underlined major genomic differences in the proportion of fixed alleles among the investigated nuclei. Some of these differences highlighted genomic regions, including genes involved in general metabolism and development already detected in QTL for growth, size, skeletal deformity, and adaptation to variation of oxygen levels in other teleosts. The obtained results pointed out the need to control the genetic effect of breeding programs in this species to avoid the reduction of genetic variability within populations and the increase in inbreeding level that, in turn, might lead to an increased frequency of alleles with deleterious effects. Full article

(This article belongs to the Special Issue Genomics in Aquaculture and Fisheries)

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11 pages, 1689 KiB

Open AccessEditor’s ChoiceArticle

The Expanding Phenotypical Spectrum of WARS2-Related Disorder: Four Novel Cases with a Common Recurrent Variant

by Martje G. Pauly, G. Christoph Korenke, Sokhna Haissatou Diaw, Anne Grözinger, Ana Cazurro-Gutiérrez, Belén Pérez-Dueñas, Victoria González, Alfons Macaya, Ana Teresa Serrano Antón, Borut Peterlin, Ivana Babić Božović, Aleš Maver, Alexander Münchau and Katja Lohmann

Genes 2023, 14(4), 822; https://doi.org/10.3390/genes14040822 - 29 Mar 2023

Cited by 2 | Viewed by 3674

Abstract

Biallelic variants in the mitochondrial form of the tryptophanyl-tRNA synthetases (WARS2) can cause a neurodevelopmental disorder with movement disorders including early-onset tremor–parkinsonism syndrome. Here, we describe four new patients, who all presented at a young age with a tremor–parkinsonism syndrome and [...] Read more.

Biallelic variants in the mitochondrial form of the tryptophanyl-tRNA synthetases (WARS2) can cause a neurodevelopmental disorder with movement disorders including early-onset tremor–parkinsonism syndrome. Here, we describe four new patients, who all presented at a young age with a tremor–parkinsonism syndrome and responded well to levodopa. All patients carry the same recurrent, hypomorphic missense variant (NM_015836.4: c.37T>G; p.Trp13Gly) either together with a previously described truncating variant (NM_015836.4: c.797Cdel; p.Pro266ArgfsTer10), a novel truncating variant (NM_015836.4: c.346C>T; p.Gln116Ter), a novel canonical splice site variant (NM_015836.4: c.349-1G>A), or a novel missense variant (NM_015836.4: c.475A>C, p.Thr159Pro). We investigated the mitochondrial function in patients and found increased levels of mitochondrially encoded cytochrome C Oxidase II as part of the mitochondrial respiratory chain as well as decreased mitochondrial integrity and branching. Finally, we conducted a literature review and here summarize the broad phenotypical spectrum of reported WARS2-related disorders. In conclusion, WARS2-related disorders are diagnostically challenging diseases due to the broad phenotypic spectrum and the disease relevance of a relatively common missense change that is often filtered out in a diagnostic setting since it occurs in ~0.5% of the general European population. Full article

(This article belongs to the Section Neurogenomics)

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14 pages, 1202 KiB

Open AccessEditor’s ChoiceReview

Role of Microbiota-Modified Bile Acids in the Regulation of Intracellular Organelles and Neurodegenerative Diseases

by Yoshimitsu Kiriyama and Hiromi Nochi

Genes 2023, 14(4), 825; https://doi.org/10.3390/genes14040825 - 29 Mar 2023

Cited by 16 | Viewed by 3418

Abstract

Bile acids (BAs) are amphiphilic steroidal molecules generated from cholesterol in the liver and facilitate the digestion and absorption of fat-soluble substances in the gut. Some BAs in the intestine are modified by the gut microbiota. Because BAs are modified in a variety [...] Read more.

Bile acids (BAs) are amphiphilic steroidal molecules generated from cholesterol in the liver and facilitate the digestion and absorption of fat-soluble substances in the gut. Some BAs in the intestine are modified by the gut microbiota. Because BAs are modified in a variety of ways by different types of bacteria present in the gut microbiota, changes in the gut microbiota can affect the metabolism of BAs in the host. Although most BAs absorbed from the gut are transferred to the liver, some are transferred to the systemic circulation. Furthermore, BAs have also been detected in the brain and are thought to migrate into the brain through the systemic circulation. Although BAs are known to affect a variety of physiological functions by acting as ligands for various nuclear and cell-surface receptors, BAs have also been found to act on mitochondria and autophagy in the cell. This review focuses on the BAs modified by the gut microbiota and their roles in intracellular organelles and neurodegenerative diseases. Full article

(This article belongs to the Special Issue Human Microbiota: Current Updates on Pathogenetic Mechanisms and Methodological Advances)

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17 pages, 13774 KiB

Open AccessEditor’s ChoiceArticle

Identification and Functional Analysis of ToBPI1/LBP and ToBPI2/LBP in Anti-Bacterial Infection of Trachinotus ovatus

by Ze-Chang Bian, Xiao-Hui Cai, Kian Ann Tan, Ya-Dan Wang, Zhuang Huang, Kit Yue Kwan and Peng Xu

Genes 2023, 14(4), 826; https://doi.org/10.3390/genes14040826 - 29 Mar 2023

Cited by 3 | Viewed by 1957

Abstract

Bactericidal/permeability-increasing protein (BPI) and lipopolysaccharide-binding protein (LBP) are a group of antibacterial proteins that play an important role in the host’s innate immune defense against pathogen infection. In this study, two BPI/LBPs, named ToBPI1/LBP (1434 bp in length, 478 amino acids) and ToBPI2/LBP [...] Read more.

Bactericidal/permeability-increasing protein (BPI) and lipopolysaccharide-binding protein (LBP) are a group of antibacterial proteins that play an important role in the host’s innate immune defense against pathogen infection. In this study, two BPI/LBPs, named ToBPI1/LBP (1434 bp in length, 478 amino acids) and ToBPI2/LBP (1422 bp in length, 474 amino acids), were identified from the golden pompano. ToBPI1/LBP and ToBPI2/LBP were significantly expressed in immune-related tissues after being challenged with Streptococcus agalactiae and Vibrio alginolyticus. The two BPI/LBPs showed significant antibacterial activity against Gram-negative Escherichia coli and Gram-positive S. agalactiae and Streptococcus iniae. In contrast, the antibacterial activity against Staphylococcus aureus, Corynebacterium glutamicum, Vibrio parahaemolyticus, V. alginolyticus and Vibrio harveyi was low and decreased with time. The membrane permeability of bacteria treated with recombinant ToBPI1/LBP and ToBPI2/LBP was significantly enhanced. These results suggest that ToBPI1/LBP and ToBPI2/LBP may play important immunological roles in the immune response of the golden pompano to bacteria. This study will provide basic information and new insights into the immune response mechanism of the golden pompano to bacteria and the function of BPI/LBP. Full article

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

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15 pages, 5397 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Analysis of DREB Family Genes and Characterization of Cold Stress Responses in the Woody Plant Prunus nana

by Cheng Qian, Lulu Li, Huanhuan Guo, Gaopu Zhu, Ning Yang, Xiaoyan Tan and Han Zhao

Genes 2023, 14(4), 811; https://doi.org/10.3390/genes14040811 - 28 Mar 2023

Cited by 4 | Viewed by 2693

Abstract

Dehydration response element binding factor (DREB) is a family of plant-specific transcription factors, whose members participate in the regulation of plant responses to various abiotic stresses. Prunus nana, also known as the wild almond, is a member of the Rosaceae family that [...] Read more.

Dehydration response element binding factor (DREB) is a family of plant-specific transcription factors, whose members participate in the regulation of plant responses to various abiotic stresses. Prunus nana, also known as the wild almond, is a member of the Rosaceae family that is rare and found to grow in the wild in China. These wild almond trees are found in hilly regions in northern Xinjiang, and exhibit greater drought and cold stress resistance than cultivated almond varieties. However, the response of P. nana DREBs (PnaDREBs) under low temperature stress is still unclear. In this study, 46 DREB genes were identified in the wild almond genome, with this number being slightly lower than that in the sweet almond (Prunus dulcis cultivar ‘Nonpareil’). These DREB genes in wild almond were separated into two classes. All PnaDREB genes were located on six chromosomes. PnaDREB proteins that were classified in the same groups contained specific shared motifs, and promoter analyses revealed that PnaDREB genes harbored a range of stress-responsive elements associated with drought, low-temperature stress, light responsivity, and hormone-responsive cis-regulatory elements within their promoter regions. MicroRNA target site prediction analyses also suggested that 79 miRNAs may regulate the expression of 40 of these PnaDREB genes, with PnaDREB2. To examine if these identified PnaDREB genes responded to low temperature stress, 15 of these genes were selected including seven homologous to Arabidopsis C-repeat binding factor (CBFs), and their expression was assessed following incubation for 2 h at 25 °C, 5 °C, 0 °C, −5 °C, or −10 °C. In summary, this analysis provides an overview of the P. nana PnaDREB gene family and provides a foundation for further studies of the ability of different PnaDREB genes to regulate cold stress responses in almond plants. Full article

(This article belongs to the Special Issue Genetic Studies of Ornamental Horticulture and Floriculture)

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9 pages, 591 KiB

Open AccessEditor’s ChoiceBrief Report

Metagenomics Provides a Deeper Assessment of the Diversity of Bacterial Communities in Polar Soils Than Metabarcoding

by Burkhard Becker and Ekaterina Pushkareva

Genes 2023, 14(4), 812; https://doi.org/10.3390/genes14040812 - 28 Mar 2023

Cited by 13 | Viewed by 3513

Abstract

The diversity of soil bacteria was analyzed via metabarcoding and metagenomic approaches using DNA samples isolated from the biocrusts of 12 different Arctic and Antarctic sites. For the metabarcoding approach, the V3-4 region of the 16S rRNA was targeted. Our results showed that [...] Read more.

The diversity of soil bacteria was analyzed via metabarcoding and metagenomic approaches using DNA samples isolated from the biocrusts of 12 different Arctic and Antarctic sites. For the metabarcoding approach, the V3-4 region of the 16S rRNA was targeted. Our results showed that nearly all operational taxonomic units (OTUs = taxa) found in metabarcoding analyses were recovered in metagenomic analyses. In contrast, metagenomics identified a large number of additional OTUs absent in metabarcoding analyses. In addition, we found huge differences in the abundance of OTUs between the two methods. The reasons for these differences seem to be (1) the higher sequencing depth in metagenomics studies, which allows the detection of low-abundance community members in metagenomics, and (2) bias of primer pairs used to amplify the targeted sequence in metabarcoding, which can change the community composition dramatically even at the lower taxonomic levels. We strongly recommend using only metagenomic approaches when establishing the taxonomic profiles of whole biological communities. Full article

(This article belongs to the Special Issue Polar Genomics)

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19 pages, 2954 KiB

Open AccessEditor’s ChoiceArticle

Transcriptomic and Chromatin Landscape Analysis Reveals That Involvement of Pituitary Level Transcription Factors Modulate Incubation Behaviors of Magang Geese

by Jianye Chang, Di Fan, Jiaxin Liu, Yanglong Xu, Xuefei Huang, Yunbo Tian, Jin Xu, Yunmao Huang, Jue Ruan and Xu Shen

Genes 2023, 14(4), 815; https://doi.org/10.3390/genes14040815 - 28 Mar 2023

Cited by 2 | Viewed by 2796

Abstract

The incubation behavior of geese seriously affects their egg production performance. Studies on incubation behavior have identified functional genes, but the regulatory architecture relationship between functional genes and chromatin accessibility remains poorly understood. Here, we present an integrated analysis of open chromatin profiles [...] Read more.

The incubation behavior of geese seriously affects their egg production performance. Studies on incubation behavior have identified functional genes, but the regulatory architecture relationship between functional genes and chromatin accessibility remains poorly understood. Here, we present an integrated analysis of open chromatin profiles and transcriptome to identify the cis-regulatory element and their potential transcription factors involved in regulating incubation behavior in goose pituitary. Assay for transposase-accessible chromatin sequencing (ATAC-seq) revealed that open chromatin regions increased in the pituitary during the transition from incubation behavior to laying. We identified 920 significant differential accessible regions (DARs) in the pituitary. Compared to the laying stage, most DARs had higher chromatin accessibility in the brooding stage. Motif analysis of open DARs showed that the most significant transcription factor (TF) occupied sites predominantly enriched in motifs binding to the RFX family (RFX5, RFX2, and RFX1). While the majority of TF motifs enriched under sites of the nuclear receptor (NR) family (ARE, GRE, and PGR) in closed DARs at the incubation behavior stage. Footprint analysis indicated that the transcription factor RFX family exhibited higher binding on chromatin at the brooding stage. To further elucidate the effect of changes in chromatin accessibility on gene expression levels, a comparison of the transcriptome revealed 279 differentially expressed genes (DEGs). The transcriptome changes were associated with processes of steroid biosynthesis. By integrating ATAC-seq and RNA-seq, few DARs directly affect incubation behavior by regulating the transcription levels of genes. Five DAR-related DEGs were found to be closely related to maintaining the incubation behavior in geese. Footprinting analysis revealed a set of transcription factors (RFX1, RFX2, RFX3, RFX5, BHLHA15, SIX1, and DUX) which displayed the highest activity at the brooding stage. SREBF2 was predicted to be the unique differentially expressed transcription factor whose mRNA level was down-regulated and enriched in hyper-accessible regions of PRL in the broody stage. In the present study, we comprehensively profiled the transcriptome and chromatin accessibility in the pituitary related to incubation behavior. Our findings provided insight into the identification and analysis of regulatory elements in goose incubation behavior. The epigenetic alterations profiled here can help decipher the epigenetic mechanisms that contribute to the regulation of incubation behavior in birds. Full article

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

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15 pages, 1845 KiB

Open AccessEditor’s ChoiceArticle

Molecular Design-Based Breeding: A Kinship Index-Based Selection Method for Complex Traits in Small Livestock Populations

by Jiamin Gu, Jianwei Guo, Zhenyang Zhang, Yuejin Xu, Qamar Raza Qadri, Zhe Zhang, Zhen Wang, Qishan Wang and Yuchun Pan

Genes 2023, 14(4), 807; https://doi.org/10.3390/genes14040807 - 27 Mar 2023

Cited by 1 | Viewed by 3437

Abstract

Genomic selection (GS) techniques have improved animal breeding by enhancing the prediction accuracy of breeding values, particularly for traits that are difficult to measure and have low heritability, as well as reducing generation intervals. However, the requirement to establish genetic reference populations can [...] Read more.

Genomic selection (GS) techniques have improved animal breeding by enhancing the prediction accuracy of breeding values, particularly for traits that are difficult to measure and have low heritability, as well as reducing generation intervals. However, the requirement to establish genetic reference populations can limit the application of GS in pig breeds with small populations, especially when small populations make up most of the pig breeds worldwide. We aimed to propose a kinship index based selection (KIS) method, which defines an ideal individual with information on the beneficial genotypes for the target trait. Herein, the metric for assessing selection decisions is a beneficial genotypic similarity between the candidate and the ideal individual; thus, the KIS method can overcome the need for establishing genetic reference groups and continuous phenotype determination. We also performed a robustness test to make the method more aligned with reality. Simulation results revealed that compared to conventional genomic selection methods, the KIS method is feasible, particularly, when the population size is relatively small. Full article

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

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45 pages, 1211 KiB

Open AccessEditor’s ChoiceReview

Microsatellites as Molecular Markers with Applications in Exploitation and Conservation of Aquatic Animal Populations

by Roman Wenne

Genes 2023, 14(4), 808; https://doi.org/10.3390/genes14040808 - 27 Mar 2023

Cited by 28 | Viewed by 8630

Abstract

A large number of species and taxa have been studied for genetic polymorphism. Microsatellites have been known as hypervariable neutral molecular markers with the highest resolution power in comparison with any other markers. However, the discovery of a new type of molecular marker—single [...] Read more.

A large number of species and taxa have been studied for genetic polymorphism. Microsatellites have been known as hypervariable neutral molecular markers with the highest resolution power in comparison with any other markers. However, the discovery of a new type of molecular marker—single nucleotide polymorphism (SNP) has put the existing applications of microsatellites to the test. To ensure good resolution power in studies of populations and individuals, a number of microsatellite loci from 14 to 20 was often used, which corresponds to about 200 independent alleles. Recently, these numbers have tended to be increased by the application of genomic sequencing of expressed sequence tags (ESTs) and the choice of the most informative loci for genotyping depends on the aims of research. Examples of successful applications of microsatellite molecular markers in aquaculture, fisheries, and conservation genetics in comparison to SNPs are summarized in this review. Microsatellites can be considered superior markers in such topics as kinship and parentage analysis in cultured and natural populations, the assessment of gynogenesis, androgenesis and ploidization. Microsatellites can be coupled with SNPs for mapping QTL. Microsatellites will continue to be used in research of genetic diversity in cultured stocks, and also in natural populations as an economically advantageous genotyping technique. Full article

(This article belongs to the Section Population and Evolutionary Genetics and Genomics)

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17 pages, 2991 KiB

Open AccessEditor’s ChoiceArticle

An Attempt to Identify the Medaka Receptor for Somatolactin Alpha Using a Reverse Genetics Approach

by Yuko Moroki, Mamiko Komori, Yuko Ogawa, Erina Nagumo, Haruna Ohno and Shoji Fukamachi

Genes 2023, 14(4), 796; https://doi.org/10.3390/genes14040796 - 26 Mar 2023

Cited by 2 | Viewed by 2324

Abstract

Somatolactin alpha (SLα) is a fish-specific hormone involved in body color regulation. The growth hormone (GH) is another hormone that is expressed in all vertebrates and promotes growth. These peptide hormones act by binding to receptors (SLα receptor (SLR) and GH receptor (GHR)); [...] Read more.

Somatolactin alpha (SLα) is a fish-specific hormone involved in body color regulation. The growth hormone (GH) is another hormone that is expressed in all vertebrates and promotes growth. These peptide hormones act by binding to receptors (SLα receptor (SLR) and GH receptor (GHR)); however, the relationships between these ligands and their receptors vary among species. Here, we first performed phylogenetic tree reconstruction by collecting the amino-acid sequences classified as SLR, GHR, or GHR-like from bony fish. Second, we impaired SLR or GHR functions in medaka (Oryzias sakaizumii) using CRISPR/Cas9. Lastly, we analyzed SLR and GHR mutants for phenotypes to deduce their functions. Phylogenetic tree reconstruction was performed using a total of 222 amino-acid sequences from 136 species, which revealed that many GHRa and GHRb are vaguely termed as GHR or GHR-like, while showing no orthologous/paralogous relationships. SLR and GHR mutants were successfully established for phenotyping. SLR mutants exhibited premature lethality after hatching, indicating an essential role for SLR in normal growth. GHR mutations did not affect viability, body length, or body color. These results provide no evidence that either SLR or GHR functions as a receptor for SLα; rather, phylogenetically and functionally, they seem to be receptors for GH, although their (subfunctionalized) roles warrant further investigation. Full article

(This article belongs to the Special Issue Genetic Studies of Fish)

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19 pages, 793 KiB

Open AccessEditor’s ChoiceArticle

Adaptively Integrative Association between Multivariate Phenotypes and Transcriptomic Data for Complex Diseases

by Yujia Li, Yusi Fang, Hung-Ching Chang, Michael Gorczyca, Peng Liu and George C. Tseng

Genes 2023, 14(4), 798; https://doi.org/10.3390/genes14040798 - 26 Mar 2023

Viewed by 1950

Abstract

Phenotype–gene association studies can uncover disease mechanisms for translational research. Association with multiple phenotypes or clinical variables in complex diseases has the advantage of increasing statistical power and offering a holistic view. Existing multi-variate association methods mostly focus on SNP-based genetic associations. In [...] Read more.

Phenotype–gene association studies can uncover disease mechanisms for translational research. Association with multiple phenotypes or clinical variables in complex diseases has the advantage of increasing statistical power and offering a holistic view. Existing multi-variate association methods mostly focus on SNP-based genetic associations. In this paper, we extend and evaluate two adaptive Fisher’s methods, namely AFp and AFz, from the p-value combination perspective for phenotype–mRNA association analysis. The proposed method effectively aggregates heterogeneous phenotype–gene effects, allows association with different data types of phenotypes, and performs the selection of the associated phenotypes. Variability indices of the phenotype–gene effect selection are calculated by bootstrap analysis, and the resulting co-membership matrix identifies gene modules clustered by phenotype–gene effect. Extensive simulations demonstrate the superior performance of AFp compared to existing methods in terms of type I error control, statistical power and biological interpretation. Finally, the method is separately applied to three sets of transcriptomic and clinical datasets from lung disease, breast cancer, and brain aging and generates intriguing biological findings. Full article

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

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20 pages, 1802 KiB

Open AccessEditor’s ChoiceReview

Computational Biology Helps Understand How Polyploid Giant Cancer Cells Drive Tumor Success

by Matheus Correia Casotti, Débora Dummer Meira, Aléxia Stefani Siqueira Zetum, Bruno Cancian de Araújo, Danielle Ribeiro Campos da Silva, Eldamária de Vargas Wolfgramm dos Santos, Fernanda Mariano Garcia, Flávia de Paula, Gabriel Mendonça Santana, Luana Santos Louro, Lyvia Neves Rebello Alves, Raquel Furlani Rocon Braga, Raquel Silva dos Reis Trabach, Sara Santos Bernardes, Thomas Erik Santos Louro, Eduardo Cremonese Filippi Chiela, Guido Lenz, Elizeu Fagundes de Carvalho and Iúri Drumond Louro

Genes 2023, 14(4), 801; https://doi.org/10.3390/genes14040801 - 26 Mar 2023

Cited by 18 | Viewed by 5726

Abstract

Precision and organization govern the cell cycle, ensuring normal proliferation. However, some cells may undergo abnormal cell divisions (neosis) or variations of mitotic cycles (endopolyploidy). Consequently, the formation of polyploid giant cancer cells (PGCCs), critical for tumor survival, resistance, and immortalization, can occur. [...] Read more.

Precision and organization govern the cell cycle, ensuring normal proliferation. However, some cells may undergo abnormal cell divisions (neosis) or variations of mitotic cycles (endopolyploidy). Consequently, the formation of polyploid giant cancer cells (PGCCs), critical for tumor survival, resistance, and immortalization, can occur. Newly formed cells end up accessing numerous multicellular and unicellular programs that enable metastasis, drug resistance, tumor recurrence, and self-renewal or diverse clone formation. An integrative literature review was carried out, searching articles in several sites, including: PUBMED, NCBI-PMC, and Google Academic, published in English, indexed in referenced databases and without a publication time filter, but prioritizing articles from the last 3 years, to answer the following questions: (i) “What is the current knowledge about polyploidy in tumors?”; (ii) “What are the applications of computational studies for the understanding of cancer polyploidy?”; and (iii) “How do PGCCs contribute to tumorigenesis?” Full article

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

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11 pages, 850 KiB

Open AccessEditor’s ChoiceCommunication

The Role of Genetic Testing in Children Requiring Surgery for Ectopia Lentis

by Mohammud Musleh, Adam Bull, Emma Linton, Jingshu Liu, Sarah Waller, Claire Hardcastle, Jill Clayton-Smith, Vinod Sharma, Graeme C. Black, Susmito Biswas, Jane L. Ashworth and Panagiotis I. Sergouniotis

Genes 2023, 14(4), 791; https://doi.org/10.3390/genes14040791 - 25 Mar 2023

Cited by 2 | Viewed by 2333

Abstract

Non-traumatic ectopia lentis can be isolated or herald an underlying multisystemic disorder. Technological advances have revolutionized genetic testing for many ophthalmic disorders, and this study aims to provide insights into the clinical utility of genetic analysis in paediatric ectopia lentis. Children that underwent [...] Read more.

Non-traumatic ectopia lentis can be isolated or herald an underlying multisystemic disorder. Technological advances have revolutionized genetic testing for many ophthalmic disorders, and this study aims to provide insights into the clinical utility of genetic analysis in paediatric ectopia lentis. Children that underwent lens extraction for ectopia lentis between 2013 and 2017 were identified, and gene panel testing findings and surgical outcomes were collected. Overall, 10/11 cases received a probable molecular diagnosis. Genetic variants were identified in four genes: FBN1 (associated with Marfan syndrome and cardiovascular complications; n = 6), ADAMTSL4 (associated with non-syndromic ectopia lentis; n = 2), LTBP2 (n = 1) and ASPH (n = 1). Parents appeared unaffected in 6/11 cases; the initial presentation of all six of these children was to an ophthalmologist, and only 2/6 had FBN1 variants. Notably, 4/11 cases required surgery before the age of 4 years, and only one of these children carried an FBN1 variant. In summary, in this retrospective cohort study, panel-based genetic testing pointed to a molecular diagnosis in >90% of paediatric ectopia lentis cases requiring surgery. In a subset of study participants, genetic analysis revealed changes in genes that have not been linked to extraocular manifestations and highlighted that extensive systemic investigations were not required in these individuals. We propose the introduction of genetic testing early in the diagnostic pathway in children with ectopia lentis. Full article

(This article belongs to the Special Issue Molecular Diagnosis and Disease Mechanisms in Eye Disorders)

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12 pages, 1501 KiB

Open AccessEditor’s ChoiceArticle

T-Cell Receptor Repertoire Characteristics Associated with Prognostic Significance in High-Grade Serous Ovarian Carcinoma

by Ju-Won Kim, Sewha Kim, So-Yun Yang, Je-Gun Joung and Sohyun Hwang

Genes 2023, 14(4), 785; https://doi.org/10.3390/genes14040785 - 24 Mar 2023

Cited by 1 | Viewed by 2210

Abstract

High-grade serous ovarian carcinoma (HGSOC) is a fatal gynecological malignancy. Somatic recombination occurring during T-cell receptor (TCR) development results in TCR diversity, and the TCR repertoire, thus produced, is associated with immune response. This study analyzed the difference in the TCR repertoire and [...] Read more.

High-grade serous ovarian carcinoma (HGSOC) is a fatal gynecological malignancy. Somatic recombination occurring during T-cell receptor (TCR) development results in TCR diversity, and the TCR repertoire, thus produced, is associated with immune response. This study analyzed the difference in the TCR repertoire and their prognostic significance in 51 patients with HGSOC. The patient’s clinical characteristics, gene expression pattern, TCR clonotypes, and degree of tumor-infiltrating leukocytes (TILs) were analyzed, and the patients were divided into groups depending on their recurrence pattern, tumor-infiltrating leukocyte (TIL) score, and homologous recombinant repair pathway deficiency (HRD)-associated mutations. The TCR repertoire was low in patients with recurrence and showed the expansion of eight TCR segments. Interestingly, a few genes correlated with the TCRs also showed a difference in expression according to the prognosis. Among them, seven genes were related to immune responses and KIAA1199 was up-regulated in ovarian cancer. Our study shows that the differences in the TCR repertoire in patients with ovarian cancer and their associated immune pathways could affect the prognosis of HGSOC. Full article

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

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25 pages, 7695 KiB

Open AccessEditor’s ChoiceArticle

Unveiling the Impact of Gene Presence/Absence Variation in Driving Inter-Individual Sequence Diversity within the CRP-I Gene Family in Mytilus spp.

by Nicolò Gualandi, Davide Fracarossi, Damiano Riommi, Marco Sollitto, Samuele Greco, Mario Mardirossian, Sabrina Pacor, Tiago Hori, Alberto Pallavicini and Marco Gerdol

Genes 2023, 14(4), 787; https://doi.org/10.3390/genes14040787 - 24 Mar 2023

Cited by 5 | Viewed by 2543

Abstract

Mussels (Mytilus spp.) tolerate infections much better than other species living in the same marine coastal environment thanks to a highly efficient innate immune system, which exploits a remarkable diversification of effector molecules involved in mucosal and humoral responses. Among these, antimicrobial [...] Read more.

Mussels (Mytilus spp.) tolerate infections much better than other species living in the same marine coastal environment thanks to a highly efficient innate immune system, which exploits a remarkable diversification of effector molecules involved in mucosal and humoral responses. Among these, antimicrobial peptides (AMPs) are subjected to massive gene presence/absence variation (PAV), endowing each individual with a potentially unique repertoire of defense molecules. The unavailability of a chromosome-scale assembly has so far prevented a comprehensive evaluation of the genomic arrangement of AMP-encoding loci, preventing an accurate ascertainment of the orthology/paralogy relationships among sequence variants. Here, we characterized the CRP-I gene cluster in the blue mussel Mytilus edulis, which includes about 50 paralogous genes and pseudogenes, mostly packed in a small genomic region within chromosome 5. We further reported the occurrence of widespread PAV within this family in the Mytilus species complex and provided evidence that CRP-I peptides likely adopt a knottin fold. We functionally characterized the synthetic peptide sCRP-I H1, assessing the presence of biological activities consistent with other knottins, revealing that mussel CRP-I peptides are unlikely to act as antimicrobial agents or protease inhibitors, even though they may be used as defense molecules against infections from eukaryotic parasites. Full article

(This article belongs to the Special Issue Aquaculture Genetics: Latest Advances and Prospects)

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15 pages, 1062 KiB

Open AccessEditor’s ChoiceReview

ATRX/DAXX: Guarding the Genome against the Hazards of ALT

by Sarah F. Clatterbuck Soper and Paul S. Meltzer

Genes 2023, 14(4), 790; https://doi.org/10.3390/genes14040790 - 24 Mar 2023

Cited by 12 | Viewed by 4887

Abstract

Proliferating cells must enact a telomere maintenance mechanism to ensure genomic stability. In a subset of tumors, telomeres are maintained not by telomerase, but through a homologous recombination-based mechanism termed Alternative Lengthening of Telomeres or ALT. The ALT process is linked to mutations [...] Read more.

Proliferating cells must enact a telomere maintenance mechanism to ensure genomic stability. In a subset of tumors, telomeres are maintained not by telomerase, but through a homologous recombination-based mechanism termed Alternative Lengthening of Telomeres or ALT. The ALT process is linked to mutations in the ATRX/DAXX/H3.3 histone chaperone complex. This complex is responsible for depositing non-replicative histone variant H3.3 at pericentric and telomeric heterochromatin but has also been found to have roles in ameliorating replication in repeat sequences and in promoting DNA repair. In this review, we will discuss ways in which ATRX/DAXX helps to protect the genome, and how loss of this complex allows ALT to take hold. Full article

(This article belongs to the Special Issue DNA Damage and Repair at the Crossroad with Telomeres)

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13 pages, 1963 KiB

Open AccessEditor’s ChoiceArticle

Correlation between Parental Transcriptome and Field Data for the Characterization of Heterosis in Chinese Cabbage

by Ru Li, Min Tian, Qiong He and Lugang Zhang

Genes 2023, 14(4), 776; https://doi.org/10.3390/genes14040776 - 23 Mar 2023

Cited by 1 | Viewed by 1739

Abstract

In Chinese cabbage breeding, hybrids have made a terrific contribution due to heterosis, the superior performance of offspring compared to their inbred parents. Since the development of new, top-performing hybrids requires a large scale of human and material resources, the prediction of hybrid [...] Read more.

In Chinese cabbage breeding, hybrids have made a terrific contribution due to heterosis, the superior performance of offspring compared to their inbred parents. Since the development of new, top-performing hybrids requires a large scale of human and material resources, the prediction of hybrid performance is of utmost interest to plant breeders. In our research, leaf transcriptome data from eight parents were used to investigate if they might be employed as markers to predict hybrid performance and heterosis. In Chinese cabbage, heterosis of plant growth weight (PGW) and heterosis of head weight (HW) were more obvious than other traits. The number of differential expression genes (DEGs) between parents was related to the PGW, length of the biggest outer leaf (LOL), leaf head height (LHH), leaf head width (LHW), HW, leaf number of head (LNH) and plant height (PH) of hybrids, and up-regulated DEGs number was also associated with these traits. Euclidean and binary distances of parental gene expression levels were significantly correlated with the PGW, LOL, LHH, LHW, HW and PH of hybrids. Additionally, there was a significant correlation between the parental expression levels of multiple genes involved in the ribosomal metabolic pathway and hybrid observations and heterosis in PGW, with the BrRPL23A gene showing the highest correlation with the MPH of PGW(r = 0.75). Therefore, leaf transcriptome data can preliminarily predict the hybrid performance and select parents in Chinese cabbage. Full article

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

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22 pages, 1790 KiB

Open AccessEditor’s ChoiceReview

Machine Learning-Assisted Approaches in Modernized Plant Breeding Programs

by Mohsen Yoosefzadeh Najafabadi, Mohsen Hesami and Milad Eskandari

Genes 2023, 14(4), 777; https://doi.org/10.3390/genes14040777 - 23 Mar 2023

Cited by 57 | Viewed by 10011

Abstract

In the face of a growing global population, plant breeding is being used as a sustainable tool for increasing food security. A wide range of high-throughput omics technologies have been developed and used in plant breeding to accelerate crop improvement and develop new [...] Read more.

In the face of a growing global population, plant breeding is being used as a sustainable tool for increasing food security. A wide range of high-throughput omics technologies have been developed and used in plant breeding to accelerate crop improvement and develop new varieties with higher yield performance and greater resilience to climate changes, pests, and diseases. With the use of these new advanced technologies, large amounts of data have been generated on the genetic architecture of plants, which can be exploited for manipulating the key characteristics of plants that are important for crop improvement. Therefore, plant breeders have relied on high-performance computing, bioinformatics tools, and artificial intelligence (AI), such as machine-learning (ML) methods, to efficiently analyze this vast amount of complex data. The use of bigdata coupled with ML in plant breeding has the potential to revolutionize the field and increase food security. In this review, some of the challenges of this method along with some of the opportunities it can create will be discussed. In particular, we provide information about the basis of bigdata, AI, ML, and their related sub-groups. In addition, the bases and functions of some learning algorithms that are commonly used in plant breeding, three common data integration strategies for the better integration of different breeding datasets using appropriate learning algorithms, and future prospects for the application of novel algorithms in plant breeding will be discussed. The use of ML algorithms in plant breeding will equip breeders with efficient and effective tools to accelerate the development of new plant varieties and improve the efficiency of the breeding process, which are important for tackling some of the challenges facing agriculture in the era of climate change. Full article

(This article belongs to the Collection Feature Papers: 'Plant Genetics and Genomics' Section)

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13 pages, 604 KiB

Open AccessEditor’s ChoiceReview

Redox-Based Strategies against Infections by Eukaryotic Pathogens

by Cindy Vallières, Marie-Pierre Golinelli-Cohen, Olivier Guittet, Michel Lepoivre, Meng-Er Huang and Laurence Vernis

Genes 2023, 14(4), 778; https://doi.org/10.3390/genes14040778 - 23 Mar 2023

Cited by 8 | Viewed by 2571

Abstract

Redox homeostasis is an equilibrium between reducing and oxidizing reactions within cells. It is an essential, dynamic process, which allows proper cellular reactions and regulates biological responses. Unbalanced redox homeostasis is the hallmark of many diseases, including cancer or inflammatory responses, and can [...] Read more.

Redox homeostasis is an equilibrium between reducing and oxidizing reactions within cells. It is an essential, dynamic process, which allows proper cellular reactions and regulates biological responses. Unbalanced redox homeostasis is the hallmark of many diseases, including cancer or inflammatory responses, and can eventually lead to cell death. Specifically, disrupting redox balance, essentially by increasing pro-oxidative molecules and favouring hyperoxidation, is a smart strategy to eliminate cells and has been used for cancer treatment, for example. Selectivity between cancer and normal cells thus appears crucial to avoid toxicity as much as possible. Redox-based approaches are also employed in the case of infectious diseases to tackle the pathogens specifically, with limited impacts on host cells. In this review, we focus on recent advances in redox-based strategies to fight eukaryotic pathogens, especially fungi and eukaryotic parasites. We report molecules recently described for causing or being associated with compromising redox homeostasis in pathogens and discuss therapeutic possibilities. Full article

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

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13 pages, 4130 KiB

Open AccessEditor’s ChoiceArticle

The Synchronized Progression from Mitosis to Meiosis in Female Primordial Germ Cells between Layers and Broilers

by Yuxiao Ma, Wenhui Wu, Yun Zhang, Xuzhao Wang, Jiahui Wei, Xiaotong Guo, Man Xue and Guiyu Zhu

Genes 2023, 14(4), 781; https://doi.org/10.3390/genes14040781 - 23 Mar 2023

Cited by 3 | Viewed by 2427

Abstract

Layer and broiler hens show a dramatic difference in the volume and frequency of egg production. However, it is unclear whether the intrinsic competency of oocyte generation is also different between the two types of chicken. All oocytes were derived from the primordial [...] Read more.

Layer and broiler hens show a dramatic difference in the volume and frequency of egg production. However, it is unclear whether the intrinsic competency of oocyte generation is also different between the two types of chicken. All oocytes were derived from the primordial germ cells (PGC) in the developing embryo, and female PGC proliferation (mitosis) and the subsequent differentiation (meiosis) determine the ultimate ovarian pool of germ cells available for future ovulation. In this study, we systematically compared the cellular phenotype and gene expression patterns during PGC mitosis (embryonic day 10, E10) and meiosis (E14) between female layers and broilers to determine whether the early germ cell development is also subjected to the selective breeding of egg production traits. We found that PGCs from E10 showed much higher activity in cell propagation and were enriched in cell proliferation signaling pathways than PGCs from E14 in both types of chicken. A common set of genes, namely insulin-like growth factor 2 (IGF2) and E2F transcription factor 4 (E2F4), were identified as the major regulators of cell proliferation in E10 PGCs of both strains. In addition, we found that E14 PGCs from both strains showed an equal ability to initiate meiosis, which was associated with the upregulation of key genes for meiotic initiation. The intrinsic cellular dynamics during the transition from proliferation to differentiation of female germ cells were conserved between layers and broilers. Hence, we surmise that other non-cell autonomous mechanisms involved in germ-somatic cell interactions would contribute to the divergence of egg production performance between layers and broilers. Full article

(This article belongs to the Special Issue Livestock: Genomics, Genetics and Breeding)

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13 pages, 6805 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Identification and Expression Analysis of TPS Gene Family in Liriodendron chinense

by Zijian Cao, Qianxi Ma, Yuhao Weng, Jisen Shi, Jinhui Chen and Zhaodong Hao

Genes 2023, 14(3), 770; https://doi.org/10.3390/genes14030770 - 22 Mar 2023

Cited by 11 | Viewed by 4038

Abstract

Terpenoids play a key role in plant growth and development, supporting resistance regulation and terpene synthase (TPS), which is the last link in the synthesis process of terpenoids. Liriodendron chinense, commonly called the Chinese tulip tree, is a rare and endangered tree species [...] Read more.

Terpenoids play a key role in plant growth and development, supporting resistance regulation and terpene synthase (TPS), which is the last link in the synthesis process of terpenoids. Liriodendron chinense, commonly called the Chinese tulip tree, is a rare and endangered tree species of the family Magnoliaceae. However, the genome-wide identification of the TPS gene family and its transcriptional responses to development and abiotic stress are still unclear. In the present study, we identified a total of 58 TPS genes throughout the L. chinense genome. A phylogenetic tree analysis showed that they were clustered into five subfamilies and unevenly distributed across six chromosomes. A cis-acting element analysis indicated that LcTPSs were assumed to be highly responsive to stress hormones, such as methyl jasmonate (MeJA) and abscisic acid (ABA). Consistent with this, transcriptome data showed that most LcTPS genes responded to abiotic stress, such as cold, drought, and hot stress, at the transcriptional level. Further analysis showed that LcTPS genes were expressed in a tissue-dependent manner, especially in buds, leaves, and bark. Quantitative reverse transcription PCR (qRT-PCR) analysis confirmed that LcTPS expression was significantly higher in mature leaves compared to young leaves. These results provide a reference for understanding the function and role of the TPS family, laying a foundation for further study of the regulation of TPS in terpenoid biosynthesis in L. chinense. Full article

(This article belongs to the Special Issue Abiotic Stress in Land Plants: Molecular Genetics and Genomics)

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