Genes

10 pages, 1412 KiB

Open AccessConcept Paper

Following Excitation/Inhibition Ratio Homeostasis from Synapse to EEG in Monogenetic Neurodevelopmental Disorders

by Lisa Geertjens, Torben W. van Voorst, Arianne Bouman, Maaike A. van Boven, Tjitske Kleefstra, Matthijs Verhage, Klaus Linkenkaer-Hansen, Nael Nadif Kasri, L. Niels Cornelisse and Hilgo Bruining

Genes 2022, 13(2), 390; https://doi.org/10.3390/genes13020390 - 21 Feb 2022

Cited by 4 | Viewed by 2905

Abstract

Pharmacological options for neurodevelopmental disorders are limited to symptom suppressing agents that do not target underlying pathophysiological mechanisms. Studies on specific genetic disorders causing neurodevelopmental disorders have elucidated pathophysiological mechanisms to develop more rational treatments. Here, we present our concerted multi-level strategy ‘BRAINMODEL’, [...] Read more.

Pharmacological options for neurodevelopmental disorders are limited to symptom suppressing agents that do not target underlying pathophysiological mechanisms. Studies on specific genetic disorders causing neurodevelopmental disorders have elucidated pathophysiological mechanisms to develop more rational treatments. Here, we present our concerted multi-level strategy ‘BRAINMODEL’, focusing on excitation/inhibition ratio homeostasis across different levels of neuroscientific interrogation. The aim is to develop personalized treatment strategies by linking iPSC-based models and novel EEG measurements to patient report outcome measures in individual patients. We focus our strategy on chromatin- and SNAREopathies as examples of severe genetic neurodevelopmental disorders with an unmet need for rational interventions. Full article

(This article belongs to the Special Issue From Genes to Therapy in Autism Spectrum Disorder)

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16 pages, 2594 KiB

Open AccessArticle

Early Markers of Cardiovascular Disease Associated with Clinical Data and Autosomal Ancestry in Patients with Type 1 Diabetes: A Cross-Sectional Study in an Admixed Brazilian Population

by Roberta Maria Duailibe Ferreira Reis, Rossana Santiago de Sousa Azulay, Maria da Glória Tavares, Gilvan Cortês Nascimento, Sabrina da Silva Pereira Damianse, Viviane Chaves de Carvalho Rocha, Ana Gregória Almeida, Débora Cristina Ferreira Lago, Vandilson Rodrigues, Marcelo Magalhães, Carla Souza Sobral, Conceição Parente, Joana França, Jacqueline Ribeiro, Paulo Cézar Dias Ferraz, Carlos Alberto Azulay Junior, Dayse Aparecida Silva, Marília Brito Gomes and Manuel dos Santos Faria

Genes 2022, 13(2), 389; https://doi.org/10.3390/genes13020389 - 21 Feb 2022

Viewed by 1741

Abstract

Patients with type 1 diabetes (T1D) have a higher risk of developing cardiovascular disease (CVD), which is a major cause of death in this population. This study investigates early markers of CVD associated with clinical data and autosomal ancestry in T1D patients from [...] Read more.

Patients with type 1 diabetes (T1D) have a higher risk of developing cardiovascular disease (CVD), which is a major cause of death in this population. This study investigates early markers of CVD associated with clinical data and autosomal ancestry in T1D patients from an admixed Brazilian population. A cross-sectional study was conducted with 99 T1D patients. The mean age of the study sample was 27.6 years and the mean duration of T1D was 14.4 years. The frequencies of abnormalities of the early markers of CVD were 19.6% in the ankle-brachial index (ABI), 4.1% in the coronary artery calcium score (CACS), and 5% in the carotid Doppler. A significant percentage of agreement was observed for the comparison of the frequency of abnormalities between CACS and carotid Doppler (92.2%, p = 0.041). There was no significant association between the level of autosomal ancestry proportions and early markers of CVD. The ABI was useful in the early identification of CVD in asymptomatic young patients with T1D and with a short duration of disease. Although CACS and carotid Doppler are non-invasive tests, carotid Doppler is more cost-effective, and both have limitations in screening for CVD in young patients with a short duration of T1D. We did not find a statistically significant relationship between autosomal ancestry proportions and early CVD markers in an admixed Brazilian population. Full article

(This article belongs to the Special Issue Genetics of Cardiovascular Metabolism)

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15 pages, 13317 KiB

Open AccessArticle

Characterization and Functional Study of FAM49B Reveals Its Effect on Cell Proliferation in HEK293T Cells

by Yijian Chen, Yuyan Jiang, Jihui Lao, Yankuan Zhou, Lida Su and Xiao Huang

Genes 2022, 13(2), 388; https://doi.org/10.3390/genes13020388 - 21 Feb 2022

Viewed by 2042

Abstract

FAM49B/Fam49b is a member of the Fam49 (Family with sequence similarity 49) gene family, which is characterized by the conserved domain, DUF1394 (Domain of Unknown Function 1394). It has also been named CYRI-B (CYFIP related RAC1 interactor B), implicating its important function of [...] Read more.

FAM49B/Fam49b is a member of the Fam49 (Family with sequence similarity 49) gene family, which is characterized by the conserved domain, DUF1394 (Domain of Unknown Function 1394). It has also been named CYRI-B (CYFIP related RAC1 interactor B), implicating its important function of regulating RAC1-driven cytoskeleton remolding. In this study, to further investigate its functions and mechanisms affecting cell behaviors, HEK293T cells (where FAM49B is highly expressed) were used to establish a FAM49B knockout cell line by CRISPR/Cas9 genome editing technology. Our data have clearly revealed that there are triple alleles of FAM49B in the genome of HEK293T cells. Meanwhile, the proliferation deficiency of the FAM49B KO HEK293T cell line and the significantly changed cell proliferation related gene expression profiles, such as CCND1, have been uncovered. At the same time, the existence of isoform 3 has been confirmed in HEK293T cells. Our studies have suggested that FAM49B may also affect cell proliferation via Cyclins, besides its influence on the cytoskeleton. Full article

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

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10 pages, 1542 KiB

Open AccessCommunication

Distinct Minor Splicing Patterns across Cancers

by Lauren Levesque, Nicole Salazar and Scott William Roy

Genes 2022, 13(2), 387; https://doi.org/10.3390/genes13020387 - 21 Feb 2022

Cited by 3 | Viewed by 2222

Abstract

In human cells, the U12 spliceosome, also known as the minor spliceosome, is responsible for the splicing of 0.5% of introns, while the major U2 spliceosome is responsible for the other 99.5%. While many studies have been done to characterize and understand splicing [...] Read more.

In human cells, the U12 spliceosome, also known as the minor spliceosome, is responsible for the splicing of 0.5% of introns, while the major U2 spliceosome is responsible for the other 99.5%. While many studies have been done to characterize and understand splicing dysregulation in cancer, almost all of them have focused on U2 splicing and ignored U12 splicing, despite evidence suggesting minor splicing is involved in cell cycle regulation. In this study, we analyzed RNA-seq data from The Cancer Genome Atlas for 14 different cohorts to determine differential splicing of minor introns in tumor and adjacent normal tissue. We found that in some cohorts, such as breast cancer, there was a strong skew towards minor introns showing increased splicing in the tumor; in others, such as the renal chromophobe cell carcinoma cohort, the opposite pattern was found, with minor introns being much more likely to have decreased splicing in the tumor. Further analysis of gene expression did not reveal any candidate regulatory mechanisms that could cause these different minor splicing phenotypes between cohorts. Our data suggest context-dependent roles of the minor spliceosome in tumorigenesis and provides a foundation for further investigation of minor splicing in cancer, which could then serve as a basis for novel therapeutic strategies. Full article

(This article belongs to the Section RNA)

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17 pages, 4981 KiB

Open AccessArticle

Cluster-Based Analysis of Retinitis Pigmentosa Modifiers Using Drosophila Eye Size and Gene Expression Data

by James Amstutz, Amal Khalifa, Rebecca Palu and Kaushara Jahan

Genes 2022, 13(2), 386; https://doi.org/10.3390/genes13020386 - 21 Feb 2022

Cited by 3 | Viewed by 1904

Abstract

The goal of this research is to computationally identify candidate modifiers for retinitis pigmentosa (RP), a group of rare genetic disorders that trigger the cellular degeneration of retinal tissue. RP being subject to phenotypic variation complicates diagnosis and treatment of the disease. In [...] Read more.

The goal of this research is to computationally identify candidate modifiers for retinitis pigmentosa (RP), a group of rare genetic disorders that trigger the cellular degeneration of retinal tissue. RP being subject to phenotypic variation complicates diagnosis and treatment of the disease. In a previous study, modifiers of RP were identified by an association between genetic variation in the DNA sequence and variation in eye size in a well-characterized Drosophila model of RP. This study will instead focus on RNA expression data to identify candidate modifier genes whose expression is correlated with phenotypic variation in eye size. The proposed approach uses the K-Means algorithm to cluster 171 Drosophila strains based on their expression profiles for 18,140 genes in adult females. This algorithm is designed to investigate the correlation between Drosophila eye size and genetic expression and gather suspect genes from clusters with abnormally large or small eyes. The clustering algorithm was implemented using the R scripting language and successfully identified 10 suspected candidate modifiers for RP. This analysis was followed by a validation study that tested seven candidate modifiers and found that the loss of five of them significantly altered the degeneration phenotype and thus can be labeled as a bona fide modifier of disease. Full article

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

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14 pages, 2819 KiB

Open AccessArticle

Salinity Gradient Controls Microbial Community Structure and Assembly in Coastal Solar Salterns

by Tianran Song, Qiyun Liang, Zhaozhong Du, Xiaoqun Wang, Guanjun Chen, Zongjun Du and Dashuai Mu

Genes 2022, 13(2), 385; https://doi.org/10.3390/genes13020385 - 21 Feb 2022

Cited by 14 | Viewed by 3033

Abstract

Salinity acts as a critical environmental filter on microbial communities in natural systems, negatively affecting microbial diversity. However, how salinity affects microbial community assembly remains unclear. This study used Wendeng multi-pond saltern as a model to evaluate the prokaryotic community composition and diversity [...] Read more.

Salinity acts as a critical environmental filter on microbial communities in natural systems, negatively affecting microbial diversity. However, how salinity affects microbial community assembly remains unclear. This study used Wendeng multi-pond saltern as a model to evaluate the prokaryotic community composition and diversity and quantify the relative importance of ecological processes across salinity gradients. The results showed that low-saline salterns (45–80 g/L) exhibited higher bacterial diversity than high-saline salterns (175–265 g/L). The relative abundance of taxa assigned to Halomicrobiaceae, Rhodobacteraceae, Saprospiraceae, and Thiotrichaceae exhibited a hump-shaped dependence on increasing salinity. Salinity and pH were the primary environmental factors that directly or indirectly determined the composition and diversity of prokaryotic communities. Microbial co-occurrence network dynamics were more complex in the sediment than in the water of salterns. An infer Community Assembly Mechanisms by Phylogenetic-bin-based null model analysis (iCAMP) showed that microbial community assembly in sediment and water differed. Our findings provide more information about microbial community structure and the importance of various ecological processes in controlling microbial community diversity and succession along salinity gradients in water and sediment. Full article

(This article belongs to the Special Issue When Genes Meet Microbial Ecology and Evolution)

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12 pages, 1328 KiB

Open AccessArticle

Consequences of the Last Glacial Period on the Genetic Diversity of Southeast Asians

by Catarina Branco, Marina Kanellou, Antonio González-Martín and Miguel Arenas

Genes 2022, 13(2), 384; https://doi.org/10.3390/genes13020384 - 21 Feb 2022

Cited by 2 | Viewed by 2775

Abstract

The last glacial period (LGP) promoted a loss of genetic diversity in Paleolithic populations of modern humans from diverse regions of the world by range contractions and habitat fragmentation. However, this period also provided some currently submersed lands, such as the Sunda shelf [...] Read more.

The last glacial period (LGP) promoted a loss of genetic diversity in Paleolithic populations of modern humans from diverse regions of the world by range contractions and habitat fragmentation. However, this period also provided some currently submersed lands, such as the Sunda shelf in Southeast Asia (SEA), that could have favored the expansion of our species. Concerning the latter, still little is known about the influence of the lowering sea level on the genetic diversity of current SEA populations. Here, we applied approximate Bayesian computation, based on extensive spatially explicit computer simulations, to evaluate the fitting of mtDNA data from diverse SEA populations with alternative evolutionary scenarios that consider and ignore the LGP and migration through long-distance dispersal (LDD). We found that both the LGP and migration through LDD should be taken into consideration to explain the currently observed genetic diversity in these populations and supported a rapid expansion of first populations throughout SEA. We also found that temporarily available lands caused by the low sea level of the LGP provided additional resources and migration corridors that favored genetic diversity. We conclude that migration through LDD and temporarily available lands during the LGP should be considered to properly understand and model the first expansions of modern humans. Full article

(This article belongs to the Special Issue Trends in Population Genetics and Identification—Impact on Anthropology)

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12 pages, 926 KiB

Open AccessArticle

Alpha Satellite RNA Levels Are Upregulated in the Blood of Patients with Metastatic Castration-Resistant Prostate Cancer

by Sven Ljubić, Antonio Sermek, Angela Prgomet Sečan, Marin Prpić, Blanka Jakšić, Jure Murgić, Ana Fröbe, Đurđica Ugarković and Isidoro Feliciello

Genes 2022, 13(2), 383; https://doi.org/10.3390/genes13020383 - 20 Feb 2022

Cited by 7 | Viewed by 2698

Abstract

The aberrant overexpression of alpha satellite DNA is characteristic of many human cancers including prostate cancer; however, it is not known whether the change in the alpha satellite RNA amount occurs in the peripheral tissues of cancer patients, such as blood. Here, we [...] Read more.

The aberrant overexpression of alpha satellite DNA is characteristic of many human cancers including prostate cancer; however, it is not known whether the change in the alpha satellite RNA amount occurs in the peripheral tissues of cancer patients, such as blood. Here, we analyse the level of intracellular alpha satellite RNA in the whole blood of cancer prostate patients at different stages of disease and compare it with the levels found in healthy controls. Our results reveal a significantly increased level of intracellular alpha satellite RNA in the blood of metastatic cancers patients, particularly those with metastatic castration-resistant prostate cancer relative to controls. In the blood of patients with localised tumour, no significant change relative to the controls was detected. Our results show a link between prostate cancer pathogenesis and blood intracellular alpha satellite RNA levels. We discuss the possible mechanism which could lead to the increased level of blood intracellular alpha satellite RNA at a specific metastatic stage of prostate cancer. Additionally, we analyse the clinically accepted prostate cancer biomarker PSA in all samples and discuss the possibility that alpha satellite RNA can serve as a novel prostate cancer diagnostic blood biomarker. Full article

(This article belongs to the Special Issue Non-coding DNA in Human Health and Diseases)

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22 pages, 4330 KiB

Open AccessArticle

Single-Cell Transcriptome and Network Analyses Unveil Key Transcription Factors Regulating Mesophyll Cell Development in Maize

by Shentong Tao, Peng Liu, Yining Shi, Yilong Feng, Jingjing Gao, Lifen Chen, Aicen Zhang, Xuejiao Cheng, Hairong Wei, Tao Zhang and Wenli Zhang

Genes 2022, 13(2), 374; https://doi.org/10.3390/genes13020374 - 20 Feb 2022

Cited by 12 | Viewed by 5643

Abstract

Background: Maize mesophyll (M) cells play important roles in various biological processes such as photosynthesis II and secondary metabolism. Functional differentiation occurs during M-cell development, but the underlying mechanisms for regulating M-cell development are largely unknown. Results: We conducted single-cell RNA sequencing (scRNA-seq) [...] Read more.

Background: Maize mesophyll (M) cells play important roles in various biological processes such as photosynthesis II and secondary metabolism. Functional differentiation occurs during M-cell development, but the underlying mechanisms for regulating M-cell development are largely unknown. Results: We conducted single-cell RNA sequencing (scRNA-seq) to profile transcripts in maize leaves. We then identified coregulated modules by analyzing the resulting pseudo-time-series data through gene regulatory network analyses. WRKY, ERF, NAC, MYB and Heat stress transcription factor (HSF) families were highly expressed in the early stage, whereas CONSTANS (CO)-like (COL) and ERF families were highly expressed in the late stage of M-cell development. Construction of regulatory networks revealed that these transcript factor (TF) families, especially HSF and COL, were the major players in the early and later stages of M-cell development, respectively. Integration of scRNA expression matrix with TF ChIP-seq and Hi-C further revealed regulatory interactions between these TFs and their targets. HSF1 and COL8 were primarily expressed in the leaf bases and tips, respectively, and their targets were validated with protoplast-based ChIP-qPCR, with the binding sites of HSF1 being experimentally confirmed. Conclusions: Our study provides evidence that several TF families, with the involvement of epigenetic regulation, play vital roles in the regulation of M-cell development in maize. Full article

(This article belongs to the Section RNA)

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11 pages, 1042 KiB

Open AccessReview

Current and Future Approaches to Classify VUSs in LGMD-Related Genes

by Chengcheng Li, Gabe Haller and Conrad C. Weihl

Genes 2022, 13(2), 382; https://doi.org/10.3390/genes13020382 - 19 Feb 2022

Cited by 3 | Viewed by 2097

Abstract

Next-generation sequencing (NGS) has revealed large numbers of genetic variants in LGMD-related genes, with most of them classified as variants of uncertain significance (VUSs). VUSs are genetic changes with unknown pathological impact and present a major challenge in genetic test interpretation and disease [...] Read more.

Next-generation sequencing (NGS) has revealed large numbers of genetic variants in LGMD-related genes, with most of them classified as variants of uncertain significance (VUSs). VUSs are genetic changes with unknown pathological impact and present a major challenge in genetic test interpretation and disease diagnosis. Understanding the phenotypic consequences of VUSs can provide clinical guidance regarding LGMD risk and therapy. In this review, we provide a brief overview of the subtypes of LGMD, disease diagnosis, current classification systems for investigating VUSs, and a potential deep mutational scanning approach to classify VUSs in LGMD-related genes. Full article

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

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15 pages, 679 KiB

Open AccessFeature PaperArticle

Leveraging Gene-Level Prediction as Informative Covariate in Hypothesis Weighting Improves Power for Rare Variant Association Studies

by Ying Ji, Rui Chen, Quan Wang, Qiang Wei, Ran Tao and Bingshan Li

Genes 2022, 13(2), 381; https://doi.org/10.3390/genes13020381 - 19 Feb 2022

Viewed by 2019

Abstract

Gene-based rare variant association studies (RVASs) have low power due to the infrequency of rare variants and the large multiple testing burden. To correct for multiple testing, traditional false discovery rate (FDR) procedures which depend solely on P-values are often used. Recently, Independent [...] Read more.

Gene-based rare variant association studies (RVASs) have low power due to the infrequency of rare variants and the large multiple testing burden. To correct for multiple testing, traditional false discovery rate (FDR) procedures which depend solely on P-values are often used. Recently, Independent Hypothesis Weighting (IHW) was developed to improve the detection power while maintaining FDR control by leveraging prior information for each hypothesis. Here, we present a framework to increase power of gene-based RVASs by incorporating prior information using IHW. We first build supervised machine learning models to assign each gene a prediction score that measures its disease risk, using the input of multiple biological features, fed with high-confidence risk genes and local background genes selected near GWAS significant loci as the training set. Then we use the prediction scores as covariates to prioritize RVAS results via IHW. We demonstrate the effectiveness of this framework through applications to RVASs in schizophrenia and autism spectrum disorder. We found sizeable improvements in the number of significant associations compared to traditional FDR approaches, and independent evidence supporting the relevance of the genes identified by our framework but not traditional FDR, demonstrating the potential of our framework to improve power of gene-based RVASs. Full article

(This article belongs to the Special Issue Statistical Genetics in Human Diseases)

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11 pages, 270 KiB

Open AccessReview

A Primer for Single-Cell Sequencing in Non-Model Organisms

by James M. Alfieri, Guosong Wang, Michelle M. Jonika, Clare A. Gill, Heath Blackmon and Giridhar N. Athrey

Genes 2022, 13(2), 380; https://doi.org/10.3390/genes13020380 - 19 Feb 2022

Cited by 8 | Viewed by 3302

Abstract

Single-cell sequencing technologies have led to a revolution in our knowledge of the diversity of cell types, connections between biological levels of organization, and relationships between genotype and phenotype. These advances have mainly come from using model organisms; however, using single-cell sequencing in [...] Read more.

Single-cell sequencing technologies have led to a revolution in our knowledge of the diversity of cell types, connections between biological levels of organization, and relationships between genotype and phenotype. These advances have mainly come from using model organisms; however, using single-cell sequencing in non-model organisms could enable investigations of questions inaccessible with typical model organisms. This primer describes a general workflow for single-cell sequencing studies and considerations for using non-model organisms (limited to multicellular animals). Importantly, single-cell sequencing, when further applied in non-model organisms, will allow for a deeper understanding of the mechanisms between genotype and phenotype and the basis for biological variation. Full article

(This article belongs to the Special Issue Single-Cell Bioinformatics and Machine Learning)

17 pages, 1096 KiB

Open AccessArticle

Bifidobacterium Is Enriched in Gut Microbiome of Kashmiri Women with Polycystic Ovary Syndrome

by Saqib Hassan, Marika A. Kaakinen, Harmen Draisma, Liudmila Zudina, Mohd A. Ganie, Aafia Rashid, Zhanna Balkhiyarova, George S. Kiran, Paris Vogazianos, Christos Shammas, Joseph Selvin, Athos Antoniades, Ayse Demirkan and Inga Prokopenko

Genes 2022, 13(2), 379; https://doi.org/10.3390/genes13020379 - 18 Feb 2022

Cited by 13 | Viewed by 3283

Abstract

Polycystic ovary syndrome (PCOS) is a very common endocrine condition in women in India. Gut microbiome alterations were shown to be involved in PCOS, yet it is remarkably understudied in Indian women who have a higher incidence of PCOS as compared to other [...] Read more.

Polycystic ovary syndrome (PCOS) is a very common endocrine condition in women in India. Gut microbiome alterations were shown to be involved in PCOS, yet it is remarkably understudied in Indian women who have a higher incidence of PCOS as compared to other ethnic populations. During the regional PCOS screening program among young women, we recruited 19 drug naive women with PCOS and 20 control women at the Sher-i-Kashmir Institute of Medical Sciences, Kashmir, North India. We profiled the gut microbiome in faecal samples by 16S rRNA sequencing and included 40/58 operational taxonomic units (OTUs) detected in at least 1/3 of the subjects with relative abundance (RA) ≥ 0.1%. We compared the RAs at a family/genus level in PCOS/non-PCOS groups and their correlation with 33 metabolic and hormonal factors, and corrected for multiple testing, while taking the variation in day of menstrual cycle at sample collection, age and BMI into account. Five genera were significantly enriched in PCOS cases: Sarcina, Megasphaera, and previously reported for PCOS Bifidobacterium, Collinsella and Paraprevotella confirmed by different statistical models. At the family level, the relative abundance of Bifidobacteriaceae was enriched, whereas Peptococcaceae was decreased among cases. We observed increased relative abundance of Collinsella and Paraprevotella with higher fasting blood glucose levels, and Paraprevotella and Alkalibacterium with larger hip, waist circumference, weight, and Peptococcaceae with lower prolactin levels. We also detected a novel association between Eubacterium and follicle-stimulating hormone levels and between Bifidobacterium and alkaline phosphatase, independently of the BMI of the participants. Our report supports that there is a relationship between gut microbiome composition and PCOS with links to specific reproductive health metabolic and hormonal predictors in Indian women. Full article

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

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24 pages, 1188 KiB

Open AccessEditor’s ChoiceReview

Epigenetic and Epitranscriptomic Control in Prostate Cancer

by Judith López, Ana M. Añazco-Guenkova, Óscar Monteagudo-García and Sandra Blanco

Genes 2022, 13(2), 378; https://doi.org/10.3390/genes13020378 - 18 Feb 2022

Cited by 14 | Viewed by 3806

Abstract

The initiation of prostate cancer has been long associated with DNA copy-number alterations, the loss of specific chromosomal regions and gene fusions, and driver mutations, especially those of the Androgen Receptor. Non-mutational events, particularly DNA and RNA epigenetic dysregulation, are emerging as key [...] Read more.

The initiation of prostate cancer has been long associated with DNA copy-number alterations, the loss of specific chromosomal regions and gene fusions, and driver mutations, especially those of the Androgen Receptor. Non-mutational events, particularly DNA and RNA epigenetic dysregulation, are emerging as key players in tumorigenesis. In this review we summarize the molecular changes linked to epigenetic and epitranscriptomic dysregulation in prostate cancer and the role that alterations to DNA and RNA modifications play in the initiation and progression of prostate cancer. Full article

(This article belongs to the Special Issue Epigenomics and Epitranscriptomics Crosstalk)

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Graphical abstract

18 pages, 4095 KiB

Open AccessArticle

A Two-Part Mixed Model for Differential Expression Analysis in Single-Cell High-Throughput Gene Expression Data

by Yang Shi, Ji-Hyun Lee, Huining Kang and Hui Jiang

Genes 2022, 13(2), 377; https://doi.org/10.3390/genes13020377 - 18 Feb 2022

Cited by 3 | Viewed by 2629

Abstract

The high-throughput gene expression data generated from recent single-cell RNA sequencing (scRNA-seq) and parallel single-cell reverse transcription quantitative real-time PCR (scRT-qPCR) technologies enable biologists to study the function of transcriptome at the level of individual cells. Compared with bulk RNA-seq and RT-qPCR gene [...] Read more.

The high-throughput gene expression data generated from recent single-cell RNA sequencing (scRNA-seq) and parallel single-cell reverse transcription quantitative real-time PCR (scRT-qPCR) technologies enable biologists to study the function of transcriptome at the level of individual cells. Compared with bulk RNA-seq and RT-qPCR gene expression data, single-cell data show notable distinct features, including excessive zero expression values, high variability, and clustered design. We propose to model single-cell high-throughput gene expression data using a two-part mixed model, which not only adequately accounts for the aforementioned features of single-cell expression data but also provides the flexibility of adjusting for covariates. An efficient computational algorithm, automatic differentiation, is used for estimating the model parameters. Compared with existing methods, our approach shows improved power for detecting differential expressed genes in single-cell high-throughput gene expression data. Full article

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

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26 pages, 4142 KiB

Open AccessArticle

Was the Last Bacterial Common Ancestor a Monoderm after All?

by Raphaël R. Léonard, Eric Sauvage, Valérian Lupo, Amandine Perrin, Damien Sirjacobs, Paulette Charlier, Frédéric Kerff and Denis Baurain

Genes 2022, 13(2), 376; https://doi.org/10.3390/genes13020376 - 18 Feb 2022

Cited by 5 | Viewed by 3513

Abstract

The very nature of the last bacterial common ancestor (LBCA), in particular the characteristics of its cell wall, is a critical issue to understand the evolution of life on earth. Although knowledge of the relationships between bacterial phyla has made progress with the [...] Read more.

The very nature of the last bacterial common ancestor (LBCA), in particular the characteristics of its cell wall, is a critical issue to understand the evolution of life on earth. Although knowledge of the relationships between bacterial phyla has made progress with the advent of phylogenomics, many questions remain, including on the appearance or disappearance of the outer membrane of diderm bacteria (also called Gram-negative bacteria). The phylogenetic transition between monoderm (Gram-positive bacteria) and diderm bacteria, and the associated peptidoglycan expansion or reduction, requires clarification. Herein, using a phylogenomic tree of cultivated and characterized bacteria as an evolutionary framework and a literature review of their cell-wall characteristics, we used Bayesian ancestral state reconstruction to infer the cell-wall architecture of the LBCA. With the same phylogenomic tree, we further revisited the evolution of the division and cell-wall synthesis (dcw) gene cluster using homology- and model-based methods. Finally, extensive similarity searches were carried out to determine the phylogenetic distribution of the genes involved with the biosynthesis of the outer membrane in diderm bacteria. Quite unexpectedly, our analyses suggest that all cultivated and characterized bacteria might have evolved from a common ancestor with a monoderm cell-wall architecture. If true, this would indicate that the appearance of the outer membrane was not a unique event and that selective forces have led to the repeated adoption of such an architecture. Due to the lack of phenotypic information, our methodology cannot be applied to all extant bacteria. Consequently, our conclusion might change once enough information is made available to allow the use of an even more diverse organism selection. Full article

(This article belongs to the Special Issue The Stability and Evolution of Genes and Genomes)

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30 pages, 2321 KiB

Open AccessReview

The Regulatory Hierarchy Following Signal Integration by the CbrAB Two-Component System: Diversity of Responses and Functions

by Elizabet Monteagudo-Cascales, Eduardo Santero and Inés Canosa

Genes 2022, 13(2), 375; https://doi.org/10.3390/genes13020375 - 18 Feb 2022

Cited by 11 | Viewed by 2532

Abstract

CbrAB is a two-component system, unique to bacteria of the family Pseudomonaceae, capable of integrating signals and involved in a multitude of physiological processes that allow bacterial adaptation to a wide variety of varying environmental conditions. This regulatory system provides a great [...] Read more.

CbrAB is a two-component system, unique to bacteria of the family Pseudomonaceae, capable of integrating signals and involved in a multitude of physiological processes that allow bacterial adaptation to a wide variety of varying environmental conditions. This regulatory system provides a great metabolic versatility that results in excellent adaptability and metabolic optimization. The two-component system (TCS) CbrA–CbrB is on top of a hierarchical regulatory cascade and interacts with other regulatory systems at different levels, resulting in a robust output. Among the regulatory systems found at the same or lower levels of CbrAB are the NtrBC nitrogen availability adaptation system, the Crc/Hfq carbon catabolite repression cascade in Pseudomonas, or interactions with the GacSA TCS or alternative sigma ECF factor, such as SigX. The interplay between regulatory mechanisms controls a number of physiological processes that intervene in important aspects of bacterial adaptation and survival. These include the hierarchy in the use of carbon sources, virulence or resistance to antibiotics, stress response or definition of the bacterial lifestyle. The multiple actions of the CbrAB TCS result in an important competitive advantage. Full article

(This article belongs to the Special Issue Regulation of Microbial Biosynthetic Genes and Biodegradation Genes)

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11 pages, 899 KiB

Open AccessArticle

An Identification and Characterization of the Axolotl (Ambystoma mexicanum, Amex) Telomerase Reverse Transcriptase (Amex TERT)

by Sina Springhetti, Vesna Bucan, Christina Liebsch, Andrea Lazaridis, Peter Maria Vogt and Sarah Strauß

Genes 2022, 13(2), 373; https://doi.org/10.3390/genes13020373 - 18 Feb 2022

Cited by 2 | Viewed by 2453

Abstract

The Mexican axolotl is one of the few vertebrates that is able to replace its lost body parts during lifespan. Due to its remarkable regenerative abilities, the axolotl emerged as a model organism especially for limb regeneration. Telomeres and the telomerase enzyme are [...] Read more.

The Mexican axolotl is one of the few vertebrates that is able to replace its lost body parts during lifespan. Due to its remarkable regenerative abilities, the axolotl emerged as a model organism especially for limb regeneration. Telomeres and the telomerase enzyme are crucial for regeneration and protection against aging processes and degenerating diseases. Despite its relevance for regeneration, the axolotl telomerase and telomere length have not yet been investigated. Therefore, in the present paper, we reveal the sequence of the axolotl telomerase reverse transcriptase gene (Tert) and protein (TERT). Multiple sequence alignment (MSA) showed the known conserved RT- and TERT-specific motifs and residues found in other TERTs. In addition, we establish methods to determine the Tert expression (RT-PCR) and telomerase activity (Q-TRAP) of adult axolotl and blastema tissues. We found that both differentiated forelimb tissue and regenerating blastema tissue express Tert and show telomerase activity. Furthermore, blastema tissue appears to exhibit a higher Tert expression and telomerase activity. The presence of active telomerase in adult somatic cells is a decisive difference to somatic cells of non-regenerating vertebrates, such as humans. These findings indicate that telomere biology may play a key role in the regenerative abilities of cells. Full article

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

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6 pages, 1189 KiB

Open AccessCase Report

Clinical, Histological, Cytogenetic and Molecular Analysis of Monozygous Twins with Wilms Tumor

by Katarzyna Iwańczyk, Bartosz Czachowski, Patrycja Sosnowska-Sienkiewicz, Gabriela Telman, Paulina Ciążyńska, Przemysław Mańkowski and Danuta Januszkiewicz-Lewandowska

Genes 2022, 13(2), 372; https://doi.org/10.3390/genes13020372 - 18 Feb 2022

Cited by 2 | Viewed by 2094

Abstract

The familial occurrence of childhood cancers has been proven for a long time. Wilms’ tumors often do not have a clear germline genetic cause. However, approximately 2% of all nephroblastoma cases are familial. Descriptions of twins with the same cancer are extremely rare, [...] Read more.

The familial occurrence of childhood cancers has been proven for a long time. Wilms’ tumors often do not have a clear germline genetic cause. However, approximately 2% of all nephroblastoma cases are familial. Descriptions of twins with the same cancer are extremely rare, so our aim was to present the background of the available literature of the occurrence of Wilms’ tumor in a pair of monozygotic twin girls with detailed clinical, histological, and molecular analysis. Two twins were born of unrelated Caucasian parents. Family history revealed no known chronic diseases or malformations. At the age of 3.5 years, the first twin was admitted to the emergency department due to hematuria and abdominal pain. Ultrasound examination revealed an enlarged right kidney, 12.8 cm, with a mass in the upper pole measuring 56 × 69 × 78 mm. The second girl was referred for an abdominal ultrasound, which revealed a right kidney measuring 8.6 cm with a central mass measuring 54 × 45 × 41 mm. Both children underwent surgical resection, and the histopathological result showed a mixed form of nephroblastoma, predominantly epithelioid with residual blastemal compartment. Detailed clinical, histological, cytogenetic, and molecular analyses were performed on both sisters. It was also decided to identify environmental factors. Information was obtained that the girls’ parents run a farm and regularly use pesticides and chemical rodenticides. Based on our observations and the available literature, Wilms tumor in monozygotic twins may be present. Both genetic and environmental factors may be involved in the development of tumors. After excluding methylation abnormalities and mutations in the genes studied, we questioned whether the onset of Wilms tumor in both sisters could be the result of exposure of the twins’ parents to pesticides. Full article

(This article belongs to the Section Cytogenomics)

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17 pages, 4800 KiB

Open AccessArticle

scInTime: A Computational Method Leveraging Single-Cell Trajectory and Gene Regulatory Networks to Identify Master Regulators of Cellular Differentiation

by Qian Xu, Guanxun Li, Daniel Osorio, Yan Zhong, Yongjian Yang, Yu-Te Lin, Xiuren Zhang and James J. Cai

Genes 2022, 13(2), 371; https://doi.org/10.3390/genes13020371 - 18 Feb 2022

Cited by 4 | Viewed by 3875

Abstract

Trajectory inference (TI) or pseudotime analysis has dramatically extended the analytical framework of single-cell RNA-seq data, allowing regulatory genes contributing to cell differentiation and those involved in various dynamic cellular processes to be identified. However, most TI analysis procedures deal with individual genes [...] Read more.

Trajectory inference (TI) or pseudotime analysis has dramatically extended the analytical framework of single-cell RNA-seq data, allowing regulatory genes contributing to cell differentiation and those involved in various dynamic cellular processes to be identified. However, most TI analysis procedures deal with individual genes independently while overlooking the regulatory relations between genes. Integrating information from gene regulatory networks (GRNs) at different pseudotime points may lead to more interpretable TI results. To this end, we introduce scInTime—an unsupervised machine learning framework coupling inferred trajectory with single-cell GRNs (scGRNs) to identify master regulatory genes. We validated the performance of our method by analyzing multiple scRNA-seq data sets. In each of the cases, top-ranking genes predicted by scInTime supported their functional relevance with corresponding signaling pathways, in line with the results of available functional studies. Overall results demonstrated that scInTime is a powerful tool to exploit pseudotime-series scGRNs, allowing for a clear interpretation of TI results toward more significant biological insights. Full article

(This article belongs to the Special Issue Single-Cell Bioinformatics and Machine Learning)

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15 pages, 1672 KiB

Open AccessTechnical Note

Analysing miRNA-Target Gene Networks in Inflammatory Bowel Disease and Other Complex Diseases Using Transcriptomic Data

by John P. Thomas, Marton Ölbei, Johanne Brooks-Warburton, Tamas Korcsmaros and Dezso Modos

Genes 2022, 13(2), 370; https://doi.org/10.3390/genes13020370 - 18 Feb 2022

Cited by 4 | Viewed by 2909

Abstract

Patients with inflammatory bowel disease (IBD) are known to have perturbations in microRNA (miRNA) levels as well as altered miRNA regulation. Although experimental methods have provided initial insights into the functional consequences that may arise due to these changes, researchers are increasingly utilising [...] Read more.

Patients with inflammatory bowel disease (IBD) are known to have perturbations in microRNA (miRNA) levels as well as altered miRNA regulation. Although experimental methods have provided initial insights into the functional consequences that may arise due to these changes, researchers are increasingly utilising novel bioinformatics approaches to further dissect the role of miRNAs in IBD. The recent exponential increase in transcriptomics datasets provides an excellent opportunity to further explore the role of miRNAs in IBD pathogenesis. To effectively understand miRNA-target gene interactions from gene expression data, multiple database resources are required, which have become available in recent years. In this technical note, we provide a step-by-step protocol for utilising these state-of-the-art resources, as well as systems biology approaches to understand the role of miRNAs in complex disease pathogenesis. We demonstrate through a case study example how to combine the resulting miRNA-target gene networks with transcriptomics data to find potential disease-specific miRNA regulators and miRNA-target genes in Crohn’s disease. This approach could help to identify miRNAs that may have important disease-modifying effects in IBD and other complex disorders, and facilitate the discovery of novel therapeutic targets. Full article

(This article belongs to the Special Issue Multidisciplinary Approaches in IBD Genetics)

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15 pages, 3665 KiB

Open AccessArticle

The Complete Chloroplast Genome of Carya cathayensis and Phylogenetic Analysis

by Jianshuang Shen, Xueqin Li, Xia Chen, Xiaoling Huang and Songheng Jin

Genes 2022, 13(2), 369; https://doi.org/10.3390/genes13020369 - 18 Feb 2022

Cited by 15 | Viewed by 2923

Abstract

Carya cathayensis, an important economic nut tree, is narrowly endemic to eastern China in the wild. The complete cp genome of C. cathayensis was sequenced with NGS using an Illumina HiSeq2500, analyzed, and compared to its closely related species. The cp genome [...] Read more.

Carya cathayensis, an important economic nut tree, is narrowly endemic to eastern China in the wild. The complete cp genome of C. cathayensis was sequenced with NGS using an Illumina HiSeq2500, analyzed, and compared to its closely related species. The cp genome is 160,825 bp in length with an overall GC content of 36.13%, presenting a quadripartite structure comprising a large single copy (LSC; 90,115 bp), a small single copy (SSC; 18,760 bp), and a pair of inverted repeats (IRs; 25,975 bp). The genome contains 129 genes, including 84 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. A total of 252 simple sequence repeats (SSRs) and 55 long repeats were identified. Gene selective pressure analysis showed that seven genes (rps15, rpoA, rpoB, petD, ccsA, atpI, and ycf1-2) were possibly under positive selection compared with the other Juglandaceae species. Phylogenetic relationships of 46 species inferred that Juglandaceae is monophyletic, and that C. cathayensis is sister to Carya kweichowensis and Carya illinoinensis. The genome comparison revealed that there is a wide variability of the junction sites, and there is higher divergence in the noncoding regions than in coding regions. These results suggest a great potential in phylogenetic research. The newly characterized cp genome of C. cathayensis provides valuable information for further studies of this economically important species. Full article

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

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9 pages, 438 KiB

Open AccessArticle

Exome Evaluation of Autism-Associated Genes in Amazon American Populations

by Giovana E. da Costa, Giordane L. Fernandes, Juliana C. G. Rodrigues, Diana F. da V. B. Leal, Lucas F. Pastana, Esdras E. B. Pereira, Paulo P. Assumpção, Rommel M. R. Burbano, Sidney E. B. dos Santos, João F. Guerreiro, Marianne R. Fernandes and Ney P. C. dos Santos

Genes 2022, 13(2), 368; https://doi.org/10.3390/genes13020368 - 18 Feb 2022

Cited by 3 | Viewed by 1968

Abstract

Autism spectrum disorder is a neurodevelopmental disorder, affecting one in 160 children worldwide. The causes of autism are still poorly understood, but research shows the relevance of genetic factors in its pathophysiology, including the CHD8, SCN2A, FOXP1 and SYNGAP1 genes. Information [...] Read more.

Autism spectrum disorder is a neurodevelopmental disorder, affecting one in 160 children worldwide. The causes of autism are still poorly understood, but research shows the relevance of genetic factors in its pathophysiology, including the CHD8, SCN2A, FOXP1 and SYNGAP1 genes. Information about the genetic influence on various diseases, including autism, in the Amerindian population from Amazon, is still scarce. We investigated 35 variants of the CHD8, SCN2A, FOXP1, and SYNGAP1 gene in Amazonian Amerindians in comparison with publicly available population frequencies from the 1000 Genomes Project database. Our study identified 16 variants in the Amerindian population of the Amazon with frequencies significantly different from the other populations. Among them, the SCN2A (rs17183814, rs75109281, and rs150453735), FOXP1 (rs56850311 and rs939845), and SYNGAP1 (rs9394145 and rs115441992) variants presented higher frequency than all other populations analyzed. In addition, nine variants were found with lower frequency among the Amerindians: CHD8 (rs35057134 and rs10467770), SCN2A (rs3769951, rs2304014, rs1838846, and rs7593568), FOXP1 (rs112773801 and rs56850311), and SYNGAP1 (rs453590). These data show the unique genetic profile of the indigenous population of the Brazilian Amazon. Knowledge of these variants can help to understand the pathophysiology and diagnosis of autism among Amerindians, Brazilians, and in admixed populations that have contributions from this ethnic group. Full article

(This article belongs to the Special Issue Progress in Genetics of Autism)

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Graphical abstract

18 pages, 328 KiB

Open AccessReview

Myotonic Dystrophies: A Genetic Overview

by Payam Soltanzadeh

Genes 2022, 13(2), 367; https://doi.org/10.3390/genes13020367 - 17 Feb 2022

Cited by 7 | Viewed by 4881

Abstract

Myotonic dystrophies (DM) are the most common muscular dystrophies in adults, which can affect other non-skeletal muscle organs such as the heart, brain and gastrointestinal system. There are two genetically distinct types of myotonic dystrophy: myotonic dystrophy type 1 (DM1) and myotonic dystrophy [...] Read more.

Myotonic dystrophies (DM) are the most common muscular dystrophies in adults, which can affect other non-skeletal muscle organs such as the heart, brain and gastrointestinal system. There are two genetically distinct types of myotonic dystrophy: myotonic dystrophy type 1 (DM1) and myotonic dystrophy type 2 (DM2), both dominantly inherited with significant overlap in clinical manifestations. DM1 results from CTG repeat expansions in the 3′-untranslated region (3′UTR) of the DMPK (dystrophia myotonica protein kinase) gene on chromosome 19, while DM2 is caused by CCTG repeat expansions in intron 1 of the CNBP (cellular nucleic acid-binding protein) gene on chromosome 3. Recent advances in genetics and molecular biology, especially in the field of RNA biology, have allowed better understanding of the potential pathomechanisms involved in DM. In this review article, core clinical features and genetics of DM are presented followed by a discussion on the current postulated pathomechanisms and therapeutic approaches used in DM, including the ones currently in human clinical trial phase. Full article

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

22 pages, 42995 KiB

Open AccessFeature PaperArticle

Transcriptomics-Based Identification of Genes Related to Tapetum Degradation and Microspore Development in Lily

by Juanjuan Sui, Wenjie Jia, Yin Xin and Yuanyuan Zhang

Genes 2022, 13(2), 366; https://doi.org/10.3390/genes13020366 - 17 Feb 2022

Viewed by 2017

Abstract

Lily is a popular and economically ornamental crop around the world. However, its high production of pollen grains causes serious problems to consumers, including allergies and staining of clothes. During anther development, the tapetum is a crucial step for pollen formation and microspore [...] Read more.

Lily is a popular and economically ornamental crop around the world. However, its high production of pollen grains causes serious problems to consumers, including allergies and staining of clothes. During anther development, the tapetum is a crucial step for pollen formation and microspore release. Therefore, it is important to understand the mechanism of tapetum degradation and microspore development in lily where free pollen contamination occurs. Here, we used the cut lily cultivar ‘Siberia’ to characterize the process of tapetum degradation through the use of cytology and transcriptomic methods. The cytological observation indicated that, as the lily buds developed from 4 cm (Lo 4 cm) to 8 cm (Lo 8 cm), the tapetum completed the degradation process and the microspores matured. Furthermore, by comparing the transcriptome profiling among three developmental stages (Lo 4 cm, Lo 6 cm and Lo 8 cm), we identified 27 differentially expressed genes. These 27 genes were classed into 4 groups by function, namely, cell division and expansion, cell-wall morphogenesis, transcription factors, LRR-RLK (leucine-rich repeat receptor-like kinases), plant hormone biosynthesis and transduction. Quantitative real-time PCR was performed as validation of the transcriptome data. These selected genes are candidate genes for the tapetum degradation and microspore development of lily and our work provides a theoretical basis for breeding new lily cultivars without pollen. Full article

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

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15 pages, 3638 KiB

Open AccessArticle

Multi-Level Analysis and Identification of Tumor Mutational Burden Genes across Cancer Types

by Shuangkuai Wang, Yuantao Tong, Hui Zong, Xuewen Xu, M. James C. Crabbe, Ying Wang and Xiaoyan Zhang

Genes 2022, 13(2), 365; https://doi.org/10.3390/genes13020365 - 17 Feb 2022

Cited by 4 | Viewed by 2313

Abstract

Tumor mutational burden (TMB) is considered a potential biomarker for predicting the response and effect of immune checkpoint inhibitors (ICIs). However, there are still inconsistent standards of gene panels using next-generation sequencing and poor correlation between the TMB genes, immune cell infiltrating, and [...] Read more.

Tumor mutational burden (TMB) is considered a potential biomarker for predicting the response and effect of immune checkpoint inhibitors (ICIs). However, there are still inconsistent standards of gene panels using next-generation sequencing and poor correlation between the TMB genes, immune cell infiltrating, and prognosis. We applied text-mining technology to construct specific TMB-associated gene panels cross various cancer types. As a case exploration, Pearson’s correlation between TMB genes and immune cell infiltrating was further analyzed in colorectal cancer. We then performed LASSO Cox regression to construct a prognosis predictive model and calculated the risk score of each sample for receiver operating characteristic (ROC) analysis. The results showed that the assessment of TMB gene panels performed well with fewer than 500 genes, highly mutated genes, and the inclusion of synonymous mutations and immune regulatory and drug-target genes. Moreover, the analysis of TMB differentially expressed genes (DEGs) suggested that JAKMIP1 was strongly correlated with the gene expression level of CD8⁺ T cell markers in colorectal cancer. Additionally, the prognosis predictive model based on 19 TMB DEGs reached AUCs of 0.836, 0.818, and 0.787 in 1-, 3-, and 5-year OS models, respectively (C-index: 0.810). In summary, the gene panel performed well and TMB DEGs showed great potential value in immune cell infiltration and in predicting survival. Full article

(This article belongs to the Special Issue Bioinformatic Analysis of NGS Data)

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14 pages, 10181 KiB

Open AccessArticle

Epigenetic and Physiological Responses to Varying Root-Zone Temperatures in Greenhouse Rocket

by Aphrodite Tsaballa, Ilektra Sperdouli, Evangelia V. Avramidou, Ioannis Ganopoulos, Athanasios Koukounaras and Georgios K. Ntinas

Genes 2022, 13(2), 364; https://doi.org/10.3390/genes13020364 - 17 Feb 2022

Cited by 3 | Viewed by 1671

Abstract

Greenhouse production of baby leaf vegetables grown in hydroponic floating trays has become extremely popular in recent years. Rocket (Eruca sativa Mill.) can grow in temperatures varying between 10 and 20 °C; nevertheless, a root-zone temperature (RZT) range of 18–23 °C is [...] Read more.

Greenhouse production of baby leaf vegetables grown in hydroponic floating trays has become extremely popular in recent years. Rocket (Eruca sativa Mill.) can grow in temperatures varying between 10 and 20 °C; nevertheless, a root-zone temperature (RZT) range of 18–23 °C is considered optimal for high productivity, photosynthesis, and production of metabolites. Maintaining such temperatures in winter raises production costs and prevents sustainability. In this study, we tested the impact of lower RZT on plants’ status and recorded their responses while providing energy for heating using photovoltaic solar panels. We used three hydroponic tanks for cultivation; a non-heated (control) tank (12 °C) and two heated tanks; a solar panel-powered one (16 °C) and a public grid-powered one (22 °C). Methylation-sensitive amplified polymorphisms (MSAP) analysis of global methylation profiles and chlorophyll fluorescence analysis were employed to assess methylation and physiology levels of rocket leaves. We found that there is demethylation at 16 °C RZT in comparison to 22 °C RZT. Reduction of temperature at 12 °C did not reduce methylation levels further but rather increased them. Furthermore, at 16 °C, the effective quantum yield of photosystem II (PSII) photochemistry (ΦPSII) was significantly higher, with a higher PSII electron transport rate (ETR) and a significantly decreased non-regulated energy loss (ΦΝO), suggesting a better light energy use by rocket plants with higher photosynthetic performance. ΦPSII was significantly negatively correlated with DNA methylation levels. Our results show that at 16 °C RZT, where plants grow efficiently without being affected by the cold, DNA methylation and photosynthesis apparatus systems are altered. These findings corroborate previous results where hydroponic production of rocket at RZT of 16 °C is accompanied by sufficient yield showing that rocket can effectively grow in suboptimal yet sustainable root-zone temperatures. Full article

(This article belongs to the Special Issue Plant Genomics and Epigenomics in Breeding for Yield, Quality, and Sustainability)

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7 pages, 1124 KiB

Open AccessCase Report

Genotype-Phenotype Correlation in Familial BAG3 Mutation Dilated Cardiomyopathy

by Karolina Mėlinytė-Ankudavičė, Marius Šukys, Jurgita Plisienė, Renaldas Jurkevičius and Eglė Ereminienė

Genes 2022, 13(2), 363; https://doi.org/10.3390/genes13020363 - 17 Feb 2022

Cited by 3 | Viewed by 2131

Abstract

We report the case of a 22-year-old male who visited a cardiologist after the first episode of atrial fibrillation (AF). Echocardiography and magnetic resonance imaging revealed decreased left ventricular (LV) systolic function with dilated LV. An intermittent second-degree AV (atrioventricular) block was detected [...] Read more.

We report the case of a 22-year-old male who visited a cardiologist after the first episode of atrial fibrillation (AF). Echocardiography and magnetic resonance imaging revealed decreased left ventricular (LV) systolic function with dilated LV. An intermittent second-degree AV (atrioventricular) block was detected during 24 h Holter monitoring. Genetic test revealed the pathogenic variant of the BAG3 (BLC2-associated athanogene 3) gene. Due to the high risk of heart failure (HF) progression and ventricular arrhythmias, an event recorder was implanted and a pathogenetic HF treatment was prescribed. The analysis of genealogy revealed that the patient’s father, at the age of 32, was diagnosed with dilated cardiomyopathy (DCM) and recurrent AF episodes. Genetic testing also confirmed a pathogenic variant of the BAG3 gene. Currently, with the optimal treatment of HF, the patient’s disease has been stable for three years and the condition is closely monitored on an outpatient basis. So, we demonstrate the importance of early detection for genetic testing and the unusual stability exhibited by the patient‘s optimal medical therapy for 3 years. Full article

(This article belongs to the Collection Genotype-Phenotype Study in Disease)

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27 pages, 1785 KiB

Open AccessReview

The Role of VHL in the Development of von Hippel-Lindau Disease and Erythrocytosis

by Petra Hudler and Mojca Urbancic

Genes 2022, 13(2), 362; https://doi.org/10.3390/genes13020362 - 17 Feb 2022

Cited by 12 | Viewed by 5738

Abstract

Von Hippel-Lindau disease (VHL disease or VHL syndrome) is a familial multisystem neoplastic syndrome stemming from germline disease-associated variants of the VHL tumor suppressor gene on chromosome 3. VHL is involved, through the EPO-VHL-HIF signaling axis, in oxygen sensing and adaptive response to [...] Read more.

Von Hippel-Lindau disease (VHL disease or VHL syndrome) is a familial multisystem neoplastic syndrome stemming from germline disease-associated variants of the VHL tumor suppressor gene on chromosome 3. VHL is involved, through the EPO-VHL-HIF signaling axis, in oxygen sensing and adaptive response to hypoxia, as well as in numerous HIF-independent pathways. The diverse roles of VHL confirm its implication in several crucial cellular processes. VHL variations have been associated with the development of VHL disease and erythrocytosis. The association between genotypes and phenotypes still remains ambiguous for the majority of mutations. It appears that there is a distinction between erythrocytosis-causing VHL variations and VHL variations causing VHL disease with tumor development. Understanding the pathogenic effects of VHL variants might better predict the prognosis and optimize management of the patient. Full article

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

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20 pages, 2504 KiB

Open AccessArticle

Small RNA and Degradome Sequencing Reveal Important MicroRNA Function in Nicotiana tabacum Response to Bemisia tabaci

by Wen-Hao Han, Jun-Xia Wang, Feng-Bin Zhang, Yu-Xiao Liu, He Wu and Xiao-Wei Wang

Genes 2022, 13(2), 361; https://doi.org/10.3390/genes13020361 - 17 Feb 2022

Cited by 5 | Viewed by 1960

Abstract

MicroRNAs (miRNAs), a class of small non-coding regulatory RNAs, are key molecules in many biological and metabolic processes of plant growth, development and stress response via targeting mRNAs. The phloem-feeding insect whitefly Bemisia tabaci (Hemiptera, Aleyrodidae) is a serious pest that causes devastating [...] Read more.

MicroRNAs (miRNAs), a class of small non-coding regulatory RNAs, are key molecules in many biological and metabolic processes of plant growth, development and stress response via targeting mRNAs. The phloem-feeding insect whitefly Bemisia tabaci (Hemiptera, Aleyrodidae) is a serious pest that causes devastating harm to agricultural production worldwide. However, the function of host miRNAs in the response to whitefly infestation remains unclear. Here, we sequenced the small RNA and degradome of tobacco (Nicotiana tabacum L.), after and before infestation by B. tabaci. We identified 1291 miRNAs belonging to 138 miRNA families including 706 known miRNAs and 585 novel miRNAs. A total of 47 miRNAs were differentially expressed, of which 30 were upregulated and 17 were downregulated by whitefly exposure. Then, computational analysis showed that the target genes of differential miRNAs were involved in R gene regulation, plant innate immunity, plant pathogen defense, the plant hormone signal pathway and abiotic stress tolerance. Furthermore, degradome analysis demonstrated that 253 mRNAs were cleaved by 66 miRNAs. Among them, the targets cleaved by upregulated miR6025, miR160, miR171, miR166 and miR168 are consistent with our prediction, suggesting that pathogen-related miRNAs may function in plant defense against whitefly. Moreover, our results show that plant miRNA response and miRNA-mediated post-transcriptional regulation for phloem-feeding insect infestation are similar to pathogen invasion. Our study provides additional data to further elucidate how host plants respond and defend the phloem-feeding insects. Full article

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

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