Genes

13 pages, 1041 KiB

Open AccessEditor’s ChoiceArticle

Germline CNV Detection through Whole-Exome Sequencing (WES) Data Analysis Enhances Resolution of Rare Genetic Diseases

by Faidon-Nikolaos Tilemis, Nikolaos M. Marinakis, Danai Veltra, Maria Svingou, Kyriaki Kekou, Anastasios Mitrakos, Maria Tzetis, Konstantina Kosma, Periklis Makrythanasis, Joanne Traeger-Synodinos and Christalena Sofocleous

Genes 2023, 14(7), 1490; https://doi.org/10.3390/genes14071490 - 21 Jul 2023

Cited by 20 | Viewed by 4514

Abstract

Whole-Exome Sequencing (WES) has proven valuable in the characterization of underlying genetic defects in most rare diseases (RDs). Copy Number Variants (CNVs) were initially thought to escape detection. Recent technological advances enabled CNV calling from WES data with the use of accurate and [...] Read more.

Whole-Exome Sequencing (WES) has proven valuable in the characterization of underlying genetic defects in most rare diseases (RDs). Copy Number Variants (CNVs) were initially thought to escape detection. Recent technological advances enabled CNV calling from WES data with the use of accurate and highly sensitive bioinformatic tools. Amongst 920 patients referred for WES, 454 unresolved cases were further analysed using the ExomeDepth algorithm. CNVs were called, evaluated and categorized according to ACMG/ClinGen recommendations. Causative CNVs were identified in 40 patients, increasing the diagnostic yield of WES from 50.7% (466/920) to 55% (506/920). Twenty-two CNVs were available for validation and were all confirmed; of these, five were novel. Implementation of the ExomeDepth tool promoted effective identification of phenotype-relevant and/or novel CNVs. Among the advantages of calling CNVs from WES data, characterization of complex genotypes comprising both CNVs and SNVs minimizes cost and time to final diagnosis, while allowing differentiation between true or false homozygosity, as well as compound heterozygosity of variants in AR genes. The use of a specific algorithm for calling CNVs from WES data enables ancillary detection of different types of causative genetic variants, making WES a critical first-tier diagnostic test for patients with RDs. Full article

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

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11 pages, 3141 KiB

Open AccessEditor’s ChoiceArticle

ranchSATdb: A Genome-Wide Simple Sequence Repeat (SSR) Markers Database of Livestock Species for Mutant Germplasm Characterization and Improving Farm Animal Health

by Naveen Duhan, Simardeep Kaur and Rakesh Kaundal

Genes 2023, 14(7), 1481; https://doi.org/10.3390/genes14071481 - 20 Jul 2023

Cited by 3 | Viewed by 2285

Abstract

Microsatellites, also known as simple sequence repeats (SSRs), are polymorphic loci that play an important role in genome research, animal breeding, and disease control. Ranch animals are important components of agricultural landscape. The ranch animal SSR database, ranchSATdb, is a web resource [...] Read more.

Microsatellites, also known as simple sequence repeats (SSRs), are polymorphic loci that play an important role in genome research, animal breeding, and disease control. Ranch animals are important components of agricultural landscape. The ranch animal SSR database, ranchSATdb, is a web resource which contains 15,520,263 putative SSR markers. This database provides a comprehensive tool for performing end-to-end marker selection, from SSRs prediction to generating marker primers and their cross-species feasibility, visualization of the resulting markers, and finding similarities between the genomic repeat sequences all in one place without the need to switch between other resources. The user-friendly online interface allows users to browse SSRs by genomic coordinates, repeat motif sequence, chromosome, motif type, motif frequency, and functional annotation. Users may enter their preferred flanking area around the repeat to retrieve the nucleotide sequence, they can investigate SSRs present in the genic or the genes between SSRs, they can generate custom primers, and they can also execute in silico validation of primers using electronic PCR. For customized sequences, an SSR prediction pipeline called miSATminer is also built. New species will be added to this website’s database on a regular basis throughout time. To improve animal health via genomic selection, we hope that ranchSATdb will be a useful tool for mapping quantitative trait loci (QTLs) and marker-assisted selection. The web-resource is freely accessible at https://bioinfo.usu.edu/ranchSATdb/. Full article

(This article belongs to the Special Issue Breeding and Functional Genomics in Animals)

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12 pages, 1364 KiB

Open AccessEditor’s ChoiceArticle

ERCC1 and MGMT Methylation as a Predictive Marker of Relapse and FOLFOX Response in Colorectal Cancer Patients from South Tunisia

by Dhouha Jamai, Raja Gargouri, Boulbaba Selmi and Abdelmajid Khabir

Genes 2023, 14(7), 1467; https://doi.org/10.3390/genes14071467 - 19 Jul 2023

Cited by 3 | Viewed by 1793

Abstract

Genetic and epigenetic modifications present a major cause of relapse and treatment failure in colorectal cancer. This study aims to appreciate the prognostic and predictive value of ERRC1 and MGMT methylation. We also studied the prognostic impact of the ERCC1 rs11615 polymorphism as [...] Read more.

Genetic and epigenetic modifications present a major cause of relapse and treatment failure in colorectal cancer. This study aims to appreciate the prognostic and predictive value of ERRC1 and MGMT methylation. We also studied the prognostic impact of the ERCC1 rs11615 polymorphism as well as its expression. Methylation profiles of ERCC1 and MGMT were tested by methylation-specific PCR. A polymorphism of ERCC1 was studied using PCR-RFLP and its expression was examined by immunohistochemistry. ERCC1 was methylated in 44.6% of colorectal adenocarcinoma while MGMT was methylated in 69% of cases. MGMT methylation was strongly associated with lymph node metastasis, lymph invasion, venous invasion, perineural invasion, distant metastasis and relapse. Patients with methylation of both genes were more likely to have a poor prognosis and display chemoresistance. IHC analysis revealed that ERCC1 staining was noted in 52.8% of colorectal adenocarcinoma and inversely related to distant metastasis and cancer recurrence. Kaplan Meier analysis revealed that the worst overall survival was significantly associated with ERCC1 and MGMT methylation while decreased ERCC1 expression and T/T genotype exhibited the best overall survival. The methylation of MGMT, alone or combined with ERCC1, is predictive for poor prognosis, short overall survival and chemotherapy response in colorectal cancer. Full article

(This article belongs to the Special Issue Genetics and Genomics of Colorectal Cancer and Related Diseases)

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8 pages, 391 KiB

Open AccessEditor’s ChoiceArticle

Associations of HLA Polymorphisms with Chronic Kidney Disease in Japanese Rheumatoid Arthritis Patients

by Takashi Higuchi, Shomi Oka, Hiroshi Furukawa, Kota Shimada, Atsushi Hashimoto, Akiko Komiya, Toshihiro Matsui, Naoshi Fukui and Shigeto Tohma

Genes 2023, 14(7), 1470; https://doi.org/10.3390/genes14071470 - 19 Jul 2023

Cited by 1 | Viewed by 1893

Abstract

Objectives: The prevalence of chronic kidney disease (CKD) was reported to be higher in rheumatoid arthritis (RA) patients than in normal healthy individuals. Human leukocyte antigen (HLA) was associated with RA or CKD. Few studies on the association of HLA with [...] Read more.

Objectives: The prevalence of chronic kidney disease (CKD) was reported to be higher in rheumatoid arthritis (RA) patients than in normal healthy individuals. Human leukocyte antigen (HLA) was associated with RA or CKD. Few studies on the association of HLA with CKD in RA have been reported. Here, we investigated the association of HLA polymorphisms with CKD in Japanese RA patients. Methods: HLA-DRB1 genotyping was conducted in 351 Japanese RA patients with CKD (estimated glomerular filtration rate [eGFR] lower than 60 [mL/min/1.73 m²]) and 959 without CKD (eGFR equal to or higher than 60 [mL/min/1.73 m²]). Associations of allele carrier frequencies of DRB1 with CKD were examined in the RA patients. Results: There was an association of DRB1*13:02 with CKD in RA, but this did not achieve statistical significance (p = 0.0265, odds ratio [OR] 1.70, pc = 0.7412, 95% confidence interval [CI] 1.09–2.64). The DR6 serological group was associated with CKD in RA (p = 0.0008, OR 1.65, 95% CI 1.24–2.20). A gene-dosage effect of DR6 was not detected. Logistic regression analysis showed that the association of DR6 with CKD in RA was independent of clinical characteristics. Conclusions: The present study first revealed the independent predisposing association of DR6 with CKD in Japanese RA patients, although DR6 is known to be protective against RA. Our data suggest direct or indirect roles of HLA for the development of CKD in RA, but the mechanisms are not clear. Full article

(This article belongs to the Special Issue From Genetic to Molecular Basis of Kidney Damage)

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14 pages, 3267 KiB

Open AccessEditor’s ChoiceArticle

Comparative Analysis of the PYL Gene Family in Three Ipomoea Species and the Expression Profiling of IbPYL Genes during Abiotic Stress Response in Sweetpotato

by Lei Zhang, Weihan Song, Guosheng Xin, Mingku Zhu and Xiaoqing Meng

Genes 2023, 14(7), 1471; https://doi.org/10.3390/genes14071471 - 19 Jul 2023

Cited by 4 | Viewed by 1416

Abstract

Abscisic acid (ABA), a critical phytohormone that regulates plant development and stress response, is sensed by the ABA receptors PYR/PYL/RCAR (PYLs). The PYL genes have been widely studied in multiple plant species, while a systematic analysis of PYL genes in the genus Ipomoea [...] Read more.

Abscisic acid (ABA), a critical phytohormone that regulates plant development and stress response, is sensed by the ABA receptors PYR/PYL/RCAR (PYLs). The PYL genes have been widely studied in multiple plant species, while a systematic analysis of PYL genes in the genus Ipomoea remains unperformed. Here, a total of 13, 14, and 14 PYLs were identified in Ipomoea batatas, Ipomoea trifida, and Ipomoea triloba, respectively. Fragment duplication was speculated to play prominent roles in Ipomoea PYL gene expansions. These Ipomoea PYLs were classified into three subfamilies via phylogenetic analysis, which was supported by exon–intron structures and conserved motif analyses. Additionally, the interspecies collinearity analysis further depicted a potential evolutionary relationship between them. Moreover, qRT-PCR analysis showed that multiple IbPYLs are highly and differentially responsive to abiotic stress treatments, suggesting their potential roles in sweetpotato stress responses. Taken together, these data provide valuable insights into the PYLs in the genus Ipomoea, which may be useful for their further functional analysis of their defense against environmental changes. Full article

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

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15 pages, 6832 KiB

Open AccessEditor’s ChoiceArticle

Identification of the Light-Harvesting Chlorophyll a/b Binding Protein Gene Family in Peach (Prunus persica L.) and Their Expression under Drought Stress

by Li Wang, Jia Wei, Xingyun Shi, Weihong Qian, Jan Mehmood, Yiming Yin and Huijuan Jia

Genes 2023, 14(7), 1475; https://doi.org/10.3390/genes14071475 - 19 Jul 2023

Cited by 21 | Viewed by 2555

Abstract

In higher plants, light-harvesting chlorophyll a/b binding (Lhc) proteins play a vital role in photosynthetic processes and are widely involved in the regulation of plant growth, development, and response to abiotic stress. However, the Lhc gene family has not been well identified in [...] Read more.

In higher plants, light-harvesting chlorophyll a/b binding (Lhc) proteins play a vital role in photosynthetic processes and are widely involved in the regulation of plant growth, development, and response to abiotic stress. However, the Lhc gene family has not been well identified in peaches (Prunus persica L.). In this study, 19 PpLhc genes were identified in the peach genome database, which were unevenly distributed on all chromosomes. Phylogenetic analysis demonstrated that PpLhc proteins could be divided into three major subfamilies, each of whose members had different exon–intron structures but shared similar conserved motifs. A total of 17 different kinds of cis-regulatory elements were identified in the promoter regions of all PpLhc genes, which could be classified into three categories: plant growth and development, stress response, and phytohormone response. In addition, transcriptomic data analysis and RT-qPCR results revealed that the expression profiles of some PpLhc genes changed under drought treatment, suggesting the crucial roles of Lhc genes in the regulation of plant tolerance to drought stress. Taken together, these findings will provide valuable information for future functional studies of PpLhc genes, especially in response to drought stress. Full article

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

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17 pages, 1961 KiB

Open AccessEditor’s ChoiceArticle

Candidate Gene Association Studies in Atopic Dermatitis in Participants of European and Asian Ancestry: A Systematic Review and Meta-Analysis

by Alexandros Pontikas, Charalabos Antonatos, Evangelos Evangelou and Yiannis Vasilopoulos

Genes 2023, 14(7), 1456; https://doi.org/10.3390/genes14071456 - 17 Jul 2023

Cited by 4 | Viewed by 5172

Abstract

Atopic dermatitis (AD) has been extensively investigated for genetic associations utilizing both candidate gene approaches and genome-wide scans. Here, we comprehensively evaluated the available literature to determine the association of candidate genes in AD to gain additional insight into the etiopathogenesis of the [...] Read more.

Atopic dermatitis (AD) has been extensively investigated for genetic associations utilizing both candidate gene approaches and genome-wide scans. Here, we comprehensively evaluated the available literature to determine the association of candidate genes in AD to gain additional insight into the etiopathogenesis of the disease. We systematically screened all studies that explored the association between polymorphisms and AD risks in cases of European and Asian ancestry and synthesized the available evidence through a random-effects meta-analysis. We identified 99 studies that met our inclusion/exclusion criteria that examined 17 candidate loci in Europeans and 14 candidate genes in Asians. We confirmed the significant associations between FLG variants in both European and Asian populations and AD risk, while synthesis of the available data revealed novel loci mapped to IL18 and TGFB1 genes in Europeans and IL12RB1 and MIF in Asians that have not yet been identified by genome-wide association studies. Our findings provide comprehensive evidence for AD risk loci in cases of both European and Asian ancestries, validating previous associations as well as revealing novel loci that could imply previously unexplored biological pathways. Full article

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

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15 pages, 3940 KiB

Open AccessEditor’s ChoiceArticle

Mn-XRN1 Has an Inhibitory Effect on Ovarian Reproduction in Macrobrachium nipponense

by Tianyong Chen, Huwei Yuan, Hui Qiao, Sufei Jiang, Wenyi Zhang, Yiwei Xiong, Hongtuo Fu and Shubo Jin

Genes 2023, 14(7), 1454; https://doi.org/10.3390/genes14071454 - 16 Jul 2023

Cited by 1 | Viewed by 1777

Abstract

XRN1 is an exoribonuclease that degrades mRNA in the cytoplasm along the 5′–3′ direction. A previous study indicated that it may be involved in the reproduction of Macrobrachium nipponense. Quantitative real-time PCR was used to detect the spatiotemporal expression pattern of Mn-XRN1 [...] Read more.

XRN1 is an exoribonuclease that degrades mRNA in the cytoplasm along the 5′–3′ direction. A previous study indicated that it may be involved in the reproduction of Macrobrachium nipponense. Quantitative real-time PCR was used to detect the spatiotemporal expression pattern of Mn-XRN1. At the tissue level, Mn-XRN1 was significantly expressed in the ovary. During development, Mn-XRN1 was significantly expressed at the CS stage of the embryo, on the 10th day post-larval and in the O2 stage of ovarian reproduction. The in situ hybridization results showed the location of Mn-XRN1 in the ovary. The expression of Mn-VASA was significantly increased after in vivo injection of Mn-XRN1 dsRNA. This suggests that Mn-XRN1 negatively regulates the expression of Mn-VASA. Furthermore, we counted the number of M. nipponense at various stages of ovarian reproduction on different days after RNAi. The results showed that ovarian development was significantly accelerated. In general, the results of the present study indicate that Mn-XRN1 has an inhibitory effect on the ovarian maturation of M. nipponense. The inhibitory effect might be through negative regulation of Mn-VASA. Full article

(This article belongs to the Special Issue Fish and Shellfish Genetics and Breeding)

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13 pages, 4384 KiB

Open AccessEditor’s ChoiceArticle

Dissection of the Genetic Basis of Resistance to Stem Rot in Cultivated Peanuts (Arachis hypogaea L.) through Genome-Wide Association Study

by Liying Yan, Wanduo Song, Zhihui Wang, Dongyang Yu, Hari Sudini, Yanping Kang, Yong Lei, Dongxin Huai, Yuning Chen, Xin Wang, Qianqian Wang and Boshou Liao

Genes 2023, 14(7), 1447; https://doi.org/10.3390/genes14071447 - 14 Jul 2023

Cited by 4 | Viewed by 2061

Abstract

Peanut (Arachis hypogaea) is an important oilseed and cash crop worldwide, contributing an important source of edible oil and protein for human nutrition. However, the incidence of stem rot disease caused by Athelia rolfsii poses a major challenge to peanut cultivation, [...] Read more.

Peanut (Arachis hypogaea) is an important oilseed and cash crop worldwide, contributing an important source of edible oil and protein for human nutrition. However, the incidence of stem rot disease caused by Athelia rolfsii poses a major challenge to peanut cultivation, resulting in significant yield losses. In this study, a panel of 202 peanut accessions was evaluated for their resistance to stem rot by inoculating plants in the field with A. rolfsii-infested oat grains in three environments. The mean disease index value of each environment for accessions in subsp. fasitigiate and subsp. hypogaea showed no significant difference. Accessions from southern China displayed the lowest disease index value compared to those from other ecological regions. We used whole-genome resequencing to analyze the genotypes of the accessions and to identify significant SNPs associated with stem rot resistance through genome-wide association study (GWAS). A total of 121 significant SNPs associated with stem rot resistance in peanut were identified, with phenotypic variation explained (PVE) ranging from 12.23% to 15.51%. A total of 27 candidate genes within 100 kb upstream and downstream of 23 significant SNPs were annotated, which have functions related to recognition, signal transduction, and defense response. These significant SNPs and candidate genes provide valuable information for further validation and molecular breeding to improve stem rot resistance in peanut. Full article

(This article belongs to the Special Issue Peanut Genetics and Omics)

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12 pages, 1315 KiB

Open AccessEditor’s ChoiceEditorial

Non-Coding RNAs in Human Health and Diseases

by Deborah J. Good

Genes 2023, 14(7), 1429; https://doi.org/10.3390/genes14071429 - 11 Jul 2023

Cited by 20 | Viewed by 3760

Abstract

Non-coding RNAs (ncRNAs) are, arguably, the enigma of the RNA transcriptome. Even though there are more annotated ncRNAs (25,967) compared to mRNAs (19,827), we know far less about each of the genes that produce ncRNA, especially in terms of their regulation, molecular functions, [...] Read more.

Non-coding RNAs (ncRNAs) are, arguably, the enigma of the RNA transcriptome. Even though there are more annotated ncRNAs (25,967) compared to mRNAs (19,827), we know far less about each of the genes that produce ncRNA, especially in terms of their regulation, molecular functions, and interactions. Further, we are only beginning to understand the role of differential regulation or function of ncRNAs caused by genetic and epigenetic perturbations, such as single nucleotide variants (SNV), deletions, insertions, and histone/DNA modifications. The 22 papers in this Special Issue describe the emerging roles of ncRNAs in neurological, cardiovascular, immune, and hepatic systems, to name a few, as well as in diseases such as cancer, Prader–Willi Syndrome, cardiac arrhythmias, and diabetes. As we begin to understand the function and regulation of this class of RNAs, strategies targeting ncRNAs could lead to improved therapeutic interventions for some conditions. Full article

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

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17 pages, 4928 KiB

Open AccessEditor’s ChoiceArticle

Characterization and Potential Function Analysis of the SRS Gene Family in Brassica napus

by Ming Hu, Meili Xie, Xiaobo Cui, Junyan Huang, Xiaohui Cheng, Lijiang Liu, Shunping Yan, Shengyi Liu and Chaobo Tong

Genes 2023, 14(7), 1421; https://doi.org/10.3390/genes14071421 - 10 Jul 2023

Cited by 3 | Viewed by 2051

Abstract

SRS (SHI-related sequence) transcription factors play a crucial role in plant growth, development, and abiotic stress response. Although Brassica napus (B. napus) is one of the most important oil crops in the world, the role of SRS genes in B. napus ( [...] Read more.

SRS (SHI-related sequence) transcription factors play a crucial role in plant growth, development, and abiotic stress response. Although Brassica napus (B. napus) is one of the most important oil crops in the world, the role of SRS genes in B. napus (BnSRS) has not been well investigated. Therefore, we employed a bioinformatics approach to identify BnSRS genes from genomic data and investigated their characteristics, functions, and expression patterns, to gain a better understanding of how this gene family is involved in plant development and growth. The results revealed that there were 34 BnSRS gene family members in the genomic sequence of B. napus, unevenly distributed throughout the sequence. Based on the phylogenetic analysis, these BnSRS genes could be divided into four subgroups, with each group sharing comparable conserved motifs and gene structure. Analysis of the upstream promoter region showed that BnSRS genes may regulate hormone responses, biotic and abiotic stress response, growth, and development in B. napus. The protein-protein interaction analysis revealed the involvement of BnSRS genes in various biological processes and metabolic pathways. Our analysis of BnSRS gene expression showed that 23 BnSRS genes in the callus tissue exhibited a dominant expression pattern, suggesting their critical involvement in cell dedifferentiation, cell division, and tissue development. In addition, association analysis between genotype and agronomic traits revealed that BnSRS genes may be linked to some important agronomic traits in B. napus, suggesting that BnSRS genes were widely involved in the regulation of important agronomic traits (including C16.0, C18.0, C18.1, C18.2 C18.3, C20.1, C22.1, GLU, protein, TSW, and FFT). In this study, we predicted the evolutionary relationships and potential functions of BnSRS gene family members, providing a basis for the development of BnSRS gene functions which could facilitate targeted functional studies and genetic improvement for elite breeding in B. napus. Full article

(This article belongs to the Special Issue Genetics of Biotic and Abiotic Stress Response in Crops)

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8 pages, 503 KiB

Open AccessEditor’s ChoiceBrief Report

Collagen Gene Variants and Anterior Cruciate Ligament Rupture in Italian Athletes: A Preliminary Report

by Myosotis Massidda, Laura Flore, Marco Scorcu, Giovanni Monteleone, Alessandra Tiloca, Massimiliano Salvi, Filippo Tocco and Carla M. Calò

Genes 2023, 14(7), 1418; https://doi.org/10.3390/genes14071418 - 9 Jul 2023

Cited by 4 | Viewed by 1985

Abstract

Several studies have investigated the role of genetics in anterior cruciate ligament (ACL) rupture, often returning conflicting results. The present pilot study aimed to analyze the association between six Single Nucleotide Polymorphisms (SNPs) (rs1800012; rs12722; rs13946; rs240736; rs970547; and rs4870723, located on the [...] Read more.

Several studies have investigated the role of genetics in anterior cruciate ligament (ACL) rupture, often returning conflicting results. The present pilot study aimed to analyze the association between six Single Nucleotide Polymorphisms (SNPs) (rs1800012; rs12722; rs13946; rs240736; rs970547; and rs4870723, located on the COL1A1, COL5A1, COL12A1, and COL14A1 genes), and ACL rupture, among Italian athletes. A hypothesis-driven association study was conducted. In total, 181 male and female athletes (n = 86 injured; n = 96 non-injured) were genotyped for the prioritized variants. All polymorphisms were genotyped using PCR RFLP, with the only exception being the rs1800012 on the COL1A1 gene, which was detected using MTPA PCR. The allele frequency distribution fell within the worldwide range. Despite the evident population variability, no selective pressure signals were recorded using PBS analysis. No significant difference was detected between the cases and controls for any of the SNPs (rs1800012; rs13946; rs240736; rs970547, and rs4870723) included in the analyses (p > 0.008, Bonferroni-adjusted for multiple comparisons). Moreover, no significant differences were found when males and females were assessed separately. Further investigations based on a larger sample size are needed, in order to draw solid conclusions for the influence between collagen genes and ACL rupture. Full article

(This article belongs to the Special Issue Genetic Basis of Sports Athletes)

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18 pages, 1098 KiB

Open AccessEditor’s ChoiceReview

miRNAs: Potential as Biomarkers and Therapeutic Targets for Cancer

by Atonu Chakrabortty, Daniel J. Patton, Bruce F. Smith and Payal Agarwal

Genes 2023, 14(7), 1375; https://doi.org/10.3390/genes14071375 - 29 Jun 2023

Cited by 116 | Viewed by 16294

Abstract

MicroRNAs (miRNAs) are single-stranded, non-coding RNA molecules that regulate gene expression post-transcriptionally by binding to messenger RNAs. miRNAs are important regulators of gene expression, and their dysregulation is implicated in many human and canine diseases. Most cancers tested to date have been shown [...] Read more.

MicroRNAs (miRNAs) are single-stranded, non-coding RNA molecules that regulate gene expression post-transcriptionally by binding to messenger RNAs. miRNAs are important regulators of gene expression, and their dysregulation is implicated in many human and canine diseases. Most cancers tested to date have been shown to express altered miRNA levels, which indicates their potential importance in the oncogenic process. Based on this evidence, numerous miRNAs have been suggested as potential cancer biomarkers for both diagnosis and prognosis. miRNA-based therapies have also been tested in different cancers and have provided measurable clinical benefits to patients. In addition, understanding miRNA biogenesis and regulatory mechanisms in cancer can provide important knowledge about resistance to chemotherapies, leading to more personalized cancer treatment. In this review, we comprehensively summarized the importance of miRNA in human and canine cancer research. We discussed the current state of development and potential for the miRNA as both a diagnostic marker and a therapeutic target. Full article

(This article belongs to the Special Issue MicroRNA in Cancers)

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14 pages, 973 KiB

Open AccessEditor’s ChoiceSystematic Review

Spinal Muscular Atrophy Treatment in Patients Identified by Newborn Screening—A Systematic Review

by Karolina Aragon-Gawinska, Charlotte Mouraux, Tamara Dangouloff and Laurent Servais

Genes 2023, 14(7), 1377; https://doi.org/10.3390/genes14071377 - 29 Jun 2023

Cited by 48 | Viewed by 6464

Abstract

Background: In spinal muscular atrophy, clinical trial results indicated that disease-modifying treatments are highly effective when given prior to symptom onset, which has prompted newborn screening programs in growing number of countries. However, prognosis of those patients cannot be inferred from clinical trials [...] Read more.

Background: In spinal muscular atrophy, clinical trial results indicated that disease-modifying treatments are highly effective when given prior to symptom onset, which has prompted newborn screening programs in growing number of countries. However, prognosis of those patients cannot be inferred from clinical trials conducted in presymptomatic individuals, as in some cases disease presents very early. Methods: we conducted a systematic review of articles published up to January 2023. Results: Among 35 patients with three SMN2 copies treated before 42 days of age and followed-up for at least 18 months, all but one achieved autonomous ambulation. Of 41 patients with two SMN2 copies, who were non-symptomatic at treatment initiation, all achieved a sitting position independently and 31 were able to walk. Of 16 patients with two SMN2 copies followed-up for at least 18 months who presented with symptoms at treatment onset, 3 achieved the walking milestone and all but one were able to sit without support. Conclusions: evaluation of data from 18 publications indicates that the results of early treatment depend on the number of SMN2 copies and the initial neurological status of the patient. Full article

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

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20 pages, 375 KiB

Open AccessEditor’s ChoiceReview

Clinical and Genetic Aspects of Alopecia Areata: A Cutting Edge Review

by Chih-Yi Ho, Chiu-Yen Wu, Jeff Yi-Fu Chen and Ching-Ying Wu

Genes 2023, 14(7), 1362; https://doi.org/10.3390/genes14071362 - 28 Jun 2023

Cited by 20 | Viewed by 8925

Abstract

Alopecia areata (AA) is a chronic, non-scarring, immune-mediated skin disease that affects approximately 0.5–2% of the global population. The etiology of AA is complex and involves genetic and environmental factors, with significant advancements in genetic research occurring in recent years. In addition to [...] Read more.

Alopecia areata (AA) is a chronic, non-scarring, immune-mediated skin disease that affects approximately 0.5–2% of the global population. The etiology of AA is complex and involves genetic and environmental factors, with significant advancements in genetic research occurring in recent years. In addition to well-known genes such as PTPN22, CTLA4, and IL2, which have been widely supported as being associated with AA, an increasing number of specific gene-related loci have been discovered through advances in genetic research. For instance, gene analysis of microRNAs can reveal the critical role of miRNAs in regulating gene expression, aiding in the understanding of cellular and organismal functional regulatory mechanisms. Furthermore, numerous studies have confirmed the existence of correlations between AA and other immune-related diseases. Examples include hyperthyroidism and rheumatoid arthritis. By understanding the interrelationships between AA and other immune diseases, we can further comprehend potential shared genetic foundations or pathogenic mechanisms among different diseases. Genetic research plays a crucial role in unraveling the pathogenesis of AA, as the identification of genetic variations associated with AA can assist in formulating more effective and targeted treatment strategies. Full article

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

29 pages, 1822 KiB

Open AccessEditor’s ChoiceReview

Biomarkers in Breast Cancer: An Old Story with a New End

by Lyvia Neves Rebello Alves, Débora Dummer Meira, Luiza Poppe Merigueti, Matheus Correia Casotti, Diego do Prado Ventorim, Jucimara Ferreira Figueiredo Almeida, Valdemir Pereira de Sousa, Marllon Cindra Sant’Ana, Rahna Gonçalves Coutinho da Cruz, Luana Santos Louro, Gabriel Mendonça Santana, Thomas Erik Santos Louro, Rhana Evangelista Salazar, Danielle Ribeiro Campos da Silva, Aléxia Stefani Siqueira Zetum, Raquel Silva dos Reis Trabach, Flávia Imbroisi Valle Errera, Flávia de Paula, Eldamária de Vargas Wolfgramm dos Santos, Elizeu Fagundes de Carvalho and Iúri Drumond Louro Show full author list Hide full author list

Genes 2023, 14(7), 1364; https://doi.org/10.3390/genes14071364 - 28 Jun 2023

Cited by 50 | Viewed by 12229

Abstract

Breast cancer is the second most frequent cancer in the world. It is a heterogeneous disease and the leading cause of cancer mortality in women. Advances in molecular technologies allowed for the identification of new and more specifics biomarkers for breast cancer diagnosis, [...] Read more.

Breast cancer is the second most frequent cancer in the world. It is a heterogeneous disease and the leading cause of cancer mortality in women. Advances in molecular technologies allowed for the identification of new and more specifics biomarkers for breast cancer diagnosis, prognosis, and risk prediction, enabling personalized treatments, improving therapy, and preventing overtreatment, undertreatment, and incorrect treatment. Several breast cancer biomarkers have been identified and, along with traditional biomarkers, they can assist physicians throughout treatment plan and increase therapy success. Despite the need of more data to improve specificity and determine the real clinical utility of some biomarkers, others are already established and can be used as a guide to make treatment decisions. In this review, we summarize the available traditional, novel, and potential biomarkers while also including gene expression profiles, breast cancer single-cell and polyploid giant cancer cells. We hope to help physicians understand tumor specific characteristics and support decision-making in patient-personalized clinical management, consequently improving treatment outcome. Full article

(This article belongs to the Special Issue Genotyping and Prognostic Markers in Cancers)

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10 pages, 1983 KiB

Open AccessEditor’s ChoiceArticle

A High-Quality Chromosome-Level Genome Assembly of a Snail Cipangopaludina cathayensis (Gastropoda: Viviparidae)

by Benhe Ma, Wu Jin, Huiyun Fu, Bing Sun, Su Yang, Xueyan Ma, Haibo Wen, Xiaoping Wu, Haihua Wang and Xiaojuan Cao

Genes 2023, 14(7), 1365; https://doi.org/10.3390/genes14071365 - 28 Jun 2023

Cited by 2 | Viewed by 2825

Abstract

Cipangopaludina cathayensis (Gastropoda: Prosobranchia; Mesogastropoda; Viviparidae) is widely distributed in the freshwater habitats of China. It is an economically important snail with high edible and medicinal value. However, the genomic resources and the reference genome of this snail are lacking. In this study, [...] Read more.

Cipangopaludina cathayensis (Gastropoda: Prosobranchia; Mesogastropoda; Viviparidae) is widely distributed in the freshwater habitats of China. It is an economically important snail with high edible and medicinal value. However, the genomic resources and the reference genome of this snail are lacking. In this study, we assembled the first chromosome-level genome of C. cathayensis. The preliminary assembly genome was 1.48 Gb in size, with a contig N50 size of 93.49 Mb. The assembled sequences were anchored to nine pseudochromosomes using Hi-C data. The final genome after Hi-C correction was 1.48 Gb, with a contig N50 of 98.49 Mb and scaffold N50 of 195.21 Mb. The anchored rate of the chromosome was 99.99%. A total of 22,702 protein-coding genes were predicted. Phylogenetic analyses indicated that C. cathayensis diverged with Bellamya purificata approximately 158.10 million years ago. There were 268 expanded and 505 contracted gene families in C. cathayensis when compared with its most recent common ancestor. Five putative genes under positive selection in C. cathayensis were identified (false discovery rate <0.05). These genome data provide a valuable resource for evolutionary studies of the family Viviparidae, and for the genetic improvement of C. cathayensis. Full article

(This article belongs to the Special Issue Genetic Improvement of Aquatic Species)

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29 pages, 2361 KiB

Open AccessEditor’s ChoiceReview

Potential Applications of Nanoparticles in Improving the Outcome of Lung Cancer Treatment

by Agnishwar Girigoswami and Koyeli Girigoswami

Genes 2023, 14(7), 1370; https://doi.org/10.3390/genes14071370 - 28 Jun 2023

Cited by 28 | Viewed by 8334

Abstract

Lung cancer is managed using conventional therapies, including chemotherapy, radiation therapy, or a combination of both. Each of these therapies has its own limitations, such as the indiscriminate killing of normal as well as cancer cells, the solubility of the chemotherapeutic drugs, rapid [...] Read more.

Lung cancer is managed using conventional therapies, including chemotherapy, radiation therapy, or a combination of both. Each of these therapies has its own limitations, such as the indiscriminate killing of normal as well as cancer cells, the solubility of the chemotherapeutic drugs, rapid clearance of the drugs from circulation before reaching the tumor site, the resistance of cancer cells to radiation, and over-sensitization of normal cells to radiation. Other treatment modalities include gene therapy, immunological checkpoint inhibitors, drug repurposing, and in situ cryo-immune engineering (ICIE) strategy. Nanotechnology has come to the rescue to overcome many shortfalls of conventional therapies. Some of the nano-formulated chemotherapeutic drugs, as well as nanoparticles and nanostructures with surface modifications, have been used for effective cancer cell killing and radio sensitization, respectively. Nano-enabled drug delivery systems act as cargo to deliver the sensitizer molecules specifically to the tumor cells, thereby enabling the radiation therapy to be more effective. In this review, we have discussed the different conventional chemotherapies and radiation therapies used for inhibiting lung cancer. We have also discussed the improvement in chemotherapy and radiation sensitization using nanoparticles. Full article

(This article belongs to the Special Issue Molecular Mechanisms Responsible for Radiation-Induced Toxicity of Normal Tissue)

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11 pages, 2055 KiB

Open AccessEditor’s ChoiceArticle

Occurrence of L1M Elements in Chromosomal Rearrangements Associated to Chronic Myeloid Leukemia (CML): Insights from Patient-Specific Breakpoints Characterization

by Alberto L’Abbate, Vittoria Moretti, Ester Pungolino, Giovanni Micheloni, Roberto Valli, Annalisa Frattini, Matteo Barcella, Francesco Acquati, Rolland A Reinbold, Lucy Costantino, Fulvio Ferrara, Alessandra Trojani, Mario Ventura, Giovanni Porta and Roberto Cairoli

Genes 2023, 14(7), 1351; https://doi.org/10.3390/genes14071351 - 27 Jun 2023

Cited by 1 | Viewed by 2353

Abstract

Chronic myeloid leukemia (CML) is a rare myeloproliferative disorder caused by the reciprocal translocation t(9;22)(q34;q11) in hematopoietic stem cells (HSCs). This chromosomal translocation results in the formation of an extra-short chromosome 22, called a Philadelphia chromosome (Ph), containing the BCR-ABL1 fusion gene responsible [...] Read more.

Chronic myeloid leukemia (CML) is a rare myeloproliferative disorder caused by the reciprocal translocation t(9;22)(q34;q11) in hematopoietic stem cells (HSCs). This chromosomal translocation results in the formation of an extra-short chromosome 22, called a Philadelphia chromosome (Ph), containing the BCR-ABL1 fusion gene responsible for the expression of a constitutively active tyrosine kinase that causes uncontrolled growth and replication of leukemic cells. Mechanisms behind the formation of this chromosomal rearrangement are not well known, even if, as observed in tumors, repetitive DNA may be involved as core elements in chromosomal rearrangements. We have participated in the explorative investigations of the PhilosoPhi34 study to evaluate residual Ph+ cells in patients with negative FISH analysis on CD34+/lin- cells with gDNA qPCR. Using targeted next-generation deep sequencing strategies, we analyzed the genomic region around the t(9;22) translocations of 82 CML patients and one CML cell line and assessed the relevance of interspersed repeat elements at breakpoints (BP). We found a statistically higher presence of LINE elements, in particular belonging to the subfamily L1M, in BP cluster regions of both chromosome 22 and 9 compared to the whole human genome. These data suggest that L1M elements could be potential drivers of t(9;22) translocation leading to the generation of the BCR-ABL1 chimeric gene and the expression of the active BCR-ABL1-controlled tyrosine kinase chimeric protein responsible for CML. Full article

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

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11 pages, 1274 KiB

Open AccessEditor’s ChoiceArticle

Polymorphism, Genetic Effect, and Association with Egg-Laying Performance of Chahua Chickens Matrix Metalloproteinases 13 Promoter

by Yanli Du, Changwei Cao, Yong Liu, Xiannian Zi, Yang He, Hongmei Shi, Jinbo Zhao, Changrong Ge and Kun Wang

Genes 2023, 14(7), 1352; https://doi.org/10.3390/genes14071352 - 27 Jun 2023

Cited by 2 | Viewed by 1445

Abstract

Matrix metalloproteinases are a group of proteases involved in the regulation of ovarian follicular development and ovulation. Among the different MMPs, MMP13 is known to play an important role in reproduction. Therefore, this study aimed to screen the molecular genetic markers of the [...] Read more.

Matrix metalloproteinases are a group of proteases involved in the regulation of ovarian follicular development and ovulation. Among the different MMPs, MMP13 is known to play an important role in reproduction. Therefore, this study aimed to screen the molecular genetic markers of the MMP13 gene that affect the egg-laying performance of Chahua chickens. Polymerase chain reaction (PCR) and sequencing were performed in the 5′ regulation region of the MMP13 gene to detect loci significantly related to the egg-laying performance of Chahua chickens. A double fluorescence reporting system, quantitative reverse transcription PCR (RT-qPCR), and Western blotting were used to study whether gene expression was regulated by identified sites, providing a theoretical basis to improve egg production in Chahua chickens. The results revealed six single nucleotide polymorphisms (SNPs; A-1887T, T-1889C, A-1890T, T-2252C, T-2329C, and C-2360A) in the promoter region of the MMP13 gene. Further analysis revealed that hens with T^-1890-C^-1889-T^-1887/T^-1890-C^-1889-T^-1887 (mutant type, MT) had an earlier age at first egg (AFE) than hens with A^-1890-T^-1889-A^-1887/A^-1890-T^-1889-A^-1887 (wild type, WT; p < 0.05). RT-qPCR showed that the relative expression level of the MMP13 gene in the ovarian tissues of individuals with the mutation was higher than that of individuals with the wild gene (p < 0.05). Western blot results confirmed higher levels of the MMP13 protein in MT ovaries compared to those in WT ovaries. Thus, this study suggests that mutation sites on the MMP13 promoter may affect gene expression. In conclusion, the MMP13 gene in Chahua chickens may be significant for egg-laying performance, and the polymorphism in its promoter region could be used as a molecular marker to improve egg-laying performance. Full article

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

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10 pages, 2170 KiB

Open AccessEditor’s ChoiceArticle

Rhabdomyosarcoma Associated with Core Myopathy/Malignant Hyperthermia: Combined Effect of Germline Variants in RYR1 and ASPSCR1 May Play a Role

by Pamela V. Andrade, Joilson M. Santos, Anne C. B. Teixeira, Vanessa F. Sogari, Michelle S. Almeida, Fabiano M. Callegari, Ana C. V. Krepischi, Acary S. B. Oliveira, Mariz Vainzof and Helga C. A. Silva

Genes 2023, 14(7), 1360; https://doi.org/10.3390/genes14071360 - 27 Jun 2023

Cited by 1 | Viewed by 2515

Abstract

Rhabdomyosarcomas have been described in association with thyroid disease, dermatomyositis, Duchenne muscular dystrophy, and in muscular dystrophy models but not in patients with ryanodine receptor-1 gene (RYR1) pathogenic variants. We described here an 18-year-old male who reported a cervical nodule. Magnetic [...] Read more.

Rhabdomyosarcomas have been described in association with thyroid disease, dermatomyositis, Duchenne muscular dystrophy, and in muscular dystrophy models but not in patients with ryanodine receptor-1 gene (RYR1) pathogenic variants. We described here an 18-year-old male who reported a cervical nodule. Magnetic resonance images revealed a mass in the ethmoidal sinus corresponding to rhabdomyosarcoma. As his father died from malignant hyperthermia (MH), an in vitro contracture test was conducted and was positive for MH susceptibility. Muscle histopathological analysis in the biopsy showed the presence of cores. Molecular analysis using NGS sequencing identified germline variants in the RYR1 and ASPSCR1 (alveolar soft part sarcoma) genes. This report expands the spectrum of diseases associated with rhabdomyosarcomas and a possible differential diagnosis of soft tissue tumors in patients with RYR1 variants. Full article

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

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18 pages, 1229 KiB

Open AccessEditor’s ChoiceReview

Therapeutic Targeting of DNA Replication Stress in Cancer

by Long Gu, Robert J. Hickey and Linda H. Malkas

Genes 2023, 14(7), 1346; https://doi.org/10.3390/genes14071346 - 26 Jun 2023

Cited by 18 | Viewed by 7257

Abstract

This article reviews the currently used therapeutic strategies to target DNA replication stress for cancer treatment in the clinic, highlighting their effectiveness and limitations due to toxicity and drug resistance. Cancer cells experience enhanced spontaneous DNA damage due to compromised DNA replication machinery, [...] Read more.

This article reviews the currently used therapeutic strategies to target DNA replication stress for cancer treatment in the clinic, highlighting their effectiveness and limitations due to toxicity and drug resistance. Cancer cells experience enhanced spontaneous DNA damage due to compromised DNA replication machinery, elevated levels of reactive oxygen species, loss of tumor suppressor genes, and/or constitutive activation of oncogenes. Consequently, these cells are addicted to DNA damage response signaling pathways and repair machinery to maintain genome stability and support survival and proliferation. Chemotherapeutic drugs exploit this genetic instability by inducing additional DNA damage to overwhelm the repair system in cancer cells. However, the clinical use of DNA-damaging agents is limited by their toxicity and drug resistance often arises. To address these issues, the article discusses a potential strategy to target the cancer-associated isoform of proliferating cell nuclear antigen (caPCNA), which plays a central role in the DNA replication and damage response network. Small molecule and peptide agents that specifically target caPCNA can selectively target cancer cells without significant toxicity to normal cells or experimental animals. Full article

(This article belongs to the Special Issue DNA Replication/Repair, and the DNA Damage Response in Human Disease 2023)

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12 pages, 2286 KiB

Open AccessEditor’s ChoiceArticle

Study on the Protective Immunity Induced by Pseudotyped Baculovirus Expressing the E Protein of Tembusu Virus in Ducklings

by Zheng Ni, Tao Yun, Liu Chen, Weicheng Ye, Jionggang Hua, Yinchu Zhu, Guangqing Liu and Cun Zhang

Genes 2023, 14(7), 1316; https://doi.org/10.3390/genes14071316 - 22 Jun 2023

Cited by 1 | Viewed by 1751

Abstract

The Duck Tembusu virus (DTMUV), a pathogenic flavivirus, has been causing significant economic losses in the Chinese poultry industry since 2010. This virus can severely decrease egg production and inhibit the growth of laying ducks and ducklings. While many vaccines have been developed [...] Read more.

The Duck Tembusu virus (DTMUV), a pathogenic flavivirus, has been causing significant economic losses in the Chinese poultry industry since 2010. This virus can severely decrease egg production and inhibit the growth of laying ducks and ducklings. While many vaccines have been developed to prevent DTMUV infection, fresh outbreaks continue to occur, as few effective vaccines are available. The E glycoprotein of DTMUV is the primary target for inducing protective immunity in the natural host. Therefore, we conducted an investigation and successfully developed a recombinant baculovirus containing the DTMUV E gene. Ducklings were then vaccinated with the purified protein derived from this virus as a potential vaccine candidate. Our findings demonstrated that the E glycoprotein of DTMUV was highly expressed in Sf9 cells. The vaccination of ducklings with the recombinant baculovirus Bac-E resulted in the induction of strong humoral and cellular immune responses. Most significantly, we observed that the vaccine provided 100% protective immunity against lethal challenges with the DTMUV YY5 strain. Full article

(This article belongs to the Special Issue Molecular Genetics in Livestock Production and Disease Resistance)

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12 pages, 1379 KiB

Open AccessEditor’s ChoiceReview

Genetics of Generalized Pustular Psoriasis: Current Understanding and Implications for Future Therapeutics

by Syuan-Fei Yang, Min-Huei Lin, Pei-Chen Chou, Sheng-Kai Hu, Sin-Yi Shih, Hsin-Su Yu and Sebastian Yu

Genes 2023, 14(6), 1297; https://doi.org/10.3390/genes14061297 - 20 Jun 2023

Cited by 18 | Viewed by 4482

Abstract

Psoriasis is a chronic inflammatory skin disease characterized by the appearance of clearly demarcated erythematous and scaly plaques. It can be divided into various types, including plaque, nail, guttate, inverse, and pustular psoriasis. Plaque psoriasis is the most commonly occurring type, though there [...] Read more.

Psoriasis is a chronic inflammatory skin disease characterized by the appearance of clearly demarcated erythematous and scaly plaques. It can be divided into various types, including plaque, nail, guttate, inverse, and pustular psoriasis. Plaque psoriasis is the most commonly occurring type, though there is another rare but severe pustular autoinflammatory skin disease called generalized pustular psoriasis (GPP), which manifests with acute episodes of pustulation and systemic symptoms. Though the etiopathogenesis of psoriasis is not yet fully understood, a growing body of literature has demonstrated that both genetic and environmental factors play a role. The discovery of genetic mutations associated with GPP has shed light on our comprehension of the mechanisms of the disease, promoting the development of targeted therapies. This review will summarize genetic determinants as known and provide an update on the current and potential treatments for GPP. The pathogenesis and clinical presentation of the disease are also included for a comprehensive discussion. Full article

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

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36 pages, 4543 KiB

Open AccessEditor’s ChoiceReview

Multi-Omics Pipeline and Omics-Integration Approach to Decipher Plant’s Abiotic Stress Tolerance Responses

by Rajib Roychowdhury, Soumya Prakash Das, Amber Gupta, Parul Parihar, Kottakota Chandrasekhar, Umakanta Sarker, Ajay Kumar, Devade Pandurang Ramrao and Chinta Sudhakar

Genes 2023, 14(6), 1281; https://doi.org/10.3390/genes14061281 - 16 Jun 2023

Cited by 78 | Viewed by 11387

Abstract

The present day’s ongoing global warming and climate change adversely affect plants through imposing environmental (abiotic) stresses and disease pressure. The major abiotic factors such as drought, heat, cold, salinity, etc., hamper a plant’s innate growth and development, resulting in reduced yield and [...] Read more.

The present day’s ongoing global warming and climate change adversely affect plants through imposing environmental (abiotic) stresses and disease pressure. The major abiotic factors such as drought, heat, cold, salinity, etc., hamper a plant’s innate growth and development, resulting in reduced yield and quality, with the possibility of undesired traits. In the 21st century, the advent of high-throughput sequencing tools, state-of-the-art biotechnological techniques and bioinformatic analyzing pipelines led to the easy characterization of plant traits for abiotic stress response and tolerance mechanisms by applying the ‘omics’ toolbox. Panomics pipeline including genomics, transcriptomics, proteomics, metabolomics, epigenomics, proteogenomics, interactomics, ionomics, phenomics, etc., have become very handy nowadays. This is important to produce climate-smart future crops with a proper understanding of the molecular mechanisms of abiotic stress responses by the plant’s genes, transcripts, proteins, epigenome, cellular metabolic circuits and resultant phenotype. Instead of mono-omics, two or more (hence ‘multi-omics’) integrated-omics approaches can decipher the plant’s abiotic stress tolerance response very well. Multi-omics-characterized plants can be used as potent genetic resources to incorporate into the future breeding program. For the practical utility of crop improvement, multi-omics approaches for particular abiotic stress tolerance can be combined with genome-assisted breeding (GAB) by being pyramided with improved crop yield, food quality and associated agronomic traits and can open a new era of omics-assisted breeding. Thus, multi-omics pipelines together are able to decipher molecular processes, biomarkers, targets for genetic engineering, regulatory networks and precision agriculture solutions for a crop’s variable abiotic stress tolerance to ensure food security under changing environmental circumstances. Full article

(This article belongs to the Special Issue Abiotic Stress in Plants: Present and Future)

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15 pages, 1121 KiB

Open AccessEditor’s ChoiceSystematic Review

Possible Effects of Uremic Toxins p-Cresol, Indoxyl Sulfate, p-Cresyl Sulfate on the Development and Progression of Colon Cancer in Patients with Chronic Renal Failure

by Rossella Di Paola, Ananya De, Raafiah Izhar, Marianna Abate, Silvia Zappavigna, Anna Capasso, Alessandra F. Perna, Antonella La Russa, Giovambattista Capasso, Michele Caraglia and Mariadelina Simeoni

Genes 2023, 14(6), 1257; https://doi.org/10.3390/genes14061257 - 13 Jun 2023

Cited by 20 | Viewed by 3800

Abstract

Chronic kidney disease (CKD) induces several systemic effects, including the accumulation and production of uremic toxins responsible for the activation of various harmful processes. Gut dysbiosis has been widely described in CKD patients, even in the early stages of the disease. The abundant [...] Read more.

Chronic kidney disease (CKD) induces several systemic effects, including the accumulation and production of uremic toxins responsible for the activation of various harmful processes. Gut dysbiosis has been widely described in CKD patients, even in the early stages of the disease. The abundant discharge of urea and other waste substances into the gut favors the selection of an altered intestinal microbiota in CKD patients. The prevalence of bacteria with fermentative activity leads to the release and accumulation in the gut and in the blood of several substances, such as p-Cresol (p-C), Indoxyl Sulfate (IS) and p-Cresyl Sulfate (p-CS). Since these metabolites are normally eliminated in the urine, they tend to accumulate in the blood of CKD patients proportionally to renal impairment. P-CS, IS and p-C play a fundamental role in the activation of various pro-tumorigenic processes, such as chronic systemic inflammation, the increase in the production of free radicals and immune dysfunction. An up to two-fold increase in the incidence of colon cancer development in CKD has been reported in several studies, although the pathogenic mechanisms explaining this compelling association have not yet been described. Based on our literature review, it appears likely the hypothesis of a role of p-C, IS and p-CS in colon cancer development and progression in CKD patients. Full article

(This article belongs to the Special Issue From Genetic to Molecular Basis of Kidney Damage)

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12 pages, 2406 KiB

Open AccessEditor’s ChoiceArticle

Properties of INDETERMINATE DOMAIN Proteins from Physcomitrium patens: DNA-Binding, Interaction with GRAS Proteins, and Transcriptional Activity

by Saiful Islam Khan, Ren Yamada, Ryoichi Shiroma, Tatsuki Abe and Akiko Kozaki

Genes 2023, 14(6), 1249; https://doi.org/10.3390/genes14061249 - 11 Jun 2023

Cited by 1 | Viewed by 3545

Abstract

INDETERMINATE DOMAIN (IDD) proteins are plant-specific transcription factors that interact with GRAS proteins, such as DELLA and SHORT ROOT (SHR), to regulate target genes. The combination of IDD and DELLA proteins regulates genes involved in gibberellic acid (GA) synthesis and GA signaling, whereas [...] Read more.

INDETERMINATE DOMAIN (IDD) proteins are plant-specific transcription factors that interact with GRAS proteins, such as DELLA and SHORT ROOT (SHR), to regulate target genes. The combination of IDD and DELLA proteins regulates genes involved in gibberellic acid (GA) synthesis and GA signaling, whereas the combination of IDD with the complex of SHR and SCARECROW, another GRAS protein, regulates genes involved in root tissue formation. Previous bioinformatic research identified seven IDDs, two DELLA, and two SHR genes in Physcomitrium patens, a model organism for non-vascular plants (bryophytes), which lack a GA signaling pathway and roots. In this study, DNA-binding properties and protein–protein interaction of IDDs from P. patens (PpIDD) were analyzed. Our results showed that the DNA-binding properties of PpIDDs were largely conserved between moss and seed plants. Four PpIDDs showed interaction with Arabidopsis DELLA (AtDELLA) proteins but not with PpDELLAs, and one PpIDD showed interaction with PpSHR but not with AtSHR. Moreover, AtIDD10 (JACKDAW) interacted with PpSHR but not with PpDELLAs. Our results indicate that DELLA proteins have modified their structure to interact with IDD proteins during evolution from moss lineage to seed plants, whereas the interaction of IDD and SHR was already present in moss lineage. Full article

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

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12 pages, 750 KiB

Open AccessEditor’s ChoiceArticle

Success and Pitfalls of Genetic Testing in Undiagnosed Diseases: Whole Exome Sequencing and Beyond

by Valeria Barili, Enrico Ambrosini, Vera Uliana, Melissa Bellini, Giulia Vitetta, Davide Martorana, Ilenia Rita Cannizzaro, Antonietta Taiani, Erika De Sensi, Patrizia Caggiati, Sarah Hilton, Siddharth Banka and Antonio Percesepe

Genes 2023, 14(6), 1241; https://doi.org/10.3390/genes14061241 - 10 Jun 2023

Cited by 6 | Viewed by 3367

Abstract

Novel approaches to uncover the molecular etiology of neurodevelopmental disorders (NDD) are highly needed. Even using a powerful tool such as whole exome sequencing (WES), the diagnostic process may still prove long and arduous due to the high clinical and genetic heterogeneity of [...] Read more.

Novel approaches to uncover the molecular etiology of neurodevelopmental disorders (NDD) are highly needed. Even using a powerful tool such as whole exome sequencing (WES), the diagnostic process may still prove long and arduous due to the high clinical and genetic heterogeneity of these conditions. The main strategies to improve the diagnostic rate are based on family segregation, re-evaluation of the clinical features by reverse-phenotyping, re-analysis of unsolved NGS-based cases and epigenetic functional studies. In this article, we described three selected cases from a cohort of patients with NDD in which trio WES was applied, in order to underline the typical challenges encountered during the diagnostic process: (1) an ultra-rare condition caused by a missense variant in MEIS2, identified through the updated Solve-RD re-analysis; (2) a patient with Noonan-like features in which the NGS analysis revealed a novel variant in NIPBL causing Cornelia de Lange syndrome; and (3) a case with de novo variants in genes involved in the chromatin-remodeling complex, for which the study of the epigenetic signature excluded a pathogenic role. In this perspective, we aimed to (i) provide an example of the relevance of the genetic re-analysis of all unsolved cases through network projects on rare diseases; (ii) point out the role and the uncertainties of the reverse phenotyping in the interpretation of the genetic results; and (iii) describe the use of methylation signatures in neurodevelopmental syndromes for the validation of the variants of uncertain significance. Full article

(This article belongs to the Section Genetic Diagnosis)

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16 pages, 3618 KiB

Open AccessEditor’s ChoiceArticle

The Role of Chromatin Assembly Factors in Induced Mutagenesis at Low Levels of DNA Damage

by Tatiyana A. Evstyukhina, Elena A. Alekseeva, Vyacheslav T. Peshekhonov, Irina I. Skobeleva, Dmitriy V. Fedorov and Vladimir G. Korolev

Genes 2023, 14(6), 1242; https://doi.org/10.3390/genes14061242 - 10 Jun 2023

Cited by 4 | Viewed by 1629

Abstract

The problem of low-dose irradiation has been discussed in the scientific literature for several decades, but it is impossible to come to a generally accepted conclusion about the presence of any specific features of low-dose irradiation in contrast to acute irradiation. We were [...] Read more.

The problem of low-dose irradiation has been discussed in the scientific literature for several decades, but it is impossible to come to a generally accepted conclusion about the presence of any specific features of low-dose irradiation in contrast to acute irradiation. We were interested in the effect of low doses of UV radiation on the physiological processes, including repair processes in cells of the yeast Saccharomyces cerevisiae, in contrast to high doses of radiation. Cells utilize excision repair and DNA damage tolerance pathways without significant delay of the cell cycle to address low levels of DNA damage (such as spontaneous base lesions). For genotoxic agents, there is a dose threshold below which checkpoint activation is minimal despite the measurable activity of the DNA repair pathways. Here we report that at ultra-low levels of DNA damage, the role of the error-free branch of post-replicative repair in protection against induced mutagenesis is key. However, with an increase in the levels of DNA damage, the role of the error-free repair branch is rapidly decreasing. We demonstrate that with an increase in the amount of DNA damage from ultra-small to high, asf1Δ-specific mutagenesis decreases catastrophically. A similar dependence is observed for mutants of gene-encoding subunits of the NuB4 complex. Elevated levels of dNTPs caused by the inactivation of the SML1 gene are responsible for high spontaneous reparative mutagenesis. The Rad53 kinase plays a key role in reparative UV mutagenesis at high doses, as well as in spontaneous repair mutagenesis at ultra-low DNA damage levels. Full article

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

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14 pages, 2987 KiB

Open AccessEditor’s ChoiceCase Report

Molecular Modeling Analysis Provides Genotype–Phenotype Correlation Insights in a Patient with Ankyloblepharon-Ectodermal Dysplasia-Clefting Syndrome

by Anna Douka, Lambros Goutzanis, Dimitrios Vlachakis, George P. Chrousos and Christos Yapijakis

Genes 2023, 14(6), 1246; https://doi.org/10.3390/genes14061246 - 10 Jun 2023

Cited by 2 | Viewed by 3366

Abstract

Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome is a rare autosomal dominant disorder. AEC is caused by mutations in the TP63 gene that encodes the tumor suppressor p63 protein, itself involved in the regulation of epidermal proliferation, development, and differentiation. We present here a typical [...] Read more.

Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome is a rare autosomal dominant disorder. AEC is caused by mutations in the TP63 gene that encodes the tumor suppressor p63 protein, itself involved in the regulation of epidermal proliferation, development, and differentiation. We present here a typical AEC case of a four-year-old girl with extensive skin erosions and erythroderma of the scalp and the trunk, and to a lesser extent of the limbs, nail dystrophy on the fingers and toes, xerophthalmia, a high-arched palate, oligodontia, and hypohidrosis. Mutation analysis of the TP63 gene detected a de novo missense mutation in exon 14 (c.1799G>T; p.Gly600Val). We discuss the phenotype–genotype correlation by presenting the clinical features of AEC in the patient, and the effect of the detected mutation in p63 structure and function using protein structural modeling, in view of similar cases in the literature. We performed a molecular modeling study in order to link the effect on the protein structure level of the missense mutation G600V. We noted that the introduction of the bulkier Valine residue in place of the slim Glycine residue caused a significantly altered 3D conformational arrangement of that protein region, pushing away the adjacent antiparallel α helix. We propose that the introduced locally altered structure of the G600V mutant p63 has a significant functional effect on specific protein–protein interactions, thus affecting the clinical phenotype. Full article

(This article belongs to the Special Issue Head and Neck Genetics)

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17 pages, 9587 KiB

Open AccessEditor’s ChoiceArticle

Estimation of DNA Degradation in Archaeological Human Remains

by Antonella Bonfigli, Patrizia Cesare, Anna Rita Volpe, Sabrina Colafarina, Alfonso Forgione, Massimo Aloisi, Osvaldo Zarivi and Anna Maria Giuseppina Poma

Genes 2023, 14(6), 1238; https://doi.org/10.3390/genes14061238 - 9 Jun 2023

Cited by 3 | Viewed by 3000

Abstract

The evaluation of the integrity and quantity of DNA extracted from archaeological human remains is a fundamental step before using the latest generation sequencing techniques in the study of evolutionary processes. Ancient DNA is highly fragmented and chemically modified; therefore, the present study [...] Read more.

The evaluation of the integrity and quantity of DNA extracted from archaeological human remains is a fundamental step before using the latest generation sequencing techniques in the study of evolutionary processes. Ancient DNA is highly fragmented and chemically modified; therefore, the present study aims to identify indices that can allow the identification of potentially amplifiable and sequenceable DNA samples, reducing failures and research costs. Ancient DNA was extracted from five human bone remains from the archaeological site of Amiternum L’Aquila, Italy dating back to the 9th–12th century and was compared with standard DNA fragmented by sonication. Given the different degradation kinetics of mitochondrial DNA compared to nuclear DNA, the mitochondrially encoded 12s RNA and 18s ribosomal RNA genes were taken into consideration; fragments of various sizes were amplified in qPCR and the size distribution was thoroughly investigated. DNA damage degree was evaluated by calculating damage frequency (λ) and the ratio between the amount of the different fragments and that of the smallest fragment (Q). The results demonstrate that both indices were found to be suitable for identifying, among the samples tested, those less damaged and suitable for post-extraction analysis; mitochondrial DNA is more damaged than nuclear, in fact, amplicons up to 152 bp and 253 bp, respectively are obtained. Full article

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

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16 pages, 4156 KiB

Open AccessEditor’s ChoiceArticle

Comparative Mitochondrial Genomes between the Genera Amiota and Phortica (Diptera: Drosophilidae) with Evolutionary Insights into D-Loop Sequence Variability

by Caihong Zhang, Yalian Wang, Hongwei Chen and Jia Huang

Genes 2023, 14(6), 1240; https://doi.org/10.3390/genes14061240 - 9 Jun 2023

Cited by 2 | Viewed by 1652

Abstract

To address the limited number of mitochondrial genomes (mitogenomes) in the subfamily Steganinae (Diptera: Drosophilidae), we assembled 12 complete mitogenomes for six representative species in the genus Amiota and six representative species in the genus Phortica. We performed a series of comparative [...] Read more.

To address the limited number of mitochondrial genomes (mitogenomes) in the subfamily Steganinae (Diptera: Drosophilidae), we assembled 12 complete mitogenomes for six representative species in the genus Amiota and six representative species in the genus Phortica. We performed a series of comparative and phylogenetic analyses for these 12 Steganinae mitogenomes, paying special attention to the commonalities and differences in the D-loop sequences. Primarily determined by the lengths of the D-loop regions, the sizes of the Amiota and Phortica mitogenomes ranged from 16,143–16,803 bp and 15,933–16,290 bp, respectively. Our results indicated that the sizes of genes and intergenic nucleotides (IGNs), codon usage and amino acid usage, compositional skewness levels, evolutionary rates of protein-coding genes (PCGs), and D-loop sequence variability all showed unambiguous genus-specific characteristics and provided novel insights into the evolutionary implications between and within Amiota and Phortica. Most of the consensus motifs were found downstream of the D-loop regions, and some of them showed distinct genus-specific patterns. In addition, the D-loop sequences were phylogenetically informative as the data sets of PCGs and/or rRNAs, especially within the genus Phortica. Full article

(This article belongs to the Special Issue Molecular Evolution, Mitochondrial Genomics and Mitochondrial Genome Expression in Animals)

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17 pages, 4000 KiB

Open AccessEditor’s ChoiceArticle

Vitrification with Dimethyl Sulfoxide Induces Transcriptomic Alteration of Gene and Transposable Element Expression in Immature Human Oocytes

by Ashley Wiltshire, Renata Schaal, Fang Wang, Tiffany Tsou, Wilson McKerrow and David Keefe

Genes 2023, 14(6), 1232; https://doi.org/10.3390/genes14061232 - 8 Jun 2023

Cited by 7 | Viewed by 2646

Abstract

Despite substantial advancements in the field of cryobiology, oocyte and embryo cryopreservation still compromise developmental competence. Furthermore, dimethyl sulfoxide (DMSO), one of the most commonly used cryoprotectants, has been found to exert potent effects on the epigenetic landscape of cultured human cells, as [...] Read more.

Despite substantial advancements in the field of cryobiology, oocyte and embryo cryopreservation still compromise developmental competence. Furthermore, dimethyl sulfoxide (DMSO), one of the most commonly used cryoprotectants, has been found to exert potent effects on the epigenetic landscape of cultured human cells, as well as mouse oocytes and embryos. Little is known about its impact on human oocytes. Additionally, few studies investigate the effects of DMSO on transposable elements (TE), the control of which is essential for the maintenance of genomic instability. The objective of this study was to investigate the impact of vitrification with DMSO-containing cryoprotectant on the transcriptome, including on TEs, of human oocytes. Twenty-four oocytes at the GV stage were donated by four healthy women undergoing elective oocyte cryopreservation. Oocytes were paired such that half from each patient were vitrified with DMSO-containing cryoprotectant (Vitrified Cohort), while the other half were snap frozen in phosphate buffer, unexposed to DMSO (Non-Vitrified Cohort). All oocytes underwent RNA sequencing via a method with high fidelity for single cell analysis, and which allows for the analysis of TE expression through Switching Mechanism at the 5′-end of the RNA Transcript sequencing 2 (SMARTseq2), followed by functional enrichment analysis. Of the 27,837 genes identified by SMARTseq2, 7331 (26.3%) were differentially expressed (p < 0.05). There was a significant dysregulation of genes involved in chromatin and histone modification. Mitochondrial function, as well as the Wnt, insulin, mTOR, HIPPO, and MAPK signaling pathways were also altered. The expression of TEs was positively correlated with the expression of PIWIL2, DNMT3A, and DNMT3B, and negatively correlated with age. These findings suggest that the current standard process of oocyte vitrification, involving DMSO-containing cryoprotectant, induces significant transcriptome changes, including those involving TEs. Full article

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

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32 pages, 1104 KiB

Open AccessEditor’s ChoiceReview

Genes and Athletic Performance: The 2023 Update

by Ekaterina A. Semenova, Elliott C. R. Hall and Ildus I. Ahmetov

Genes 2023, 14(6), 1235; https://doi.org/10.3390/genes14061235 - 8 Jun 2023

Cited by 65 | Viewed by 31032

Abstract

Phenotypes of athletic performance and exercise capacity are complex traits influenced by both genetic and environmental factors. This update on the panel of genetic markers (DNA polymorphisms) associated with athlete status summarises recent advances in sports genomics research, including findings from candidate gene [...] Read more.

Phenotypes of athletic performance and exercise capacity are complex traits influenced by both genetic and environmental factors. This update on the panel of genetic markers (DNA polymorphisms) associated with athlete status summarises recent advances in sports genomics research, including findings from candidate gene and genome-wide association (GWAS) studies, meta-analyses, and findings involving larger-scale initiatives such as the UK Biobank. As of the end of May 2023, a total of 251 DNA polymorphisms have been associated with athlete status, of which 128 genetic markers were positively associated with athlete status in at least two studies (41 endurance-related, 45 power-related, and 42 strength-related). The most promising genetic markers include the AMPD1 rs17602729 C, CDKN1A rs236448 A, HFE rs1799945 G, MYBPC3 rs1052373 G, NFIA-AS2 rs1572312 C, PPARA rs4253778 G, and PPARGC1A rs8192678 G alleles for endurance; ACTN3 rs1815739 C, AMPD1 rs17602729 C, CDKN1A rs236448 C, CPNE5 rs3213537 G, GALNTL6 rs558129 T, IGF2 rs680 G, IGSF3 rs699785 A, NOS3 rs2070744 T, and TRHR rs7832552 T alleles for power; and ACTN3 rs1815739 C, AR ≥21 CAG repeats, LRPPRC rs10186876 A, MMS22L rs9320823 T, PHACTR1 rs6905419 C, and PPARG rs1801282 G alleles for strength. It should be appreciated, however, that elite performance still cannot be predicted well using only genetic testing. Full article

(This article belongs to the Special Issue Feature Papers: Molecular Genetics and Genomics 2023)

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13 pages, 2215 KiB

Open AccessEditor’s ChoiceReview

Plant Promoters: Their Identification, Characterization, and Role in Gene Regulation

by Liliana Villao-Uzho, Tatiana Chávez-Navarrete, Ricardo Pacheco-Coello, Eduardo Sánchez-Timm and Efrén Santos-Ordóñez

Genes 2023, 14(6), 1226; https://doi.org/10.3390/genes14061226 - 6 Jun 2023

Cited by 34 | Viewed by 11334

Abstract

One of the strategies to overcome diseases or abiotic stress in crops is the use of improved varieties. Genetic improvement could be accomplished through different methods, including conventional breeding, induced mutation, genetic transformation, or gene editing. The gene function and regulated expression through [...] Read more.

One of the strategies to overcome diseases or abiotic stress in crops is the use of improved varieties. Genetic improvement could be accomplished through different methods, including conventional breeding, induced mutation, genetic transformation, or gene editing. The gene function and regulated expression through promoters are necessary for transgenic crops to improve specific traits. The variety of promoter sequences has increased in the generation of genetically modified crops because they could lead to the expression of the gene responsible for the improved trait in a specific manner. Therefore, the characterization of the promoter activity is necessary for the generation of biotechnological crops. That is why several analyses have focused on identifying and isolating promoters using techniques such as reverse transcriptase-polymerase chain reaction (RT-PCR), genetic libraries, cloning, and sequencing. Promoter analysis involves the plant genetic transformation method, a potent tool for determining the promoter activity and function of genes in plants, contributing to understanding gene regulation and plant development. Furthermore, the study of promoters that play a fundamental role in gene regulation is highly relevant. The study of regulation and development in transgenic organisms has made it possible to understand the benefits of directing gene expression in a temporal, spatial, and even controlled manner, confirming the great diversity of promoters discovered and developed. Therefore, promoters are a crucial tool in biotechnological processes to ensure the correct expression of a gene. This review highlights various types of promoters and their functionality in the generation of genetically modified crops. Full article

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

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10 pages, 401 KiB

Open AccessEditor’s ChoiceArticle

Characteristics of Neuroimaging and Behavioural Phenotype in Polish Patients with PIGV-CDG—An Observational Study and Literature Review

by Michal Hutny, Patryk Lipinski and Aleksandra Jezela-Stanek

Genes 2023, 14(6), 1208; https://doi.org/10.3390/genes14061208 - 31 May 2023

Cited by 1 | Viewed by 2751

Abstract

Congenital disorders of glycosylation (CDGs) are a wide group of genetic diseases characterised by a severe clinical spectrum, consisting of developmental delays, dysmorphisms, and neurological deficits. Mutations in the PIGV gene lead to a disorder called hyperphosphatasia with impaired intellectual development syndrome 1 [...] Read more.

Congenital disorders of glycosylation (CDGs) are a wide group of genetic diseases characterised by a severe clinical spectrum, consisting of developmental delays, dysmorphisms, and neurological deficits. Mutations in the PIGV gene lead to a disorder called hyperphosphatasia with impaired intellectual development syndrome 1 (HPMRS1), distinct from other CDGs in terms of hyperphosphatemia related to abnormal ALP activity and brachytelephalangy. This article discusses the phenotype of six Polish patients with HPMRS1 with a special focus on behavioural and imaging features, which were not addressed in 26 previously reported cases. The medical records of six patients aged 6 to 22 years were collected and analysed. In all cases, the same PIGV homozygotic mutation (c.1022C>A; p.Ala341Glu) was found, although the patients presented a diverse spectrum of neurological and developmental disorders, concerning in most cases the muscular tonus and general developmental delay. The most prevalent dysmorphic features included hypertelorism, high palate, and finger anomalies, whereas other characteristics present in all previously described cases, such as a short, broad nose and brachytelephalangy, were less frequently observed. Similarly to previous reports, the magnetic resonance (MR) and computed tomography (CT) head scans returned varied results, including physiological and pathological brain images in equal measure, the latter of which consisted of cortical atrophy, delayed myelination, hydrocephalus, and hypoplastic corpus callosum. Each patient exhibited symptoms characteristic of autism spectrum disorders, especially in terms of attention deficits, as well as controlling and expressing emotions. The most common type of sensory processing disorder was over-responsivity. Despite the low prevalence of HPMRS1, the patients reported in the literature presented a rather uniform phenotype, which does not correspond with the one found in each individual of the studied group. Behavioural disorders and sensory impairment require additional care and awareness considering the global developmental delay often observed in these patients. Full article

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

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11 pages, 274 KiB

Open AccessEditor’s ChoiceArticle

Associations between Lipid Profiles and Graves’ Orbitopathy can Be HLA-Dependent

by Magdalena Stasiak, Katarzyna Zawadzka-Starczewska, Bogusław Tymoniuk, Bartłomiej Stasiak and Andrzej Lewiński

Genes 2023, 14(6), 1209; https://doi.org/10.3390/genes14061209 - 31 May 2023

Cited by 5 | Viewed by 1736

Abstract

The risk of Graves’ orbitopathy (GO) is related to the human leukocyte antigen (HLA) profile and was demonstrated to be increased in patients with elevated total cholesterol (TC) and/or low-density lipoprotein (LDL) cholesterol. We hypothesized that there were some HLA alleles that were [...] Read more.

The risk of Graves’ orbitopathy (GO) is related to the human leukocyte antigen (HLA) profile and was demonstrated to be increased in patients with elevated total cholesterol (TC) and/or low-density lipoprotein (LDL) cholesterol. We hypothesized that there were some HLA alleles that were related to both GO and TC and/or LDL levels. Therefore, the aim of the study was to compare the TC/LDL results in patients in whom GO-related HLA alleles were present to those in whom they did not occur. HLA classes were genotyped using a next-generation sequencing method in 118 patients with Graves’ disease (GD), including 63 and 55 patients with and without GO, respectively. Lipid profiles were assessed at the time of the GD diagnosis. A significant correlation between the presence of GO high-risk alleles (HLA-B*37:01 and C*03:02) and higher TC/LDL levels was found. Additionally, the presence of alleles associated with non-GO GD (HLA-C*17:01 and B*08:01), as well as alleles in linkage disequilibrium with B*08:01 (i.e., HLA-DRB1*03:01 and DQB1*02:01), was correlated with lower TC levels. These results further confirm the significance of TC/LDL in the risk of GO development and provide evidence that associations between TC/LDL and GO can be HLA-dependent. Full article

(This article belongs to the Special Issue Genetics of Complex Human Disease)

21 pages, 5346 KiB

Open AccessEditor’s ChoiceArticle

Chromosome-Level Genome Assembly and Circadian Gene Repertoire of the Patagonia Blennie Eleginops maclovinus—The Closest Ancestral Proxy of Antarctic Cryonotothenioids

by Chi-Hing Christina Cheng, Angel G. Rivera-Colón, Bushra Fazal Minhas, Loralee Wilson, Niraj Rayamajhi, Luis Vargas-Chacoff and Julian M. Catchen

Genes 2023, 14(6), 1196; https://doi.org/10.3390/genes14061196 - 30 May 2023

Cited by 3 | Viewed by 2581

Abstract

The basal South American notothenioid Eleginops maclovinus (Patagonia blennie or róbalo) occupies a uniquely important phylogenetic position in Notothenioidei as the singular closest sister species to the Antarctic cryonotothenioid fishes. Its genome and the traits encoded therein would be the nearest representatives of [...] Read more.

The basal South American notothenioid Eleginops maclovinus (Patagonia blennie or róbalo) occupies a uniquely important phylogenetic position in Notothenioidei as the singular closest sister species to the Antarctic cryonotothenioid fishes. Its genome and the traits encoded therein would be the nearest representatives of the temperate ancestor from which the Antarctic clade arose, providing an ancestral reference for deducing polar derived changes. In this study, we generated a gene- and chromosome-complete assembly of the E. maclovinus genome using long read sequencing and HiC scaffolding. We compared its genome architecture with the more basally divergent Cottoperca gobio and the derived genomes of nine cryonotothenioids representing all five Antarctic families. We also reconstructed a notothenioid phylogeny using 2918 proteins of single-copy orthologous genes from these genomes that reaffirmed E. maclovinus’ phylogenetic position. We additionally curated E. maclovinus’ repertoire of circadian rhythm genes, ascertained their functionality by transcriptome sequencing, and compared its pattern of gene retention with C. gobio and the derived cryonotothenioids. Through reconstructing circadian gene trees, we also assessed the potential role of the retained genes in cryonotothenioids by referencing to the functions of the human orthologs. Our results found E. maclovinus to share greater conservation with the Antarctic clade, solidifying its evolutionary status as the direct sister and best suited ancestral proxy of cryonotothenioids. The high-quality genome of E. maclovinus will facilitate inquiries into cold derived traits in temperate to polar evolution, and conversely on the paths of readaptation to non-freezing habitats in various secondarily temperate cryonotothenioids through comparative genomic analyses. Full article

(This article belongs to the Special Issue Polar Genomics)

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11 pages, 977 KiB

Open AccessEditor’s ChoiceSystematic Review

Diagnostic Yield of Exome Sequencing in Fetuses with Sonographic Features of Skeletal Dysplasias but Normal Karyotype or Chromosomal Microarray Analysis: A Systematic Review

by Kai Yeung Tse, Ilham Utama Surya, Rima Irwinda, Kwok Yin Leung, Yuen Ha Ting, Ye Cao and Kwong Wai Choy

Genes 2023, 14(6), 1203; https://doi.org/10.3390/genes14061203 - 30 May 2023

Cited by 7 | Viewed by 3359

Abstract

Skeletal dysplasias are a group of diseases characterized by bone and joint abnormalities, which can be detected during prenatal ultrasound. Next-generation sequencing has rapidly revolutionized molecular diagnostic approaches in fetuses with structural anomalies. This review studies the additional diagnostic yield of prenatal exome [...] Read more.

Skeletal dysplasias are a group of diseases characterized by bone and joint abnormalities, which can be detected during prenatal ultrasound. Next-generation sequencing has rapidly revolutionized molecular diagnostic approaches in fetuses with structural anomalies. This review studies the additional diagnostic yield of prenatal exome sequencing in fetuses with prenatal sonographic features of skeletal dysplasias. This was a systematic review by searching PubMed for studies published between 2013 and July 2022 that identified the diagnostic yield of exome sequencing after normal karyotype or chromosomal microarray analysis (CMA) for cases with suspected fetal skeletal dysplasias based on prenatal ultrasound. We identified 10 out of 85 studies representing 226 fetuses. The pooled additional diagnostic yield was 69.0%. The majority of the molecular diagnoses involved de novo variants (72%), while 8.7% of cases were due to inherited variants. The incremental diagnostic yield of exome sequencing over CMA was 67.4% for isolated short long bones and 77.2% for non-isolated cases. Among phenotypic subgroup analyses, features with the highest additional diagnostic yield were an abnormal skull (83.3%) and a small chest (82.5%). Prenatal exome sequencing should be considered for cases with suspected fetal skeletal dysplasias with or without a negative karyotype or CMA results. Certain sonographic features, including an abnormal skull and small chest, may indicate a potentially higher diagnostic yield. Full article

(This article belongs to the Special Issue Novel Insights into Prenatal Genetic Testing)

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14 pages, 2527 KiB

Open AccessEditor’s ChoiceArticle

Identifying Candidate Genes for Litter Size and Three Morphological Traits in Youzhou Dark Goats Based on Genome-Wide SNP Markers

by Xiaoyan Sun, Qunhao Niu, Jing Jiang, Gaofu Wang, Peng Zhou, Jie Li, Cancan Chen, Liangjia Liu, Lingyang Xu and Hangxing Ren

Genes 2023, 14(6), 1183; https://doi.org/10.3390/genes14061183 - 29 May 2023

Cited by 17 | Viewed by 3557

Abstract

This study aimed to reveal the potential genetic basis for litter size, coat colour, black middorsal stripe and skin colour by combining genome-wide association analysis (GWAS) and selection signature analysis and ROH detection within the Youzhou dark (YZD) goat population (n = 206) [...] Read more.

This study aimed to reveal the potential genetic basis for litter size, coat colour, black middorsal stripe and skin colour by combining genome-wide association analysis (GWAS) and selection signature analysis and ROH detection within the Youzhou dark (YZD) goat population (n = 206) using the Illumina GoatSNP54 BeadChip. In the GWAS, we identified one SNP (snp54094-scaffold824-899720) on chromosome 11 for litter size, two SNPs on chromosome 26 (snp11508-scaffold142-1990450, SORCS3) and chromosome 12 (snp55048-scaffold842-324525, LOC102187779) for coat colour and one SNP on chromosome 18 (snp56013-scaffold873-22716, TCF25) for the black middorsal stripe. In contrast, no SNPs were identified for skin colour. In selection signature analysis, 295 significant iHS genomic regions with a mean |iHS| score > 2.66, containing selection signatures encompassing 232 candidate genes were detected. In particular, 43 GO terms and one KEGG pathway were significantly enriched in the selected genes, which may contribute to the excellent environmental adaptability and characteristic trait formation during the domestication of YZD goats. In ROH detection, we identified 4446 ROH segments and 282 consensus ROH regions, among which nine common genes overlapped with those detected using the iHS method. Some known candidate genes for economic traits such as reproduction (TSHR, ANGPT4, CENPF, PIBF1, DACH1, DIS3, CHST1, COL4A1, PRKD1 and DNMT3B) and development and growth (TNPO2, IFT80, UCP2, UCP3, GHRHR, SIM1, CCM2L, CTNNA3 and CTNNA1) were revealed by iHS and ROH detection. Overall, this study is limited by the small population size, which affects the results of GWAS to a certain extent. Nevertheless, our findings could provide the first overview of the genetic mechanism underlying these important traits and provide novel insights into the future conservation and utilisation of Chinese goat germplasm resources. Full article

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

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17 pages, 5311 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Characterization and Sequence Polymorphism Analyses of Glycine max Fibrillin (FBN) Revealed Its Role in Response to Drought Condition

by Muhammad Zeshan Zafer, Muhammad Hammad Nadeem Tahir, Zulqurnain Khan, Muhammad Sajjad, Xiangkuo Gao, Muhammad Amir Bakhtavar, Ummara Waheed, Maria Siddique, Zhide Geng and Shoaib Ur Rehman

Genes 2023, 14(6), 1188; https://doi.org/10.3390/genes14061188 - 29 May 2023

Cited by 3 | Viewed by 2117

Abstract

The fibrillin (FBN) gene family is widely distributed in all photosynthetic organisms. Members of this gene family are involved in plant growth and development and their response to various biotic and abiotic stress factors. In this study, 16 members of FBN [...] Read more.

The fibrillin (FBN) gene family is widely distributed in all photosynthetic organisms. Members of this gene family are involved in plant growth and development and their response to various biotic and abiotic stress factors. In this study, 16 members of FBN were identified in Glycine max and characterized by using different bioinformatics tools. Phylogenetic analysis classified FBN genes into seven groups. The presence of stress-related cis-elements in the upstream region of GmFBN highlighted their role in tolerance against abiotic stresses. To further decipher the function, physiochemical properties, conserved motifs, chromosomal localization, subcellular localization, and cis-acting regulatory elements were also analyzed. Gene expression analysis based on FPKM values revealed that GmFBNs greatly enhanced soybean drought tolerance and controlled the expression of several genes involved in drought response, except for GmFBN-4, GmFBN-5, GmFBN-6, GmFBN-7 and GmFBN-9. For high throughput genotyping, an SNP-based CAPS marker was also developed for the GmFBN-15 gene. The CAPS marker differentiated soybean genotypes based on the presence of either the GmFBN-15-G or GmFBN-15-A alleles in the CDS region. Association analysis showed that G. max accessions containing the GmFBN-15-A allele at the respective locus showed higher thousand seed weight compared to accessions containing the GmFBN-15-G allele. This research has provided the basic information to further decipher the function of FBN in soybean. Full article

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

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21 pages, 1572 KiB

Open AccessEditor’s ChoiceReview

Peptides of a Feather: How Computation Is Taking Peptide Therapeutics under Its Wing

by Thomas David Daniel Kazmirchuk, Calvin Bradbury-Jost, Taylor Ann Withey, Tadesse Gessese, Taha Azad, Bahram Samanfar, Frank Dehne and Ashkan Golshani

Genes 2023, 14(6), 1194; https://doi.org/10.3390/genes14061194 - 29 May 2023

Cited by 18 | Viewed by 4748

Abstract

Leveraging computation in the development of peptide therapeutics has garnered increasing recognition as a valuable tool to generate novel therapeutics for disease-related targets. To this end, computation has transformed the field of peptide design through identifying novel therapeutics that exhibit enhanced pharmacokinetic properties [...] Read more.

Leveraging computation in the development of peptide therapeutics has garnered increasing recognition as a valuable tool to generate novel therapeutics for disease-related targets. To this end, computation has transformed the field of peptide design through identifying novel therapeutics that exhibit enhanced pharmacokinetic properties and reduced toxicity. The process of in-silico peptide design involves the application of molecular docking, molecular dynamics simulations, and machine learning algorithms. Three primary approaches for peptide therapeutic design including structural-based, protein mimicry, and short motif design have been predominantly adopted. Despite the ongoing progress made in this field, there are still significant challenges pertaining to peptide design including: enhancing the accuracy of computational methods; improving the success rate of preclinical and clinical trials; and developing better strategies to predict pharmacokinetics and toxicity. In this review, we discuss past and present research pertaining to the design and development of in-silico peptide therapeutics in addition to highlighting the potential of computation and artificial intelligence in the future of disease therapeutics. Full article

(This article belongs to the Topic Bioinformatics in Drug Design and Discovery)

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9 pages, 480 KiB

Open AccessEditor’s ChoiceArticle

Rett-like Phenotypes in HNRNPH2-Related Neurodevelopmental Disorder

by Joseph Nicho Gonzalez, Sylvie Goldman, Melissa T. Carter and Jennifer M. Bain

Genes 2023, 14(6), 1154; https://doi.org/10.3390/genes14061154 - 26 May 2023

Cited by 1 | Viewed by 3493

Abstract

Rett Syndrome (RTT) is a neurodevelopmental disorder with a prevalence of 1:10,000 to 15,000 females worldwide. Classic Rett Syndrome presents in early childhood with a period of developmental regression, loss of purposeful hand skills along with hand stereotypies, gait abnormalities, and loss of [...] Read more.

Rett Syndrome (RTT) is a neurodevelopmental disorder with a prevalence of 1:10,000 to 15,000 females worldwide. Classic Rett Syndrome presents in early childhood with a period of developmental regression, loss of purposeful hand skills along with hand stereotypies, gait abnormalities, and loss of acquired speech. Atypical RTT is diagnosed when a child shows some but not all the phenotypes of classic RTT, along with additional supporting criteria. Over 95% of classic RTT cases are attributed to pathogenic variants in Methyl-CpG Binding Protein 2 (MECP2), though additional genes have been implicated in other RTT cases, particularly those with the atypical RTT clinical picture. Other genetic etiologies have emerged with similar clinical characteristics to RTT Syndrome. Our team has characterized HNRNPH2-related neurodevelopmental disorder (HNRNPH2-RNDD) in 33 individuals associated with de novo pathogenic missense variants in the X-linked HNRNPH2 gene, characterized by developmental delay, intellectual disability, seizures, autistic-like features, and motor abnormalities. We sought to further characterize RTT clinical features in this group of individuals by using caregiver report. Twenty-six caregivers completed electronic surveys, with only 3 individuals having previously received an atypical RTT diagnosis, and no individuals with a typical RTT diagnosis. Caregivers reported a high number of behaviors and/or phenotypes consistent with RTT, including the major criteria of the syndrome, such as regression of developmental skills and abnormal gait. Based on the survey results, 12 individuals could meet the diagnostic clinical criteria for atypical RTT Syndrome. In summary, individuals with HNRNPH2-RNDD exhibit clinical characteristics that overlap with those of RTT, and therefore, HNRNPH2-RNDD, should be considered on the differential diagnosis list with this clinical picture. Full article

(This article belongs to the Special Issue Genetics of Rett Syndrome and Rett-Like Phenotypes: From Gene Discovery to Management and Treatment)

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21 pages, 4188 KiB

Open AccessEditor’s ChoiceArticle

Genetic Diversity of Durum Wheat (Triticum turgidum L. ssp. durum, Desf) Germplasm as Revealed by Morphological and SSR Markers

by Temesgen Dagnaw, Behailu Mulugeta, Teklehaimanot Haileselassie, Mulatu Geleta, Rodomiro Ortiz and Kassahun Tesfaye

Genes 2023, 14(6), 1155; https://doi.org/10.3390/genes14061155 - 26 May 2023

Cited by 14 | Viewed by 4792

Abstract

Ethiopia is considered a center of origin and diversity for durum wheat and is endowed with many diverse landraces. This research aimed to estimate the extent and pattern of genetic diversity in Ethiopian durum wheat germplasm. Thus, 104 durum wheat genotypes representing thirteen [...] Read more.

Ethiopia is considered a center of origin and diversity for durum wheat and is endowed with many diverse landraces. This research aimed to estimate the extent and pattern of genetic diversity in Ethiopian durum wheat germplasm. Thus, 104 durum wheat genotypes representing thirteen populations, three regions, and four altitudinal classes were investigated for their genetic diversity, using 10 grain quality- and grain yield-related phenotypic traits and 14 simple sequence repeat (SSR) makers. The analysis of the phenotypic traits revealed a high mean Shannon diversity index (H′ = 0.78) among the genotypes and indicated a high level of phenotypic variation. The principal component analysis (PCA) classified the genotypes into three groups. The SSR markers showed a high mean value of polymorphic information content (PIC = 0.50) and gene diversity (h = 0.56), and a moderate number of alleles per locus (Na = 4). Analysis of molecular variance (AMOVA) revealed a high level of variation within populations, regions, and altitudinal classes, accounting for 88%, 97%, and 97% of the total variation, respectively. Pairwise genetic differentiation and Nei’s genetic distance analyses identified that the cultivars are distinct from the landrace populations. The distance-based (Discriminant Analysis of Principal Component (DAPC) and Minimum Spanning Network (MSN)) and model-based population stratification (STRUCTURE) methods of clustering grouped the genotypes into two clusters. Both the phenotypic data-based PCA and the molecular data-based DAPC and MSN analyses defined distinct groupings of cultivars and landraces. The phenotypic and molecular diversity analyses highlighted the high genetic variation in the Ethiopian durum wheat gene pool. The investigated SSRs showed significant associations with one or more target phenotypic traits. The markers identify landraces with high grain yield and quality traits. This study highlights the usefulness of Ethiopian landraces for cultivar development, contributing to food security in the region and beyond. Full article

(This article belongs to the Special Issue Genetics Studies on Wheat)

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17 pages, 961 KiB

Open AccessEditor’s ChoiceReview

Breast Cancer with Brain Metastasis: Molecular Insights and Clinical Management

by Mariia Ivanova, Francesca Maria Porta, Federica Giugliano, Chiara Frascarelli, Elham Sajjadi, Konstantinos Venetis, Giulia Cursano, Giovanni Mazzarol, Elena Guerini-Rocco, Giuseppe Curigliano, Carmen Criscitiello and Nicola Fusco

Genes 2023, 14(6), 1160; https://doi.org/10.3390/genes14061160 - 26 May 2023

Cited by 20 | Viewed by 5882

Abstract

Breast cancer is the most frequently diagnosed malignancy worldwide and the leading cause of cancer-related death among women. Brain metastases are a primary contributor to mortality, as they often go undetected until late stages due to their dormant nature. Moreover, the clinical management [...] Read more.

Breast cancer is the most frequently diagnosed malignancy worldwide and the leading cause of cancer-related death among women. Brain metastases are a primary contributor to mortality, as they often go undetected until late stages due to their dormant nature. Moreover, the clinical management of brain metastases is complicated by the relevant issue of blood-brain barrier penetration. The molecular pathways involved in the formation, progression, and colonization of primary breast tumors and subsequent brain metastases are diverse, posing significant hurdles due to the heterogeneous nature of breast cancer subtypes. Despite advancements in primary breast cancer treatments, the prognosis for patients with brain metastases remains poor. In this review, we aim to highlight the biological mechanisms of breast cancer brain metastases by evaluating multi-step genetic pathways and to discuss currently available and emerging treatment strategies to propose a prospective overview of the management of this complex disease. Full article

(This article belongs to the Special Issue Genotyping and Prognostic Markers in Cancers)

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16 pages, 1485 KiB

Open AccessEditor’s ChoiceArticle

Genetic Mapping of Genotype-by-Ploidy Effects in Arabidopsis thaliana

by Cris L. Wijnen, Frank F. M. Becker, Andries A. Okkersen, C. Bastiaan de Snoo, Martin P. Boer, Fred A. van Eeuwijk, Erik Wijnker and Joost J. B. Keurentjes

Genes 2023, 14(6), 1161; https://doi.org/10.3390/genes14061161 - 26 May 2023

Cited by 2 | Viewed by 1891

Abstract

Plants can express different phenotypic responses following polyploidization, but ploidy-dependent phenotypic variation has so far not been assigned to specific genetic factors. To map such effects, segregating populations at different ploidy levels are required. The availability of an efficient haploid inducer line in [...] Read more.

Plants can express different phenotypic responses following polyploidization, but ploidy-dependent phenotypic variation has so far not been assigned to specific genetic factors. To map such effects, segregating populations at different ploidy levels are required. The availability of an efficient haploid inducer line in Arabidopsis thaliana allows for the rapid development of large populations of segregating haploid offspring. Because Arabidopsis haploids can be self-fertilised to give rise to homozygous doubled haploids, the same genotypes can be phenotyped at both the haploid and diploid ploidy level. Here, we compared the phenotypes of recombinant haploid and diploid offspring derived from a cross between two late flowering accessions to map genotype × ploidy (G × P) interactions. Ploidy-specific quantitative trait loci (QTLs) were detected at both ploidy levels. This implies that mapping power will increase when phenotypic measurements of monoploids are included in QTL analyses. A multi-trait analysis further revealed pleiotropic effects for a number of the ploidy-specific QTLs as well as opposite effects at different ploidy levels for general QTLs. Taken together, we provide evidence of genetic variation between different Arabidopsis accessions being causal for dissimilarities in phenotypic responses to altered ploidy levels, revealing a G × P effect. Additionally, by investigating a population derived from late flowering accessions, we revealed a major vernalisation-specific QTL for variation in flowering time, countering the historical bias of research in early flowering accessions. Full article

(This article belongs to the Special Issue Genetics and Breeding of Polyploid Plants)

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20 pages, 2543 KiB

Open AccessEditor’s ChoiceArticle

Association of Gene Variants with Seasonal Variation in Muscle Strength and Aerobic Capacity in Elite Skiers

by Benedikt Gasser, Walter O. Frey, Paola Valdivieso, Johannes Scherr, Jörg Spörri and Martin Flück

Genes 2023, 14(6), 1165; https://doi.org/10.3390/genes14061165 - 26 May 2023

Cited by 1 | Viewed by 2347

Abstract

Background: The training of elite skiers follows a systematic seasonal periodization with a preparation period, when anaerobic muscle strength, aerobic capacity, and cardio-metabolic recovery are specifically conditioned to provide extra capacity for developing ski-specific physical fitness in the subsequent competition period. We hypothesized [...] Read more.

Background: The training of elite skiers follows a systematic seasonal periodization with a preparation period, when anaerobic muscle strength, aerobic capacity, and cardio-metabolic recovery are specifically conditioned to provide extra capacity for developing ski-specific physical fitness in the subsequent competition period. We hypothesized that periodization-induced alterations in muscle and metabolic performance demonstrate important variability, which in part is explained by gene-associated factors in association with sex and age. Methods: A total of 34 elite skiers (20.4 ± 3.1 years, 19 women, 15 men) underwent exhaustive cardiopulmonary exercise and isokinetic strength testing before and after the preparation and subsequent competition periods of the World Cup skiing seasons 2015–2018. Biometric data were recorded, and frequent polymorphisms in five fitness genes, ACE-I/D (rs1799752), TNC (rs2104772), ACTN3 (rs1815739), and PTK2 (rs7460, rs7843014), were determined with specific PCR reactions on collected DNA. Relative percentage changes of cardio-pulmonary and skeletal muscle metabolism and performance over the two seasonal periods were calculated for 160 data points and subjected to analysis of variance (ANOVA) to identify hypothesized and novel associations between performance alterations and the five respective genotypes and determine the influence of age × sex. A threshold of 0.1 for the effect size (h2) was deemed appropriate to identify relevant associations and motivate a post hoc test to localize effects. Results: The preparation and competition periods produced antidromic functional changes, the extent of which varied with increasing importance for anaerobic strength, aerobic performance, cardio-metabolic efficiency, and cardio-metabolic/muscle recovery. Only peak RER (−14%), but not anaerobic strength and peak aerobic performance, and parameters characterizing cardio-metabolic efficiency, differed between the first and last studied skiing seasons because improvements over the preparation period were mostly lost over the competition period. A number of functional parameters demonstrated associations of variability in periodic changes with a given genotype, and this was considerably influenced by athlete “age”, but not “sex”. This concerned age-dependent associations between periodic changes in muscle-related parameters, such as anaerobic strength for low and high angular velocities of extension and flexion and blood lactate concentration, with rs1799752 and rs2104772, whose gene products relate to sarcopenia. By contrast, the variance in period-dependent changes in body mass and peak VO2 with rs1799752 and rs2104772, respectively, was independent of age. Likely, the variance in periodic changes in the reliance of aerobic performance on lactate, oxygen uptake, and heart rate was associated with rs1815739 independent of age. These associations manifested at the post hoc level in genotype-associated differences in critical performance parameters. ACTN3 T-allele carriers demonstrated, compared to non-carriers, largely different periodic changes in the muscle-associated parameters of aerobic metabolism during exhaustive exercise, including blood lactate and respiration exchange ratio. The homozygous T-allele carriers of rs2104772 demonstrated the largest changes in extension strength at low angular velocity during the preparation period. Conclusions: Physiological characteristics of performance in skiing athletes undergo training period-dependent seasonal alterations the extent of which is largest for muscle metabolism-related parameters. Genotype associations for the variability in changes of aerobic metabolism-associated power output during exhaustive exercise and anaerobic peak power over the preparation and competition period motivate personalized training regimes. This may help to predict and maximize the benefit of physical conditioning of elite skiers based on chronological characteristics and the polymorphisms of the ACTN3, ACE, and TNC genes investigated here. Full article

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

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13 pages, 10150 KiB

Open AccessEditor’s ChoiceArticle

Evaluating the Differential Response of Transcription Factors in Diploid versus Autotetraploid Rice Leaves Subjected to Diverse Saline–Alkali Stresses

by Ningning Wang, Yingkai Wang, Chenxi Wang, Zitian Leng, Fan Qi, Shiyan Wang, Yiming Zhou, Weilong Meng, Keyan Liu, Chunying Zhang and Jian Ma

Genes 2023, 14(6), 1151; https://doi.org/10.3390/genes14061151 - 25 May 2023

Cited by 2 | Viewed by 1673

Abstract

Saline–alkali stress is a significant abiotic stress factor that impacts plant growth, development, and crop yield. Consistent with the notion that genome-wide replication events can enhance plant stress resistance, autotetraploid rice exhibited a higher level of tolerance to saline–alkali stress than its donor [...] Read more.

Saline–alkali stress is a significant abiotic stress factor that impacts plant growth, development, and crop yield. Consistent with the notion that genome-wide replication events can enhance plant stress resistance, autotetraploid rice exhibited a higher level of tolerance to saline–alkali stress than its donor counterparts, which is reflected by differential gene expression between autotetraploid and diploid rice in response to salt, alkali, and saline–alkali stress. In this study, we investigated the expression of the transcription factors (TFs) in the leaf tissues of autotetraploid and diploid rice under different types of saline–alkali stress. Transcriptome analysis identified a total of 1040 genes from 55 TF families that were altered in response to these stresses, with a significantly higher number in autotetraploid rice compared to diploid rice. Contrarily, under these stresses, the number of expressed TF genes in autotetraploid rice was greater than that in diploid rice for all three types of stress. In addition to the different numbers, the differentially expressed TF genes were found to be from significantly distinct TF families between autotetraploid and diploid rice genotypes. The GO enrichment analysis unraveled that all the DEGs were distributed with differentially biological functions in rice, in particular those that were enriched in the pathways of phytohormones and salt resistance, signal transduction, and physiological and biochemical metabolism in autotetraploid rice compared to its diploid counterpart. This may provide useful guidance for studying the biological roles of polyploidization in plant resilience in response to saline–alkali stress. Full article

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

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9 pages, 481 KiB

Open AccessEditor’s ChoiceArticle

Longitudinal Analysis of Contrasts in Gene Expression Data

by Georg Hahn, Tanya Novak, Jeremy C. Crawford, Adrienne G. Randolph and Christoph Lange

Genes 2023, 14(6), 1134; https://doi.org/10.3390/genes14061134 - 24 May 2023

Cited by 1 | Viewed by 1642

Abstract

We are interested in detecting a departure from the baseline in a longitudinal analysis in the context of multiple organ dysfunction syndrome (MODS). In particular, we are given gene expression reads at two time points for a fixed number of genes and individuals. [...] Read more.

We are interested in detecting a departure from the baseline in a longitudinal analysis in the context of multiple organ dysfunction syndrome (MODS). In particular, we are given gene expression reads at two time points for a fixed number of genes and individuals. The individuals can be subdivided into two groups, denoted as groups A and B. Using the two time points, we compute a contrast of gene expression reads per individual and gene. The age of each individual is known and it is used to compute, for each gene separately, a linear regression of the gene expression contrasts on the individual’s age. Looking at the intercept of the linear regression to detect a departure from the baseline, we aim to reliably single out those genes for which there is a difference in the intercept among those individuals in group A and not in group B. In this work, we develop testing methodology for this setting based on two hypothesis tests—one under the null and one under an appropriately formulated alternative. We demonstrate the validity of our approach using a dataset created by bootstrapping from a real data application in the context of multiple organ dysfunction syndrome (MODS). Full article

(This article belongs to the Section Bioinformatics)

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31 pages, 1433 KiB

Open AccessEditor’s ChoiceReview

JAK/STAT Signaling and Cervical Cancer: From the Cell Surface to the Nucleus

by Arturo Valle-Mendiola, Adriana Gutiérrez-Hoya and Isabel Soto-Cruz

Genes 2023, 14(6), 1141; https://doi.org/10.3390/genes14061141 - 24 May 2023

Cited by 30 | Viewed by 7189

Abstract

The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway constitutes a rapid signaling module from the cell surface to the nucleus, and activates different cellular responses, such as proliferation, survival, migration, invasion, and inflammation. When the JAK/STAT pathway is altered, [...] Read more.

The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway constitutes a rapid signaling module from the cell surface to the nucleus, and activates different cellular responses, such as proliferation, survival, migration, invasion, and inflammation. When the JAK/STAT pathway is altered, it contributes to cancer progression and metastasis. STAT proteins play a central role in developing cervical cancer, and inhibiting the JAK/STAT signaling may be necessary to induce tumor cell death. Several cancers show continuous activation of different STATs, including cervical cancer. The constitutive activation of STAT proteins is associated with a poor prognosis and overall survival. The human papillomavirus (HPV) oncoproteins E6 and E7 play an essential role in cervical cancer progression, and they activate the JAK/STAT pathway and other signals that induce proliferation, survival, and migration of cancer cells. Moreover, there is a crosstalk between the JAK/STAT signaling cascade with other signaling pathways, where a plethora of different proteins activate to induce gene transcription and cell responses that contribute to tumor growth. Therefore, inhibition of the JAK/STAT pathway shows promise as a new target in cancer treatment. In this review, we discuss the role of the JAK/STAT pathway components and the role of the HPV oncoproteins associated with cellular malignancy through the JAK/STAT proteins and other signaling pathways to induce tumor growth. Full article

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

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