Genes

14 pages, 5013 KiB

Open AccessEditor’s ChoiceArticle

RNA-Sequencing Analysis Revealed Genes Associated with Sweet Potato (Ipomoea batatas (L.) Lam.) Responses to Stem Rot during Different Infection Stages

by Chen Li, Liang Zhang, Honghu Ji, Weihan Song, Ziyu Zhong, Meiqiao Jiang, Yungang Zhang, Qiang Li, Linrun Cheng and Meng Kou

Genes 2023, 14(12), 2215; https://doi.org/10.3390/genes14122215 - 14 Dec 2023

Cited by 1 | Viewed by 1743

Abstract

The sweet potato, which is an important tuber crop in China, is susceptible to a variety of pathogens and insect pests during cultivation and production. Stem rot is a common sweet potato disease that seriously affects tuber yield and quality. Unfortunately, there have [...] Read more.

The sweet potato, which is an important tuber crop in China, is susceptible to a variety of pathogens and insect pests during cultivation and production. Stem rot is a common sweet potato disease that seriously affects tuber yield and quality. Unfortunately, there have been relatively few studies on the mechanism mediating the stem rot resistance of sweet potatoes. In this study, a transcriptome sequencing analysis was completed using Xushu 48 samples at different stages (T1, T2, and T3) of the stem rot infection. The T1 vs. T2, T1 vs. T3, and T2 vs. T3 comparisons detected 44,839, 81,436, and 61,932 differentially expressed genes (DEGs), respectively. The DEGs encoded proteins primarily involved in alanine, aspartate, and glutamate metabolism (ko00250), carbon fixation in photosynthetic organisms (ko00710), and amino sugar and nucleotide sugar metabolism (ko00520). Furthermore, some candidate genes induced by phytopathogen infections were identified, including gene-encoding receptor-like protein kinases (RLK5 and RLK7), an LRR receptor-like serine/threonine protein kinase (SERK1), and transcription factors (bHLH137, ERF9, MYB73, and NAC053). The results of this study provide genetic insights that are relevant to future explorations of sweet potato stem rot resistance, while also providing the theoretical basis for breeding sweet potato varieties that are resistant to stem rot and other diseases. Full article

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

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17 pages, 3250 KiB

Open AccessEditor’s ChoiceArticle

Role of bZIP Transcription Factors in Response to NaCl Stress in Tamarix ramosissima under Exogenous Potassium (K⁺)

by Yahui Chen, Min Zhang, Dezong Sui, Jiang Jiang and Lei Wang

Genes 2023, 14(12), 2203; https://doi.org/10.3390/genes14122203 - 13 Dec 2023

Cited by 1 | Viewed by 1464

Abstract

Salt stress is a significant environmental factor affecting plant growth and development, with NaCl stress being one of the most common types of salt stress. The halophyte, Tamarix ramosissima Ledeb (T. ramosissima), is frequently utilized for the afforestation of saline-alkali [...] Read more.

Salt stress is a significant environmental factor affecting plant growth and development, with NaCl stress being one of the most common types of salt stress. The halophyte, Tamarix ramosissima Ledeb (T. ramosissima), is frequently utilized for the afforestation of saline-alkali soils. Indeed, there has been limited research and reports by experts and scholars on the regulatory mechanisms of basic leucine zipper (bZIP) genes in T. ramosissima when treated with exogenous potassium (K⁺) to alleviate the effects of NaCl stress. This study focused on the bZIP genes in T. ramosissima roots under NaCl stress with additional KCl applied. We identified key candidate genes and metabolic pathways related to bZIP and validated them through quantitative real-time PCR (qRT-PCR). The results revealed that under NaCl stress with additional KCl applied treatments at 0 h, 48 h, and 168 h, based on Pfam protein domain prediction and physicochemical property analysis, we identified 20 related bZIP genes. Notably, four bZIP genes (bZIP_2, bZIP_6, bZIP_16, and bZIP_18) were labeled with the plant hormone signal transduction pathway, showing a predominant up-regulation in expression levels. The results suggest that these genes may mediate multiple physiological pathways under NaCl stress with additional KCl applied at 48 h and 168 h, enhancing signal transduction, reducing the accumulation of ROS, and decreasing oxidative damage, thereby enhancing the tolerance of T. ramosissima to NaCl stress. This study provides gene resources and a theoretical basis for further breeding of salt-tolerant Tamarix species and the involvement of bZIP transcription factors in mitigating NaCl toxicity. Full article

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

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16 pages, 4084 KiB

Open AccessEditor’s ChoiceArticle

The Supersymmetry Genetic Code Table and Quadruplet Symmetries of DNA Molecules Are Unchangeable and Synchronized with Codon-Free Energy Mapping during Evolution

by Marija Rosandić and Vladimir Paar

Genes 2023, 14(12), 2200; https://doi.org/10.3390/genes14122200 - 12 Dec 2023

Cited by 4 | Viewed by 1955

Abstract

The Supersymmetry Genetic code (SSyGC) table is based on five physicochemical symmetries: (1) double mirror symmetry on the principle of the horizontal and vertical mirror symmetry axis between all bases (purines [A, G) and pyrimidines (U, C)] and (2) of bases in the [...] Read more.

The Supersymmetry Genetic code (SSyGC) table is based on five physicochemical symmetries: (1) double mirror symmetry on the principle of the horizontal and vertical mirror symmetry axis between all bases (purines [A, G) and pyrimidines (U, C)] and (2) of bases in the form of codons; (3) direct–complement like codon/anticodon symmetry in the sixteen alternating boxes of the genetic code columns; (4) A + T-rich and C + G-rich alternate codons in the same row between both columns of the genetic code; (5) the same position between divided and undivided codon boxes in relation to horizontal mirror symmetry axis. The SSyGC table has a unique physicochemical purine–pyrimidine symmetry net which is as the core symmetry common for all, with more than thirty different nuclear and mitochondrial genetic codes. This net is present in the SSyGC table of all RNA and DNA living species. None of these symmetries are present in the Standard Genetic Code (SGC) table which is constructed on the alphabetic horizontal and vertical U-C-A-G order of bases. Here, we show that the free energy value of each codon incorporated as fundamentally mapping the “energy code” in the SSyGC table is compatible with mirror symmetry. On the other hand, in the SGC table, the same free energy values of codons are dispersed and a mirror symmetry between them is not recognizable. At the same time, the mirror symmetry of the SSyGC table and the DNA quadruplets together with our classification of codons/trinucleotides are perfectly imbedded in the mirror symmetry energy mapping of codons/trinucleotides and point out in favor of maintaining the integrity of the genetic code and DNA genome. We also argue that physicochemical symmetries of the SSyGC table in the manner of the purine–pyrimidine symmetry net, the quadruplet symmetry of DNA molecule, and the free energy of codons have remined unchanged during all of evolution. The unchangeable and universal symmetry properties of the genetic code, DNA molecules, and the energy code are decreasing disorder between codons/trinucleotides and shed a new light on evolution. Diversity in all living species on Earth is broad, but the symmetries of the Supersymmetry Genetic Code as the code of life and the DNA quadruplets related to the “energy code” are unique, unchangeable, and have the power of natural laws. Full article

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

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10 pages, 2178 KiB

Open AccessEditor’s ChoiceCase Report

A Rare Case of Concurrent 2q34q36 Duplication and 2q37 Deletion in a Neonate with Syndromic Features

by Francesco Nicola Riviello, Alessia Daponte, Emanuela Ponzi, Romina Ficarella, Paola Orsini, Roberta Bucci, Mario Ventura, Francesca Antonacci, Claudia Rita Catacchio and Mattia Gentile

Genes 2023, 14(12), 2194; https://doi.org/10.3390/genes14122194 - 10 Dec 2023

Cited by 1 | Viewed by 1796

Abstract

Large-scale genomic structural variations can have significant clinical implications, depending on the specific altered genomic region. Briefly, 2q37 microdeletion syndrome is a prevalent subtelomeric deletion disorder characterized by variable-sized deletions. Affected patients exhibit a wide range of clinical manifestations, including short stature, facial [...] Read more.

Large-scale genomic structural variations can have significant clinical implications, depending on the specific altered genomic region. Briefly, 2q37 microdeletion syndrome is a prevalent subtelomeric deletion disorder characterized by variable-sized deletions. Affected patients exhibit a wide range of clinical manifestations, including short stature, facial dysmorphism, and features of autism spectrum disorder, among others. Conversely, isolated duplications of proximal chromosome 2q are rare and lack a distinct phenotype. In this report, we provide an extensive molecular analysis of a 15-day-old newborn referred for syndromic features. Our analysis reveals an 8.5 Mb microdeletion at 2q37.1, which extends to the telomere, in conjunction with an 8.6 Mb interstitial microduplication at 2q34q36.1. Our findings underscore the prominence of 2q37 terminal deletions as commonly reported genomic anomalies. We compare our patient’s phenotype with previously reported cases in the literature to contribute to a more refined classification of 2q37 microdeletion syndrome and assess the potential impact of 2q34q36.1 microduplication. We also investigate multiple hypotheses to clarify the genetic mechanisms responsible for the observed genomic rearrangement. Full article

(This article belongs to the Special Issue Human Developmental Disability, Neurogenetics and Rare Diseases: From Basic Science to Genetic Counseling)

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17 pages, 2782 KiB

Open AccessEditor’s ChoiceArticle

Polymer Modeling Reveals Interplay between Physical Properties of Chromosomal DNA and the Size and Distribution of Condensin-Based Chromatin Loops

by Daniel Kolbin, Benjamin L. Walker, Caitlin Hult, John Donoghue Stanton, David Adalsteinsson, M. Gregory Forest and Kerry Bloom

Genes 2023, 14(12), 2193; https://doi.org/10.3390/genes14122193 - 9 Dec 2023

Cited by 3 | Viewed by 2030

Abstract

Transient DNA loops occur throughout the genome due to thermal fluctuations of DNA and the function of SMC complex proteins such as condensin and cohesin. Transient crosslinking within and between chromosomes and loop extrusion by SMCs have profound effects on high-order chromatin organization [...] Read more.

Transient DNA loops occur throughout the genome due to thermal fluctuations of DNA and the function of SMC complex proteins such as condensin and cohesin. Transient crosslinking within and between chromosomes and loop extrusion by SMCs have profound effects on high-order chromatin organization and exhibit specificity in cell type, cell cycle stage, and cellular environment. SMC complexes anchor one end to DNA with the other extending some distance and retracting to form a loop. How cells regulate loop sizes and how loops distribute along chromatin are emerging questions. To understand loop size regulation, we employed bead–spring polymer chain models of chromatin and the activity of an SMC complex on chromatin. Our study shows that (1) the stiffness of the chromatin polymer chain, (2) the tensile stiffness of chromatin crosslinking complexes such as condensin, and (3) the strength of the internal or external tethering of chromatin chains cooperatively dictate the loop size distribution and compaction volume of induced chromatin domains. When strong DNA tethers are invoked, loop size distributions are tuned by condensin stiffness. When DNA tethers are released, loop size distributions are tuned by chromatin stiffness. In this three-way interaction, the presence and strength of tethering unexpectedly dictates chromatin conformation within a topological domain. Full article

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

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10 pages, 2037 KiB

Open AccessEditor’s ChoiceCase Report

Optical Genome Mapping Helps to Identify BCR::JAK2 Rearrangement Arising from Cryptic Complex Chromosomal Aberrations: A Case Report and Literature Review

by Neelam Vanjari, Guilin Tang, Gokce A. Toruner, Wei Wang, Beenu Thakral, Ming Zhao, Bhavana J. Dave, Joseph D. Khoury, L. Jeffrey Medeiros and Zhenya Tang

Genes 2023, 14(12), 2188; https://doi.org/10.3390/genes14122188 - 8 Dec 2023

Cited by 1 | Viewed by 2631

Abstract

We report a case of myeloproliferative neoplasm, not otherwise specified (MPN-NOS)-transformed AML with BCR::JAK2 rearrangement. Chromosomal analysis indicated a simple abnormal karyotype 46,XY,t(7;17)(q21;q24),t(9;22)(p24;q11.2). Fluorescence in situ hybridization (FISH) using a BCR/ABL1/ASS1 probe set suggested a possible BCR rearrangement and a reflex JAK2 breakapart [...] Read more.

We report a case of myeloproliferative neoplasm, not otherwise specified (MPN-NOS)-transformed AML with BCR::JAK2 rearrangement. Chromosomal analysis indicated a simple abnormal karyotype 46,XY,t(7;17)(q21;q24),t(9;22)(p24;q11.2). Fluorescence in situ hybridization (FISH) using a BCR/ABL1/ASS1 probe set suggested a possible BCR rearrangement and a reflex JAK2 breakapart probe indicated JAK2 rearrangement, most likely partnered with BCR. Optical genome mapping (OGM) analysis confirmed BCR::JAK2 derived through an inv(9)(p24p13) after a t(9;22)(p13;q11.2) in this case. Due to the complexity of chromosomal aberrations, disruption and/or rearrangement of other genes such as KIF24::BCR, JAK2::KIF24/UBAP1, and CDK6:SOX9 were also identified by OGM. Although the functionality and clinical importance of these novel rearrangements were unknown, disruption of these genes might be associated with a poorer response to chemotherapy and disease progression. We also reviewed all cases with BCR::JAK2 rearrangement reported in the literature. In conclusion, a suspected t(9;22)/BCR::JAK2 rearrangement warrants further characterization with genomic assays such as OGM, whole chromosome sequencing, and RNA sequencing to explore other gene disruptions and/or rearrangements. Full article

(This article belongs to the Section Cytogenomics)

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14 pages, 3866 KiB

Open AccessEditor’s ChoiceArticle

Transcriptome Profiling after Early Spinal Cord Injury in the Axolotl and Its Comparison with Rodent Animal Models through RNA-Seq Data Analysis

by Juan Carlos González-Orozco, Itzel Escobedo-Avila and Iván Velasco

Genes 2023, 14(12), 2189; https://doi.org/10.3390/genes14122189 - 8 Dec 2023

Cited by 1 | Viewed by 2483

Abstract

Background: Traumatic spinal cord injury (SCI) is a disabling condition that affects millions of people around the world. Currently, no clinical treatment can restore spinal cord function. Comparison of molecular responses in regenerating to non-regenerating vertebrates can shed light on neural restoration. The [...] Read more.

Background: Traumatic spinal cord injury (SCI) is a disabling condition that affects millions of people around the world. Currently, no clinical treatment can restore spinal cord function. Comparison of molecular responses in regenerating to non-regenerating vertebrates can shed light on neural restoration. The axolotl (Ambystoma mexicanum) is an amphibian that regenerates regions of the brain or spinal cord after damage. Methods: In this study, we compared the transcriptomes after SCI at acute (1–2 days after SCI) and sub-acute (6–7 days post-SCI) periods through the analysis of RNA-seq public datasets from axolotl and non-regenerating rodents. Results: Genes related to wound healing and immune responses were upregulated in axolotls, rats, and mice after SCI; however, the immune-related processes were more prevalent in rodents. In the acute phase of SCI in the axolotl, the molecular pathways and genes associated with early development were upregulated, while processes related to neuronal function were downregulated. Importantly, the downregulation of processes related to sensorial and motor functions was observed only in rodents. This analysis also revealed that genes related to pluripotency, cytoskeleton rearrangement, and transposable elements (e.g., Sox2, Krt5, and LOC100130764) were among the most upregulated in the axolotl. Finally, gene regulatory networks in axolotls revealed the early activation of genes related to neurogenesis, including Atf3/4 and Foxa2. Conclusions: Immune-related processes are upregulated shortly after SCI in axolotls and rodents; however, a strong immune response is more noticeable in rodents. Genes related to early development and neurogenesis are upregulated beginning in the acute stage of SCI in axolotls, while the loss of motor and sensory functions is detected only in rodents during the sub-acute period of SCI. The approach employed in this study might be useful for designing and establishing regenerative therapies after SCI in mammals, including humans. Full article

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

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17 pages, 5286 KiB

Open AccessEditor’s ChoiceArticle

Cloning, Identification, and Functional Analysis of the Foxl2 Gene in Procambarus clarkii

by Jin Huang, Weilin Zhu, Min Peng, Chunling Yang, Xiaohan Chen, Tiejun Wu, Digang Zeng, Yongzhen Zhao and Xiuli Chen

Genes 2023, 14(12), 2190; https://doi.org/10.3390/genes14122190 - 8 Dec 2023

Cited by 2 | Viewed by 1734

Abstract

Procambarus clarkii is the most widely distributed freshwater shrimp in China, with important economic value and great potential for development. The forkheadboxL2 (Foxl2) gene has been found to be involved in the reproductive development of many crustaceans. To understand the role [...] Read more.

Procambarus clarkii is the most widely distributed freshwater shrimp in China, with important economic value and great potential for development. The forkheadboxL2 (Foxl2) gene has been found to be involved in the reproductive development of many crustaceans. To understand the role of the Foxl2 gene in the gonad development of P. clarkii, we designed CDS-specific primers for the P. clarkii Foxl2 (PcFoxl2) gene and cloned its CDS sequence using RT-PCR. The nucleotide and protein sequence information was then analyzed through bioinformatics analysis. The expression and subcellular localization of PcFoxl2 in various tissues were detected using qRT-PCR and in situ hybridization. The effects of PcFoxl2 knockdown on gonad development were investigated using RNA interference. The results showed that the CDS length of the PcFoxl2 gene was 1614 bp and encoded 537 amino acids. Protein sequence comparison and phylogenetic analysis showed that PcFoxl2 was the closest relative to Crayfish. qRT-PCR analysis indicated that the expression level of PcFoxl2 in the testis was significantly higher (>40 fold) than that in the ovary (p < 0.01). The in situ hybridization results showed that PcFoxl2 was expressed in both the cytoplasm and the nucleus of egg cells, and that the expression was strongest in egg cells at the early stage of yolk synthesis, while weak in the secondary oocytes. The positive signal was strongest in the spermatocyte nucleolus, while only a trace signal was observed in the cytoplasm. After interfering with the PcFoxl2 gene using dsRNA, the expression of PcFoxl2 in the RNA interference group was significantly lower than that in the control group, and this interference effect lasted for one week. Moreover, the gonad index of the experimental group was significantly lower than that of the control group (p < 0.05) after 10 days of P. clarkii cultivation following PcFoxl2 knockdown. The expression levels of the nanos and S3a genes, which are related to gonad development, decreased significantly after PcFoxl2 gene interference. The results suggest that the Foxl2 gene is involved in the growth and development of gonads, particularly in the development of testis, and is related to the early development of oocytes. This study provides a theoretical basis for the artificial breeding of P. clarkii. Full article

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

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16 pages, 896 KiB

Open AccessEditor’s ChoiceArticle

Whole Genome Analysis of SNV and Indel Polymorphism in Common Marmosets (Callithrix jacchus)

by R. Alan Harris, Muthuswamy Raveendran, Wes Warren, Hillier W. LaDeana, Chad Tomlinson, Tina Graves-Lindsay, Richard E. Green, Jenna K. Schmidt, Julia C. Colwell, Allison T. Makulec, Shelley A. Cole, Ian H. Cheeseman, Corinna N. Ross, Saverio Capuano III, Evan E. Eichler, Jon E. Levine and Jeffrey Rogers

Genes 2023, 14(12), 2185; https://doi.org/10.3390/genes14122185 - 7 Dec 2023

Cited by 1 | Viewed by 3110

Abstract

The common marmoset (Callithrix jacchus) is one of the most widely used nonhuman primate models of human disease. Owing to limitations in sequencing technology, early genome assemblies of this species using short-read sequencing suffered from gaps. In addition, the genetic diversity [...] Read more.

The common marmoset (Callithrix jacchus) is one of the most widely used nonhuman primate models of human disease. Owing to limitations in sequencing technology, early genome assemblies of this species using short-read sequencing suffered from gaps. In addition, the genetic diversity of the species has not yet been adequately explored. Using long-read genome sequencing and expert annotation, we generated a high-quality genome resource creating a 2.898 Gb marmoset genome in which most of the euchromatin portion is assembled contiguously (contig N50 = 25.23 Mbp, scaffold N50 = 98.2 Mbp). We then performed whole genome sequencing on 84 marmosets sampling the genetic diversity from several marmoset research centers. We identified a total of 19.1 million single nucleotide variants (SNVs), of which 11.9 million can be reliably mapped to orthologous locations in the human genome. We also observed 2.8 million small insertion/deletion variants. This dataset includes an average of 5.4 million SNVs per marmoset individual and a total of 74,088 missense variants in protein-coding genes. Of the 4956 variants orthologous to human ClinVar SNVs (present in the same annotated gene and with the same functional consequence in marmoset and human), 27 have a clinical significance of pathogenic and/or likely pathogenic. This important marmoset genomic resource will help guide genetic analyses of natural variation, the discovery of spontaneous functional variation relevant to human disease models, and the development of genetically engineered marmoset disease models. Full article

(This article belongs to the Special Issue Primate Phylogeny and Genetics)

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12 pages, 2072 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Association Study of Arsenic Accumulation in Polished Rice

by Zheng Dong, Liang Guo, Xiaoxiang Li, Yongchao Li, Wenqiang Liu, Zuwu Chen, Licheng Liu, Zhixi Liu, Yujing Guo and Xiaowu Pan

Genes 2023, 14(12), 2186; https://doi.org/10.3390/genes14122186 - 7 Dec 2023

Cited by 4 | Viewed by 1820

Abstract

The accumulation of arsenic (As) in rice poses a significant threat to food safety and human health. Breeding rice varieties with low As accumulation is an effective strategy for mitigating the health risks associated with arsenic-contaminated rice. However, the genetic mechanisms underlying As [...] Read more.

The accumulation of arsenic (As) in rice poses a significant threat to food safety and human health. Breeding rice varieties with low As accumulation is an effective strategy for mitigating the health risks associated with arsenic-contaminated rice. However, the genetic mechanisms underlying As accumulation in rice grains remain incompletely understood. We evaluated the As accumulation capacity of 313 diverse rice accessions grown in As-contaminated soils with varying As concentrations. Six rice lines with low As accumulation were identified. Additionally, a genome-wide association studies (GWAS) analysis identified 5 QTLs significantly associated with As accumulation, with qAs4 being detected in both of the experimental years. Expression analysis demonstrated that the expression of LOC_Os04g50680, which encodes an MYB transcription factor, was up-regulated in the low-As-accumulation accessions compared to the high-As-accumulation accessions after As treatment. Therefore, LOC_Os04g50680 was selected as a candidate gene for qAs4. These findings provide insights for exploiting new functional genes associated with As accumulation and facilitating the development of low-As-accumulation rice varieties through marker-assisted breeding. Full article

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

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15 pages, 4439 KiB

Open AccessEditor’s ChoiceReview

Resisting the Resistance: Navigating BTK Mutations in Chronic Lymphocytic Leukemia (CLL)

by Alexandra Chirino, Skye Montoya, Anita Safronenka and Justin Taylor

Genes 2023, 14(12), 2182; https://doi.org/10.3390/genes14122182 - 6 Dec 2023

Cited by 17 | Viewed by 5517

Abstract

Bruton’s tyrosine kinase (BTK) plays a key role in the B-cell receptor (BCR) signaling pathway and confers anti-apoptotic and proliferative properties to malignant B-cells in chronic lymphocytic leukemia (CLL). Small molecule BTK inhibitors were designed to bind BTK’s active site and block downstream [...] Read more.

Bruton’s tyrosine kinase (BTK) plays a key role in the B-cell receptor (BCR) signaling pathway and confers anti-apoptotic and proliferative properties to malignant B-cells in chronic lymphocytic leukemia (CLL). Small molecule BTK inhibitors were designed to bind BTK’s active site and block downstream signaling. These drugs have now been used in the treatment of thousands of patients with CLL, the most common form of leukemia in the western hemisphere. However, adverse effects of early generations of BTK inhibitors and resistance to treatment have led to the development of newer, more selective and non-covalent BTK inhibitors. As the use of these newer generation BTK inhibitors has increased, novel BTK resistance mutations have come to light. This review aims to discuss previously known and novel BTK mutations, their mechanisms of resistance, and their relationship with patient treatment. Also discussed here are future studies that are needed to investigate the underlying cause allowing these mutations to occur and how they incite resistance. New treatments on the horizon that attempt to maneuver around these resistance mutations can be met with new resistance mutations, creating an unmet need for patients with CLL. Novel therapies and combinations that address all forms of resistance are discussed. Full article

(This article belongs to the Special Issue Research Progress in Hematological Malignancies: A Molecular Genetics Perspective)

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13 pages, 2943 KiB

Open AccessEditor’s ChoiceArticle

Optical Genome Mapping as a Tool to Unveil New Molecular Findings in Hematological Patients with Complex Chromosomal Rearrangements

by Nicoletta Coccaro, Antonella Zagaria, Luisa Anelli, Francesco Tarantini, Giuseppina Tota, Maria Rosa Conserva, Cosimo Cumbo, Elisa Parciante, Immacolata Redavid, Giuseppe Ingravallo, Crescenzio Francesco Minervini, Angela Minervini, Giorgina Specchia, Pellegrino Musto and Francesco Albano

Genes 2023, 14(12), 2180; https://doi.org/10.3390/genes14122180 - 5 Dec 2023

Cited by 2 | Viewed by 2103

Abstract

Standard cytogenetic techniques (chromosomal banding analysis—CBA, and fluorescence in situ hybridization—FISH) show limits in characterizing complex chromosomal rearrangements and structural variants arising from two or more chromosomal breaks. In this study, we applied optical genome mapping (OGM) to fully characterize two cases of [...] Read more.

Standard cytogenetic techniques (chromosomal banding analysis—CBA, and fluorescence in situ hybridization—FISH) show limits in characterizing complex chromosomal rearrangements and structural variants arising from two or more chromosomal breaks. In this study, we applied optical genome mapping (OGM) to fully characterize two cases of complex chromosomal rearrangements at high resolution. In case 1, an acute myeloid leukemia (AML) patient showing chromothripsis, OGM analysis was fully concordant with classic cytogenetic techniques and helped to better refine chromosomal breakpoints. The OGM results of case 2, a patient with non-Hodgkin lymphoma, were only partially in agreement with previous cytogenetic analyses and helped to better define clonal heterogeneity, overcoming the bias related to clonal selection due to cell culture of cytogenetic techniques. In both cases, OGM analysis led to the identification of molecular markers, helping to define the pathogenesis, classification, and prognosis of the analyzed patients. Despite extensive efforts to study hematologic diseases, standard cytogenetic methods display unsurmountable limits, while OGM is a tool that has the power to overcome these limitations and provide a cytogenetic analysis at higher resolution. As OGM also shows limits in defining regions of a repetitive nature, combining OGM with CBA to obtain a complete cytogenetic characterization would be desirable. Full article

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

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24 pages, 19496 KiB

Open AccessEditor’s ChoiceArticle

The Stilbene Synthase Family in Arachis: A Genome-Wide Study and Functional Characterization in Response to Stress

by Ana Cristina Miranda Brasileiro, Marcos Aparecido Gimenes, Bruna Medeiros Pereira, Ana Paula Zotta Mota, Matheus Nascimento Aguiar, Andressa Cunha Quintana Martins, Mario Alfredo Saraiva Passos and Patricia Messenberg Guimaraes

Genes 2023, 14(12), 2181; https://doi.org/10.3390/genes14122181 - 5 Dec 2023

Cited by 5 | Viewed by 1977

Abstract

Peanut (Arachis hypogaea) and its wild relatives are among the few species that naturally synthesize resveratrol, a well-known stilbenoid phytoalexin that plays a crucial role in plant defense against biotic and abiotic stresses. Resveratrol has received considerable attention due to its [...] Read more.

Peanut (Arachis hypogaea) and its wild relatives are among the few species that naturally synthesize resveratrol, a well-known stilbenoid phytoalexin that plays a crucial role in plant defense against biotic and abiotic stresses. Resveratrol has received considerable attention due to its health benefits, such as preventing and treating various human diseases and disorders. Chalcone (CHS) and Stilbene (STS) Synthases are plant-specific type III Polyketide Synthases (PKSs) that share the same substrates and are key branch enzymes in the biosynthesis of flavonoids and stilbenoids, respectively. Although resveratrol accumulation in response to external stimulus has been described in peanut, there are no comprehensive studies of the CHS and STS gene families in the genus Arachis. In the present study, we identified and characterized 6 CHS and 46 STS genes in the tetraploid peanut and an average of 4 CHS and 22 STS genes in three diploid wild species (Arachis duranensis, Arachis ipaënsis and Arachis stenosperma). The CHS and STS gene and protein structures, chromosomal distributions, phylogenetic relationships, conserved amino acid domains, and cis-acting elements in the promoter regions were described for all Arachis species studied. Based on gene expression patterns of wild A. stenosperma STS genes in response to different biotic and abiotic stresses, we selected the candidate AsSTS4 gene, which is strongly induced by ultraviolet (UV) light exposure, for further functional investigation. The AsSTS4 overexpression in peanut hairy roots significantly reduced (47%) root-knot nematode infection, confirming that stilbene synthesis activation in transgenic plants can increase resistance to pathogens. These findings contribute to understanding the role of resveratrol in stress responses in Arachis species and provide the basis for genetic engineering for improved production of valuable secondary metabolites in plants. Full article

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

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12 pages, 1257 KiB

Open AccessEditor’s ChoiceReview

A Contemporary Review of the Genomic Associations of Coronary Artery Myocardial Bridging

by Peyton Moore, Paul Murdock, Akash Ramanathan and Mohanakrishnan Sathyamoorthy

Genes 2023, 14(12), 2175; https://doi.org/10.3390/genes14122175 - 4 Dec 2023

Cited by 3 | Viewed by 3466

Abstract

Background: Myocardial bridging (MB) is a congenital coronary artery anomaly that has limited molecular disease state characterization. Though a large portion of individuals may be asymptomatic, the myocardial ischemia caused by this anomaly can lead to angina, acute coronary syndrome, coronary artery disease, [...] Read more.

Background: Myocardial bridging (MB) is a congenital coronary artery anomaly that has limited molecular disease state characterization. Though a large portion of individuals may be asymptomatic, the myocardial ischemia caused by this anomaly can lead to angina, acute coronary syndrome, coronary artery disease, and sudden cardiac death in patients. Objective: This study aims to summarize and consolidate the current literature regarding the genomic associations of myocardial bridge development and, in doing so, prompt further investigation into the molecular basis of myocardial bridge development. Methods: We performed a systematic literature review of myocardial bridging using the key search terms “Myocardial Bridging” AND (“Gene” OR “Allelic Variants” OR “Genomic”) in the databases of PubMed, CINAHL, EMBASE, and Cochran. We then performed a detailed review of the resulting abstracts and a full-text screening, summarizing these findings in this report. Results: In total, we identified eight articles discussing the associated genomics behind MB development. Studies included review articles, case reports and genomic studies that led to the discussion of several genes: DES (E434K), FBN1 (I1175M), and COMMD10; MACROD2, SLMAP, MYH7 (A1157G), and DPP6 (A714T); MYH7 (A862V); SCN2B (E31D); and NOTCH1 (R2313Q), and to the discussion of miRNAs (miR-29b, miR-151-3p, miR-126, miR-503-3p, and miR-645). Conclusions: Our study is the first to summarize the genes and molecular regulators related to myocardial bridges as they exist in the current literature. This work concludes that definitive evidence is lacking, warranting much broader genetic and genomic studies. Full article

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

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19 pages, 4080 KiB

Open AccessEditor’s ChoiceArticle

Comparative Transcriptome Analysis of Galeruca daurica Reveals Cold Tolerance Mechanisms

by Hongling Zhang, Feilong Sun, Wenbing Zhang, Xia Gao, Lei Du, Xiaopeng Yun, Yanyan Li, Ling Li, Baoping Pang and Yao Tan

Genes 2023, 14(12), 2177; https://doi.org/10.3390/genes14122177 - 4 Dec 2023

Cited by 4 | Viewed by 1759

Abstract

Galeruca daurica (Joannis) is a pest species with serious outbreaks in the Inner Mongolian grasslands in recent years, and its larvae and eggs are extremely cold-tolerant. To gain a deeper understanding of the molecular mechanism of its cold-tolerant stress response, we performed de [...] Read more.

Galeruca daurica (Joannis) is a pest species with serious outbreaks in the Inner Mongolian grasslands in recent years, and its larvae and eggs are extremely cold-tolerant. To gain a deeper understanding of the molecular mechanism of its cold-tolerant stress response, we performed de novo transcriptome assembly of G. daurica via RNA-Seq and compared the differentially expressed genes (DEGs) of first- and second-instar larvae grown and developed indoors and outdoors, respectively. The results show that cold tolerance in G. daurica is associated with changes in gene expression mainly involved in the glycolysis/gluconeogenesis pathway, the fatty acid biosynthesis pathway and the production of heat shock proteins (HSPs). Compared with the control group (indoor), the genes associated with gluconeogenesis, fatty acid biosynthesis and HSP production were up-regulated in the larvae grown and developed outdoors. While the changes in these genes were related to the physiological metabolism and growth of insects, it was hypothesized that the proteins encoded by these genes play an important role in cold tolerance in insects. In addition, we also investigated the expression of genes related to the metabolic pathway of HSPs, and the results show that the HSP-related genes were significantly up-regulated in the larvae of G. daurica grown and developed outdoors compared with the indoor control group. Finally, we chose to induce significant expression differences in the Hsp70 gene (Hsp70A1, Hsp70-2 and Hsp70-3) via RNAi to further illustrate the role of heat stress proteins in cold tolerance on G. daurica larvae. The results show that separate and mixed injections of dsHSP70A1, dsHsp70-2 and dsHsp70-3 significantly reduced expression levels of the target genes in G. daurica larvae. The super-cooling point (SCP) and the body fluid freezing point (FP) of the test larvae were determined after RNAi using the thermocouple method, and it was found that silencing the Hsp70 genes significantly increased the SCP and FP of G. daurica larvae, which validated the role of heat shock proteins in the cold resistance of G. daurica larvae. Our findings provide an important theoretical basis for further excavating the key genes and proteins in response to extremely cold environments and analyzing the molecular mechanism of cold adaptation in insects in harsh environments. Full article

(This article belongs to the Special Issue Molecular Mechanism of Insect Response to Abiotic and Biotic Stress)

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15 pages, 1069 KiB

Open AccessEditor’s ChoiceReview

Transformative Approaches for Sustainable Weed Management: The Power of Gene Drive and CRISPR-Cas9

by Yaiphabi Kumam, Harold N Trick, P.V. Vara Prasad and Mithila Jugulam

Genes 2023, 14(12), 2176; https://doi.org/10.3390/genes14122176 - 4 Dec 2023

Cited by 3 | Viewed by 3296

Abstract

Weeds can negatively impact crop yields and the ecosystem’s health. While many weed management strategies have been developed and deployed, there is a greater need for the development of sustainable methods for employing integrated weed management. Gene drive systems can be used as [...] Read more.

Weeds can negatively impact crop yields and the ecosystem’s health. While many weed management strategies have been developed and deployed, there is a greater need for the development of sustainable methods for employing integrated weed management. Gene drive systems can be used as one of the approaches to suppress the aggressive growth and reproductive behavior of weeds, although their efficacy is yet to be tested. Their popularity in insect pest management has increased, however, with the advent of CRISPR-Cas9 technology, which provides specificity and precision in editing the target gene. This review focuses on the different types of gene drive systems, including the use of CRISPR-Cas9-based systems and their success stories in pest management, while also exploring their possible applications in weed species. Factors that govern the success of a gene drive system in weeds, including the mode of reproduction, the availability of weed genome databases, and well-established transformation protocols are also discussed. Importantly, the risks associated with the release of weed populations with gene drive-bearing alleles into wild populations are also examined, along with the importance of addressing ecological consequences and ethical concerns. Full article

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

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13 pages, 1494 KiB

Open AccessEditor’s ChoiceArticle

Exploring the Effect of High-Energy Heavy Ion Beam on Rice Genome: Transposon Activation

by Xiaoting Wen, Jingpeng Li, Fu Yang, Xin Zhang and Yiwei Li

Genes 2023, 14(12), 2178; https://doi.org/10.3390/genes14122178 - 4 Dec 2023

Cited by 2 | Viewed by 1585

Abstract

High-energy heavy ion beams are a new type of physical mutagen that can produce a wide range of phenotypic variations. In order to understand the mechanism of high-energy heavy ion beams, we resequenced the whole genome of individual plants with obvious phenotypic variations [...] Read more.

High-energy heavy ion beams are a new type of physical mutagen that can produce a wide range of phenotypic variations. In order to understand the mechanism of high-energy heavy ion beams, we resequenced the whole genome of individual plants with obvious phenotypic variations in rice. The sequence alignment results revealed a large number of SNPs and InDels, as well as genetic variations related to grain type and heading date. The distribution of SNP and InDel on chromosomes is random, but they often occur in the up/downstream regions and the intergenic region. Mutagenesis can cause changes in transposons such as Dasheng, mPing, Osr13 and RIRE2, affecting the stability of the genome. This study obtained the major gene mutation types, discovered differentially active transposons, screened out gene variants related to phenotype, and explored the mechanism of high-energy heavy ion beam radiation on rice genes. Full article

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

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13 pages, 5061 KiB

Open AccessEditor’s ChoiceArticle

Research on the Pathogenesis of Cognitive and Neurofunctional Impairments in Patients with Noonan Syndrome: The Role of Rat Sarcoma–Mitogen Activated Protein Kinase Signaling Pathway Gene Disturbances

by Natalia Braun-Walicka, Agnieszka Pluta, Tomasz Wolak, Edyta Maj, Agnieszka Maryniak, Monika Gos, Anna Abramowicz, Aleksandra Landowska, Ewa Obersztyn and Jerzy Bal

Genes 2023, 14(12), 2173; https://doi.org/10.3390/genes14122173 - 3 Dec 2023

Cited by 3 | Viewed by 2015

Abstract

Noonan syndrome (NS) is one of the most common genetic conditions inherited mostly in an autosomal dominant manner with vast heterogeneity in clinical and genetic features. Patients with NS might have speech disturbances, memory and attention deficits, limitations in daily functioning, and decreased [...] Read more.

Noonan syndrome (NS) is one of the most common genetic conditions inherited mostly in an autosomal dominant manner with vast heterogeneity in clinical and genetic features. Patients with NS might have speech disturbances, memory and attention deficits, limitations in daily functioning, and decreased overall intelligence. Here, 34 patients with Noonan syndrome and 23 healthy controls were enrolled in a study involving gray and white matter volume evaluation using voxel-based morphometry (VBM), white matter connectivity measurements using diffusion tensor imaging (DTI), and resting-state functional magnetic resonance imaging (rs-fMRI). Fractional anisotropy (FA) and mean diffusivity (MD) probability distributions were calculated. Cognitive abilities were assessed using the Stanford Binet Intelligence Scales. Reductions in white matter connectivity were detected using DTI in NS patients. The rs-fMRI revealed hyper-connectivity in NS patients between the sensorimotor network and language network and between the sensorimotor network and salience network in comparison to healthy controls. NS patients exhibited decreased verbal and nonverbal IQ compared to healthy controls. The assessment of the microstructural alterations of white matter as well as the resting-state functional connectivity (rsFC) analysis in patients with NS may shed light on the mechanisms responsible for cognitive and neurofunctional impairments. Full article

(This article belongs to the Special Issue Genetics and Genomics of Heritable Pediatric Disorders)

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16 pages, 705 KiB

Open AccessEditor’s ChoicePerspective

The Application of Genetic Risk Scores in Rheumatic Diseases: A Perspective

by Lotta M. Vaskimo, Georgy Gomon, Najib Naamane, Heather J. Cordell, Arthur Pratt and Rachel Knevel

Genes 2023, 14(12), 2167; https://doi.org/10.3390/genes14122167 - 1 Dec 2023

Cited by 2 | Viewed by 1977

Abstract

Modest effect sizes have limited the clinical applicability of genetic associations with rheumatic diseases. Genetic risk scores (GRSs) have emerged as a promising solution to translate genetics into useful tools. In this review, we provide an overview of the recent literature on GRSs [...] Read more.

Modest effect sizes have limited the clinical applicability of genetic associations with rheumatic diseases. Genetic risk scores (GRSs) have emerged as a promising solution to translate genetics into useful tools. In this review, we provide an overview of the recent literature on GRSs in rheumatic diseases. We describe six categories for which GRSs are used: (a) disease (outcome) prediction, (b) genetic commonalities between diseases, (c) disease differentiation, (d) interplay between genetics and environmental factors, (e) heritability and transferability, and (f) detecting causal relationships between traits. In our review of the literature, we identified current lacunas and opportunities for future work. First, the shortage of non-European genetic data restricts the application of many GRSs to European populations. Next, many GRSs are tested in settings enriched for cases that limit the transferability to real life. If intended for clinical application, GRSs are ideally tested in the relevant setting. Finally, there is much to elucidate regarding the co-occurrence of clinical traits to identify shared causal paths and elucidate relationships between the diseases. GRSs are useful instruments for this. Overall, the ever-continuing research on GRSs gives a hopeful outlook into the future of GRSs and indicates significant progress in their potential applications. Full article

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

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23 pages, 43209 KiB

Open AccessEditor’s ChoiceArticle

Assessing the Influence of HGT on the Evolution of Stress Responses in Microbial Communities from Shark Bay, Western Australia

by Emilie J. Skoog, Gregory P. Fournier and Tanja Bosak

Genes 2023, 14(12), 2168; https://doi.org/10.3390/genes14122168 - 1 Dec 2023

Cited by 1 | Viewed by 2193

Abstract

Pustular microbial mats in Shark Bay, Western Australia, are modern analogs of microbial systems that colonized peritidal environments before the evolution of complex life. To understand how these microbial communities evolved to grow and metabolize in the presence of various environmental stresses, the [...] Read more.

Pustular microbial mats in Shark Bay, Western Australia, are modern analogs of microbial systems that colonized peritidal environments before the evolution of complex life. To understand how these microbial communities evolved to grow and metabolize in the presence of various environmental stresses, the horizontal gene transfer (HGT) detection tool, MetaCHIP, was used to identify the horizontal transfer of genes related to stress response in 83 metagenome-assembled genomes from a Shark Bay pustular mat. Subsequently, maximum-likelihood phylogenies were constructed using these genes and their most closely related homologs from other environments in order to determine the likelihood of these HGT events occurring within the pustular mat. Phylogenies of several stress-related genes—including those involved in response to osmotic stress, oxidative stress and arsenic toxicity—indicate a potentially long history of HGT events and are consistent with these transfers occurring outside of modern pustular mats. The phylogeny of a particular osmoprotectant transport gene reveals relatively recent adaptations and suggests interactions between Planctomycetota and Myxococcota within these pustular mats. Overall, HGT phylogenies support a potentially broad distribution in the relative timing of the HGT events of stress-related genes and demonstrate ongoing microbial adaptations and evolution in these pustular mat communities. Full article

(This article belongs to the Special Issue Phylogenomics and Molecular Evolution)

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25 pages, 2304 KiB

Open AccessEditor’s ChoiceReview

Navigating the Complex Landscape of Fibrodysplasia Ossificans Progressiva: From Current Paradigms to Therapeutic Frontiers

by Saeed Anwar and Toshifumi Yokota

Genes 2023, 14(12), 2162; https://doi.org/10.3390/genes14122162 - 30 Nov 2023

Cited by 7 | Viewed by 5498

Abstract

Fibrodysplasia ossificans progressiva (FOP) is an enigmatic, ultra-rare genetic disorder characterized by progressive heterotopic ossification, wherein soft connective tissues undergo pathological transformation into bone structures. This incapacitating process severely limits patient mobility and poses formidable challenges for therapeutic intervention. Predominantly caused by missense [...] Read more.

Fibrodysplasia ossificans progressiva (FOP) is an enigmatic, ultra-rare genetic disorder characterized by progressive heterotopic ossification, wherein soft connective tissues undergo pathological transformation into bone structures. This incapacitating process severely limits patient mobility and poses formidable challenges for therapeutic intervention. Predominantly caused by missense mutations in the ACVR1 gene, this disorder has hitherto defied comprehensive mechanistic understanding and effective treatment paradigms. This write-up offers a comprehensive overview of the contemporary understanding of FOP’s complex pathobiology, underscored by advances in molecular genetics and proteomic studies. We delve into targeted therapy, spanning genetic therapeutics, enzymatic and transcriptional modulation, stem cell therapies, and innovative immunotherapies. We also highlight the intricate complexities surrounding clinical trial design for ultra-rare disorders like FOP, addressing fundamental statistical limitations, ethical conundrums, and methodological advancements essential for the success of interventional studies. We advocate for the adoption of a multi-disciplinary approach that converges bench-to-bedside research, clinical expertise, and ethical considerations to tackle the challenges of ultra-rare diseases like FOP and comparable ultra-rare diseases. In essence, this manuscript serves a dual purpose: as a definitive scientific resource for ongoing and future FOP research and a call to action for innovative solutions to address methodological and ethical challenges that impede progress in the broader field of medical research into ultra-rare conditions. Full article

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

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14 pages, 7145 KiB

Open AccessEditor’s ChoiceArticle

RNA-Sequencing Analysis Reveals the Role of Mitochondrial Energy Metabolism Alterations and Immune Cell Activation in Form-Deprivation and Lens-Induced Myopia in Mice

by Hojung Kim, Wonmin Lee, Ye-Ah Kim, Sanghyeon Yu, Jisu Jeong, Yueun Choi, Yoonsung Lee, Yong Hwan Park, Min Seok Kang, Man S. Kim and Tae Gi Kim

Genes 2023, 14(12), 2163; https://doi.org/10.3390/genes14122163 - 30 Nov 2023

Cited by 1 | Viewed by 2437

Abstract

Myopia is a substantial global public health concern primarily linked to the elongation of the axial length of the eyeball. While numerous animal models have been employed to investigate myopia, the specific contributions of genetic factors and the intricate signaling pathways involved remain [...] Read more.

Myopia is a substantial global public health concern primarily linked to the elongation of the axial length of the eyeball. While numerous animal models have been employed to investigate myopia, the specific contributions of genetic factors and the intricate signaling pathways involved remain incompletely understood. In this study, we conducted RNA-seq analysis to explore genes and pathways in two distinct myopia-inducing mouse models: form-deprivation myopia (FDM) and lens-induced myopia (LIM). Comparative analysis with a control group revealed significant differential expression of 2362 genes in FDM and 503 genes in LIM. Gene Set Enrichment Analysis (GSEA) identified a common immune-associated pathway between LIM and FDM, with LIM exhibiting more extensive interactions. Notably, downregulation was observed in OxPhos complex III of FDM and complex IV of LIM. Subunit A of complex I was downregulated in LIM but upregulated in FDM. Additionally, complex V was upregulated in LIM but downregulated in FDM. These findings suggest a connection between alterations in energy metabolism and immune cell activation, shedding light on a novel avenue for understanding myopia’s pathophysiology. Our research underscores the necessity for a comprehensive approach to comprehending myopia development, which integrates insights from energy metabolism, oxidative stress, and immune response pathways. Full article

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

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13 pages, 19204 KiB

Open AccessEditor’s ChoiceArticle

The Genetic Diversity of White-Backed Planthoppers (Sogatella furcifera) between Myanmar and Yunnan Province of China

by Yue Liu, Khin Nyein Chan, Xiangyong Li, Xueqing Zhao, Dong Chu, Yanqiong Yin, Ying Liu and Aidong Chen

Genes 2023, 14(12), 2164; https://doi.org/10.3390/genes14122164 - 30 Nov 2023

Cited by 1 | Viewed by 1734

Abstract

In order to clarify the migration route and the source of white-backed planthopper (WBPH) (Sogatella furcifera) between Myanmar and Yunnan Province, China, we collected six populations throughout Myanmar and five populations around the border areas in Yunnan Province, China. A total [...] Read more.

In order to clarify the migration route and the source of white-backed planthopper (WBPH) (Sogatella furcifera) between Myanmar and Yunnan Province, China, we collected six populations throughout Myanmar and five populations around the border areas in Yunnan Province, China. A total of 790 base pairs in the mtDNA COI genes from 416 individuals were obtained. A total of 43 haplotypes were identified, among which 37 were unique haplotypes, and the remaining 6 were shared among different populations. Two common shared haplotypes (H_1 and H_2) had a widespread distribution in all populations and accounted for 88.8% of the total haplotype frequency, suggesting a high-level gene flow among the Myanmar and Yunnan populations. Bayesian skyline plot (BSP) analysis results indicated that the effective population size of WBPH expanded between about 10,000 and 7000 years ago, and S. furcifera might follow the post-LGM (Last Glacial Maximum) expansion pattern. Based on the total migrant (N_em) value, it can be deduced that north and northeast Myanmar were the primary migration sources for WBPH populations in the southwest and south Yunnan regions. This study aims to contribute to the sustainable regional management of this important rice pest and provide new insights into the genetic diversity of WBPH in Southeast Asia. Full article

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

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17 pages, 12764 KiB

Open AccessEditor’s ChoiceArticle

Comparative Transcriptomic Assessment of Chemosensory Genes in Adult and Larval Olfactory Organs of Cnaphalocrocis medinalis

by Hai-Tao Du, Jia-Qi Lu, Kun Ji, Chu-Chu Wang, Zhi-Chao Yao, Fang Liu and Yao Li

Genes 2023, 14(12), 2165; https://doi.org/10.3390/genes14122165 - 30 Nov 2023

Cited by 1 | Viewed by 1575

Abstract

The rice leaf folder, Cnaphalocrocis medinalis (Lepidoptera: Pyralidae), is a notorious pest of rice in Asia. The larvae and adults of C. medinalis utilize specialized chemosensory systems to adapt to different environmental odors and physiological behaviors. However, the differences in chemosensory genes between [...] Read more.

The rice leaf folder, Cnaphalocrocis medinalis (Lepidoptera: Pyralidae), is a notorious pest of rice in Asia. The larvae and adults of C. medinalis utilize specialized chemosensory systems to adapt to different environmental odors and physiological behaviors. However, the differences in chemosensory genes between the olfactory organs of these two different developmental stages remain unclear. Here, we conducted a transcriptome analysis of larvae heads, male antennae, and female antennae in C. medinalis and identified 131 putative chemosensory genes, including 32 OBPs (8 novel OBPs), 23 CSPs (2 novel CSPs), 55 ORs (17 novel ORs), 19 IRs (5 novel IRs) and 2 SNMPs. Comparisons between larvae and adults of C. medinalis by transcriptome and RT-qPCR analysis revealed that the number and expression of chemosensory genes in larval heads were less than that of adult antennae. Only 17 chemosensory genes (7 OBPs and 10 CSPs) were specifically or preferentially expressed in the larval heads, while a total of 101 chemosensory genes (21 OBPs, 9 CSPs, 51 ORs, 18 IRs, and 2 SNMPs) were specifically or preferentially expressed in adult antennae. Our study found differences in chemosensory gene expression between larvae and adults, suggesting their specialized functions at different developmental stages of C. medinalis. These results provide a theoretical basis for screening chemosensory genes as potential molecular targets and developing novel management strategies to control C. medinalis. Full article

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

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13 pages, 4235 KiB

Open AccessEditor’s ChoiceArticle

A Proposal of the Ur-RNAome

by Miryam Palacios-Pérez and Marco V. José

Genes 2023, 14(12), 2158; https://doi.org/10.3390/genes14122158 - 29 Nov 2023

Cited by 2 | Viewed by 1794

Abstract

It is widely accepted that the earliest RNA molecules were folded into hairpins or mini-helixes. Herein, we depict the 2D and 3D conformations of those earliest RNA molecules with only RNY triplets, which Eigen proposed as the primeval genetic code. We selected 26 [...] Read more.

It is widely accepted that the earliest RNA molecules were folded into hairpins or mini-helixes. Herein, we depict the 2D and 3D conformations of those earliest RNA molecules with only RNY triplets, which Eigen proposed as the primeval genetic code. We selected 26 species (13 bacteria and 13 archaea). We found that the free energy of RNY hairpins was consistently lower than that of their corresponding shuffled controls. We found traces of the three ribosomal RNAs (16S, 23S, and 5S), tRNAs, 6S RNA, and the RNA moieties of RNase P and the signal recognition particle. Nevertheless, at this stage of evolution there was no genetic code (as seen in the absence of the peptidyl transferase centre and any vestiges of the anti-Shine–Dalgarno sequence). Interestingly, we detected the anticodons of both glycine (GCC) and threonine (GGU) in the hairpins of proto-tRNA. Full article

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

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13 pages, 1810 KiB

Open AccessEditor’s ChoiceArticle

Alu Methylation Patterns in Type 1 Diabetes: A Case-Control Study

by Andromachi Katsanou, Charilaos A. Kostoulas, Evangelos Liberopoulos, Agathocles Tsatsoulis, Ioannis Georgiou and Stelios Tigas

Genes 2023, 14(12), 2149; https://doi.org/10.3390/genes14122149 - 28 Nov 2023

Cited by 1 | Viewed by 1762

Abstract

Evidence suggests that genome-wide hypomethylation may promote genomic instability and cellular senescence, leading to chronic complications in people with diabetes mellitus. Limited data are however available on the Alu methylation status in patients with type 1 diabetes (T1D). Methods: We investigated DNA [...] Read more.

Evidence suggests that genome-wide hypomethylation may promote genomic instability and cellular senescence, leading to chronic complications in people with diabetes mellitus. Limited data are however available on the Alu methylation status in patients with type 1 diabetes (T1D). Methods: We investigated DNA methylation levels and patterns of Alu methylation in the peripheral blood of 36 patients with T1D and 29 healthy controls, matched for age and sex, by using the COmbined Bisulfite Restriction Analysis method (COBRA). Results: Total Alu methylation rate (mC) was similar between patients with T1D and controls (67.3% (64.4–70.9%) vs. 68.0% (62.0–71.1%), p = 0.874). However, patients with T1D had significantly higher levels of the partial Alu methylation pattern (mCuC + uCmC) (41.9% (35.8–45.8%) vs. 36.0% (31.7–40.55%), p = 0.004) compared to healthy controls. In addition, a positive correlation between levels of glycated hemoglobin (HbA1c) and the partially methylated loci (mCuC + uCmC) was observed (Spearman’s rho = 0.293, p = 0.018). Furthermore, significant differences were observed between patients with T1D diagnosed before and after the age of 15 years regarding the total methylation mC, the methylated pattern mCmC and the unmethylated pattern uCuC (p = 0.040, p = 0.044 and p = 0.040, respectively). Conclusions: In conclusion, total Alu methylation rates were similar, but the partial Alu methylation pattern (mCuC + uCmC) was significantly higher in patients with T1D compared to healthy controls. Furthermore, this pattern was associated positively with the levels of HbA1c and negatively with the age at diagnosis. Full article

(This article belongs to the Section Epigenomics)

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15 pages, 2982 KiB

Open AccessEditor’s ChoiceArticle

Genetic and Transcriptome Analyses of Callus Browning in Chaling Common Wild Rice (Oryza rufipogon Griff.)

by Lingyi Qiu, Jingjing Su, Yongcai Fu and Kun Zhang

Genes 2023, 14(12), 2138; https://doi.org/10.3390/genes14122138 - 27 Nov 2023

Cited by 4 | Viewed by 1888

Abstract

Callus browning during tissue culture of indica rice is genotype dependent, thus limiting the application of genetic transformation for editing-assisted breeding and elucidation of gene function. Here, using 124 introgression lines (HCLs) derived from a cross between the indica rice 9311 and Chaling [...] Read more.

Callus browning during tissue culture of indica rice is genotype dependent, thus limiting the application of genetic transformation for editing-assisted breeding and elucidation of gene function. Here, using 124 introgression lines (HCLs) derived from a cross between the indica rice 9311 and Chaling common wild rice and 2059 SNPs for single-point and interval analysis, we identified two major QTLs, qCBT7 on chromosome 7 and qCBT10 on chromosome 10, related to callus browning, explaining 8–13% of callus browning. Moreover, we performed RNA-seq of two introgression lines with low callus browning, HCL183 and HCL232, with Oryza. rufipogon introgression fragments on chromosomes 10 and 7, respectively. Three candidate genes (Os07g0620700, Os10g0361000, and Os10g0456800) with upregulation were identified by combining interval mapping and weighted gene coexpression network analysis using the DEGs. The qRT-PCR results of the three candidate genes were consistent with those of RNA-seq. The differentiation of indica and japonica subspecies Oryza. sativa and Oryza. rufipogon suggests that these candidate genes are possibly unique in Oryza. rufipogon. GO analyses of hub genes revealed that callus browning may be mainly associated with ethylene and hormone signaling pathways. The results lay a foundation for future cloning of qCBT7 or qCBT10 and will improve genetic transformation efficiency in rice. Full article

(This article belongs to the Special Issue 5Gs in Crop Genetic and Genomic Improvement)

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7 pages, 566 KiB

Open AccessEditor’s ChoiceBrief Report

Comparison of Hi-C-Based Scaffolding Tools on Plant Genomes

by Yuze Hou, Li Wang and Weihua Pan

Genes 2023, 14(12), 2147; https://doi.org/10.3390/genes14122147 - 27 Nov 2023

Cited by 2 | Viewed by 1979

Abstract

De novo genome assembly holds paramount significance in the field of genomics. Scaffolding, as a pivotal component within the genome assembly process, is instrumental in determining the orientation and arrangement of contigs, ultimately facilitating the generation of a chromosome-level assembly. Scaffolding is contingent [...] Read more.

De novo genome assembly holds paramount significance in the field of genomics. Scaffolding, as a pivotal component within the genome assembly process, is instrumental in determining the orientation and arrangement of contigs, ultimately facilitating the generation of a chromosome-level assembly. Scaffolding is contingent on supplementary linkage information, including paired-end reads, bionano, physical mapping, genetic mapping, and Hi-C (an abbreviation for High-throughput Chromosome Conformation Capture). In recent years, Hi-C has emerged as the predominant source of linkage information in scaffolding, attributed to its capacity to offer long-range signals, leading to the development of numerous Hi-C-based scaffolding tools. However, to the best of our knowledge, there has been a paucity of comprehensive studies assessing and comparing the efficacy of these tools. In order to address this gap, we meticulously selected six tools, namely LACHESIS, pin_hic, YaHS, SALSA2, 3d-DNA, and ALLHiC, and conducted a comparative analysis of their performance across haploid, diploid, and polyploid genomes. This endeavor has yielded valuable insights in advancing the field of genome scaffolding research. Full article

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

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22 pages, 4149 KiB

Open AccessEditor’s ChoiceArticle

Analysis of Nucleotide Variations in Human G-Quadruplex Forming Regions Associated with Disease States

by Aryan Neupane, Julia H. Chariker and Eric C. Rouchka

Genes 2023, 14(12), 2125; https://doi.org/10.3390/genes14122125 - 25 Nov 2023

Cited by 3 | Viewed by 1991

Abstract

While the role of G quadruplex (G4) structures has been identified in cancers and metabolic disorders, single nucleotide variations (SNVs) and their effect on G4s in disease contexts have not been extensively studied. The COSMIC and CLINVAR databases were used to detect SNVs [...] Read more.

While the role of G quadruplex (G4) structures has been identified in cancers and metabolic disorders, single nucleotide variations (SNVs) and their effect on G4s in disease contexts have not been extensively studied. The COSMIC and CLINVAR databases were used to detect SNVs present in G4s to identify sequence level changes and their effect on the alteration of the G4 secondary structure. A total of 37,515 G4 SNVs in the COSMIC database and 2378 in CLINVAR were identified. Of those, 7236 COSMIC (19.3%) and 457 (19%) of the CLINVAR variants result in G4 loss, while 2728 (COSMIC) and 129 (CLINVAR) SNVs gain a G4 structure. The remaining variants potentially affect the folding energy without affecting the presence of a G4. Analysis of mutational patterns in the G4 structure shows a higher selective pressure (3-fold) in the coding region on the template strand compared to the reverse strand. At the same time, an equal proportion of SNVs were observed among intronic, promoter, and enhancer regions across strands. Full article

(This article belongs to the Section Bioinformatics)

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14 pages, 2282 KiB

Open AccessEditor’s ChoiceArticle

Unraveling the Genetic Basis of Feed Efficiency in Cattle through Integrated DNA Methylation and CattleGTEx Analysis

by Zhenbin Hu, Clarissa Boschiero, Cong-Jun Li, Erin E. Connor, Ransom L. Baldwin VI and George E. Liu

Genes 2023, 14(12), 2121; https://doi.org/10.3390/genes14122121 - 24 Nov 2023

Cited by 5 | Viewed by 2517

Abstract

Feed costs can amount to 75 percent of the total overhead cost of raising cows for milk production. Meanwhile, the livestock industry is considered a significant contributor to global climate change due to the production of greenhouse gas emissions, such as methane. Indeed, [...] Read more.

Feed costs can amount to 75 percent of the total overhead cost of raising cows for milk production. Meanwhile, the livestock industry is considered a significant contributor to global climate change due to the production of greenhouse gas emissions, such as methane. Indeed, the genetic basis of feed efficiency (FE) is of great interest to the animal research community. Here, we explore the epigenetic basis of FE to provide base knowledge for the development of genomic tools to improve FE in cattle. The methylation level of 37,554 CpG sites was quantified using a mammalian methylation array (HorvathMammalMethylChip40) for 48 Holstein cows with extreme residual feed intake (RFI). We identified 421 CpG sites related to 287 genes that were associated with RFI, several of which were previously associated with feeding or digestion issues. Activator of transcription and developmental regulation (AUTS2) is associated with digestive disorders in humans, while glycerol-3-phosphate dehydrogenase 2 (GPD2) encodes a protein on the inner mitochondrial membrane, which can regulate glucose utilization and fatty acid and triglyceride synthesis. The extensive expression and co-expression of these genes across diverse tissues indicate the complex regulation of FE in cattle. Our study provides insight into the epigenetic basis of RFI and gene targets to improve FE in dairy cattle. Full article

(This article belongs to the Section Epigenomics)

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13 pages, 1623 KiB

Open AccessEditor’s ChoiceArticle

The New Mitochondrial Genome of Hemiculterella wui (Cypriniformes, Xenocyprididae): Sequence, Structure, and Phylogenetic Analyses

by Renyi Zhang, Tingting Zhu and Feng Yu

Genes 2023, 14(12), 2110; https://doi.org/10.3390/genes14122110 - 22 Nov 2023

Cited by 4 | Viewed by 1366

Abstract

Hemiculterella wui is an endemic small freshwater fish, distributed in the Pearl River system and Qiantang River, China. In this study, we identified and annotated the complete mitochondrial genome sequence of H. wui. The mitochondrial genome was 16,619 bp in length and [...] Read more.

Hemiculterella wui is an endemic small freshwater fish, distributed in the Pearl River system and Qiantang River, China. In this study, we identified and annotated the complete mitochondrial genome sequence of H. wui. The mitochondrial genome was 16,619 bp in length and contained 13 protein coding genes (PCGs), two rRNA genes, 22 tRNA genes, and one control region. The nucleotide composition of the mitochondrial genome was 29.9% A, 25.3% T, 27.4% C, and 17.5% G, respectively. Most PCGs used the ATG start codon, except COI and ATPase 8 started with the GTG start codon. Five PCGs used the TAA termination codon and ATPase 8 ended with the TAG stop codon, and the remaining seven genes used two incomplete stop codons (T and TA). Most of the tRNA genes showed classical cloverleaf secondary structures, except that tRNA^Ser(AGY) lacked the dihydrouracil loop. The average Ka/Ks value of the ATPase 8 gene was the highest, while the average Ka/Ks value of the COI gene was the lowest. Phylogenetic analyses showed that H. wui has a very close relationship with Pseudohemiculter dispar and H. sauvagei. This study will provide a valuable basis for further studies of taxonomy and phylogenetic analyses in H. wui and Xenocyprididae. Full article

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

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15 pages, 2219 KiB

Open AccessEditor’s ChoiceArticle

Inferring Causalities of Environmental and Genetic Factors for Differential Somatic Cell Count and Mastitis Pathogens in Dairy Cows Using Structural Equation Modelling

by Patricia Wagner, Kerstin Brügemann, Tong Yin, Petra Engel and Sven König

Genes 2023, 14(11), 2102; https://doi.org/10.3390/genes14112102 - 19 Nov 2023

Cited by 2 | Viewed by 1737

Abstract

The aim of this study was to establish and evaluate a structural equation model to infer causal relationships among environmental and genetic factors on udder health. For this purpose, 537 Holstein Friesian cows were genotyped, and milk samples were analyzed for novel traits [...] Read more.

The aim of this study was to establish and evaluate a structural equation model to infer causal relationships among environmental and genetic factors on udder health. For this purpose, 537 Holstein Friesian cows were genotyped, and milk samples were analyzed for novel traits including differential somatic cell counts and specific mastitis pathogens. In the structural model, four latent variables (intramammary infection (IMI), production, time and genetics) were defined, which were explained using manifest measurable variables. The measurable variables included udder pathogens and somatic differential cell counts, milk composition, as well as significant SNP markers from previous genome-wide associations for major and minor pathogens. The housing system effect (i.e., compost-bedded pack barns versus cubicle barns) indicated a small influence on IMI with a path coefficient of −0.05. However, housing system significantly affected production (0.37), with ongoing causal effects on IMI (0.17). Thus, indirect associations between housing and udder health could be inferred via structural equation modeling. Furthermore, genotype by environment interactions on IMI can be represented, i.e., the detection of specific latent variables such as significant SNP markers only for specific housing systems. For the latent variable genetics, especially one SNP is of primary interest. This SNP is located in the EVA1A gene, which plays a fundamental role in the MAPK1 signaling pathway. Other identified genes (e.g., CTNNA3 and CHL1) support results from previous studies, and this gene also contributes to mechanisms of the MAPK1 signaling pathway. Full article

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

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20 pages, 16197 KiB

Open AccessEditor’s ChoiceArticle

Transcriptomic Analysis Reveals CBF-Dependent and CBF-Independent Pathways under Low-Temperature Stress in Teak (Tectona grandis)

by Miaomiao Liu, Guang Yang, Wenlong Zhou, Xianbang Wang, Qiang Han, Jiange Wang and Guihua Huang

Genes 2023, 14(11), 2098; https://doi.org/10.3390/genes14112098 - 18 Nov 2023

Cited by 4 | Viewed by 1818

Abstract

Teak is a rare tropical tree with high economic value, and it is one of the world’s main afforestation trees. Low temperature is the main problem for introducing and planting this species in subtropical or temperate zones. Low-temperature acclimation can enhance the resistance [...] Read more.

Teak is a rare tropical tree with high economic value, and it is one of the world’s main afforestation trees. Low temperature is the main problem for introducing and planting this species in subtropical or temperate zones. Low-temperature acclimation can enhance the resistance of teak to low-temperature stress, but the mechanism for this is still unclear. We studied the gene expression of two-year-old teak seedlings under a rapid temperature drop from 20 °C to 4 °C using RNA-seq and WGCNA analyses. The leaves in the upper part of the plants developed chlorosis 3 h after the quick transition, and the grades of chlorosis were increased after 9 h, with the addition of water stains and necrotic spots. Meanwhile, the SOD and proline contents in teak leaves increased with the prolonged cold stress time. We also identified 36,901 differentially expressed genes, among which 1055 were novel. Notably, CBF2 and CBF4 were significantly induced by low temperatures, while CBF1 and CBF3 were not. Furthermore, WGCNA successfully identified a total of fourteen modules, which consist of three modules associated with cold stress response genes, two modules linked to CBF2 and CBF4, and one module correlated with the CBF-independent pathway gene HY5. The transformation experiments showed that TgCBF2 and TgCBF4 improved cold resistance in Arabidopsis plants. Full article

(This article belongs to the Special Issue Plant Genetic Diversity and Omics Research)

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21 pages, 5007 KiB

Open AccessEditor’s ChoiceArticle

Transcriptomic Landscape of Circulating Extracellular Vesicles in Heart Transplant Ischemia–Reperfusion

by SeoJeong Joo, Kishor Dhaygude, Sofie Westerberg, Rainer Krebs, Maija Puhka, Emil Holmström, Simo Syrjälä, Antti I. Nykänen and Karl Lemström

Genes 2023, 14(11), 2101; https://doi.org/10.3390/genes14112101 - 18 Nov 2023

Cited by 3 | Viewed by 2728

Abstract

Ischemia–reperfusion injury (IRI) is an inevitable event during heart transplantation, which is known to exacerbate damage to the allograft. However, the precise mechanisms underlying IRI remain incompletely understood. Here, we profiled the whole transcriptome of plasma extracellular vesicles (EVs) by RNA sequencing from [...] Read more.

Ischemia–reperfusion injury (IRI) is an inevitable event during heart transplantation, which is known to exacerbate damage to the allograft. However, the precise mechanisms underlying IRI remain incompletely understood. Here, we profiled the whole transcriptome of plasma extracellular vesicles (EVs) by RNA sequencing from 41 heart transplant recipients immediately before and at 12 h after transplant reperfusion. We found that the expression of 1317 protein-coding genes in plasma EVs was changed at 12 h after reperfusion. Upregulated genes of plasma EVs were related to metabolism and immune activation, while downregulated genes were related to cell survival and extracellular matrix organization. In addition, we performed correlation analyses between EV transcriptome and intensity of graft IRI (i.e., cardiomyocyte injury), as well as EV transcriptome and primary graft dysfunction, as well as any biopsy-proven acute rejection after heart transplantation. We ultimately revealed that at 12 h after reperfusion, 4 plasma EV genes (ITPKA, DDIT4L, CD19, and CYP4A11) correlated with both cardiomyocyte injury and primary graft dysfunction, suggesting that EVs are sensitive indicators of reperfusion injury reflecting lipid metabolism-induced stress and imbalance in calcium homeostasis. In conclusion, we show that profiling plasma EV gene expression may enlighten the mechanisms of heart transplant IRI. Full article

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

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13 pages, 1292 KiB

Open AccessEditor’s ChoiceArticle

Unveiling the Genetic Basis Underlying Rice Anther Culturability via Segregation Distortion Analysis in Doubled Haploid Population

by Bin Sun, Xiaorui Ding, Junhua Ye, Yuting Dai, Can Cheng, Jihua Zhou, Fuan Niu, Rongjian Tu, Qiyan Hu, Kaizhen Xie, Yue Qiu, Hongyu Li, Zhizun Feng, Chenbing Shao, Liming Cao, Anpeng Zhang and Huangwei Chu

Genes 2023, 14(11), 2086; https://doi.org/10.3390/genes14112086 - 17 Nov 2023

Cited by 1 | Viewed by 2006

Abstract

Anther culture (AC) is a valuable technique in rice breeding. However, the genetic mechanisms underlying anther culturability remain elusive, which has hindered its widespread adoption in rice breeding programs. During AC, microspores carrying favorable alleles for AC are selectively regenerated, leading to segregation [...] Read more.

Anther culture (AC) is a valuable technique in rice breeding. However, the genetic mechanisms underlying anther culturability remain elusive, which has hindered its widespread adoption in rice breeding programs. During AC, microspores carrying favorable alleles for AC are selectively regenerated, leading to segregation distortion (SD) of chromosomal regions linked to these alleles in the doubled haploid (DH) population. Using the AC method, a DH population was generated from the japonica hybrid rice Shenyou 26. A genetic map consisting of 470 SNPs was constructed using this DH population, and SD analysis was performed at both the single- and two-locus levels to dissect the genetic basis underlying anther culturability. Five segregation distortion loci (SDLs) potentially linked to anther culturability were identified. Among these, SDL5 exhibited an overrepresentation of alleles from the female parent, while SDL1.1, SDL1.2, SDL2, and SDL7 displayed an overrepresentation of alleles from the male parent. Furthermore, six pairs of epistatic interactions (EPIs) that influenced two-locus SDs in the DH population were discovered. A cluster of genetic loci, associated with EPI-1, EPI-3, EPI-4, and EPI-5, overlapped with SDL1.1, indicating that the SDL1.1 locus may play a role in regulating anther culturability via both additive and epistatic mechanisms. These findings provide valuable insights into the genetic control of anther culturability in rice and lay the foundation for future research focused on identifying the causal genes associated with anther culturability. Full article

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

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12 pages, 2458 KiB

Open AccessEditor’s ChoiceArticle

The Whole-Exome Sequencing of a Cohort of 19 Families with Adolescent Idiopathic Scoliosis (AIS): Candidate Pathways

by Laura Marie-Hardy, Thomas Courtin, Hugues Pascal-Moussellard, Serge Zakine and Alexis Brice

Genes 2023, 14(11), 2094; https://doi.org/10.3390/genes14112094 - 17 Nov 2023

Cited by 2 | Viewed by 1996

Abstract

A significant genetic involvement has been known for decades to exist in adolescent idiopathic scoliosis (AIS), a spine deformity affecting 1–3% of the world population. However, though biomechanical and endocrinological theories have emerged, no clear pathophysiological explanation has been found. Data from the [...] Read more.

A significant genetic involvement has been known for decades to exist in adolescent idiopathic scoliosis (AIS), a spine deformity affecting 1–3% of the world population. However, though biomechanical and endocrinological theories have emerged, no clear pathophysiological explanation has been found. Data from the whole-exome sequencing performed on 113 individuals in 19 multi-generational families with AIS have been filtered and analyzed via interaction pathways and functional category analysis (Varaft, Bingo and Panther). The subsequent list of 2566 variants has been compared to the variants already described in the literature, with an 18% match rate. The familial analysis in two families reveals mutations in the BICD2 gene, supporting the involvement of the muscular system in AIS etiology. The cellular component analysis revealed significant enrichment in myosin-related and neuronal activity-related categories. All together, these results reinforce the suspected role of the neuronal and muscular systems, highlighting the calmodulin pathway and suggesting a role of DNA-binding activities in AIS physiopathology. Full article

(This article belongs to the Topic Bone-Related Diseases: From Molecular Mechanisms to Therapy Development)

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8 pages, 252 KiB

Open AccessEditor’s ChoiceArticle

Association of a Single Nucleotide Variant in TERT with Airway Disease in Japanese Rheumatoid Arthritis Patients

by Takashi Higuchi, Shomi Oka, Hiroshi Furukawa, Kota Shimada, Shinichiro Tsunoda, Satoshi Ito, Akira Okamoto, Misuzu Fujimori, Tadashi Nakamura, Masao Katayama, Koichiro Saisho, Satoshi Shinohara, Toshihiro Matsui, Kiyoshi Migita, Shouhei Nagaoka and Shigeto Tohma

Genes 2023, 14(11), 2084; https://doi.org/10.3390/genes14112084 - 16 Nov 2023

Cited by 1 | Viewed by 1336

Abstract

Interstitial lung disease and airway disease (AD) are often complicated with rheumatoid arthritis (RA) and have a poor prognosis. Several studies reported genetic associations with interstitial lung disease in RA. However, few genetic studies have examined the susceptibility to AD in RA patients. [...] Read more.

Interstitial lung disease and airway disease (AD) are often complicated with rheumatoid arthritis (RA) and have a poor prognosis. Several studies reported genetic associations with interstitial lung disease in RA. However, few genetic studies have examined the susceptibility to AD in RA patients. Here, we investigated whether single nucleotide variants susceptible to idiopathic pulmonary fibrosis might be associated with interstitial lung disease or AD in Japanese RA patients. Genotyping of rs2736100 [C/A] in TERT and rs1278769 [G/A] in ATP11A was conducted in 98 RA patients with usual interstitial pneumonia, 120 with nonspecific interstitial pneumonia (NSIP), 227 with AD, and 422 without chronic lung disease using TaqMan assays. An association with AD in RA was found for rs2736100 (p = 0.0043, Pc = 0.0129, odds ratio [OR] 1.40, 95% confidence interval [CI] 1.11–1.77). ATP11A rs1278769 was significantly associated with NSIP in older RA patients (>65 years, p = 0.0010, OR 2.15, 95% CI 1.35–3.40). This study first reported an association of rs2736100 with AD in RA patients and ATP11A rs1278769 with NSIP in older RA patients. Full article

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

15 pages, 2273 KiB

Open AccessEditor’s ChoiceArticle

Selective Sweeps in Cattle Genomes in Response to the Influence of Urbanization and Environmental Contamination

by Silpa Mullakkalparambil Velayudhan, Shahin Alam, Tong Yin, Kerstin Brügemann, Andreas Buerkert, Veerasamy Sejian, Raghavendra Bhatta, Eva Schlecht and Sven König

Genes 2023, 14(11), 2083; https://doi.org/10.3390/genes14112083 - 15 Nov 2023

Cited by 1 | Viewed by 2282

Abstract

A genomic study was conducted to identify the effects of urbanization and environmental contaminants with heavy metals on selection footprints in dairy cattle populations reared in the megacity of Bengaluru, South India. Dairy cattle reared along the rural–urban interface of Bengaluru with/without access [...] Read more.

A genomic study was conducted to identify the effects of urbanization and environmental contaminants with heavy metals on selection footprints in dairy cattle populations reared in the megacity of Bengaluru, South India. Dairy cattle reared along the rural–urban interface of Bengaluru with/without access to roughage from public lakeshores were selected. The genotyped animals were subjected to the cross-population–extended haplotype homozygosity (XP-EHH) methodology to infer selection sweeps caused by urbanization (rural, mixed, and urban) and environmental contamination with cadmium and lead. We postulated that social-ecological challenges contribute to mechanisms of natural selection. A number of selection sweeps were identified when comparing the genomes of cattle located in rural, mixed, or urban regions. The largest effects were identified on BTA21, displaying pronounced peaks for selection sweeps for all three urbanization levels (urban_vs_rural, urban_vs_mixed and rural_vs_mixed). Selection sweeps are located in chromosomal segments in close proximity to the genes lrand rab interactor 3 (RIN3), solute carrier family 24 member 4 (SLC24A4), tetraspanin 3 (TSPAN3), and proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1). Functional enrichment analyses of the selection sweeps for all three comparisons revealed a number of gene ontology (GO) and KEGG terms, which were associated with reproduction, metabolism, and cell signaling-related functional mechanisms. Likewise, a number of the chromosomal segments under selection were observed when creating cattle groups according to cadmium and lead contaminations. Stronger and more intense positive selection sweeps were observed for the cadmium contaminated group, i.e., signals of selection on BTA 16 and BTA19 in close proximity to genes regulating the somatotropic axis (growth factor receptor bound protein 2 (GRB2) and cell ion exchange (chloride voltage-gated channel 6 (CLCN6)). A few novel, so far uncharacterized genes, mostly with effects on immune physiology, were identified. The lead contaminated group revealed sweeps which were annotated with genes involved in carcass traits (TNNC2, SLC12A5, and GABRA4), milk yield (HTR1D, SLCO3A1, TEK, and OPCML), reproduction (GABRA4), hypoxia/stress response (OPRD1 and KDR), cell adhesion (PCDHGC3), inflammatory response (ADORA2A), and immune defense mechanism (ALCAM). Thus, the findings from this study provide a deeper insight into the genomic regions under selection under the effects of urbanization and environmental contamination. Full article

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

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12 pages, 2881 KiB

Open AccessEditor’s ChoiceArticle

Variants of IFNL4 Gene in Amazonian and Northern Brazilian Populations

by Carolina Cabral Angelim, Letícia Dias Martins, Álesson Adam Fonseca Andrade, Fabiano Cordeiro Moreira, João Farias Guerreiro, Paulo Pimentel de Assumpção, Sidney Emanuel Batista dos Santos and Greice de Lemos Cardoso Costa

Genes 2023, 14(11), 2075; https://doi.org/10.3390/genes14112075 - 14 Nov 2023

Cited by 1 | Viewed by 1890

Abstract

Since the discovery of the polymorphic nature of the IFNL4 gene, its variants have been investigated and associated with several viral diseases, with an emphasis on hepatitis C. However, the impacts of these variants on mixed-race and native populations in the northern region [...] Read more.

Since the discovery of the polymorphic nature of the IFNL4 gene, its variants have been investigated and associated with several viral diseases, with an emphasis on hepatitis C. However, the impacts of these variants on mixed-race and native populations in the northern region of Brazil are scarce. We investigated three variants of the IFNL4 gene in populations from this location, which were among the 14 most frequent variants in worldwide populations, and compared the frequencies obtained to populational data from the 1000 Genomes Project, gnomAD and ABraOM databases. Our results demonstrate that mixed-race and native populations from the northern region of Brazil present frequencies like those of European and Asian groups for the rs74597329 and rs11322783 variants, and like all populations presented for the rs4803221 variant. These data reinforce the role of world populations in shaping the genetic profile of Brazilian populations, indicate patterns of illness according to the expressed genotype, and infer an individual predisposition to certain diseases. Full article

(This article belongs to the Special Issue Genetic Variants in Human Population and Diseases)

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14 pages, 800 KiB

Open AccessEditor’s ChoiceReview

The Regulatory Role of MicroRNAs in Obesity and Obesity-Derived Ailments

by Javier A. Benavides-Aguilar, Andrea Torres-Copado, José Isidoro-Sánchez, Surajit Pathak, Asim K. Duttaroy, Antara Banerjee and Sujay Paul

Genes 2023, 14(11), 2070; https://doi.org/10.3390/genes14112070 - 13 Nov 2023

Cited by 19 | Viewed by 3890

Abstract

Obesity is a condition that is characterized by the presence of excessive adipose tissue in the body. Obesity has become one of the main health concerns worldwide since it can lead to other chronic ailments, such as type 2 diabetes or fatty liver [...] Read more.

Obesity is a condition that is characterized by the presence of excessive adipose tissue in the body. Obesity has become one of the main health concerns worldwide since it can lead to other chronic ailments, such as type 2 diabetes or fatty liver disease, and it could be an aggravating factor in infections. MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression and can play an important role in controlling crucial biological processes involved in the onset of obesity, such as lipogenesis, adipogenesis, lipid metabolism, or the regulation of cytokines and chemokines. Moreover, chemical compounds present in food or food packaging can alter miRNA expression and regulate the aforementioned biological mechanisms related to diabetes onset and progression. Furthermore, therapies, such as bariatric surgery and aerobic exercise training, can also influence the expression profile of miRNAs in obesity. Therefore, the present review provides insight into the current research on the role of miRNAs in obesity and obesity-derived ailments, intending to develop novel therapies to effectively manage these disorders. Full article

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

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14 pages, 909 KiB

Open AccessEditor’s ChoiceArticle

Genetic Spectrum and Cascade Screening of Familial Hypercholesterolemia in Routine Clinical Setting in Hong Kong

by Man-Kwan Yip, Elaine Yin-Wah Kwan, Jenny Yin-Yan Leung, Emmy Yuen-Fun Lau and Wing-Tat Poon

Genes 2023, 14(11), 2071; https://doi.org/10.3390/genes14112071 - 13 Nov 2023

Cited by 3 | Viewed by 2005

Abstract

Familial hypercholesterolemia (FH) is a prevalent but often underdiagnosed monogenic disorder affecting lipoprotein metabolism, and genetic testing for FH has not been widely conducted in Asia in the past. In this cross-sectional study of 31 probands (19 adults and 12 children) and an [...] Read more.

Familial hypercholesterolemia (FH) is a prevalent but often underdiagnosed monogenic disorder affecting lipoprotein metabolism, and genetic testing for FH has not been widely conducted in Asia in the past. In this cross-sectional study of 31 probands (19 adults and 12 children) and an addition of 15 individuals (12 adults and 3 children), who underwent genetic testing and cascade screening for FH, respectively, during the period between February 2015 and July 2023, we identified a total of 25 distinct LDLR variants in 71.0% unrelated probands. Among the adult proband cohort, a higher proportion of genetically confirmed cases exhibited a positive family history of premature cardiovascular disease. Treatment intensity required to achieve an approximate 50% reduction in pretreatment low-density lipoprotein cholesterol (LDL-C) exhibited potentially better diagnostic performance compared to pretreatment LDL-C levels, Dutch Lipid Clinic Network Diagnostic Criteria (DLCNC) score, and modified DLCNC score. Adult individuals identified through cascade screening demonstrated less severe phenotypes, and fewer of them met previously proposed local criteria for FH genetic testing compared to the probands, indicating that cascade screening played a crucial role in the early detection of new cases that might otherwise have gone undiagnosed. These findings underscore the significance of genetic testing and cascade screening in the accurate identification and management of FH cases. Full article

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

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9 pages, 1250 KiB

Open AccessEditor’s ChoiceCase Report

In Tandem Intragenic Duplication of Doublesex and Mab-3-Related Transcription Factor 1 (DMRT1) in an SRY-Negative Boy with a 46,XX Disorder of Sex Development

by Veronica Bertini, Fulvia Baldinotti, Pietro Parma, Nina Tyutyusheva, Margherita Sepich, Giulia Bertolucci, Camillo Rosano, Maria Adelaide Caligo, Diego Peroni, Angelo Valetto and Silvano Bertelloni

Genes 2023, 14(11), 2067; https://doi.org/10.3390/genes14112067 - 12 Nov 2023

Cited by 2 | Viewed by 1675

Abstract

Disorders of sexual development (DSDs) encompass a group of congenital conditions associated with atypical development of internal and external genital structures. Among those with DSDs are 46,XX males, whose condition mainly arises due to the translocation of SRY onto an X chromosome or [...] Read more.

Disorders of sexual development (DSDs) encompass a group of congenital conditions associated with atypical development of internal and external genital structures. Among those with DSDs are 46,XX males, whose condition mainly arises due to the translocation of SRY onto an X chromosome or an autosome. In the few SRY-negative 46,XX males, overexpression of other pro-testis genes or failure of pro-ovarian/anti-testis genes may be involved, even if a non-negligible number of cases remain unexplained. A three-year-old boy with an SRY-negative 46,XX karyotype showed a normal male phenotype and normal prepubertal values for testicular hormones. A heterozygous de novo in tandem duplication of 50,221 bp, which encompassed exons 2 and 3 of the Doublesex and Mab-3-related transcription factor 1 (DMRT1) gene, was detected using MPLA, CGH-array analysis, and Sanger sequencing. Both breakpoints were in the intronic regions, and this duplication did not stop or shift the coding frame. Additional pathogenic or uncertain variants were not found in a known pro-testis/anti-ovary gene cascade using a custom NGS panel and whole genome sequencing. The duplication may have allowed DMRT1 to escape the transcriptional repression that normally occurs in 46,XX fetal gonads and thus permitted the testicular determination cascade to switch on. So far, no case of SRY-negative 46,XX DSD with alterations in DMRT1 has been described. Full article

(This article belongs to the Special Issue Genetic Architecture in Complex Traits)

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15 pages, 580 KiB

Open AccessEditor’s ChoiceReview

Workability of mRNA Sequencing for Predicting Protein Abundance

by Elena A. Ponomarenko, George S. Krasnov, Olga I. Kiseleva, Polina A. Kryukova, Viktoriia A. Arzumanian, Georgii V. Dolgalev, Ekaterina V. Ilgisonis, Andrey V. Lisitsa and Ekaterina V. Poverennaya

Genes 2023, 14(11), 2065; https://doi.org/10.3390/genes14112065 - 11 Nov 2023

Cited by 16 | Viewed by 4065

Abstract

Transcriptomics methods (RNA-Seq, PCR) today are more routine and reproducible than proteomics methods, i.e., both mass spectrometry and immunochemical analysis. For this reason, most scientific studies are limited to assessing the level of mRNA content. At the same time, protein content (and its [...] Read more.

Transcriptomics methods (RNA-Seq, PCR) today are more routine and reproducible than proteomics methods, i.e., both mass spectrometry and immunochemical analysis. For this reason, most scientific studies are limited to assessing the level of mRNA content. At the same time, protein content (and its post-translational status) largely determines the cell’s state and behavior. Such a forced extrapolation of conclusions from the transcriptome to the proteome often seems unjustified. The ratios of “transcript-protein” pairs can vary by several orders of magnitude for different genes. As a rule, the correlation coefficient between transcriptome–proteome levels for different tissues does not exceed 0.3–0.5. Several characteristics determine the ratio between the content of mRNA and protein: among them, the rate of movement of the ribosome along the mRNA and the number of free ribosomes in the cell, the availability of tRNA, the secondary structure, and the localization of the transcript. The technical features of the experimental methods also significantly influence the levels of the transcript and protein of the corresponding gene on the outcome of the comparison. Given the above biological features and the performance of experimental and bioinformatic approaches, one may develop various models to predict proteomic profiles based on transcriptomic data. This review is devoted to the ability of RNA sequencing methods for protein abundance prediction. Full article

(This article belongs to the Special Issue Gene Regulation and Bioinformatics)

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14 pages, 3760 KiB

Open AccessEditor’s ChoiceCase Report

A Sporadic Case of COL1A1 Osteogenesis Imperfecta: From Prenatal Diagnosis to Outcomes in Infancy—Case Report and Literature Review

by Karolina Vankevičienė, Aušra Matulevičienė, Eglė Mazgelytė, Virginija Paliulytė, Ramunė Vankevičienė and Diana Ramašauskaitė

Genes 2023, 14(11), 2062; https://doi.org/10.3390/genes14112062 - 10 Nov 2023

Cited by 1 | Viewed by 3138

Abstract

Osteogenesis imperfecta (OI), also known as brittle bone disease, belongs to a rare heterogeneous group of inherited connective tissue disorders. In experienced prenatal centers, severe cases of OI can be suspected before birth from the first trimester prenatal ultrasound screening. In this article, [...] Read more.

Osteogenesis imperfecta (OI), also known as brittle bone disease, belongs to a rare heterogeneous group of inherited connective tissue disorders. In experienced prenatal centers, severe cases of OI can be suspected before birth from the first trimester prenatal ultrasound screening. In this article, we describe a case report of OI suspected at the 26th week of gestation and the patient’s outcomes in infancy one year after birth, as well as compare our case to other prenatally or soon-after-birth suspected and/or diagnosed OI clinical case reports in the literature. This case was managed by a multidisciplinary team. In this clinical case, OI was first suspected when prenatal ultrasound revealed asymmetric intrauterine growth restriction and skeletal dysplasia features. The diagnosis was confirmed after birth using COL1A1 gene variant detection via exome sequencing; the COL1A1 gene variant causes OI types I–IV. The familial history was negative for both pregnancy-related risk factors and genetic diseases. At one year old, the patient’s condition remains severe with bisphosphonate therapy. Full article

(This article belongs to the Section Genetic Diagnosis)

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11 pages, 2003 KiB

Open AccessEditor’s ChoiceArticle

Barcoding (COI) Sea Cucumber Holothuria mammata Distribution Analysis: Adriatic Rare or Common Species?

by Maya Sertić Kovačević, Ana Baričević, Petar Kružić, Maja Maurić Maljković and Bojan Hamer

Genes 2023, 14(11), 2059; https://doi.org/10.3390/genes14112059 - 9 Nov 2023

Cited by 3 | Viewed by 1805

Abstract

The overexploitation of the western Pacific Ocean has expanded the sea cucumber fishery into new regions to supply the Asian market. In 2013, sea cucumbers were removed from the Croatian marine protected species list, and commercial fishery took place for a short period [...] Read more.

The overexploitation of the western Pacific Ocean has expanded the sea cucumber fishery into new regions to supply the Asian market. In 2013, sea cucumbers were removed from the Croatian marine protected species list, and commercial fishery took place for a short period (2017–2018) in the Eastern Adriatic Sea. However, holothuroid species are difficult to distinguish. Holothuria mammata is a species that has rarely been reported in this region and strongly resembles the common species Holothuria tubulosa. This is the first study to assess the genetic diversity of sea cucumbers in the Adriatic Sea using genetic barcoding of the mitochondrial gene cytochrome c oxidase subunit 1 (COI). Specimens for barcoding were collected from the northern and central Adriatic, along with a specimen that had been previously identified as H. sp. cf. mammata based on its morphological characteristics. While genetic analyses showed identified this specimen as H. tubulosa, 30% of the collected specimens were genetically identified as H. mammata. These results call into question the historically accepted sea cucumber assemblage in the Adriatic Sea, which regarded H. mammata as a rare species and generally disregarded its presence in large census studies. Such species distribution data are extremely important in developing and monitoring a sustainable fishery. Full article

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

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17 pages, 4085 KiB

Open AccessEditor’s ChoiceReview

Penaeid Shrimp Chromosome Studies Entering the Post-Genomic Era

by Xiaojun Zhang, Jianhai Xiang, Jianbo Yuan and Fuhua Li

Genes 2023, 14(11), 2050; https://doi.org/10.3390/genes14112050 - 7 Nov 2023

Cited by 1 | Viewed by 2856

Abstract

Chromosome studies provide the foundation for comprehending inheritance, variation, systematics, and evolution. Penaeid shrimps are a group of crustaceans with great economic importance. Basic cytogenetic information obtained from these shrimps can be used to study their genome structure, chromosome relationships, chromosome variation, polyploidy [...] Read more.

Chromosome studies provide the foundation for comprehending inheritance, variation, systematics, and evolution. Penaeid shrimps are a group of crustaceans with great economic importance. Basic cytogenetic information obtained from these shrimps can be used to study their genome structure, chromosome relationships, chromosome variation, polyploidy manipulation, and breeding. The study of shrimp chromosomes experienced significant growth in the 1990s and has been closely linked to the progress of genome research since the application of next-generation sequencing technology. To date, the genome sequences of five penaeid shrimp species have been published. The availability of these genomes has ushered the study of shrimp chromosomes into the post-genomic era. Currently, research on shrimp cytogenetics not only involves chromosome counting and karyotyping, but also extends to investigating submicroscopic changes; exploring genome structure and regulation during various cell divisions; and contributing to the understanding of mechanisms related to growth, sexual control, stress resistance, and genome evolution. In this article, we provide an overview of the progress made in chromosome research on penaeid shrimp. We emphasize the mutual promotion between studies on chromosome structure and genome research and highlight the impact of chromosome-level assembly on studies of genome structure and function. Additionally, we summarize the emerging trends in post-genomic-era shrimp chromosome research. Full article

(This article belongs to the Special Issue Aquatic Animal Germplasm Resources and Genetic Breeding)

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13 pages, 571 KiB

Open AccessEditor’s ChoiceArticle

Association between NTRK2 Polymorphisms, Hippocampal Volumes and Treatment Resistance in Major Depressive Disorder

by Marco Paolini, Lidia Fortaner-Uyà, Cristina Lorenzi, Sara Spadini, Melania Maccario, Raffaella Zanardi, Cristina Colombo, Sara Poletti and Francesco Benedetti

Genes 2023, 14(11), 2037; https://doi.org/10.3390/genes14112037 - 3 Nov 2023

Cited by 4 | Viewed by 2214

Abstract

Despite the increasing availability of antidepressant drugs, a high rate of patients with major depression (MDD) does not respond to pharmacological treatments. Brain-derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) signaling is thought to influence antidepressant efficacy and hippocampal volumes, robust predictors of [...] Read more.

Despite the increasing availability of antidepressant drugs, a high rate of patients with major depression (MDD) does not respond to pharmacological treatments. Brain-derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) signaling is thought to influence antidepressant efficacy and hippocampal volumes, robust predictors of treatment resistance. We therefore hypothesized the possible role of BDNF and neurotrophic receptor tyrosine kinase 2 (NTRK2)-related polymorphisms in affecting both hippocampal volumes and treatment resistance in MDD. A total of 121 MDD inpatients underwent 3T structural MRI scanning and blood sampling to obtain genotype information. General linear models and binary logistic regressions were employed to test the effect of genetic variations related to BDNF and NTRK2 on bilateral hippocampal volumes and treatment resistance, respectively. Finally, the possible mediating role of hippocampal volumes on the relationship between genetic markers and treatment response was investigated. A significant association between one NTRK2 polymorphism with hippocampal volumes and antidepressant response was found, with significant indirect effects. Our results highlight a possible mechanistic explanation of antidepressant action, possibly contributing to the understanding of MDD pathophysiology. Full article

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

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15 pages, 6634 KiB

Open AccessEditor’s ChoiceArticle

Identification of Molecular Mechanisms Responsible for the MMP-9-1562C/T Dependent Differential Regulation of Matrix Metalloproteinase-9 Expression in Human Neuron-like Cells

by Sylwia Pabian-Jewuła, Magdalena Ambrożek-Latecka, Aneta Brągiel-Pieczonka, Klaudia Nowicka and Marcin Rylski

Genes 2023, 14(11), 2028; https://doi.org/10.3390/genes14112028 - 31 Oct 2023

Cited by 1 | Viewed by 2218

Abstract

The MMP-9-1562C/T polymorphism exerts an impact on the occurrence and progression of numerous disorders affecting the central nervous system. Using luciferase assays and Q-RT-PCR technique, we have discovered a distinct allele-specific influence of the MMP-9-1562C/T polymorphism on the MMP-9 (Extracellular Matrix Metalloproteinase-9) promoter [...] Read more.

The MMP-9-1562C/T polymorphism exerts an impact on the occurrence and progression of numerous disorders affecting the central nervous system. Using luciferase assays and Q-RT-PCR technique, we have discovered a distinct allele-specific influence of the MMP-9-1562C/T polymorphism on the MMP-9 (Extracellular Matrix Metalloproteinase-9) promoter activity and the expression of MMP-9 mRNA in human neurons derived from SH-SY5Y cells. Subsequently, by employing a pull-down assay paired with mass spectrometry analysis, EMSA (Electromobility Shift Assay), and EMSA supershift techniques, as well as DsiRNA-dependent gene silencing, we have elucidated the mechanism responsible for the allele-specific impact of the MMP-9-1562C/T polymorphism on the transcriptional regulation of the MMP-9 gene. We have discovered that the activity of the MMP-9 promoter and the expression of MMP-9 mRNA in human neurons are regulated in a manner that is specific to the MMP-9-1562C/T allele, with a stronger upregulation being attributed to the C allele. Furthermore, we have demonstrated that the allele-specific action of the MMP-9-1562C/T polymorphism on the neuronal MMP-9 expression is related to HDAC1 (Histone deacetylase 1) and ZNF384 (Zinc Finger Protein 384) transcriptional regulators. We show that HDAC1 and ZNF384 bind to the C and the T alleles differently, forming different regulatory complexes in vitro. Moreover, our data demonstrate that HDAC1 and ZNF384 downregulate MMP-9 gene promoter activity and mRNA expression in human neurons acting mostly via the T allele. Full article

(This article belongs to the Special Issue Genetic Basis of Neurodegenerative Disorders)

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14 pages, 4256 KiB

Open AccessEditor’s ChoiceArticle

Identification of Niche-Specific Gene Signatures between Malignant Tumor Microenvironments by Integrating Single Cell and Spatial Transcriptomics Data

by Jahanzeb Saqib, Beomsu Park, Yunjung Jin, Junseo Seo, Jaewoo Mo and Junil Kim

Genes 2023, 14(11), 2033; https://doi.org/10.3390/genes14112033 - 31 Oct 2023

Cited by 5 | Viewed by 3633

Abstract

The tumor microenvironment significantly affects the transcriptomic states of tumor cells. Single-cell RNA sequencing (scRNA-seq) helps elucidate the transcriptomes of individual cancer cells and their neighboring cells. However, cell dissociation results in the loss of information on neighboring cells. To address this challenge [...] Read more.

The tumor microenvironment significantly affects the transcriptomic states of tumor cells. Single-cell RNA sequencing (scRNA-seq) helps elucidate the transcriptomes of individual cancer cells and their neighboring cells. However, cell dissociation results in the loss of information on neighboring cells. To address this challenge and comprehensively assess the gene activity in tissue samples, it is imperative to integrate scRNA-seq with spatial transcriptomics. In our previous study on physically interacting cell sequencing (PIC-seq), we demonstrated that gene expression in single cells is affected by neighboring cell information. In the present study, we proposed a strategy to identify niche-specific gene signatures by harmonizing scRNA-seq and spatial transcriptomic data. This approach was applied to the paired or matched scRNA-seq and Visium platform data of five cancer types: breast cancer, gastrointestinal stromal tumor, liver hepatocellular carcinoma, uterine corpus endometrial carcinoma, and ovarian cancer. We observed distinct gene signatures specific to cellular niches and their neighboring counterparts. Intriguingly, these niche-specific genes display considerable dissimilarity to cell type markers and exhibit unique functional attributes independent of the cancer types. Collectively, these results demonstrate the potential of this integrative approach for identifying novel marker genes and their spatial relationships. Full article

(This article belongs to the Special Issue Applications and Progress in Single-Cell Genomics)

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16 pages, 5183 KiB

Open AccessEditor’s ChoiceArticle

Integrated Transcriptome Analysis of miRNAs and mRNAs in the Skeletal Muscle of Wuranke Sheep

by Yueying Yun, Rihan Wu, Xige He, Xia Qin, Lu Chen, Lina Sha, Xueyan Yun, Tadayuki Nishiumi and Gerelt Borjigin

Genes 2023, 14(11), 2034; https://doi.org/10.3390/genes14112034 - 31 Oct 2023

Cited by 3 | Viewed by 2027

Abstract

MicroRNAs (miRNAs) are regarded as important regulators in skeletal muscle development. To reveal the regulatory roles of miRNAs and their target mRNAs underlying the skeletal muscle development of Wuranke sheep, we investigated the miRNA and mRNA expression profiles in the biceps femoris [...] Read more.

MicroRNAs (miRNAs) are regarded as important regulators in skeletal muscle development. To reveal the regulatory roles of miRNAs and their target mRNAs underlying the skeletal muscle development of Wuranke sheep, we investigated the miRNA and mRNA expression profiles in the biceps femoris of these sheep at the fetal (3 months of gestation) and 3- and 15-month-old postnatal stages. Consequently, a total of 1195 miRNAs and 24,959 genes were identified. Furthermore, 474, 461, and 54 differentially expressed miRNAs (DEMs) and 6783, 7407, and 78 differentially expressed genes (DEGs) were detected among three comparative groups. Functional analysis demonstrated that the target mRNAs of the DEMs were enriched in multiple pathways related to muscle development. Moreover, the interactions among several predicted miRNA–mRNA pairs (oar-miR-133-HDAC1, oar-miR-1185-5p-MYH1/HADHA/OXCT1, and PC-5p-3703_578-INSR/ACTG1) that potentially affect skeletal muscle development were verified using dual-luciferase reporter assays. In this study, we identified the miRNA and mRNA differences in the skeletal muscle of Wuranke sheep at different developmental stages and revealed that a series of candidate miRNA–mRNA pairs may act as modulators of muscle development. These results will contribute to future studies on the function of miRNAs and their target mRNAs during skeletal muscle development in Wuranke sheep. Full article

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

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