Genes

14 pages, 262 KiB

Open AccessArticle

Theory Designed Strategies to Support Implementation of Genomics in Nephrology

by Arushi Kansal, Catherine Quinlan, Zornitza Stark, Peter G. Kerr, Andrew J. Mallett, Chandni Lakshmanan, Stephanie Best and Kushani Jayasinghe

Genes 2022, 13(10), 1919; https://doi.org/10.3390/genes13101919 - 21 Oct 2022

Cited by 2 | Viewed by 1409

Abstract

(1) Background: Genomic testing is increasingly utilized as a clinical tool; however, its integration into nephrology remains limited. The purpose of this study was to identify barriers and prioritize interventions for the widespread implementation of genomics in nephrology. (2) Methods: Qualitative, semi-structured interviews [...] Read more.

(1) Background: Genomic testing is increasingly utilized as a clinical tool; however, its integration into nephrology remains limited. The purpose of this study was to identify barriers and prioritize interventions for the widespread implementation of genomics in nephrology. (2) Methods: Qualitative, semi-structured interviews were conducted with 25 Australian adult nephrologists to determine their perspectives on interventions and models of care to support implementation of genomics in nephrology. Interviews were guided by a validated theoretical framework for the implementation of genomic medicine—the Consolidated Framework of Implementation Research (CFIR). (3) Results: Nephrologists were from 18 hospitals, with 7 having a dedicated multidisciplinary kidney genetics service. Most practiced in the public healthcare system (n = 24), a large number were early-career (n = 13), and few had genomics experience (n = 4). The top three preferred interventions were increased funding, access to genomics champions, and education and training. Where interventions to barriers were not reported, we used the CFIR/Expert Recommendations for Implementing Change matching tool to generate theory-informed approaches. The preferred model of service delivery was a multidisciplinary kidney genetics clinic. (4) Conclusions: This study identified surmountable barriers and practical interventions for the implementation of genomics in nephrology, with multidisciplinary kidney genetics clinics identified as the preferred model of care. The integration of genomics education into nephrology training, secure funding for testing, and counselling along with the identification of genomics champions should be pursued by health services more broadly. Full article

(This article belongs to the Special Issue Nephrogenetics and Kidney Genomics—the Future Is Now?)

24 pages, 6496 KiB

Open AccessArticle

Genome-Wide Identification and Characterization of the Oat (Avena sativa L.) WRKY Transcription Factor Family

by Kaiqiang Liu, Zeliang Ju, Zhifeng Jia, Guoling Liang, Xiang Ma and Wenhui Liu

Genes 2022, 13(10), 1918; https://doi.org/10.3390/genes13101918 - 21 Oct 2022

Cited by 7 | Viewed by 1959

Abstract

The WRKY family is widely involved in the regulation of plant growth and stress response and is one of the largest gene families related to plant environmental adaptation. However, no systematic studies on the WRKY family in oat (Avena sativa L.) have [...] Read more.

The WRKY family is widely involved in the regulation of plant growth and stress response and is one of the largest gene families related to plant environmental adaptation. However, no systematic studies on the WRKY family in oat (Avena sativa L.) have been conducted to date. The recently published complete genome sequence of oat enables the systematic analysis of the AsWRKYs. Based on a genome-wide study of oat, we identified 162 AsWRKYs that were unevenly distributed across 21 chromosomes; a phylogenetic tree of WRKY domains divided these genes into three groups (I, II, and III). We also analyzed the gene duplication events and identified a total of 111 gene pairs that showed strong purifying selection during the evolutionary process. Surprisingly, almost all genes evolved after the completion of subgenomic differentiation of hexaploid oat. Further studies on the functional analysis indicated that AsWRKYs were widely involved in various biological processes. Notably, expression patterns of 16 AsWRKY genes revealed that the response of AsWRKYs were affected by stress level and time. In conclusion, this study provides a reference for further analysis of the role of WRKY transcription factors in species evolution and functional differentiation. Full article

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

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30 pages, 2837 KiB

Open AccessReview

Advances in Novel Animal Vitamin C Biosynthesis Pathways and the Role of Prokaryote-Based Inferences to Understand Their Origin

by Pedro Duque, Cristina P. Vieira and Jorge Vieira

Genes 2022, 13(10), 1917; https://doi.org/10.3390/genes13101917 - 21 Oct 2022

Cited by 4 | Viewed by 2307

Abstract

Vitamin C (VC) is an essential nutrient required for the optimal function and development of many organisms. VC has been studied for many decades, and still today, the characterization of its functions is a dynamic scientific field, mainly because of its commercial and [...] Read more.

Vitamin C (VC) is an essential nutrient required for the optimal function and development of many organisms. VC has been studied for many decades, and still today, the characterization of its functions is a dynamic scientific field, mainly because of its commercial and therapeutic applications. In this review, we discuss, in a comparative way, the increasing evidence for alternative VC synthesis pathways in insects and nematodes, and the potential of myo-inositol as a possible substrate for this metabolic process in metazoans. Methodological approaches that may be useful for the future characterization of the VC synthesis pathways of Caenorhabditis elegans and Drosophila melanogaster are here discussed. We also summarize the current distribution of the eukaryote aldonolactone oxidoreductases gene lineages, while highlighting the added value of studies on prokaryote species that are likely able to synthesize VC for both the characterization of novel VC synthesis pathways and inferences on the complex evolutionary history of such pathways. Such work may help improve the industrial production of VC. Full article

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

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21 pages, 5018 KiB

Open AccessArticle

Integration of lncRNAs, Protein-Coding Genes and Pathology Images for Detecting Metastatic Melanoma

by Shuai Liu, Yusi Fan, Kewei Li, Haotian Zhang, Xi Wang, Ruofei Ju, Lan Huang, Meiyu Duan and Fengfeng Zhou

Genes 2022, 13(10), 1916; https://doi.org/10.3390/genes13101916 - 21 Oct 2022

Cited by 1 | Viewed by 1575

Abstract

Melanoma is a lethal skin disease that develops from moles. This study aimed to integrate multimodal data to predict metastatic melanoma, which is highly aggressive and difficult to treat. The proposed EnsembleSKCM method evaluated the prediction performances of long noncoding RNAs (lncRNAs), protein-coding [...] Read more.

Melanoma is a lethal skin disease that develops from moles. This study aimed to integrate multimodal data to predict metastatic melanoma, which is highly aggressive and difficult to treat. The proposed EnsembleSKCM method evaluated the prediction performances of long noncoding RNAs (lncRNAs), protein-coding messenger genes (mRNAs) and pathology images (images) for metastatic melanoma. Feature selection was used to screen for metastatic biomarkers in the lncRNA and mRNA datasets. The integrated EnsembleSKCM model was built based on the weighted results of the lncRNA-, mRNA- and image-based models. EnsembleSKCM achieved 0.9444 in the prediction accuracy of metastatic melanoma and outperformed the single-modal prediction models based on the lncRNA, mRNA and image data. The experimental data suggest the importance of integrating the complementary information from the three data modalities. WGCNA was used to analyze the relationship of molecular-level features and image features, and the results show connections between them. Another cohort was used to validate our prediction. Full article

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

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13 pages, 2141 KiB

Open AccessArticle

The Light Chain Domain and Especially the C-Terminus of Receptor-Binding Domain of the Botulinum Neurotoxin (BoNT) Are the Hotspots for Amino Acid Variability and Toxin Type Diversity

by Renmao Tian, Melissa Widel and Behzad Imanian

Genes 2022, 13(10), 1915; https://doi.org/10.3390/genes13101915 - 21 Oct 2022

Cited by 1 | Viewed by 1827

Abstract

Botulinum neurotoxins (BoNT) are the most potent toxins in the world. They are produced by a few dozens of strains within several clostridial species. The toxin that they produce can cause botulism, a flaccid paralysis in humans and other animals. With seven established [...] Read more.

Botulinum neurotoxins (BoNT) are the most potent toxins in the world. They are produced by a few dozens of strains within several clostridial species. The toxin that they produce can cause botulism, a flaccid paralysis in humans and other animals. With seven established serologically different types and over 40 subtypes, BoNTs are among the most diverse known toxins. The toxin, its structure, its function and its physiological effects on the neural cell and animal hosts along with its diversity have been the subjects of numerous studies. However, many gaps remain in our knowledge about the BoNT toxin and the species that produce them. One of these gaps involves the distribution and extent of variability along the full length of the gene and the protein as well as its domains and subdomains. In this study, we performed an extensive analysis of all of the available 143 unique BoNT-encoding genes and their products, and we investigated their diversity and evolution. Our results indicate that while the nucleotide variability is almost uniformly distributed along the entire length of the gene, the amino acid variability is not. We found that most of the differences were concentrated along the protein’s light chain (LC) domain and especially, the C-terminus of the receptor-binding domain (H_CC). These two regions of the protein are thus identified as the main source of the toxin type differentiation, and consequently, this toxin’s versatility to bind different receptors and their isoforms and act upon different substrates, thus infecting different hosts. Full article

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

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17 pages, 2419 KiB

Open AccessArticle

Supervised Machine Learning Enables Geospatial Microbial Provenance

by Chandrima Bhattacharya, Braden T. Tierney, Krista A. Ryon, Malay Bhattacharyya, Jaden J. A. Hastings, Srijani Basu, Bodhisatwa Bhattacharya, Debneel Bagchi, Somsubhro Mukherjee, Lu Wang, Elizabeth M. Henaff and Christopher E. Mason

Genes 2022, 13(10), 1914; https://doi.org/10.3390/genes13101914 - 21 Oct 2022

Cited by 3 | Viewed by 2674

Abstract

The recent increase in publicly available metagenomic datasets with geospatial metadata has made it possible to determine location-specific, microbial fingerprints from around the world. Such fingerprints can be useful for comparing microbial niches for environmental research, as well as for applications within forensic [...] Read more.

The recent increase in publicly available metagenomic datasets with geospatial metadata has made it possible to determine location-specific, microbial fingerprints from around the world. Such fingerprints can be useful for comparing microbial niches for environmental research, as well as for applications within forensic science and public health. To determine the regional specificity for environmental metagenomes, we examined 4305 shotgun-sequenced samples from the MetaSUB Consortium dataset—the most extensive public collection of urban microbiomes, spanning 60 different cities, 30 countries, and 6 continents. We were able to identify city-specific microbial fingerprints using supervised machine learning (SML) on the taxonomic classifications, and we also compared the performance of ten SML classifiers. We then further evaluated the five algorithms with the highest accuracy, with the city and continental accuracy ranging from 85–89% to 90–94%, respectively. Thereafter, we used these results to develop Cassandra, a random-forest-based classifier that identifies bioindicator species to aid in fingerprinting and can infer higher-order microbial interactions at each site. We further tested the Cassandra algorithm on the Tara Oceans dataset, the largest collection of marine-based microbial genomes, where it classified the oceanic sample locations with 83% accuracy. These results and code show the utility of SML methods and Cassandra to identify bioindicator species across both oceanic and urban environments, which can help guide ongoing efforts in biotracing, environmental monitoring, and microbial forensics (MF). Full article

(This article belongs to the Special Issue Application of Bioinformatics in Microbiome)

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14 pages, 5279 KiB

Open AccessArticle

Classification and Prognosis Analysis of Pancreatic Cancer Based on DNA Methylation Profile and Clinical Information

by Xin Li, Xuan Zhang, Xiangyu Lin, Liting Cai, Yan Wang and Zhiqiang Chang

Genes 2022, 13(10), 1913; https://doi.org/10.3390/genes13101913 - 21 Oct 2022

Cited by 5 | Viewed by 1718

Abstract

Pancreatic adenocarcinoma (PAAD) has a poor prognosis with high individual variation in the treatment response among patients; however, there is no standard molecular typing method for PAAD prognosis in clinical practice. We analyzed DNA methylation data from The Cancer Genome Atlas database, which [...] Read more.

Pancreatic adenocarcinoma (PAAD) has a poor prognosis with high individual variation in the treatment response among patients; however, there is no standard molecular typing method for PAAD prognosis in clinical practice. We analyzed DNA methylation data from The Cancer Genome Atlas database, which identified 1235 differentially methylated DNA genes between PAAD and adjacent tissue samples. Among these, 78 methylation markers independently affecting PAAD prognosis were identified after adjusting for significant clinical factors. Based on these genes, two subtypes of PAAD were identified through consistent clustering. Fourteen specifically methylated genes were further identified to be associated with survival. Further analyses of the transcriptome data identified 301 differentially expressed cancer driver genes between the two PAAD subtypes and the degree of immune cell infiltration differed significantly between the subtypes. The 14 specific genes characterizing the unique methylation patterns of the subtypes were used to construct a Bayesian network-based prognostic prediction model for typing that showed good predictive value (area under the curve value of 0.937). This study provides new insight into the heterogeneity of pancreatic tumors from an epigenetic perspective, offering new strategies and targets for personalized treatment plan evaluation and precision medicine for patients with PAAD. Full article

(This article belongs to the Special Issue DNA and RNA Epigenetics and Transcriptomics Research)

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15 pages, 1537 KiB

Open AccessArticle

Allele-Specific Disruption of a Common STAT3 Autosomal Dominant Allele Is Not Sufficient to Restore Downstream Signaling in Patient-Derived T Cells

by Saskia König, Manfred Fliegauf, Manuel Rhiel, Bodo Grimbacher, Tatjana I. Cornu, Toni Cathomen and Claudio Mussolino

Genes 2022, 13(10), 1912; https://doi.org/10.3390/genes13101912 - 20 Oct 2022

Cited by 1 | Viewed by 1558

Abstract

Dominant negative mutations in the STAT3 gene account for autosomal dominant hyper-IgE syndrome (AD-HIES). Patients typically present high IgE serum levels, recurrent infections, and soft tissue abnormalities. While current therapies focus on alleviating the symptoms, hematopoietic stem cell transplantation (HSCT) has recently been [...] Read more.

Dominant negative mutations in the STAT3 gene account for autosomal dominant hyper-IgE syndrome (AD-HIES). Patients typically present high IgE serum levels, recurrent infections, and soft tissue abnormalities. While current therapies focus on alleviating the symptoms, hematopoietic stem cell transplantation (HSCT) has recently been proposed as a strategy to treat the immunological defect and stabilize the disease, especially in cases with severe lung infections. However, because of the potentially severe side effects associated with allogeneic HSCT, this has been considered only for a few patients. Autologous HSCT represents a safer alternative but it requires the removal of the dominant negative mutation in the patients’ cells prior to transplantation. Here, we developed allele-specific CRISPR-Cas9 nucleases to selectively disrupt five of the most common STAT3 dominant negative alleles. When tested ex vivo in patient-derived hematopoietic cells, allele-specific disruption frequencies varied in an allele-dependent fashion and reached up to 62% of alleles harboring the V637M mutation without detectable alterations in the healthy STAT3 allele. However, assessment of the gene expression profiles of the STAT3 downstream target genes revealed that, upon activation of those edited patient cells, mono-allelic STAT3 expression (functional haploinsufficiency) is not able to sufficiently restore STAT3-dependent signaling in edited T cells cultured in vitro. Moreover, the stochastic mutagenesis induced by the repair of the nuclease-induced DNA break could further contribute to dominant negative effects. In summary, our results advocate for precise genome editing strategies rather than allele-specific gene disruption to correct the underlying mutations in AD-HIES. Full article

(This article belongs to the Special Issue Gene Editing for Therapy and Reverse Genetics of Blood Diseases)

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10 pages, 1858 KiB

Open AccessArticle

Evaluation of Mean Percentage of Full-Length SMN Transcripts as a Molecular Biomarker of Spinal Muscular Atrophy

by Marianna Maretina, Anna Egorova, Kristina Lanko, Vladislav Baranov and Anton Kiselev

Genes 2022, 13(10), 1911; https://doi.org/10.3390/genes13101911 - 20 Oct 2022

Cited by 3 | Viewed by 1514

Abstract

The elevation of SMN transcript and protein level remains the principal aim of SMA therapy. Still, there is no standard molecular biomarker for the assessment of its efficacy. In the current study, we tested three methods of SMN transcript level measurement using real-time [...] Read more.

The elevation of SMN transcript and protein level remains the principal aim of SMA therapy. Still, there is no standard molecular biomarker for the assessment of its efficacy. In the current study, we tested three methods of SMN transcript level measurement using real-time RT-PCR, quantitative fluorescent RT-PCR, and a semiquantitative RT-PCR gel densitometric assay. We examined several potential mRNA-based biomarkers and examined their sensitivity and reliability by comparing the obtained values in peripheral blood mononuclear cells of SMA patients, SMA carriers, and healthy individuals. We found that the mean percentage of full-length (FL-SMN) transcripts relative to the total sum of FL-SMN and exon 7-deleted (Δ7 SMN) transcripts detected by semiquantitative and quantitative fluorescence RT-PCR differed significantly between the three analyzed groups. The relevance of this biomarker was proven in an SMN2-targeting therapeutic experiment. We showed that the values of the biomarker changed significantly in SMA fibroblast cell cultures after treatment with therapeutic antisense oligonucleotides targeting the ISS-N1 site in intron 7 of the SMN2 gene. The obtained results indicate the convenience of using the mean percentage of FL-SMN transcripts determined by semiquantitative and quantitative fluorescence RT-PCR as a putative biomarker for the assessment of SMA therapy efficacy in vitro. Full article

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

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18 pages, 7239 KiB

Open AccessArticle

Selection Signature and CRISPR/Cas9-Mediated Gene Knockout Analyses Reveal ZC3H10 Involved in Cold Adaptation in Chinese Native Cattle

by Luyu Wang, Yaping Gao, Jinpeng Wang, Ning Huang, Qiang Jiang, Zhihua Ju, Chunhong Yang, Xiaochao Wei, Yao Xiao, Yaran Zhang, Ling Yang and Jinming Huang

Genes 2022, 13(10), 1910; https://doi.org/10.3390/genes13101910 - 20 Oct 2022

Cited by 1 | Viewed by 1821

Abstract

Cold stress is an important factor affecting cattle health, production performance, and reproductive efficiency. Understanding of the potential mechanism underlying genetic adaptation to local environments, particularly extreme cold environment, is limited. Here, by using FLK and hapFLK methods, we found that the Zinc [...] Read more.

Cold stress is an important factor affecting cattle health, production performance, and reproductive efficiency. Understanding of the potential mechanism underlying genetic adaptation to local environments, particularly extreme cold environment, is limited. Here, by using FLK and hapFLK methods, we found that the Zinc finger CCCH-type containing 10 (ZC3H10) gene underwent positive selection in the Menggu, Fuzhou, Anxi, and Shigatse humped cattle breeds that are distributed in the cold areas of China. Furthermore, ZC3H10 expression significantly increased in bovine fetal fibroblast (BFF) cells at 28 °C for 4 h. ZC3H10 knockout BFFs were generated using CRISPR/Cas9. Wild and ZC3H10-deleted BFFs were treated at two temperatures and were divided into four groups (WT, wild and cultured at 38 °C; KO, ZC3H10^−/− and 38 °C; WT_LT, wild, and 28 °C for 4 h; and KO_LT, ZC3H10^−/− and 28 °C for 4 h. A total of 466, 598, 519, and 650 differently expressed genes (two-fold or more than two-fold changes) were identified by determining transcriptomic difference (KO_LT vs. KO, WT_LT vs. WT, KO vs. WT, and KO_LT vs. WT_LT, respectively). Loss of ZC3H10 dysregulated pathways involved in thermogenesis and immunity, and ZC3H10 participated in immunity-related pathways induced by cold stress and regulated genes involved in glucose and lipid metabolism and lipid transport (PLTP and APOA1), thereby facilitating adaptability to cold stress. Our findings provide a foundation for further studies on the function of ZC3H10 in cold stress and development of bovine breeding strategies for combatting the influences of cold climate. Full article

(This article belongs to the Special Issue Genomic View of Cattle Breeding and Domestication)

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18 pages, 1565 KiB

Open AccessArticle

Integrated Metabolite and Transcriptome Profiling-Mediated Gene Mining of Sida cordifolia Reveals Medicinally Important Genes

by Deepthi Padmanabhan, Purushothaman Natarajan and Senthilkumar Palanisamy

Genes 2022, 13(10), 1909; https://doi.org/10.3390/genes13101909 - 20 Oct 2022

Cited by 2 | Viewed by 1995

Abstract

Sida cordifolia is a medicinal shrub that is conventionally used in the Indian system of medicine;however, the genes contributing to its medicinal properties have been minimally explored, thus limiting its application. High-throughputsequencing and Liquid Chromatography with tandem mass spectrometry(LC-MS/MS) technologies were applied to [...] Read more.

Sida cordifolia is a medicinal shrub that is conventionally used in the Indian system of medicine;however, the genes contributing to its medicinal properties have been minimally explored, thus limiting its application. High-throughputsequencing and Liquid Chromatography with tandem mass spectrometry(LC-MS/MS) technologies were applied to unravel the medicinally important bioactive compounds. As a result, transcriptomic sequencing generated more than 12 GB of clean data, and 187,215 transcripts were obtained by de novoassembly. These transcripts were broadly classified into 20 classes, based on the gene ontology classification, and 6551 unigenes were annotated using Kyoto Encyclopedia of Genes and Genomes (KEGG) database with more than 142 unigenes involved in the biosynthesis of secondary metabolites. LC-MS/MS analysis of three tissues of Sida cordifolia revealed that acacetin and procyanidin are some important metabolites identified thatcontribute to its medicinal value. Several key enzymes witha crucial role in phenylpropanoid and flavonoid biosynthetic pathways were identified, especially phenylalanine ammonia lyase, which might be an important rate-limiting enzyme. Real-Time Quantitative Reverse Transcription Polymerase chain reaction (qRT-PCR) analysis revealed enzymes, such as Phenylalanine ammonia lyase (PAL), Cinnamyl alcohol dehydrogenase 1 (CAD), Cinnamoyl-CoA reductase 1 (CF1) and Trans cinnamate 4-monooxygenase(TCM), which were predominantly expressed in root compared to leaf and stem tissue. The study provides a speculative insight for the screening of active metabolites and metabolic engineering in Sida cordifolia. Full article

(This article belongs to the Special Issue Phylogenetics, Genetics, and Breeding of Medicinal Plants)

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21 pages, 4083 KiB

Open AccessArticle

Multilocus Phylogeography and Population Genetic Analyses of Opsariichthys hainanensis Reveal Pleistocene Isolation Followed by High Gene Flow around the Gulf of Tonkin

by Junjie Wang, Wenjun Zhang, Jinxian Wu, Chao Li, Yu-Min Ju, Hung-Du Lin and Jun Zhao

Genes 2022, 13(10), 1908; https://doi.org/10.3390/genes13101908 - 20 Oct 2022

Cited by 5 | Viewed by 1418

Abstract

The ichthyofauna of continental islands is characterized by immigration through a land bridge due to fluctuating sea levels. Hainan Island is adjacent to the southern margin of mainland China and provides opportunities for understanding the origin and diversification of freshwater fishes. The aim [...] Read more.

The ichthyofauna of continental islands is characterized by immigration through a land bridge due to fluctuating sea levels. Hainan Island is adjacent to the southern margin of mainland China and provides opportunities for understanding the origin and diversification of freshwater fishes. The aim of our study was to evaluate the level of genetic variation and phylogeographic structure of Opsariichthys hainanensis on Hainan Island and mainland China, using mtDNA cyt b gene (1140 bp) and D-loop (926 bp), nuclear RAG1 gene (1506 bp), and 12 microsatellite loci. Mitochondrial phylogenetic analysis identified five major lineages according to the geographical distribution from different populations. We suggested that two dispersal events occurred: the population in the Changhua River migrated to the Red River (Lineage B), and the populations in the South Hainan region moved northwards to the North Hainan region. However, populations in Northwest Hainan Island dispersed to the populations around the Gulf of Tonkin (Lineage A1) and populations in Northeast Hainan Island dispersed to the populations in mainland China (Lineage A2). Our results indicated that the populations of O. hainanensis suffered a bottleneck event followed by a recent population expansion supported by the ABC analysis. We suggest that O. hainanensis populations were found mostly in the lowlands and a lack of suitable freshwater habitat in southern mainland China and Hainan during the Last Interglacial period, and then expansion occurred during the Last Glacial Maximum. Full article

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

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15 pages, 316 KiB

Open AccessArticle

Interactions between Environmental Factors and Glutathione S-Transferase (GST) Genes with Respect to Detectable Blood Aluminum Concentrations in Jamaican Children

by Mohammad H. Rahbar, Maureen Samms-Vaughan, Yuansong Zhao, Sepideh Saroukhani, Jan Bressler, Manouchehr Hessabi, Megan L. Grove, Sydonnie Shakespeare-Pellington and Katherine A. Loveland

Genes 2022, 13(10), 1907; https://doi.org/10.3390/genes13101907 - 20 Oct 2022

Viewed by 1215

Abstract

Aluminum (Al) is a metallic toxicant at high concentrations following natural or unnatural exposures. Dietary intake is considered as the main source of aluminum exposure in children. We used data from 366 typically developing (TD) children (ages 2–8 years) who participated as controls [...] Read more.

Aluminum (Al) is a metallic toxicant at high concentrations following natural or unnatural exposures. Dietary intake is considered as the main source of aluminum exposure in children. We used data from 366 typically developing (TD) children (ages 2–8 years) who participated as controls in an age- and sex-matched case–control study in Jamaica. We investigated additive and interactive associations among environmental factors and children’s genotypes for glutathione S-transferase (GST) genes (GSTT1, GSTM1, GSTP1), in relation to having a detectable blood aluminum concentration (BAlC) of >5.0 μg/L, using multivariable logistic regression models. Findings from interactive models revealed that the odds of having a detectable BAlC was significantly higher among children who ate string beans (p ≤ 0.01), whereas about 40% lower odds of having a detectable BAlC was observed in children with higher parental education level, (p = 0.02). A significant interaction between consumption of saltwater fish and GSTP1 in relation to having a detectable BAlC using either co-dominant or dominant genetic models (overall interaction p = 0.02 for both models) indicated that consumption of saltwater fish was associated with higher odds of having a detectable BAlC only among children with the GSTP1 Ile105Val Ile/Ile genotype using either co-dominant or dominant models [OR (95% CI) = 2.73 (1.07, 6.96), p = 0.04; and OR (95% CI) = 2.74 (1.08, 6.99), p = 0.03]. Since this is the first study from Jamaica that reports such findings, replication in other populations is warranted. Full article

(This article belongs to the Special Issue Genomics of Neuropsychiatric Disorders)

19 pages, 2929 KiB

Open AccessArticle

Genome-Wide Identification of Potential mRNAs in Drought Response in Wheat (Triticum aestivum L.)

by Muhammad Aqeel, Wajya Ajmal, Quratulain Mujahid, Maryam Murtaza, Mansour Almuqbil, Shakira Ghazanfar, Muhammad Uzair, Ayesha Wadood, Syed Mohammed Basheeruddin Asdaq, Rameesha Abid, Ghulam Muhammad Ali and Muhammad Ramzan Khan

Genes 2022, 13(10), 1906; https://doi.org/10.3390/genes13101906 - 20 Oct 2022

Cited by 1 | Viewed by 2199

Abstract

Plant cell metabolism inevitably forms an important drought-responsive mechanism, which halts crop productivity. Globally, more than 30% of the total harvested area was affected by dehydration. RNA-seq technology has enabled biologists to identify stress-responsive genes in relatively quick times. However, one shortcoming of [...] Read more.

Plant cell metabolism inevitably forms an important drought-responsive mechanism, which halts crop productivity. Globally, more than 30% of the total harvested area was affected by dehydration. RNA-seq technology has enabled biologists to identify stress-responsive genes in relatively quick times. However, one shortcoming of this technology is the inconsistent data generation compared to other parts of the world. So, we have tried, here, to generate a consensus by analyzing meta-transcriptomic data available in the public microarray database GEO NCBI. In this way, the aim was set, here, to identify stress genes commonly identified as differentially expressed (p < 0.05) then followed by downstream analyses. The search term “Drought in wheat” resulted in 233 microarray experiments from the GEO NCBI database. After discarding empty datasets containing no expression data, the large-scale meta-transcriptome analytics and one sample proportional test were carried out (Bonferroni adjusted p < 0.05) to reveal a set of 11 drought-responsive genes on a global scale. The annotation of these genes revealed that the transcription factor activity of RNA polymerase II and sequence-specific DNA-binding mechanism had a significant role during the drought response in wheat. Similarly, the primary root differentiation zone annotations, controlled by TraesCS5A02G456300 and TraesCS7B02G243600 genes, were found as top-enriched terms (p < 0.05 and Q < 0.05). The resultant standard drought genes, glycosyltransferase; Arabidopsis thaliana KNOTTED-like; bHLH family protein; Probable helicase MAGATAMA 3; SBP family protein; Cytochrome c oxidase subunit 2; Trihelix family protein; Mic1 domain-containing protein; ERF family protein; HD-ZIP I protein; and ERF family protein, are important in terms of their worldwide proved link with stress. From a future perspective, this study could be important in a breeding program contributing to increased crop yield. Moreover, the wheat varieties could be identified as drought-resistant/sensitive based on the nature of gene expression levels. Full article

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

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9 pages, 943 KiB

Open AccessArticle

Postoperative Hypocalcemia following Non-Cardiac Surgical Procedures in Children with 22q11.2 Deletion Syndrome

by Jill M. Arganbright, Meghan Tracy, Max Feldt, Srivats Narayanan, Ashna Mahadev and Janelle Noel-MacDonnell

Genes 2022, 13(10), 1905; https://doi.org/10.3390/genes13101905 - 20 Oct 2022

Cited by 3 | Viewed by 1690

Abstract

The guidelines for management of children with 22q11.2 deletion syndrome (22q11DS) highlight the risk for developing hypocalcemia after surgery and recommend monitoring calcium perioperatively. Despite this guidance, little has been published on postoperative hypocalcemia and 22q11DS. Our goals were to evaluate the frequency [...] Read more.

The guidelines for management of children with 22q11.2 deletion syndrome (22q11DS) highlight the risk for developing hypocalcemia after surgery and recommend monitoring calcium perioperatively. Despite this guidance, little has been published on postoperative hypocalcemia and 22q11DS. Our goals were to evaluate the frequency of perioperative calcium monitoring and examine how often postoperative hypocalcemia was identified. This is a retrospective chart review of patients in our 22q Center’s repository. Inclusion criteria were a diagnosis of 22q11DS and a history of a non-cardiac surgical procedure. Data collected included all non-cardiac surgeries and perioperative calcium labs. In total, 68 patients were included and underwent 305 on-cardiac surgeries. Patients in only 17% of these surgeries had postoperative calcium testing, but of those tested, 58% showed hypocalcemia. Patients with history of hypocalcemia at the time of chart review undergoing non-cardiac surgeries were tested postoperatively 40% of the time; however, 67% of these had hypocalcemia. Similarly, for patients without history of hypocalcemia, postoperative testing occurred 60% of the time, with 52% of these having hypocalcemia. This study demonstrates that postoperative hypocalcemia in children with 22q11DS following non-cardiac surgeries is common and affects patients both with and without prior history of hypocalcemia. These data support establishing a protocol for perioperative testing/management of hypocalcemia for patients with 22q11DS. Full article

(This article belongs to the Special Issue 22q11.2 Deletion Syndrome)

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15 pages, 2873 KiB

Open AccessArticle

Adaptive Response and Transcriptomic Analysis of Flax (Linum usitatissimum L.) Seedlings to Salt Stress

by Yuandong Li, Jiao Chen, Xiao Li, Haixia Jiang, Dongliang Guo, Fang Xie, Zeyang Zhang and Liqiong Xie

Genes 2022, 13(10), 1904; https://doi.org/10.3390/genes13101904 - 20 Oct 2022

Viewed by 1625

Abstract

Soil salinity constrains agricultural development in arid regions. Flax is an economically important crop in many countries, and screening or breeding salinity-resistant flax cultivars is necessary. Based on the previous screening of flaxseed cultivars C71 (salt-sensitive) and C116 (salt-tolerant) as test materials, flax [...] Read more.

Soil salinity constrains agricultural development in arid regions. Flax is an economically important crop in many countries, and screening or breeding salinity-resistant flax cultivars is necessary. Based on the previous screening of flaxseed cultivars C71 (salt-sensitive) and C116 (salt-tolerant) as test materials, flax seedlings stressed with different concentrations of NaCl (0, 100, 150, 200, and 250 mmol/L) for 21 days were used to investigate the effects of salt stress on the growth characteristics, osmotic regulators, and antioxidant capacity of these flax seedlings and to reveal the adaptive responses of flax seedlings to salt stress. The results showed that plant height and root length of flax were inhibited, with C116 showing lower growth than C71. The concentrations of osmotic adjustment substances such as soluble sugars, soluble proteins, and proline were higher in the resistant material, C116, than in the sensitive material, C71, under different concentrations of salt stress. Consistently, C116 showed a better rapid scavenging ability for reactive oxygen species (ROS) and maintained higher activities of antioxidant enzymes to balance salt injury stress by inhibiting growth under salt stress. A transcriptome analysis of flax revealed that genes related to defense and senescence were significantly upregulated, and genes related to the growth and development processes were significantly downregulated under salt stress. Our results indicated that one of the important adaptations to tolerance to high salt stress is complex physiological remediation by rapidly promoting transcriptional regulation in flax. Full article

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

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17 pages, 5255 KiB

Open AccessArticle

Comparative Biochemical and Transcriptomic Analyses Provide New Insights into Phytoplasma Infection Responses in Cucumber

by Xueting Wang, Qiming Hu, Jiaxi Wang, Lina Lou, Xuewen Xu and Xuehao Chen

Genes 2022, 13(10), 1903; https://doi.org/10.3390/genes13101903 - 19 Oct 2022

Cited by 1 | Viewed by 1797

Abstract

Flat stem and witches’ broom phytoplasma-like symptoms in the cucumber inbred line C17 were observed in a greenhouse at Yangzhou University, China for three consecutive planting seasons; these symptoms resulted in a decreased yield. To better understand the cause of these symptoms, 16S [...] Read more.

Flat stem and witches’ broom phytoplasma-like symptoms in the cucumber inbred line C17 were observed in a greenhouse at Yangzhou University, China for three consecutive planting seasons; these symptoms resulted in a decreased yield. To better understand the cause of these symptoms, 16S rRNA PCR, plant hormones, mineral elements, and RNA-seq profiling were performed using symptomatic and normal stem samples. The results showed that the causal agent was classified as the Candidatus phytoplasma asteris strain, a plant pathogenic prokaryote that could not be cultured in vitro. Measurement of plant hormones showed that auxin, salicylic acid, and jasmonic acid contents were significantly increased, whereas that of ethylene’s immediate biosynthetic precursor, 1-aminocyclopropane-1-carboxylic acid, was decreased in the phytoplasma-infected stems compared with the healthy stems. Furthermore, measurement of mineral element composition showed that magnesium, calcium, sodium, iron, and zinc concentrations significantly changed in the phytoplasma-infected cucumber stems compared with the uninfected stems. Comparative RNA-seq identified 253 differentially expressed genes, including 179 upregulated and 74 downregulated genes. Further analyses suggested that genes related to phenylpropanoid biosynthesis, phenylalanine metabolism, and plant hormone signal transduction contributed to phytoplasma infection. Taken together, this study presents the first in-depth assessment of disease symptoms and biochemical content of cucumber stems known to be infected with phytoplasma. Full article

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

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10 pages, 2061 KiB

Open AccessArticle

Identification of Candidate Genes for Twinning Births in Dezhou Donkeys by Detecting Signatures of Selection in Genomic Data

by Taifeng Xie, Shuer Zhang, Wei Shen, Guoliang Zhang, Rong Guo, Wei Zhang, Yanhang Cao, Qingjie Pan, Fengxin Liu, Yujiang Sun and Shuqin Liu

Genes 2022, 13(10), 1902; https://doi.org/10.3390/genes13101902 - 19 Oct 2022

Cited by 1 | Viewed by 1278

Abstract

Twinning trait in donkeys is an important manifestation of high fecundity, but few reports are available elucidating its genetic mechanism. To explore the genetic mechanism underlying the twin colt trait in Dezhou donkeys, DNA from 21 female Dezhou donkeys that had birthed single [...] Read more.

Twinning trait in donkeys is an important manifestation of high fecundity, but few reports are available elucidating its genetic mechanism. To explore the genetic mechanism underlying the twin colt trait in Dezhou donkeys, DNA from 21 female Dezhou donkeys that had birthed single or twin colts were collected for whole-genome resequencing. F_ST, θπ and Tajima’s D were used to detect the selective sweeps between single and twin colt fecundity in the Dezhou donkey groups. Another set of 20 female Dezhou donkeys with single or multiple follicles during estrus were selected to compare concentrations of reproductive hormone including follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E₂) and progesterone (P₄). Four candidate genes including ENO2, PTPN11, SOD2 and CD44 were identified in the present study. The CD44 gene had the highest F_ST value, and ENO2, PTPN11 and SOD2 were screened by two joint analyses (F_ST and θπ, θπ and Tajima’s D). There was no significant difference in the LH, FSH and P₄ levels between the two groups (p > 0.05); however, the serum E₂ content in the multi-follicle group was significantly higher than that in the single-follicle group (p < 0.05). The identified candidate genes may provide new insights into the genetic mechanism of donkey prolificacy and may be useful targets for further research on high reproductive efficiency. Full article

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

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16 pages, 952 KiB

Open AccessReview

Mesenchymal-Stem-Cell-Based Strategies for Retinal Diseases

by Xiteng Chen, Yuanfeng Jiang, Yanan Duan, Xiaomin Zhang and Xiaorong Li

Genes 2022, 13(10), 1901; https://doi.org/10.3390/genes13101901 - 19 Oct 2022

Cited by 7 | Viewed by 2307

Abstract

Retinal diseases are major causes of irreversible vision loss and blindness. Despite extensive research into their pathophysiology and etiology, pharmacotherapy effectiveness and surgical outcomes remain poor. Based largely on numerous preclinical studies, administration of mesenchymal stem cells (MSCs) as a therapeutic strategy for [...] Read more.

Retinal diseases are major causes of irreversible vision loss and blindness. Despite extensive research into their pathophysiology and etiology, pharmacotherapy effectiveness and surgical outcomes remain poor. Based largely on numerous preclinical studies, administration of mesenchymal stem cells (MSCs) as a therapeutic strategy for retinal diseases holds great promise, and various approaches have been applied to the therapies. However, hindered by the retinal barriers, the initial vision for the stem cell replacement strategy fails to achieve the anticipated effect and has now been questioned. Accumulating evidence now suggests that the paracrine effect may play a dominant role in MSC-based treatment, and MSC-derived extracellular vesicles emerge as a novel compelling alternative for cell-free therapy. This review summarizes the therapeutic potential and current strategies of this fascinating class of cells in retinal degeneration and other retinal dysfunctions. Full article

(This article belongs to the Special Issue Pharmaceutical Research in Stem Cells)

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12 pages, 2074 KiB

Open AccessArticle

A Novel De Novo NFKBIA Missense Mutation Associated to Ectodermal Dysplasia with Dysgammaglobulinemia

by Chai Teng Chear, Bader Abdul Kader El Farran, Marina Sham, Kavetha Ramalingam, Lokman Mohd Noh, Intan Hakimah Ismail, Mei Yee Chiow, Mohd Farid Baharin, Adiratna Mat Ripen and Saharuddin Bin Mohamad

Genes 2022, 13(10), 1900; https://doi.org/10.3390/genes13101900 - 19 Oct 2022

Cited by 3 | Viewed by 2201

Abstract

Background: Inborn errors of immunity (IEIs) are comprised of heterogeneous groups of genetic disorders affecting immune function. In this report, a 17-month-old Malay patient suspected of having Hyper IgM syndrome, a type of IEIs, was described. However, the diagnosis of Hyper IgM syndrome [...] Read more.

Background: Inborn errors of immunity (IEIs) are comprised of heterogeneous groups of genetic disorders affecting immune function. In this report, a 17-month-old Malay patient suspected of having Hyper IgM syndrome, a type of IEIs, was described. However, the diagnosis of Hyper IgM syndrome was excluded by the normal functional studies and the mild features of ectodermal dysplasia observed from a further clinical phenotype inspection. Methods: Whole-exome sequencing (WES) was performed to unravel the causative mutation in this patient. Results: The variant analysis demonstrated a novel missense mutation in NFKBIA (NM_020529:c.94A > T,NP_065390:p.Ser32Cys) and was predicted as damaging by in silico prediction tools. The NFKBIA gene encodes for IκBα, a member of nuclear factor kappa B (NF-κB) inhibitors, playing an important role in regulating NF-κB activity. The mutation occurred at the six degrons (Asp31-Ser36) in IκBα which were evolutionarily conserved across several species. Prediction analysis suggested that the substitution of Ser32Cys may cause a loss of the phosphorylation site at residue 32 and a gain of the sumoylation site at residue 38, resulting in the alteration of post-translational modifications of IκBα required for NF-κB activation. Conclusion: Our analysis hints that the post-translational modification in the NFKBIA Ser32Cys mutant would alter the signaling pathway of NF-κB. Our findings support the usefulness of WES in diagnosing IEIs and suggest the role of post-translational modification of IκBα. Full article

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

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11 pages, 2327 KiB

Open AccessArticle

A Single Nucleotide Polymorphism Translates into a Radical Amino Acid Substitution at the Ligand-Binding Site in Fasciola hepatica Carboxylesterase B

by Estefan Miranda-Miranda, Silvana Scarcella, Enrique Reynaud, Verónica Narváez-Padilla, Gisela Neira, Roberto Mera-y-Sierra, Hugo Aguilar-Díaz and Raquel Cossio-Bayugar

Genes 2022, 13(10), 1899; https://doi.org/10.3390/genes13101899 - 19 Oct 2022

Cited by 1 | Viewed by 1250

Abstract

Fasciola hepatica anthelmintic resistance may be associated with the catalytic activity of xenobiotic metabolizing enzymes. The gene expression of one of these enzymes, identified as carboxylesterase B (CestB), was previously described as inducible in adult parasites under anthelmintic treatment and exhibited a single [...] Read more.

Fasciola hepatica anthelmintic resistance may be associated with the catalytic activity of xenobiotic metabolizing enzymes. The gene expression of one of these enzymes, identified as carboxylesterase B (CestB), was previously described as inducible in adult parasites under anthelmintic treatment and exhibited a single nucleotide polymorphism at position 643 that translates into a radical amino acid substitution at position 215 from Glutamic acid to Lysine. Alphafold 3D models of both allelic sequences exhibited a significant affinity pocket rearrangement and different ligand-docking modeling results. Further bioinformatics analysis confirmed that the radical amino acid substitution is located at the ligand affinity site of the enzyme, affecting its affinity to serine hydrolase inhibitors and preferences for ester ligands. A field genotyping survey from parasite samples obtained from two developmental stages isolated from different host species from Argentina and Mexico exhibited a 37% allele distribution for 215E and a 29% allele distribution for 215K as well as a 34% E/K heterozygous distribution. No linkage to host species or geographic origin was found in any of the allele variants. Full article

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

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16 pages, 1224 KiB

Open AccessArticle

Effects of Different Rearing Systems on Lueyang Black-Bone Chickens: Meat Quality, Amino Acid Composition, and Breast Muscle Transcriptome

by Shuya Zhang, Jiqiao Zhang, Chang Cao, Yingjie Cai, Yuxiao Li, Yiping Song, Xiuyu Bao and Jianqin Zhang

Genes 2022, 13(10), 1898; https://doi.org/10.3390/genes13101898 - 19 Oct 2022

Cited by 4 | Viewed by 1653

Abstract

The quality of poultry products depends on genotype, rearing system, and environment. The aim of this study was to investigate the effects of different rearing systems on meat quality, amino acid composition, and breast muscle transcriptome from Lueyang black-bone chickens. Lueyang black-bone chickens [...] Read more.

The quality of poultry products depends on genotype, rearing system, and environment. The aim of this study was to investigate the effects of different rearing systems on meat quality, amino acid composition, and breast muscle transcriptome from Lueyang black-bone chickens. Lueyang black-bone chickens (n = 900) were randomly divided into three groups (cage, flat-net, and free-range groups), with three replicates per group (100 chickens per replicate). At 16 weeks, a total of 36 healthy chickens (six males and six females per group) were collected, and their breast muscles were sampled to detect meat quality parameters, amino acid composition, and fatty acid contents. Furthermore, breast muscles from six random hens in each group were used for RNA-seq analysis. The results revealed that the values of pH, shear force, inosine monophosphate (IMP), palmitic acid, and linoleic acid in the free-range group were significantly higher than those in the caged group (p < 0.05). Fat content in the free-range group was significantly lower than in the caged and flat-net groups (p < 0.05). Glutamate (Glu) levels, the amino acid crucial for the umami taste, was significantly higher in the free-range group than in the caged group (p < 0.05). Meanwhile, there was no significant difference between the free-range and flat-net groups (p > 0.05). The breast muscle transcriptome results showed that there were 291, 131, and 387 differently expressed genes (DEGs) among the three comparison groups (caged vs. free-range, flat-net vs. caged, and flat-net vs. free-range, respectively) that were mainly related to muscle development and amino acid metabolism pathways. To validate the accuracy of the transcriptome data, eight genes (GOS2, ASNS, NMRK2, GADL1, SMTNL2, SLC7A5, AMPD1, and GLUL) which relate to fat deposition, skeletal muscle function, and flavor formation were selected for Real-time Quantitative PCR (RT-qPCR) verification. In conclusion, these results suggested that rearing systems significantly influenced the meat quality and gene expression of Lueyang black-bone chickens. All the data proved that free-range and flat-net systems may provide better flavor to consumers by affecting the deposition of flavor substances and the expression of related genes. These findings will provide a valuable theoretical basis for the rearing system selection in the poultry industry. Full article

(This article belongs to the Section Genes & Environments)

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18 pages, 23308 KiB

Open AccessArticle

Systematic Analysis of Immune Infiltration and Predicting Prognosis in Clear Cell Renal Cell Carcinoma Based on the Inflammation Signature

by Yuke Zhang, Chunliu Shi, Yue Chen, Hongwei Wang, Feng Chen and Ping Han

Genes 2022, 13(10), 1897; https://doi.org/10.3390/genes13101897 - 19 Oct 2022

Cited by 2 | Viewed by 1566

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most frequent kind of kidney malignancy. Inflammation is a physiological response of the immune system to harmful stimuli. Notably, the role inflammation plays in ccRCC is still unknown. In this study, consensus clustering analysis sorted [...] Read more.

Clear cell renal cell carcinoma (ccRCC) is the most frequent kind of kidney malignancy. Inflammation is a physiological response of the immune system to harmful stimuli. Notably, the role inflammation plays in ccRCC is still unknown. In this study, consensus clustering analysis sorted the ccRCC specimens from the TCGA dataset into C1 and C2 clusters. The C2 cluster comprised ccRCC specimens with a high TNM stage and tumor grade. These specimens were characterized by the activation of the inflammatory response and an immunosuppressive microenvironment. A seven-gene inflammation-related risk signature was designed employing the LASSO and Cox regression analyses for the inflammation-related genes. The ccRCC specimens were classified into two groups with high and low risk by calculating the risk scores. The specimens in the group with high risk showed a poor prognosis and were positively correlated with immune inhibitory factors. Moreover, a nomogram was created by incorporating inflammation-related risk signatures and clinical characteristics. The ROC and DCA curves indicated a satisfactory efficiency of the nomogram for predicting the survival outcomes. Furthermore, we identified the potential therapeutic drug molecules through CMap analysis. The findings of our study may act as a guide for further research on new prognostic biomarkers and therapies. Full article

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

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11 pages, 1768 KiB

Open AccessArticle

Assessment of Genetic Diversity, Runs of Homozygosity, and Signatures of Selection in Tropical Milking Criollo Cattle Using Pedigree and Genomic Data

by Ricardo Martínez-Rocha, Jorge Hidalgo, Alberto Cesarani, Rodolfo Ramírez-Valverde, Rafael Núñez-Domínguez, José Guadalupe García-Muñiz and Joel Domínguez-Viveros

Genes 2022, 13(10), 1896; https://doi.org/10.3390/genes13101896 - 19 Oct 2022

Cited by 1 | Viewed by 1558

Abstract

The objective of this study was to evaluate the genetic diversity of the Tropical Milking Criollo cattle (TMC) breed in Mexico through parameters derived from pedigree and genomic information assessment. The pedigree file consisted of 3780 animals. Seventy-nine bovines were genotyped with the [...] Read more.

The objective of this study was to evaluate the genetic diversity of the Tropical Milking Criollo cattle (TMC) breed in Mexico through parameters derived from pedigree and genomic information assessment. The pedigree file consisted of 3780 animals. Seventy-nine bovines were genotyped with the medium-density single nucleotide polymorphism chip and considered a reference population for pedigree analysis. The effective population size and the probability of gene origin used to assess the evolution of genetic diversity were calculated with pedigree information. Inbreeding coefficients were evaluated based on pedigree (

F_{P e d}

), the genomic relationship matrix (

F_{G R M}

), and runs of homozygosity (

F_{R O H}

) of different length classes. The average inbreeding was 2.82 ± 2.66%, −0.7 ± 3.8%, and 10.9 ± 3.0% for

F_{P E D}

,

F_{G R M}

, and

F_{R O H}

, respectively. Correlation between

F_{P E D}

and

F_{R O H}

was significant only for runs of homozygosity > 4 Mb, indicating the

F_{P E D}

of a population with an average equivalent complete generation of five only recovers the most recent inbreeding. The parameters of the probability of gene origin indicated the existence of genetic bottlenecks and the loss of genetic diversity in the history of the TMC cattle population; however, pedigree and genomic information revealed the existence of current sufficient genetic diversity to design a sustainable breeding program. Full article

(This article belongs to the Special Issue Genomic View of Cattle Breeding and Domestication)

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16 pages, 4112 KiB

Open AccessArticle

A Novel Module Promotes Horizontal Gene Transfer in Azorhizobium caulinodans ORS571

by Mingxu Li, Qianqian Chen, Chuanhui Wu, Yiyang Li, Sanle Wang, Xuelian Chen, Bowen Qiu, Yuxin Li, Dongmei Mao, Hong Lin, Daogeng Yu, Yajun Cao, Zhi Huang, Chunhong Cui and Zengtao Zhong

Genes 2022, 13(10), 1895; https://doi.org/10.3390/genes13101895 - 19 Oct 2022

Cited by 2 | Viewed by 1713

Abstract

Azorhizobium caulinodans ORS571 contains an 87.6 kb integrative and conjugative element (ICE^Ac) that conjugatively transfers symbiosis genes to other rhizobia. Many hypothetical redundant gene fragments (rgfs) are abundant in ICE^Ac, but their potential function in horizontal gene transfer [...] Read more.

Azorhizobium caulinodans ORS571 contains an 87.6 kb integrative and conjugative element (ICE^Ac) that conjugatively transfers symbiosis genes to other rhizobia. Many hypothetical redundant gene fragments (rgfs) are abundant in ICE^Ac, but their potential function in horizontal gene transfer (HGT) is unknown. Molecular biological methods were employed to delete hypothetical rgfs, expecting to acquire a minimal ICE^Ac and consider non-functional rgfs as editable regions for inserting genes related to new symbiotic functions. We determined the significance of rgf4 in HGT and identified the physiological function of genes designated rihF1a (AZC_3879), rihF1b (AZC_RS26200), and rihR (AZC_3881). In-frame deletion and complementation assays revealed that rihF1a and rihF1b work as a unit (rihF1) that positively affects HGT frequency. The EMSA assay and lacZ-based reporter system showed that the XRE-family protein RihR is not a regulator of rihF1 but promotes the expression of the integrase (intC) that has been reported to be upregulated by the LysR-family protein, AhaR, through sensing host’s flavonoid. Overall, a conservative module containing rihF1 and rihR was characterized, eliminating the size of ICE^Ac by 18.5%. We propose the feasibility of constructing a minimal ICE^Ac element to facilitate the exchange of new genetic components essential for symbiosis or other metabolic functions between soil bacteria. Full article

(This article belongs to the Special Issue Microbe-Host Interaction)

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11 pages, 579 KiB

Open AccessReview

The PPARGC1A Is the Gene Responsible for Thrifty Metabolism Related Metabolic Diseases: A Scoping Review

by Riandini Aisyah, Ahmad Hamim Sadewa, Suryono Yudha Patria and Abdul Wahab

Genes 2022, 13(10), 1894; https://doi.org/10.3390/genes13101894 - 18 Oct 2022

Cited by 1 | Viewed by 2202

Abstract

The “thrifty genotype” hypothesis has thus far described the relationship between specific genes and the population’s resilience to food scarcity circumstances, but its link to the widespread prevalence of genetic diseases and metabolic syndrome has not been adequately mapped. The purpose of the [...] Read more.

The “thrifty genotype” hypothesis has thus far described the relationship between specific genes and the population’s resilience to food scarcity circumstances, but its link to the widespread prevalence of genetic diseases and metabolic syndrome has not been adequately mapped. The purpose of the study was to discover genes responsible for thrifty metabolism. A systematic search with keywords was performed for relevant titles. This study used the article’s database published by Pubmed, Proquest, and EBSCO from January, 2009 to September, 2022. Out of 418 papers screened for eligibility, the final evaluation determined that five studies should be included in the analysis. Results indicated that PPARGC1A Gly482Ser led to high BMI in the Tongans population but was unrelated to the onset of type 2 diabetes mellitus, but this was not the case in the Maori population. Significantly differing frequencies of PPAR C1431T and Pro12Ala gene polymorphisms were observed in the Iranian population. GWAS identification of additional genes in Asian and European populations did not produce consistent findings. As a summary, PPARGC1A Gly482Ser addresses as the gene responsible for thrifty metabolism in the Pacific population although some studies show inconsistent results. Full article

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

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20 pages, 316 KiB

Open AccessReview

A Comparative Presentation of Mouse Models That Recapitulate Most Features of Alport Syndrome

by Stavros Nikolaou and Constantinos Deltas

Genes 2022, 13(10), 1893; https://doi.org/10.3390/genes13101893 - 18 Oct 2022

Cited by 3 | Viewed by 2492

Abstract

Alport syndrome is a hereditary kidney disease caused by mutations in the three genes encoding for collagen IV: COL4A3, COL4A4, and COL4A5. Several mouse models have been created for the study of this disease with variable phenotypic outcomes. This review is [...] Read more.

Alport syndrome is a hereditary kidney disease caused by mutations in the three genes encoding for collagen IV: COL4A3, COL4A4, and COL4A5. Several mouse models have been created for the study of this disease with variable phenotypic outcomes. This review is an up-to-date presentation of the current mouse models existing in the literature with a detailed comparison of the phenotypic features characterizing each model. Although in humans it is primarily a glomerulopathy, data suggest that in some mouse models, the initial symptoms appear in the tubule-interstitial region rather than the glomerulus. Additionally, in some other models, the severity of disease in the tubule-interstitial region is affected by the genetic background. In conclusion, the phenotypic spectrum of each model appears to be affected by the model’s genetic background, the position of the genetic alteration within the gene, and the type of the genetic alteration. Despite these disparities, mouse models recapitulate with relatively high fidelity several features of the human disease, which makes them useful for studies aimed at better understanding cellular pathomechanisms and for finding new treatments. Full article

(This article belongs to the Special Issue Nephrogenetics and Kidney Genomics—the Future Is Now?)

15 pages, 2598 KiB

Open AccessArticle

RNA Modification-Related Genetic Variants in Genomic Loci Associated with Bone Mineral Density and Fracture

by Limin Han, Jingyun Wu, Mimi Wang, Zhentao Zhang, Dian Hua, Shufeng Lei and Xingbo Mo

Genes 2022, 13(10), 1892; https://doi.org/10.3390/genes13101892 - 18 Oct 2022

Cited by 4 | Viewed by 2006

Abstract

Genome-wide association studies (GWASs) have identified more than 500 loci for bone mineral density (BMD), but functional variants in these loci are less known. The aim of this study was to identify RNA modification-related SNPs (RNAm-SNPs) for BMD in GWAS loci. We evaluated [...] Read more.

Genome-wide association studies (GWASs) have identified more than 500 loci for bone mineral density (BMD), but functional variants in these loci are less known. The aim of this study was to identify RNA modification-related SNPs (RNAm-SNPs) for BMD in GWAS loci. We evaluated the association of RNAm-SNPs with quantitative heel ultrasound BMD (eBMD) in 426,824 individuals, femoral neck (FN) and lumbar spine (LS) BMD in 32,961 individuals and fracture in ~1.2 million individuals. Furthermore, we performed functional enrichment, QTL and Mendelian randomization analyses to support the functionality of the identified RNAm-SNPs. We found 300 RNAm-SNPs significantly associated with BMD, including 249 m⁶A-, 28 m¹A-, 3 m⁵C-, 7 m⁷G- and 13 A-to-I-related SNPs. m⁶A-SNPs in OP susceptibility genes, such as WNT4, WLS, SPTBN1, SEM1, FUBP3, LRP5 and JAG1, were identified and functional enrichment for m⁶A-SNPs in the eBMD GWAS dataset was detected. eQTL signals were found for nearly half of the identified RNAm-SNPs, and the affected gene expression was associated with BMD and fracture. The RNAm-SNPs were also associated with the plasma levels of proteins in cytokine-cytokine receptor interaction, PI3K-Akt signaling, NF-kappa B signaling and MAPK signaling pathways. Moreover, the plasma levels of proteins (CCL19, COL1A1, CTSB, EFNA5, IL19, INSR, KDR, LIFR, MET and PLXNB2) in these pathways were found to be associated with eBMD in Mendelian randomization analysis. This study identified functional variants and potential causal genes for BMD and fracture in GWAS loci and suggested that RNA modification may play an important role in osteoporosis. Full article

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

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17 pages, 6062 KiB

Open AccessArticle

The Banana MaWRKY18, MaWRKY45, MaWRKY60 and MaWRKY70 Genes Encode Functional Transcription Factors and Display Differential Expression in Response to Defense Phytohormones

by Sergio García-Laynes, Virginia Aurora Herrera-Valencia, Lilia Guadalupe Tamayo-Torres, Verónica Limones-Briones, Felipe Alonso Barredo-Pool, Fray Martin Baas-Espinola, Angel Gabriel Alpuche-Solís, Carlos Puch-Hau and Santy Peraza-Echeverria

Genes 2022, 13(10), 1891; https://doi.org/10.3390/genes13101891 - 18 Oct 2022

Cited by 5 | Viewed by 2010

Abstract

WRKY transcription factors (TFs) play key roles in plant defense responses through phytohormone signaling pathways. However, their functions in tropical fruit crops, especially in banana, remain largely unknown. Several WRKY genes from the model plants rice (OsWRKY45) and Arabidopsis (AtWRKY18 [...] Read more.

WRKY transcription factors (TFs) play key roles in plant defense responses through phytohormone signaling pathways. However, their functions in tropical fruit crops, especially in banana, remain largely unknown. Several WRKY genes from the model plants rice (OsWRKY45) and Arabidopsis (AtWRKY18, AtWRKY60, AtWRKY70) have shown to be attractive TFs for engineering disease resistance. In this study, we isolated four banana cDNAs (MaWRKY18, MaWRKY45, MaWRKY60, and MaWRKY70) with homology to these rice and ArabidopsisWRKY genes. The MaWRKY cDNAs were isolated from the wild banana Musa acuminata ssp. malaccensis, which is resistant to several diseases of this crop and is a progenitor of most banana cultivars. The deduced amino acid sequences of the four MaWRKY cDNAs revealed the presence of the conserved WRKY domain of ~60 amino acids and a zinc-finger motif at the N-terminus. Based on the number of WRKY repeats and the structure of the zinc-finger motif, MaWRKY18 and MaWRKY60 belong to group II of WRKY TFs, while MaWRKY45 and MaWRKY70 are members of group III. Their corresponding proteins were located in the nuclei of onion epidermal cells and were shown to be functional TFs in yeast cells. Moreover, expression analyses revealed that the majority of these MaWRKY genes were upregulated by salicylic acid (SA) or methyl jasmonate (MeJA) phytohormones, although the expression levels were relatively higher with MeJA treatment. The fact that most of these banana WRKY genes were upregulated by SA or MeJA, which are involved in systemic acquired resistance (SAR) or induced systemic resistance (ISR), respectively, make them interesting candidates for bioengineering broad-spectrum resistance in this crop. Full article

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

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17 pages, 3949 KiB

Open AccessArticle

Time-Varying Gene Expression Network Analysis Reveals Conserved Transition States in Hematopoietic Differentiation between Human and Mouse

by Shouguo Gao, Ye Chen, Zhijie Wu, Sachiko Kajigaya, Xujing Wang and Neal S. Young

Genes 2022, 13(10), 1890; https://doi.org/10.3390/genes13101890 - 18 Oct 2022

Viewed by 1684

Abstract

(1) Background: analyses of gene networks can elucidate hematopoietic differentiation from single-cell gene expression data, but most algorithms generate only a single, static network. Because gene interactions change over time, it is biologically meaningful to examine time-varying structures and to capture dynamic, even [...] Read more.

(1) Background: analyses of gene networks can elucidate hematopoietic differentiation from single-cell gene expression data, but most algorithms generate only a single, static network. Because gene interactions change over time, it is biologically meaningful to examine time-varying structures and to capture dynamic, even transient states, and cell-cell relationships. (2) Methods: a transcriptomic atlas of hematopoietic stem and progenitor cells was used for network analysis. After pseudo-time ordering with Monocle 2, LOGGLE was used to infer time-varying networks and to explore changes of differentiation gene networks over time. A range of network analysis tools were used to examine properties and genes in the inferred networks. (3) Results: shared characteristics of attributes during the evolution of differentiation gene networks showed a “U” shape of network density over time for all three branches for human and mouse. Differentiation appeared as a continuous process, originating from stem cells, through a brief transition state marked by fewer gene interactions, before stabilizing in a progenitor state. Human and mouse shared hub genes in evolutionary networks. (4) Conclusions: the conservation of network dynamics in the hematopoietic systems of mouse and human was reflected by shared hub genes and network topological changes during differentiation. Full article

(This article belongs to the Special Issue Selected Papers from the International Conference on Intelligent Biology and Medicine (ICIBM 2022))

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