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Genes, Volume 12, Issue 9 (September 2021) – 168 articles

Cover Story (view full-size image): In this article, we report the identification and characterisation of novel biallelic SYNE2 (Nesprin-2 giant; (SR5 domain)) missense mutations in a patient with autism spectrum disorder (ASD) and intellectual disability. Nesprins are typically positioned on the nuclear membrane and constitute the LINC complex (LInker of the Nucleoskeleton and Cytoskeleton), a macromolecular assembly, which mechanically tethers the cytoskeleton with the nuclear interior. This association is essential for basic cellular processes, including polarisation, migration, signalling, gene regulation and repair. Many of these functions are implicated in brain development (e.g., neurogenesis and neuronal cell migration), explaining why nesprin-2 mutations may lead to ASD. View this paper.
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Article
Mammalian SIRT6 Represses Invasive Cancer Cell Phenotypes through ATP Citrate Lyase (ACLY)-Dependent Histone Acetylation
Genes 2021, 12(9), 1460; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12091460 - 21 Sep 2021
Viewed by 412
Abstract
The modulation of dynamic histone acetylation states is key for organizing chromatin structure and modulating gene expression and is regulated by histone acetyltransferase (HAT) and histone deacetylase (HDAC) enzymes. The mammalian SIRT6 protein, a member of the Class III HDAC Sirtuin family of [...] Read more.
The modulation of dynamic histone acetylation states is key for organizing chromatin structure and modulating gene expression and is regulated by histone acetyltransferase (HAT) and histone deacetylase (HDAC) enzymes. The mammalian SIRT6 protein, a member of the Class III HDAC Sirtuin family of NAD+-dependent enzymes, plays pivotal roles in aging, metabolism, and cancer biology. Through its site-specific histone deacetylation activity, SIRT6 promotes chromatin silencing and transcriptional regulation of aging-associated, metabolic, and tumor suppressive gene expression programs. ATP citrate lyase (ACLY) is a nucleo-cytoplasmic enzyme that produces acetyl coenzyme A (acetyl-CoA), which is the required acetyl donor for lysine acetylation by HATs. In addition to playing a central role in generating cytosolic acetyl-CoA for de novo lipogenesis, a growing body of work indicates that ACLY also functions in the nucleus where it contributes to the nutrient-sensitive regulation of nuclear acetyl-CoA availability for histone acetylation in cancer cells. In this study, we have identified a novel function of SIRT6 in controlling nuclear levels of ACLY and ACLY-dependent tumor suppressive gene regulation. The inactivation of SIRT6 in cancer cells leads to the accumulation of nuclear ACLY protein and increases nuclear acetyl-CoA pools, which in turn drive locus-specific histone acetylation and the expression of cancer cell adhesion and migration genes that promote tumor invasiveness. Our findings uncover a novel mechanism of SIRT6 in suppressing invasive cancer cell phenotypes and identify acetyl-CoA responsive cell migration and adhesion genes as downstream targets of SIRT6. Full article
(This article belongs to the Special Issue Sirtuins in Stress Response, Genome Integrity and Cell Physiology)
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Review
Genetic Regulation of Avian Testis Development
Genes 2021, 12(9), 1459; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12091459 - 21 Sep 2021
Viewed by 475
Abstract
As in other vertebrates, avian testes are the site of spermatogenesis and androgen production. The paired testes of birds differentiate during embryogenesis, first marked by the development of pre-Sertoli cells in the gonadal primordium and their condensation into seminiferous cords. Germ cells become [...] Read more.
As in other vertebrates, avian testes are the site of spermatogenesis and androgen production. The paired testes of birds differentiate during embryogenesis, first marked by the development of pre-Sertoli cells in the gonadal primordium and their condensation into seminiferous cords. Germ cells become enclosed in these cords and enter mitotic arrest, while steroidogenic Leydig cells subsequently differentiate around the cords. This review describes our current understanding of avian testis development at the cell biology and genetic levels. Most of this knowledge has come from studies on the chicken embryo, though other species are increasingly being examined. In chicken, testis development is governed by the Z-chromosome-linked DMRT1 gene, which directly or indirectly activates the male factors, HEMGN, SOX9 and AMH. Recent single cell RNA-seq has defined cell lineage specification during chicken testis development, while comparative studies point to deep conservation of avian testis formation. Lastly, we identify areas of future research on the genetics of avian testis development. Full article
(This article belongs to the Special Issue Evolution and Development of Testis)
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Article
Metatranscriptomic Analysis of Human Lung Metagenomes from Patients with Lung Cancer
Genes 2021, 12(9), 1458; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12091458 - 21 Sep 2021
Viewed by 487
Abstract
This study was designed to characterize the microbiomes of the lung tissues of lung cancer patients. RNA-sequencing was performed on lung tumor samples from 49 patients with lung cancer. Metatranscriptomics data were analyzed using SAMSA2 and Kraken2 software. 16S rRNA sequencing was also [...] Read more.
This study was designed to characterize the microbiomes of the lung tissues of lung cancer patients. RNA-sequencing was performed on lung tumor samples from 49 patients with lung cancer. Metatranscriptomics data were analyzed using SAMSA2 and Kraken2 software. 16S rRNA sequencing was also performed. The heterogeneous cellular landscape and immune repertoires of the lung samples were examined using xCell and TRUST4, respectively. We found that nine bacteria were significantly enriched in the lung tissues of cancer patients, and associated with reduced overall survival (OS). We also found that subjects with mutations in the epidermal growth factor receptor gene were less likely to experience the presence of Pseudomonas. aeruginosa. We found that the presence of CD8+ T-cells, CD4+ naive T-cells, dendritic cells, and CD4+ central memory T cells were associated with a good prognosis, while the presence of pro B-cells was associated with a poor prognosis. Furthermore, high clone numbers were associated with a high ImmuneScore for all immune receptor repertoires. Clone numbers and diversity were significantly higher in unpresented subjects compared to presented subjects. Our results provide insight into the microbiota of human lung cancer, and how its composition is linked to the tumor immune microenvironment, immune receptor repertoires, and OS. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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Review
Alternative Splicing in Cardiovascular Disease—A Survey of Recent Findings
Genes 2021, 12(9), 1457; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12091457 - 21 Sep 2021
Viewed by 454
Abstract
Alternative splicing, a driver of posttranscriptional variance, differs from canonical splicing by arranging the introns and exons of an immature pre-mRNA transcript in a multitude of different ways. Although alternative splicing was discovered almost half a century ago, estimates of the proportion of [...] Read more.
Alternative splicing, a driver of posttranscriptional variance, differs from canonical splicing by arranging the introns and exons of an immature pre-mRNA transcript in a multitude of different ways. Although alternative splicing was discovered almost half a century ago, estimates of the proportion of genes that undergo alternative splicing have risen drastically over the last two decades. Deep sequencing methods and novel bioinformatic algorithms have led to new insights into the prevalence of spliced variants, tissue-specific splicing patterns and the significance of alternative splicing in development and disease. Thus far, the role of alternative splicing has been uncovered in areas ranging from heart development, the response to myocardial infarction to cardiac structural disease. Circular RNAs, a product of alternative back-splicing, were initially discovered in 1976, but landmark publications have only recently identified their regulatory role, tissue-specific expression, and transcriptomic abundance, spurring a renewed interest in the topic. The aim of this review is to provide a brief insight into some of the available findings on the role of alternative splicing in cardiovascular disease, with a focus on atherosclerosis, myocardial infarction, heart failure, dilated cardiomyopathy and circular RNAs in myocardial infarction. Full article
(This article belongs to the Special Issue Alternative Splicing in Human Physiology and Disease)
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Article
CpBBX19, a B-Box Transcription Factor Gene of Chimonanthus praecox, Improves Salt and Drought Tolerance in Arabidopsis
Genes 2021, 12(9), 1456; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12091456 - 21 Sep 2021
Viewed by 387
Abstract
Zinc-finger proteins are important transcription factors in plants, responding to adversity and regulating the growth and development of plants. However, the roles of the BBX gene family of zinc-finger proteins in wintersweet (Chimonanthus praecox) have yet to be elucidated. In this [...] Read more.
Zinc-finger proteins are important transcription factors in plants, responding to adversity and regulating the growth and development of plants. However, the roles of the BBX gene family of zinc-finger proteins in wintersweet (Chimonanthus praecox) have yet to be elucidated. In this study, a group IV subfamily BBX gene, CpBBX19, was identified and isolated from wintersweet. Quantitative real-time PCR (qRT-PCR) analyses revealed that CpBBX19 was expressed in all tissues and that expression was highest in cotyledons and inner petals. CpBBX19 was also expressed in all flower development stages, with the highest expression detected in early initiating bloom, followed by late initiating bloom and bloom. In addition, the expression of CpBBX19 was induced by different abiotic stress (cold, heat, NaCl, and drought) and hormone (ABA and MeJA) treatments. Heterologous expression of CpBBX19 in Arabidopsis thaliana (Arabidopsis) enhanced the tolerance of this plant to salt and drought stress as electrolyte leakage and malondialdehyde (MDA) concentrations in transgenic Arabidopsis after stress treatments were significantly lower than those in wild-type (WT) plants. In conclusion, this research demonstrated that CpBBX19 plays a role in the abiotic stress tolerance of wintersweet. These findings lay a foundation for future studies on the BBX gene family of wintersweet and enrich understanding of the molecular mechanism of stress resistance in wintersweet. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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Article
Improved Large-Scale Homology Search by Two-Step Seed Search Using Multiple Reduced Amino Acid Alphabets
Genes 2021, 12(9), 1455; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12091455 - 21 Sep 2021
Viewed by 503
Abstract
Metagenomic analysis, a technique used to comprehensively analyze microorganisms present in the environment, requires performing high-precision homology searches on large amounts of sequencing data, the size of which has increased dramatically with the development of next-generation sequencing. NCBI BLAST is the most widely [...] Read more.
Metagenomic analysis, a technique used to comprehensively analyze microorganisms present in the environment, requires performing high-precision homology searches on large amounts of sequencing data, the size of which has increased dramatically with the development of next-generation sequencing. NCBI BLAST is the most widely used software for performing homology searches, but its speed is insufficient for the throughput of current DNA sequencers. In this paper, we propose a new, high-performance homology search algorithm that employs a two-step seed search strategy using multiple reduced amino acid alphabets to identify highly similar subsequences. Additionally, we evaluated the validity of the proposed method against several existing tools. Our method was faster than any other existing program for ≤120,000 queries, while DIAMOND, an existing tool, was the fastest method for >120,000 queries. Full article
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Review
Sensogenomics and the Biological Background Underlying Musical Stimuli: Perspectives for a New Era of Musical Research
Genes 2021, 12(9), 1454; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12091454 - 21 Sep 2021
Viewed by 377
Abstract
What is the actual impact of music on the human being and the scope for scientific research in this realm? Compared to other areas, the study of the relationship between music and human biology has received limited attention. At the same time, evidence [...] Read more.
What is the actual impact of music on the human being and the scope for scientific research in this realm? Compared to other areas, the study of the relationship between music and human biology has received limited attention. At the same time, evidence of music’s value in clinical science, neuroscience, and social science keeps increasing. This review article synthesizes the existing knowledge of genetics related to music. While the success of genomics has been demonstrated in medical research, with thousands of genes that cause inherited diseases or a predisposition to multifactorial disorders identified, much less attention has been paid to other human traits. We argue for the development of a new discipline, sensogenomics, aimed at investigating the impact of the sensorial input on gene expression and taking advantage of new, discovery-based ‘omic’ approaches that allow for the exploration of the whole transcriptome of individuals under controlled experiments and circumstances. Full article
(This article belongs to the Section Genes & Environments)
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Article
The Mitochondrial DNA Landscape of Modern Mexico
Genes 2021, 12(9), 1453; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12091453 - 21 Sep 2021
Viewed by 1227
Abstract
Mexico is a rich source for anthropological and population genetic studies with high diversity in ethnic and linguistic groups. The country witnessed the rise and fall of major civilizations, including the Maya and Aztec, but resulting from European colonization, the population landscape has [...] Read more.
Mexico is a rich source for anthropological and population genetic studies with high diversity in ethnic and linguistic groups. The country witnessed the rise and fall of major civilizations, including the Maya and Aztec, but resulting from European colonization, the population landscape has dramatically changed. Today, the majority of Mexicans do not identify themselves as Indigenous but as admixed, and appear to have very little in common with their pre-Columbian predecessors. However, when the maternally inherited mitochondrial (mt)DNA is investigated in the modern Mexican population, this is not the case. Control region sequences of 2021 samples deriving from all over the country revealed an overwhelming Indigenous American legacy, with almost 90% of mtDNAs belonging to the four major pan-American haplogroups A2, B2, C1, and D1. This finding supports a very low European contribution to the Mexican gene pool by female colonizers and confirms the effectiveness of employing uniparental markers as a tool to reconstruct a country’s history. In addition, the distinct frequency and dispersal patterns of Indigenous American and West Eurasian clades highlight the benefit such large and country-wide databases provide for studying the impact of colonialism from a female perspective and population stratification. The importance of geographical database subsets not only for forensic application is clearly demonstrated. Full article
(This article belongs to the Special Issue The Peopling of the Americas: A Genetic Perspective)
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Article
Novel Approach Combining Transcriptional and Evolutionary Signatures to Identify New Multiciliation Genes
Genes 2021, 12(9), 1452; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12091452 - 21 Sep 2021
Viewed by 470
Abstract
Multiciliogenesis is a complex process that allows the generation of hundreds of motile cilia on the surface of specialized cells, to create fluid flow across epithelial surfaces. Dysfunction of human multiciliated cells is associated with diseases of the brain, airway and reproductive tracts. [...] Read more.
Multiciliogenesis is a complex process that allows the generation of hundreds of motile cilia on the surface of specialized cells, to create fluid flow across epithelial surfaces. Dysfunction of human multiciliated cells is associated with diseases of the brain, airway and reproductive tracts. Despite recent efforts to characterize the transcriptional events responsible for the differentiation of multiciliated cells, a lot of actors remain to be identified. In this work, we capitalize on the ever-growing quantity of high-throughput data to search for new candidate genes involved in multiciliation. After performing a large-scale screening using 10 transcriptomics datasets dedicated to multiciliation, we established a specific evolutionary signature involving Otomorpha fish to use as a criterion to select the most likely targets. Combining both approaches highlighted a list of 114 potential multiciliated candidates. We characterized these genes first by generating protein interaction networks, which showed various clusters of ciliated and multiciliated genes, and then by computing phylogenetic profiles. In the end, we selected 11 poorly characterized genes that seem like particularly promising multiciliated candidates. By combining functional and comparative genomics methods, we developed a novel type of approach to study biological processes and identify new promising candidates linked to that process. Full article
(This article belongs to the Special Issue Genetics of Rare Disease)
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Article
Genetic Diversity and Population Structure of Cowpea [Vigna unguiculata (L.) Walp.] Germplasm Collected from Togo Based on DArT Markers
Genes 2021, 12(9), 1451; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12091451 - 20 Sep 2021
Viewed by 595
Abstract
Crop genetic diversity is a sine qua non for continuous progress in the development of improved varieties, hence the need for germplasm collection, conservation and characterization. Over the years, cowpea has contributed immensely to the nutrition and economic life of the people in [...] Read more.
Crop genetic diversity is a sine qua non for continuous progress in the development of improved varieties, hence the need for germplasm collection, conservation and characterization. Over the years, cowpea has contributed immensely to the nutrition and economic life of the people in Togo. However, the bulk of varieties grown by farmers are landraces due to the absence of any serious genetic improvement activity on cowpea in the country. In this study, the genetic diversity and population structure of 255 cowpea accessions collected from five administrative regions and the agricultural research institute of Togo were assessed using 4600 informative diversity array technology (DArT) markers. Among the regions, the polymorphic information content (PIC) ranged from 0.19 to 0.27 with a mean value of 0.25. The expected heterozygosity (He) varied from 0.22 to 0.34 with a mean value of 0.31, while the observed heterozygosity (Ho) varied from 0.03 to 0.07 with an average of 0.05. The average inbreeding coefficient (FIS) varied from 0.78 to 0.89 with a mean value of 0.83, suggesting that most of the accessions are inbred. Cluster analysis and population structure identified four groups with each comprising accessions from the six different sources. Weak to moderate differentiation was observed among the populations with a genetic differentiation index varying from 0.014 to 0.117. Variation was highest (78%) among accessions within populations and lowest between populations (7%). These results revealed a moderate level of diversity among the Togo cowpea germplasm. The findings of this study constitute a foundation for genetic improvement of cowpea in Togo. Full article
(This article belongs to the Section Population and Evolutionary Genetics and Genomics)
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Article
Variation and Selection in the Putative Sperm-Binding Region of ZP3 in Muroid Rodents: A Comparison between Cricetids and Murines
Genes 2021, 12(9), 1450; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12091450 - 20 Sep 2021
Viewed by 329
Abstract
In mammals, the zona pellucida glycoprotein 3 (ZP3) is considered a primary sperm receptor of the oocyte and is hypothesized to be involved in reproductive isolation. We investigated patterns of diversity and selection in the putative sperm-binding region (pSBR) of mouse ZP3 across [...] Read more.
In mammals, the zona pellucida glycoprotein 3 (ZP3) is considered a primary sperm receptor of the oocyte and is hypothesized to be involved in reproductive isolation. We investigated patterns of diversity and selection in the putative sperm-binding region (pSBR) of mouse ZP3 across Cricetidae and Murinae, two hyperdiverse taxonomic groups within muroid rodents. In murines, the pSBR is fairly conserved, in particular the serine-rich stretch containing the glycosylation sites proposed as essential for sperm binding. In contrast, cricetid amino acid sequences of the pSBR were much more variable and the serine-rich motif, typical of murines, was generally substantially modified. Overall, our results suggest a general lack of species specificity of the pSBR across the two muroid families. We document statistical evidence of positive selection acting on exons 6 and 7 of ZP3 and identified several amino acid sites that are likely targets of selection, with most positively selected sites falling within or adjacent to the pSBR. Full article
(This article belongs to the Section Population and Evolutionary Genetics and Genomics)
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Article
Genome-Wide Survey for Microdeletions or -Duplications in 155 Patients with Lower Urinary Tract Obstructions (LUTO)
Genes 2021, 12(9), 1449; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12091449 - 20 Sep 2021
Viewed by 456
Abstract
Lower urinary tract obstruction (LUTO) is, in most cases, caused by anatomical blockage of the bladder outlet. The most common form are posterior urethral valves (PUVs), a male-limited phenotype. Here, we surveyed the genome of 155 LUTO patients to identify disease-causing CNVs. Raw [...] Read more.
Lower urinary tract obstruction (LUTO) is, in most cases, caused by anatomical blockage of the bladder outlet. The most common form are posterior urethral valves (PUVs), a male-limited phenotype. Here, we surveyed the genome of 155 LUTO patients to identify disease-causing CNVs. Raw intensity data were collected for CNVs detected in LUTO patients and 4.392 healthy controls using CNVPartition, QuantiSNP and PennCNV. Overlapping CNVs between patients and controls were discarded. Additional filtering implicated CNV frequency in the database of genomic variants, gene content and final visual inspection detecting 37 ultra-rare CNVs. After, prioritization qPCR analysis confirmed 3 microduplications, all detected in PUV patients. One microduplication (5q23.2) occurred de novo in the two remaining microduplications found on chromosome 1p36.21 and 10q23.31. Parental DNA was not available for segregation analysis. All three duplications comprised 11 coding genes: four human specific lncRNA and one microRNA. Three coding genes (FBLIM1, SLC16A12, SNCAIP) and the microRNA MIR107 have previously been shown to be expressed in the developing urinary tract of mouse embryos. We propose that duplications, rare or de novo, contribute to PUV formation, a male-limited phenotype. Full article
(This article belongs to the Special Issue De novo Mutations and the Lack of Heritability in Birth Defects)
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Article
Whole-Genome Profiles of Malay Colorectal Cancer Patients with Intact MMR Proteins
Genes 2021, 12(9), 1448; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12091448 - 20 Sep 2021
Viewed by 516
Abstract
Background: This study aimed to identify new genes associated with CRC in patients with normal mismatch repair (MMR) protein expression. Method: Whole-genome sequencing (WGS) was performed in seven early-age-onset Malay CRC patients. Potential germline genetic variants, including single-nucleotide variations and insertions and deletions [...] Read more.
Background: This study aimed to identify new genes associated with CRC in patients with normal mismatch repair (MMR) protein expression. Method: Whole-genome sequencing (WGS) was performed in seven early-age-onset Malay CRC patients. Potential germline genetic variants, including single-nucleotide variations and insertions and deletions (indels), were prioritized using functional and predictive algorithms. Results: An average of 3.2 million single-nucleotide variations (SNVs) and over 800 indels were identified. Three potential candidate variants in three genes—IFNE, PTCH2 and SEMA3D—which were predicted to affect protein function, were identified in three Malay CRC patients. In addition, 19 candidate genes—ANKDD1B, CENPM, CLDN5, MAGEB16, MAP3K14, MOB3C, MS4A12, MUC19, OR2L8, OR51Q1, OR51AR1, PDE4DIP, PKD1L3, PRIM2, PRM3, SEC22B, TPTE, USP29 and ZNF117—harbouring nonsense variants were prioritised. These genes are suggested to play a role in cancer predisposition and to be associated with cancer risk. Pathway enrichment analysis indicated significant enrichment in the olfactory signalling pathway. Conclusion: This study provides a new spectrum of insights into the potential genes, variants and pathways associated with CRC in Malay patients. Full article
(This article belongs to the Special Issue Genetic Tests)
Review
Emerging Role of isomiRs in Cancer: State of the Art and Recent Advances
Genes 2021, 12(9), 1447; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12091447 - 20 Sep 2021
Viewed by 394
Abstract
The advent of Next Generation Sequencing technologies brought with it the discovery of several microRNA (miRNA) variants of heterogeneous lengths and/or sequences. Initially ascribed to sequencing errors/artifacts, these isoforms, named isomiRs, are now considered non-canonical variants that originate from physiological processes affecting the [...] Read more.
The advent of Next Generation Sequencing technologies brought with it the discovery of several microRNA (miRNA) variants of heterogeneous lengths and/or sequences. Initially ascribed to sequencing errors/artifacts, these isoforms, named isomiRs, are now considered non-canonical variants that originate from physiological processes affecting the canonical miRNA biogenesis. To date, accurate IsomiRs abundance, biological activity, and functions are not completely understood; however, the study of isomiR biology is an area of great interest due to their high frequency in the human miRNome, their putative functions in cooperating with the canonical miRNAs, and potential for exhibiting novel functional roles. The discovery of isomiRs highlighted the complexity of the small RNA transcriptional landscape in several diseases, including cancer. In this field, the study of isomiRs could provide further insights into the miRNA biology and its implication in oncogenesis, possibly providing putative new cancer diagnostic, prognostic, and predictive biomarkers as well. In this review, a comprehensive overview of the state of research on isomiRs in different cancer types, including the most common tumors such as breast cancer, colorectal cancer, melanoma, and prostate cancer, as well as in the less frequent tumors, as for example brain tumors and hematological malignancies, will be summarized and discussed. Full article
(This article belongs to the Special Issue The Role of MicroRNA in Cancer)
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Review
p53 mRNA Metabolism Links with the DNA Damage Response
Genes 2021, 12(9), 1446; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12091446 - 20 Sep 2021
Viewed by 708
Abstract
Human cells are subjected to continuous challenges by different genotoxic stress attacks. DNA damage leads to erroneous mutations, which can alter the function of oncogenes or tumor suppressors, resulting in cancer development. To circumvent this, cells activate the DNA damage response (DDR), which [...] Read more.
Human cells are subjected to continuous challenges by different genotoxic stress attacks. DNA damage leads to erroneous mutations, which can alter the function of oncogenes or tumor suppressors, resulting in cancer development. To circumvent this, cells activate the DNA damage response (DDR), which mainly involves cell cycle regulation and DNA repair processes. The tumor suppressor p53 plays a pivotal role in the DDR by halting the cell cycle and facilitating the DNA repair processes. Various pathways and factors participating in the detection and repair of DNA have been described, including scores of RNA-binding proteins (RBPs) and RNAs. It has become increasingly clear that p53’s role is multitasking, and p53 mRNA regulation plays a prominent part in the DDR. This review is aimed at covering the p53 RNA metabolism linked to the DDR and highlights the recent findings. Full article
(This article belongs to the Special Issue Reciprocal Links between RNA Metabolism and DNA Damage)
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Article
RANTES 59029A/G Polymorphisms Associated with Diabetic Compilations in Korean Patients with Type 2 Diabetes for over 15 Years
Genes 2021, 12(9), 1445; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12091445 - 19 Sep 2021
Viewed by 623
Abstract
Background: Polymorphisms in the RANTES gene are known to be associated with several diseases related to insulin resistance. In this study, we investigated the association between RANTES 59029A/G polymorphisms and the prevalence of diabetic complications relative to obesity in Korean patients who had [...] Read more.
Background: Polymorphisms in the RANTES gene are known to be associated with several diseases related to insulin resistance. In this study, we investigated the association between RANTES 59029A/G polymorphisms and the prevalence of diabetic complications relative to obesity in Korean patients who had type 2 diabetes (T2D) for over 15 years. Methods: A single-center, retrospective case-control study was performed. We included 271 patients with a duration of diabetes greater than 15 years. Polymerase chain reaction-restriction fragment length polymorphism was used to analyze RANTES polymorphisms, identifying genotypes as GG, AG, or AA. Obesity was defined using the body mass index with a cutoff value of 25 kg/m2. Both microvascular (retinopathy and nephropathy) and macrovascular (coronary artery disease and cerebrovascular disease) complications were evaluated. Results: The duration of T2D and hemoglobin A1c values at enrollment were 24.4 ± 5.0 years and 7.8 ± 1.6%, respectively, in the non-obese group, and 25.4 ± 6.1 years and 7.7 ± 1.7%, respectively, in the obese group. The prevalence of microvascular complications was significantly higher in the obese group compared with that in the non-obese group (83.5% vs. 72.0%, p = 0.039). Compared to the non-obese group, the obese group showed a higher proportion of the patients with AA or AG genotypes (64.3% vs. 84.5%, p = 0.001). Conclusions: The A allele of the RANTES gene is associated with obesity and may affect diabetic microvascular complications in patients with T2D for over 15 years. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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Article
Genome-Wide Identification and Transcriptional Expression Profiles of Transcription Factor WRKY in Common Walnut (Juglans regia L.)
Genes 2021, 12(9), 1444; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12091444 - 19 Sep 2021
Viewed by 381
Abstract
The transcription factor WRKY is widely distributed in the plant kingdom, playing a significant role in plant growth, development and response to stresses. Walnut is an economically important temperate tree species valued for both its edible nuts and high-quality wood, and its response [...] Read more.
The transcription factor WRKY is widely distributed in the plant kingdom, playing a significant role in plant growth, development and response to stresses. Walnut is an economically important temperate tree species valued for both its edible nuts and high-quality wood, and its response to various stresses is an important factor that determines the quality of its fruit. However, in walnut trees themselves, information about the WRKY gene family remains scarce. In this paper, we perform a comprehensive study of the WRKY gene family in walnut. In total, we identified 103 WRKY genes in the common walnut that are clustered into 4 groups and distributed on 14 chromosomes. The conserved domains all contained a WRKY domain, and motif 2 was observed in most WRKYs, suggesting a high degree of conservation and similar functions within each subfamily. However, gene structure was significantly differentiated between different subfamilies. Synteny analysis indicates that there were 56 gene pairs in J. regia and A. thaliana, 76 in J. regia and J. mandshurica, 75 in J. regia and J. microcarpa, 76 in J. regia and P. trichocarpa, and 33 in J. regia and Q. robur, indicating that the WRKY gene family may come from a common ancestor. GO and KEGG enrichment analysis showed that the WRKY gene family was involved in resistance traits and the plant-pathogen interaction pathway. In anthracnose-resistant F26 fruits (AR) and anthracnose-susceptible F423 fruits (AS), transcriptome and qPCR analysis results showed that JrWRKY83, JrWRKY73 and JrWRKY74 were expressed significantly more highly in resistant cultivars, indicating that these three genes may be important contributors to stress resistance in walnut trees. Furthermore, we investigate how these three genes potentially target miRNAs and interact with proteins. JrWRKY73 was target by the miR156 family, including 12 miRNAs; this miRNA family targets WRKY genes to enhance plant defense. JrWRKY73 also interacted with the resistance gene AtMPK6, showing that it may play a crucial role in walnut defense. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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Article
Breeding Tomato Hybrids for Flavour: Comparison of GWAS Results Obtained on Lines and F1 Hybrids
Genes 2021, 12(9), 1443; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12091443 - 18 Sep 2021
Viewed by 569
Abstract
Tomato flavour is an important goal for breeders. Volatile organic compounds (VOCs) are major determinants of tomato flavour. Although most tomato varieties for fresh market are F1 hybrids, most studies on the genetic control of flavour-related traits are performed on lines. We quantified [...] Read more.
Tomato flavour is an important goal for breeders. Volatile organic compounds (VOCs) are major determinants of tomato flavour. Although most tomato varieties for fresh market are F1 hybrids, most studies on the genetic control of flavour-related traits are performed on lines. We quantified 46 VOCs in a panel of 121 small fruited lines and in a test cross panel of 165 hybrids (the previous panel plus 44 elite cherry tomato lines crossed with a common line). High and consistent heritabilities were assessed for most VOCs in the two panels, and 65% of VOC contents were strongly correlated between lines and hybrids. Additivity was observed for most VOCs. We performed genome wide association studies (GWAS) on the two panels separately, along with a third GWAS on the test cross subset carrying only F1 hybrids corresponding to the line panel. We identified 205, 183 and 138 associations, respectively. We identified numerous overlapping associations for VOCs belonging to the same metabolic pathway within each panel; we focused on seven chromosome regions with clusters of associations simultaneously involved in several key VOCs for tomato aroma. The study highlighted the benefit of testcross panels to create tasty F1 hybrid varieties. Full article
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Article
Tensor-Decomposition-Based Unsupervised Feature Extraction in Single-Cell Multiomics Data Analysis
Genes 2021, 12(9), 1442; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12091442 - 18 Sep 2021
Viewed by 626
Abstract
Analysis of single-cell multiomics datasets is a novel topic and is considerably challenging because such datasets contain a large number of features with numerous missing values. In this study, we implemented a recently proposed tensor-decomposition (TD)-based unsupervised feature extraction (FE) technique to address [...] Read more.
Analysis of single-cell multiomics datasets is a novel topic and is considerably challenging because such datasets contain a large number of features with numerous missing values. In this study, we implemented a recently proposed tensor-decomposition (TD)-based unsupervised feature extraction (FE) technique to address this difficult problem. The technique can successfully integrate single-cell multiomics data composed of gene expression, DNA methylation, and accessibility. Although the last two have large dimensions, as many as ten million, containing only a few percentage of nonzero values, TD-based unsupervised FE can integrate three omics datasets without filling in missing values. Together with UMAP, which is used frequently when embedding single-cell measurements into two-dimensional space, TD-based unsupervised FE can produce two-dimensional embedding coincident with classification when integrating single-cell omics datasets. Genes selected based on TD-based unsupervised FE are also significantly related to reasonable biological roles. Full article
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Article
Genetic Variation in PADI6-PADI4 on 1p36.13 Is Associated with Common Forms of Human Generalized Epilepsy
Genes 2021, 12(9), 1441; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12091441 - 18 Sep 2021
Viewed by 345
Abstract
We performed a genome-wide association study (GWAS) to identify genetic variation associated with common forms of idiopathic generalized epilepsy (GE) and focal epilepsy (FE). Using a cohort of 2220 patients and 14,448 controls, we searched for single nucleotide polymorphisms (SNPs) associated with GE, [...] Read more.
We performed a genome-wide association study (GWAS) to identify genetic variation associated with common forms of idiopathic generalized epilepsy (GE) and focal epilepsy (FE). Using a cohort of 2220 patients and 14,448 controls, we searched for single nucleotide polymorphisms (SNPs) associated with GE, FE and both forms combined. We did not find any SNPs that reached genome-wide statistical significance (p ≤ 5 × 10−8) when comparing all cases to all controls, and few SNPs of interest comparing FE cases to controls. However, we document multiple linked SNPs in the PADI6-PADI4 genes that reach genome-wide significance and are associated with disease when comparing GE cases alone to controls. PADI genes encode enzymes that deiminate arginine to citrulline in molecular pathways related to epigenetic regulation of histones and autoantibody formation. Although epilepsy genetics and treatment are focused strongly on ion channel and neurotransmitter mechanisms, these results suggest that epigenetic control of gene expression and the formation of autoantibodies may also play roles in epileptogenesis. Full article
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Communication
Genetic Variants and Somatic Alterations Associated with MITF-E318K Germline Mutation in Melanoma Patients
Genes 2021, 12(9), 1440; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12091440 - 18 Sep 2021
Viewed by 350
Abstract
The MITF-E318K variant has been implicated in genetic predisposition to cutaneous melanoma. We addressed the occurrence of MITF-E318K and its association with germline status of CDKN2A and MC1R genes in a hospital-based series of 248 melanoma patients including cohorts of multiple, familial, pediatric, [...] Read more.
The MITF-E318K variant has been implicated in genetic predisposition to cutaneous melanoma. We addressed the occurrence of MITF-E318K and its association with germline status of CDKN2A and MC1R genes in a hospital-based series of 248 melanoma patients including cohorts of multiple, familial, pediatric, sporadic and melanoma associated with other tumors. Seven MITF-E318K carriers were identified, spanning every group except the pediatric patients. Three carriers showed mutated CDKN2A, five displayed MC1R variants, while the sporadic carrier revealed no variants. Germline/tumor whole exome sequencing for this carrier revealed germline variants of unknown significance in ATM and FANCI genes and, in four BRAF-V600E metastases, somatic loss of the MITF wild-type allele, amplification of MITF-E318K and deletion of a 9p21.3 chromosomal region including CDKN2A and MTAP. In silico analysis of tumors from MITF-E318K melanoma carriers in the TCGA Pan-Cancer-Atlas dataset confirmed the association with BRAF mutation and 9p21.3 deletion revealing a common genetic pattern. MTAP was the gene deleted at homozygous level in the highest number of patients. These results support the utility of both germline and tumor genome analysis to define tumor groups providing enhanced information for clinical strategies and highlight the importance of melanoma prevention programs for MITF-E318K patients. Full article
(This article belongs to the Special Issue Genetics and Genomics of Melanoma)
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Article
The Mitochondrial Trigger in an Animal Model of Nonalcoholic Fatty Liver Disease
Genes 2021, 12(9), 1439; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12091439 - 18 Sep 2021
Viewed by 307
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the leading liver chronic disease featuring hepatic steatosis. Mitochondrial β-oxidation participates in the derangement of lipid metabolism at the basis of NAFLD, and mitochondrial oxidative stress contributes to the onset of the disease. We evaluated the presence [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) is the leading liver chronic disease featuring hepatic steatosis. Mitochondrial β-oxidation participates in the derangement of lipid metabolism at the basis of NAFLD, and mitochondrial oxidative stress contributes to the onset of the disease. We evaluated the presence and effects of mitochondrial oxidative stress in the liver from rats fed a high-fat plus fructose (HF-F) diet inducing NAFLD. Supplementation with dehydroepiandrosterone (DHEA), a multitarget antioxidant, was tested for efficacy in delaying NAFLD. A marked mitochondrial oxidative stress was originated by all diets, as demonstrated by the decrease in Superoxide Dismutase 2 (SOD2) and Peroxiredoxin III (PrxIII) amounts. All diets induced a decrease in mitochondrial DNA content and an increase in its oxidative damage. The diets negatively affected mitochondrial biogenesis as shown by decreased peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α), mitochondrial transcription factor A (TFAM), and the COX-IV subunit from the cytochrome c oxidase complex. The reduced amounts of Beclin-1 and lipidated LC3 II form of the microtubule-associated protein 1 light chain 3 (LC3) unveiled the diet-related autophagy’s decrease. The DHEA supplementation did not prevent the diet-induced changes. These results demonstrate the relevance of mitochondrial oxidative stress and the sequential dysfunction of the organelles in an obesogenic diet animal model of NAFLD. Full article
(This article belongs to the Special Issue Alterations in mtDNA and Mitochondrial Quality Control)
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Review
Machine Learning Modeling from Omics Data as Prospective Tool for Improvement of Inflammatory Bowel Disease Diagnosis and Clinical Classifications
Genes 2021, 12(9), 1438; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12091438 - 18 Sep 2021
Viewed by 579
Abstract
Research of inflammatory bowel disease (IBD) has identified numerous molecular players involved in the disease development. Even so, the understanding of IBD is incomplete, while disease treatment is still far from the precision medicine. Reliable diagnostic and prognostic biomarkers in IBD are limited [...] Read more.
Research of inflammatory bowel disease (IBD) has identified numerous molecular players involved in the disease development. Even so, the understanding of IBD is incomplete, while disease treatment is still far from the precision medicine. Reliable diagnostic and prognostic biomarkers in IBD are limited which may reduce efficient therapeutic outcomes. High-throughput technologies and artificial intelligence emerged as powerful tools in search of unrevealed molecular patterns that could give important insights into IBD pathogenesis and help to address unmet clinical needs. Machine learning, a subtype of artificial intelligence, uses complex mathematical algorithms to learn from existing data in order to predict future outcomes. The scientific community has been increasingly employing machine learning for the prediction of IBD outcomes from comprehensive patient data-clinical records, genomic, transcriptomic, proteomic, metagenomic, and other IBD relevant omics data. This review aims to present fundamental principles behind machine learning modeling and its current application in IBD research with the focus on studies that explored genomic and transcriptomic data. We described different strategies used for dealing with omics data and outlined the best-performing methods. Before being translated into clinical settings, the developed machine learning models should be tested in independent prospective studies as well as randomized controlled trials. Full article
(This article belongs to the Special Issue Multidisciplinary Approaches in IBD Genetics)
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Article
Metformin Triggers Apoptosis and Induction of the G0/G1 Switch 2 Gene in Macrophages
Genes 2021, 12(9), 1437; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12091437 - 17 Sep 2021
Viewed by 397
Abstract
Metformin is a widely used antidiabetic drug for the treatment of type 2 diabetes and has been recently demonstrated to possess anti-inflammatory properties via AMPK-mediated modulation of M2 macrophage activation. However, the anti-inflammatory mechanisms of metformin on inflammatory macrophages are still not fully [...] Read more.
Metformin is a widely used antidiabetic drug for the treatment of type 2 diabetes and has been recently demonstrated to possess anti-inflammatory properties via AMPK-mediated modulation of M2 macrophage activation. However, the anti-inflammatory mechanisms of metformin on inflammatory macrophages are still not fully elucidated. In this study, we found that metformin induced apoptosis in macrophages. In particular, metformin induced apoptosis of M1 macrophages, based on M1 marker genes in apoptotic macrophages. Next, we comprehensively screened metformin-responsive genes in macrophages by RNA-seq and focused on the extrinsic apoptotic signaling pathway. The G0/G1 switch 2 gene (G0S2) was robustly up-regulated by metformin in macrophages. Overexpression of G0S2 significantly induced apoptosis of macrophages in a dose-dependent manner and blunted the function of the crucial anti-apoptotic gene Bcl-2, which was significantly reduced by metformin. These findings show that metformin promoted apoptosis of macrophages, especially M1 macrophages, via G0S2 induction and provides a novel anti-inflammatory mechanism of metformin through induction of macrophage apoptosis. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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Article
Descending Dysploidy and Bidirectional Changes in Genome Size Accompanied Crepis (Asteraceae) Evolution
Genes 2021, 12(9), 1436; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12091436 - 17 Sep 2021
Viewed by 688
Abstract
The evolution of the karyotype and genome size was examined in species of Crepis sensu lato. The phylogenetic relationships, inferred from the plastid and nrITS DNA sequences, were used as a framework to infer the patterns of karyotype evolution. Five different base chromosome [...] Read more.
The evolution of the karyotype and genome size was examined in species of Crepis sensu lato. The phylogenetic relationships, inferred from the plastid and nrITS DNA sequences, were used as a framework to infer the patterns of karyotype evolution. Five different base chromosome numbers (x = 3, 4, 5, 6, and 11) were observed. A phylogenetic analysis of the evolution of the chromosome numbers allowed the inference of x = 6 as the ancestral state and the descending dysploidy as the major direction of the chromosome base number evolution. The derived base chromosome numbers (x = 5, 4, and 3) were found to have originated independently and recurrently in the different lineages of the genus. A few independent events of increases in karyotype asymmetry were inferred to have accompanied the karyotype evolution in Crepis. The genome sizes of 33 Crepis species differed seven-fold and the ancestral genome size was reconstructed to be 1C = 3.44 pg. Both decreases and increases in the genome size were inferred to have occurred within and between the lineages. The data suggest that, in addition to dysploidy, the amplification/elimination of various repetitive DNAs was likely involved in the genome and taxa differentiation in the genus. Full article
(This article belongs to the Section Cytogenomics)
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Article
Over-Expression of the Cell-Cycle Gene LaCDKB1;2 Promotes Cell Proliferation and the Formation of Normal Cotyledonary Embryos during Larix kaempferi Somatic Embryogenesis
Genes 2021, 12(9), 1435; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12091435 - 17 Sep 2021
Viewed by 563
Abstract
Somatic embryogenesis is an effective tool for the production of forest tree seedlings with desirable characteristics; however, the low initiation frequency and productivity of high-quality mature somatic embryos are still limiting factors for Larix kaempferi (Japanese larch). Here, we analyzed the expression pattern [...] Read more.
Somatic embryogenesis is an effective tool for the production of forest tree seedlings with desirable characteristics; however, the low initiation frequency and productivity of high-quality mature somatic embryos are still limiting factors for Larix kaempferi (Japanese larch). Here, we analyzed the expression pattern of L. kaempferi cyclin-dependent kinase B 1;2 (LaCDKB1;2) during somatic embryogenesis in L. kaempferi and its relationship with the cell proliferation rate. We also analyzed the effect of LaCDKB1;2 over-expression on somatic embryo quality. The results revealed a positive correlation between LaCDKB1;2 expression and the cell proliferation rate during the proliferation stage. After LaCDKB1;2 over-expression, the proliferation rate of cultures increased, and the number of somatic embryos in transgenic cultures was 2.69 times that in non-transformed cultures. Notably, the number of normal cotyledonary embryos in transgenic cultures was 3 times that in non-transformed cultures, indicating that LaCDKB1;2 not only increases the proliferation of cultures and the number of somatic embryos but also improves the quality of somatic embryos. These results provide insight into the regulatory mechanisms of somatic embryogenesis as well as new Larix breeding material. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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Article
Meiotic Behavior of Achiasmate Sex Chromosomes in the African Pygmy Mouse Mus mattheyi Offers New Insights into the Evolution of Sex Chromosome Pairing and Segregation in Mammals
Genes 2021, 12(9), 1434; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12091434 - 17 Sep 2021
Viewed by 595
Abstract
X and Y chromosomes in mammals are different in size and gene content due to an evolutionary process of differentiation and degeneration of the Y chromosome. Nevertheless, these chromosomes usually share a small region of homology, the pseudoautosomal region (PAR), which allows them [...] Read more.
X and Y chromosomes in mammals are different in size and gene content due to an evolutionary process of differentiation and degeneration of the Y chromosome. Nevertheless, these chromosomes usually share a small region of homology, the pseudoautosomal region (PAR), which allows them to perform a partial synapsis and undergo reciprocal recombination during meiosis, which ensures their segregation. However, in some mammalian species the PAR has been lost, which challenges the pairing and segregation of sex chromosomes in meiosis. The African pygmy mouse Mus mattheyi shows completely differentiated sex chromosomes, representing an uncommon evolutionary situation among mouse species. We have performed a detailed analysis of the location of proteins involved in synaptonemal complex assembly (SYCP3), recombination (RPA, RAD51 and MLH1) and sex chromosome inactivation (γH2AX) in this species. We found that neither synapsis nor chiasmata are found between sex chromosomes and their pairing is notably delayed compared to autosomes. Interestingly, the Y chromosome only incorporates RPA and RAD51 in a reduced fraction of spermatocytes, indicating a particular DNA repair dynamic on this chromosome. The analysis of segregation revealed that sex chromosomes are associated until metaphase-I just by a chromatin contact. Unexpectedly, both sex chromosomes remain labelled with γH2AX during first meiotic division. This chromatin contact is probably enough to maintain sex chromosome association up to anaphase-I and, therefore, could be relevant to ensure their reductional segregation. The results presented suggest that the regulation of both DNA repair and epigenetic modifications in the sex chromosomes can have a great impact on the divergence of sex chromosomes and their proper transmission, widening our understanding on the relationship between meiosis and the evolution of sex chromosomes in mammals. Full article
(This article belongs to the Special Issue Sex Chromosome Evolution and Meiosis)
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Article
Environmental Influences Measured by Epigenetic Clock and Vulnerability Components at Birth Impact Clinical ASD Heterogeneity
Genes 2021, 12(9), 1433; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12091433 - 17 Sep 2021
Viewed by 428
Abstract
Although Autism Spectrum Disorders (ASD) is recognized as being heavily influenced by genetic factors, the role of epigenetic and environmental factors is still being established. This study aimed to identify ASD vulnerability components based on familial history and intrauterine environmental stress exposure, explore [...] Read more.
Although Autism Spectrum Disorders (ASD) is recognized as being heavily influenced by genetic factors, the role of epigenetic and environmental factors is still being established. This study aimed to identify ASD vulnerability components based on familial history and intrauterine environmental stress exposure, explore possible vulnerability subgroups, access DNA methylation age acceleration (AA) as a proxy of stress exposure during life, and evaluate the association of ASD vulnerability components and AA to phenotypic severity measures. Principal Component Analysis (PCA) was used to search the vulnerability components from 67 mothers of autistic children. We found that PC1 had a higher correlation with psychosocial stress (maternal stress, maternal education, and social class), and PC2 had a higher correlation with biological factors (psychiatric family history and gestational complications). Comparing the methylome between above and below PC1 average subgroups we found 11,879 statistically significant differentially methylated probes (DMPs, p < 0.05). DMPs CpG sites were enriched in variably methylated regions (VMRs), most showing environmental and genetic influences. Hypermethylated probes presented higher rates in different regulatory regions associated with functional SNPs, indicating that the subgroups may have different affected regulatory regions and their liability to disease explained by common variations. Vulnerability components score moderated by epigenetic clock AA was associated with Vineland Total score (p = 0.0036, adjR2 = 0.31), suggesting risk factors with stress burden can influence ASD phenotype. Full article
(This article belongs to the Special Issue Genetic and Phenotypic Subtypes of Autism Spectrum Disorder)
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Article
Prediction of Genetic Resistance for Scrapie in Ungenotyped Sheep Using a Linear Animal Model
Genes 2021, 12(9), 1432; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12091432 - 17 Sep 2021
Viewed by 490
Abstract
Selection based on scrapie genotypes could improve the genetic resistance for scrapie in sheep. However, in practice, few animals are genotyped. The objectives were to define numerical values of scrapie resistance genotypes and adjust for their non-additive genetic effect; evaluate prediction accuracy of [...] Read more.
Selection based on scrapie genotypes could improve the genetic resistance for scrapie in sheep. However, in practice, few animals are genotyped. The objectives were to define numerical values of scrapie resistance genotypes and adjust for their non-additive genetic effect; evaluate prediction accuracy of ungenotyped animals using linear animal model; and predict and assess selection response based on estimated breeding values (EBV) of ungenotyped animals. The scrapie resistance (SR) was defined by ranking scrapie genotypes from low (0) to high (4) resistance based on genotype risk groups and was also adjusted for non-additive genetic effect of the haplotypes. Genotypes were simulated for 1,671,890 animals from pedigree. The simulated alleles were assigned to scrapie haplotypes in two scenarios of high (SRh) and low (SRl) resistance populations. A sample of 20,000 genotyped animals were used to predict ungenotyped using animal model. Prediction accuracies for ungenotyped animals for SRh and SRl were 0.60 and 0.54, and for allele content were from 0.41 to 0.71, respectively. Response to selection on SRh and SRl increased SR by 0.52 and 0.28, and on allele content from 0.13 to 0.50, respectively. In addition, the selected animals had large proportion of homozygous for the favorable haplotypes. Thus, pre-selection prior to genotyping could reduce genotyping costs for breeding programs. Using a linear animal model to predict SR makes better use of available information for the breeding programs. Full article
(This article belongs to the Special Issue Animal Domestication and Breeding)
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Article
Metagenomic Analyses of Plant Growth-Promoting and Carbon-Cycling Genes in Maize Rhizosphere Soils with Distinct Land-Use and Management Histories
Genes 2021, 12(9), 1431; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12091431 - 17 Sep 2021
Viewed by 682
Abstract
Many studies have shown that the maize rhizosphere comprises several plant growth-promoting microbes, but there is little or no study on the effects of land-use and management histories on microbial functional gene diversity in the maize rhizosphere soils in Africa. Analyzing microbial genes [...] Read more.
Many studies have shown that the maize rhizosphere comprises several plant growth-promoting microbes, but there is little or no study on the effects of land-use and management histories on microbial functional gene diversity in the maize rhizosphere soils in Africa. Analyzing microbial genes in the rhizosphere of plants, especially those associated with plant growth promotion and carbon cycling, is important for improving soil fertility and crop productivity. Here, we provide a comparative analysis of microbial genes present in the rhizosphere samples of two maize fields with different agricultural histories using shotgun metagenomics. Genes involved in the nutrient mobilization, including nifA, fixJ, norB, pstA, kefA and B, and ktrB were significantly more abundant (α = 0.05) in former grassland (F1) rhizosphere soils. Among the carbon-cycling genes, the abundance of 12 genes, including all those involved in the degradation of methane were more significant (α = 0.05) in the F1 soils, whereas only five genes were significantly more abundant in the F2 soils. α-diversity indices were different across the samples and significant differences were observed in the β diversity of plant growth-promoting and carbon-cycling genes between the fields (ANOSIM, p = 0.01 and R = 0.52). Nitrate-nitrogen (N-NO3) was the most influential physicochemical parameter (p = 0.05 and contribution = 31.3%) that affected the distribution of the functional genes across the samples. The results indicate that land-use and management histories impact the composition and diversity of plant growth-promoting and carbon-cycling genes in the plant rhizosphere. The study widens our understanding of the effects of anthropogenic activities on plant health and major biogeochemical processes in soils. Full article
(This article belongs to the Special Issue Regulation of Microbial Biosynthetic Genes and Biodegradation Genes)
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