Genes

18 pages, 6831 KiB

Open AccessEditor’s ChoiceArticle

Association Analysis of Tiller-Related Traits with EST-SSR Markers in Psathyrostachys juncea

by Zhen Li, Tian Wang, Lan Yun, Xiaomin Ren, Yong Wang and Fengling Shi

Genes 2023, 14(10), 1970; https://doi.org/10.3390/genes14101970 - 21 Oct 2023

Cited by 5 | Viewed by 1864

Psathyrostachys juncea is a long-lived perennial Gramineae grass with dense basal tillers and soft leaves. It is used widely in cold and dry areas of Eurasia and North America to establish grazing pasture and is even used as an ideal plant for revegetation [...] Read more.

Psathyrostachys juncea is a long-lived perennial Gramineae grass with dense basal tillers and soft leaves. It is used widely in cold and dry areas of Eurasia and North America to establish grazing pasture and is even used as an ideal plant for revegetation and ecological restoration. Plant architecture, especially tillering traits, is critical for bunch grasses in breeding programs, and these traits in plants are mostly quantitative traits. In this study, the genetic diversity, population structure, and linkage disequilibrium of 480 individual lines were analyzed using 127 pairs of the EST-SSR marker, and a significant association between ten plant-architecture-related traits of P. juncea and molecular markers was found. The results of the genetic diversity analysis showed that the number of observed alleles was 1.957, the number of effective alleles was 1.682, Shannon’s information index was 0.554, observed heterozygosity was 0.353, expected heterozygosity was 0.379, and the polymorphism information content was 0.300. A total of 480 individual lines were clustered into five groups based on population genetic structure, principal coordinate analysis, and unweighted pair group method with arithmetic mean analysis (UPGMA). The linkage disequilibrium coefficient (r²) was between 0.00 and 0.68, with an average of 0.04, which indicated a relatively low level of linkage disequilibrium among loci. The results of the association analysis revealed 55 significant marker–trait associations (MTA). Moreover, nine SSR markers were associated with multiple traits. This study provides tools with promising applications in the molecular selection and breeding of P. juncea germplasm. Full article

(This article belongs to the Special Issue Genetic Research and Plant Breeding 2.0)

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11 pages, 257 KiB

Open AccessEditor’s ChoiceArticle

Determination of Carrier Frequency of Actionable Pathogenic Variants in Autosomal Recessive Genetic Diseases in the Turkish Cypriot Population

by Aziz Suat Gunsel, Mahmut Cerkez Ergoren, Hatice Kemal, Haniyeh Rahbar Kafshboran, Levent Cerit, Ayla Turgay and Hamza Duygu

Genes 2023, 14(10), 1967; https://doi.org/10.3390/genes14101967 - 20 Oct 2023

Cited by 1 | Viewed by 2641

Abstract

Whole-exome DNA sequencing is a rich source of clinically useful information for specialists, patients, and their families, as well as elucidating the genetic basis of monogenic and complex diseases in clinical diagnosis. However, interpreting and reporting variants encompassing exome and genome sequence analysis [...] Read more.

Whole-exome DNA sequencing is a rich source of clinically useful information for specialists, patients, and their families, as well as elucidating the genetic basis of monogenic and complex diseases in clinical diagnosis. However, interpreting and reporting variants encompassing exome and genome sequence analysis outcome data are one of the greatest challenges of the genomic era. In this study, we aimed to investigate the frequency and allele frequency spectrum of single nucleotide variants accepted as recessive disease carrier status in Turkish Cypriot exomes. The same sequencing platform and data processing line were used for the analysis of data from 100 Turkish Cypriot whole-exome sequence analysis. Identified variants were classified according to ACMG guidelines, and pathogenic variants were confirmed in other databases such as ClinVar, HGMD, Varsome, etc. Pathogenic variants were detected in 68 genes out of 100 whole-exome sequence data. The carriage rate was the highest in the CYP21A2 gene, causing 21-hydroxylase deficiency (14.70%), 11.76% in the HBB gene causing β-thalassemia, 10.29% in the BTD gene causing biotinidase deficiency, 8.82% in the CFTR gene causing cystic fibrosis, 8.82% in the RBM8A gene causing thrombocytopenia-absent radius syndrome, which is an ultra-rare disease, and 5.88% in the GAA gene causing glycogen storage disease II. The carriage of pathogenic variants in other genes causing the disease (GJB2, PAH, GALC, CYP11B2, COL4A3, HBA1, etc.) was determined as less than 5.00%. Also, the identified variations in the mentioned gene within the examined population were reported. The most prevalent mutation in North Cyprus was a missense variant (c.1360 C>T, p.Pro454Ser) detected in the CYP21A2 gene (rs6445), and the most frequently seen variant in the HBB gene was c.93-21G>A (rs35004220). We investigated reported pathogenic variants by estimating the lower and upper limits of carrier and population frequencies for autosomal recessive diseases, for which exome sequencing may reveal additional medically relevant information. Determining the lower and upper limits of these frequencies will shed light on preventive medicine practices and governmental actions. Full article

(This article belongs to the Section Genetic Diagnosis)

13 pages, 1517 KiB

Open AccessEditor’s ChoiceArticle

Tissue Circular RNA_0004018 and 0003570 as Novel Prognostic Biomarkers for Hepatitis B-Related Hepatocellular Carcinoma

by Min-Kyu Kang, Gyeonghwa Kim, Jung Gil Park, Se Young Jang, Hye Won Lee, Won Young Tak, Young Oh Kweon, Soo Young Park, Yu Rim Lee and Keun Hur

Genes 2023, 14(10), 1963; https://doi.org/10.3390/genes14101963 - 20 Oct 2023

Cited by 10 | Viewed by 1943

Abstract

The clinical significance of hsa_circ_0004018 and hsa_circ_0003570 in patients with hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) is unclear. We aimed to explore the clinical significance and prognostic utility of these two circular RNAs (circRNAs) in patients with HBV-HCC. Based on 86 paired tissue [...] Read more.

The clinical significance of hsa_circ_0004018 and hsa_circ_0003570 in patients with hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) is unclear. We aimed to explore the clinical significance and prognostic utility of these two circular RNAs (circRNAs) in patients with HBV-HCC. Based on 86 paired tissue samples of HCC and adjacent non-HCC, the relative expression profiles of hsa_circ_0004018 and hsa_circ_0003570 were determined using quantitative real-time polymerase chain reactions. The cut-off values were the median expression of each of the two circRNAs in 86 patients with HBV-HCC. The combination group comprised patients with high levels of the two circRNAs. Clinicopathological features, body composition profiles at the L3 level, and survival rates were investigated. The expression of hsa_circ_0004018 and hsa_circ_0003570 was downregulated in HCC tissues compared with non-HCC tissues. High expression levels of hsa_circ_0003570 (hazard ratio (HR), 0.437; p = 0.009) and hsa_circ_0004018 (HR, 0.435; p = 0.005) were inversely independent risk factors for overall and progression-free survival in patients with HBV-HCC, whereas the combination group was also an inversely independent risk factor for overall (HR, 0.399; p = 0.005) and progression-free survival (HR, 0.422; p = 0.003) in patients with HBV-HCC. The combination of hsa_circ_0003570 and hsa_circ_0004018 may be a potential prognostic biomarker for HBV-HCC. Full article

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

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19 pages, 5219 KiB

Open AccessEditor’s ChoiceArticle

Notch Signaling Regulates Mouse Perivascular Adipose Tissue Function via Mitochondrial Pathways

by Chenhao Yang, Xuehui Yang, Anne Harrington, Christian Potts, Abigail Kaija, Larisa Ryzhova and Lucy Liaw

Genes 2023, 14(10), 1964; https://doi.org/10.3390/genes14101964 - 20 Oct 2023

Cited by 6 | Viewed by 2711

Abstract

Perivascular adipose tissue (PVAT) regulates vascular function by secreting vasoactive substances. In mice, Notch signaling is activated in the PVAT during diet-induced obesity, and leads to the loss of the thermogenic phenotype and adipocyte whitening due to increased lipid accumulation. We used the [...] Read more.

Perivascular adipose tissue (PVAT) regulates vascular function by secreting vasoactive substances. In mice, Notch signaling is activated in the PVAT during diet-induced obesity, and leads to the loss of the thermogenic phenotype and adipocyte whitening due to increased lipid accumulation. We used the Adiponectin-Cre (Adipoq-Cre) strain to activate a ligand-independent Notch1 intracellular domain transgene (N1ICD) to drive constitutive Notch signaling in the adipose tissues (N1ICD;Adipoq-Cre). We previously found that constitutive activation of Notch1 signaling in the PVAT phenocopied the effects of diet-induced obesity. To understand the downstream pathways activated by Notch signaling, we performed a proteomic analysis of the PVAT from control versus N1ICD;Adipoq-Cre mice. This comparison identified prominent changes in the protein signatures related to metabolism, adipocyte homeostasis, mitochondrial function, and ferroptosis. PVAT-derived stromal vascular fraction cells were derived from our mouse strains to study the cellular and molecular phenotypes during adipogenic induction. We found that cells with activated Notch signaling displayed decreased mitochondrial respiration despite similar levels of adipogenesis and mitochondrial number. We observed variable regulation of the proteins related to mitochondrial dynamics and ferroptosis, including PHB3, PINK1, pDRP1, and the phospholipid hydroperoxidase GPX4. Mitochondria regulate some forms of ferroptosis, which is a regulated process of cell death driven by lipid peroxidation. Accordingly, we found that Notch activation promoted lipid peroxidation and ferroptosis in PVAT-derived adipocytes. Because the PVAT phenotype is a regulator of vascular reactivity, we tested the effect of Notch activation in PVAT on vasoreactivity using wire myography. The aortae from the N1ICD;Adipoq-Cre mice had increased vasocontraction and decreased vasorelaxation in a PVAT-dependent and age-dependent manner. Our data provide support for the novel concept that increased Notch signaling in the adipose tissue leads to PVAT whitening, impaired mitochondrial function, increased ferroptosis, and loss of a protective vasodilatory signal. Our study advances our understanding of how Notch signaling in adipocytes affects mitochondrial dynamics, which impacts vascular physiology. Full article

(This article belongs to the Special Issue Cellular and Developmental Biology of Lipid Metabolism)

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17 pages, 7345 KiB

Open AccessEditor’s ChoiceArticle

Systematic Pan-Cancer Analysis Reveals X-C Motif Chemokine Receptor 1 as a Prognostic and Immunological Biomarker

by Likun Cui, Liye Zhu, Jie Chen, Chunzhen Li, Yizhi Yu and Sheng Xu

Genes 2023, 14(10), 1961; https://doi.org/10.3390/genes14101961 - 19 Oct 2023

Cited by 3 | Viewed by 2361

Abstract

Chemokines and their receptors play an important role in immune monitoring and immune defense during tumor growth and metastasis. However, their prognostic roles in pan-cancer have not been elucidated. In this work, we screened all chemokine receptors in pan-cancer and discovered X-C Motif [...] Read more.

Chemokines and their receptors play an important role in immune monitoring and immune defense during tumor growth and metastasis. However, their prognostic roles in pan-cancer have not been elucidated. In this work, we screened all chemokine receptors in pan-cancer and discovered X-C Motif Chemokine Receptor 1 (XCR1) as a reliable immunological and prognostic biomarker in pan-cancer using bioinformation. The TCGA database served as the foundation for the primary research database analysis in this work. XCR1 was downregulated in tumors. Patients with reduced XCR1 showed worse prognoses and a concomitant decrease in immune cell infiltration (DCs and CD8⁺ T cells). According to a gene enrichment study, XCR1 enhanced immune system performance by promoting T-cell infiltration through the C-X-C Motif Chemokine Ligand 9 (CXCL9)- C-X-C Motif Chemokine Receptor 3 (CXCR3) axis. In addition, XCR1 is mainly expressed in infiltrated DCs and some malignant cells in tumor tissues. Our data revealed the important role of XCR1 in remodeling the tumor microenvironment and predicting the survival prognosis, which could also be used as a sensitive biomarker for tumor immunotherapy. Full article

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

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12 pages, 2900 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Association Study of the Reproductive Traits of the Dazu Black Goat (Capra hircus) Using Whole-Genome Resequencing

by Xingqiang Fang, Bowen Gu, Meixi Chen, Ruifan Sun, Jipan Zhang, Le Zhao and Yongju Zhao

Genes 2023, 14(10), 1960; https://doi.org/10.3390/genes14101960 - 19 Oct 2023

Cited by 10 | Viewed by 2760

Abstract

Reproductive traits are the basic economic traits of goats and important indicators in goat breeding. In this study, Dazu black goats (DBGs; n = 150), an important Chinese local goat breed with excellent reproductive performance, were used to screen for important variation loci [...] Read more.

Reproductive traits are the basic economic traits of goats and important indicators in goat breeding. In this study, Dazu black goats (DBGs; n = 150), an important Chinese local goat breed with excellent reproductive performance, were used to screen for important variation loci and genes of reproductive traits. Through genome-wide association studies (GWAS), 18 SNPs were found to be associated with kidding traits (average litter size, average litter size in the first three parity, and average litter size in the first six parity), and 10 SNPs were associated with udder traits (udder depth, teat diameter, teat length, and supernumerary teat). After gene annotation of the associated SNPs and in combination with relevant references, the candidate genes, namely ATP1A1, LRRC4C, SPCS2, XRRA1, CELF4, NTM, TMEM45B, ATE1, and FGFR2, were associated with udder traits, while the ENSCHIG00000017110, SLC9A8, GLRB, GRIA2, GASK1B, and ENSCHIG00000026285 genes were associated with litter size. These SNPs and candidate genes can provide useful biological information for improvement of the reproductive traits of goats. Full article

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

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13 pages, 1312 KiB

Open AccessEditor’s ChoiceArticle

Multi-Trait Exome-Wide Association Study of Back Pain-Related Phenotypes

by Irina V. Zorkoltseva, Elizaveta E. Elgaeva, Nadezhda M. Belonogova, Anatoliy V. Kirichenko, Gulnara R. Svishcheva, Maxim B. Freidin, Frances M. K. Williams, Pradeep Suri, Yakov A. Tsepilov and Tatiana I. Axenovich

Genes 2023, 14(10), 1962; https://doi.org/10.3390/genes14101962 - 19 Oct 2023

Cited by 3 | Viewed by 2181

Abstract

Back pain (BP) is a major contributor to disability worldwide, with heritability estimated at 40–60%. However, less than half of the heritability is explained by common genetic variants identified by genome-wide association studies. More powerful methods and rare and ultra-rare variant analysis may [...] Read more.

Back pain (BP) is a major contributor to disability worldwide, with heritability estimated at 40–60%. However, less than half of the heritability is explained by common genetic variants identified by genome-wide association studies. More powerful methods and rare and ultra-rare variant analysis may offer additional insight. This study utilized exome sequencing data from the UK Biobank to perform a multi-trait gene-based association analysis of three BP-related phenotypes: chronic back pain, dorsalgia, and intervertebral disc disorder. We identified the SLC13A1 gene as a contributor to chronic back pain via loss-of-function (LoF) and missense variants. This gene has been previously detected in two studies. A multi-trait approach uncovered the novel FSCN3 gene and its impact on back pain through LoF variants. This gene deserves attention because it is only the second gene shown to have an effect on back pain due to LoF variants and represents a promising drug target for back pain therapy. Full article

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

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13 pages, 8743 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Identification and Expression Analysis of Lipoxygenase Genes in Rose (Rosa chinensis)

by Wenqi Dong, Bo Jiao, Jiao Wang, Lei Sun, Songshuo Li, Zhiming Wu, Junping Gao and Shuo Zhou

Genes 2023, 14(10), 1957; https://doi.org/10.3390/genes14101957 - 18 Oct 2023

Cited by 3 | Viewed by 2020

Abstract

Lipoxygenases (LOX) play pivotal roles in plant resistance to stresses. However, no study has been conducted on LOX gene identification at the whole genome scale in rose (Rosa chinensis). In this study, a total of 17 RcLOX members were identified in [...] Read more.

Lipoxygenases (LOX) play pivotal roles in plant resistance to stresses. However, no study has been conducted on LOX gene identification at the whole genome scale in rose (Rosa chinensis). In this study, a total of 17 RcLOX members were identified in the rose genome. The members could be classified into three groups: 9-LOX, Type I 13-LOX, and Type II 13-LOX. Similar gene structures and protein domains can be found in RcLOX members. The RcLOX genes were spread among all seven chromosomes, with unbalanced distributions, and several tandem and proximal duplication events were found among RcLOX members. Expressions of the RcLOX genes were tissue-specific, while every RcLOX gene could be detected in at least one tissue. The expression levels of most RcLOX genes could be up-regulated by aphid infestation, suggesting potential roles in aphid resistance. Our study offers a systematic analysis of the RcLOX genes in rose, providing useful information not only for further gene cloning and functional exploration but also for the study of aphid resistance. Full article

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

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8 pages, 707 KiB

Open AccessEditor’s ChoiceCase Report

Identification of a Novel FOXP1 Variant in a Patient with Hypotonia, Intellectual Disability, and Severe Speech Impairment

by Mario Benvenuto, Pietro Palumbo, Ester Di Muro, Concetta Simona Perrotta, Tommaso Mazza, Giuseppa Maria Luana Mandarà, Orazio Palumbo and Massimo Carella

Genes 2023, 14(10), 1958; https://doi.org/10.3390/genes14101958 - 18 Oct 2023

Cited by 2 | Viewed by 2203

Abstract

The FOXP subfamily includes four different transcription factors: FOXP1, FOXP2, FOXP3, and FOXP4, all with important roles in regulating gene expression from early development through adulthood. Haploinsufficiency of FOXP1, due to deleterious variants (point mutations, copy number variants) disrupting the gene, leads [...] Read more.

The FOXP subfamily includes four different transcription factors: FOXP1, FOXP2, FOXP3, and FOXP4, all with important roles in regulating gene expression from early development through adulthood. Haploinsufficiency of FOXP1, due to deleterious variants (point mutations, copy number variants) disrupting the gene, leads to an emerging disorder known as “FOXP1 syndrome”, mainly characterized by intellectual disability, language impairment, dysmorphic features, and multiple congenital abnormalities with or without autistic features in some affected individuals (MIM 613670). Here we describe a 10-year-old female patient, born to unrelated parents, showing hypotonia, intellectual disability, and severe language delay. Targeted resequencing analysis allowed us to identify a heterozygous de novo FOXP1 variant c.1030C>T, p.(Gln344Ter) classified as likely pathogenetic according to the American College of Medical Genetics and Genomics guidelines. To the best of our knowledge, our patient is the first to date to report carrying this stop mutation, which is, for this reason, useful for broadening the molecular spectrum of FOXP1 clinically relevant variants. In addition, our results highlight the utility of next-generation sequencing in establishing an etiological basis for heterogeneous conditions such as neurodevelopmental disorders and providing additional insight into the phenotypic features of FOXP1-related syndrome. Full article

(This article belongs to the Special Issue Molecular Basis and Genetics of Intellectual Disability)

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10 pages, 716 KiB

Open AccessEditor’s ChoiceBrief Report

Alternative Genetic Diagnoses in Axenfeld–Rieger Syndrome Spectrum

by Linda M. Reis, David J. Amor, Raad A. Haddad, Catherine B. Nowak, Kim M. Keppler-Noreuil, Smith Ann Chisholm and Elena V. Semina

Genes 2023, 14(10), 1948; https://doi.org/10.3390/genes14101948 - 17 Oct 2023

Cited by 9 | Viewed by 3558

Abstract

Axenfeld–Rieger anomaly (ARA) is a specific ocular disorder that is frequently associated with other systemic abnormalities. PITX2 and FOXC1 variants explain the majority of individuals with Axenfeld–Rieger syndrome (ARS) but leave ~30% unsolved. Here, we present pathogenic/likely pathogenic variants in nine families with [...] Read more.

Axenfeld–Rieger anomaly (ARA) is a specific ocular disorder that is frequently associated with other systemic abnormalities. PITX2 and FOXC1 variants explain the majority of individuals with Axenfeld–Rieger syndrome (ARS) but leave ~30% unsolved. Here, we present pathogenic/likely pathogenic variants in nine families with ARA/ARS or similar phenotypes affecting five different genes/regions. USP9X and JAG1 explained three families each. USP9X was recently linked with syndromic cognitive impairment that includes hearing loss, dental defects, ventriculomegaly, Dandy–Walker malformation, skeletal anomalies (hip dysplasia), and other features showing a significant overlap with FOXC1-ARS. Anterior segment anomalies are not currently associated with USP9X, yet our cases demonstrate ARA, congenital glaucoma, corneal neovascularization, and cataracts. The identification of JAG1 variants, linked with Alagille syndrome, in three separate families with a clinical diagnosis of ARA/ARS highlights the overlapping features and high variability of these two phenotypes. Finally, intragenic variants in CDK13, BCOR, and an X chromosome deletion encompassing HCCS and AMELX (linked with ocular and dental anomalies, correspondingly) were identified in three additional cases with ARS. Accurate diagnosis has important implications for clinical management. We suggest that broad testing such as exome sequencing be applied as a second-tier test for individuals with ARS with normal results for PITX2/FOXC1 sequencing and copy number analysis, with attention to the described genes/regions. Full article

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

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12 pages, 275 KiB

Open AccessEditor’s ChoiceReview

The Role of miRNA Expression Profile in Sudden Cardiac Death Cases

by Alessia Bernini Di Michele, Valerio Onofri, Mauro Pesaresi and Chiara Turchi

Genes 2023, 14(10), 1954; https://doi.org/10.3390/genes14101954 - 17 Oct 2023

Cited by 2 | Viewed by 2334

Abstract

Sudden cardiac death (SCD) is one of the leading causes of death in the world and for this reason it has attracted the attention of numerous researchers in the field of legal medicine. It is not easy to determine the cause in a [...] Read more.

Sudden cardiac death (SCD) is one of the leading causes of death in the world and for this reason it has attracted the attention of numerous researchers in the field of legal medicine. It is not easy to determine the cause in a SCD case and the available methods used for diagnosis cannot always give an exhaustive answer. In addition, the molecular analysis of genes does not lead to a clear conclusion, but it could be interesting to focus attention on the expression level of miRNAs, a class of non-coding RNA of about 22 nucleotides. The role of miRNAs is to regulate the gene expression through complementary binding to 3′-untraslated regions of miRNAs, leading to the inhibition of translation or to mRNA degradation. In recent years, several studies were performed with the aim of exploring the use of these molecules as biomarkers for SCD cases, and to also distinguish the causes that lead to cardiac death. In this review, we summarize experiments, evidence, and results of different studies on the implication of miRNAs in SCD cases. We discuss the different biological starting materials with their respective advantages and disadvantages, studying miRNA expression on tissue (fresh-frozen tissue and FFPE tissue), circulating cell-free miRNAs in blood of patients affected by cardiac disease at high risk of SCD, and exosomal miRNAs analyzed from serum of people who died from SCD. Full article

(This article belongs to the Special Issue State-of-the-Art in Forensic Genetics)

22 pages, 36382 KiB

Open AccessEditor’s ChoiceArticle

Phylogenomic Analysis of Cytochrome P450 Gene Superfamily and Their Association with Flavonoids Biosynthesis in Peanut (Arachis hypogaea L.)

by Kun Zhang, Yongmei Qin, Wei Sun, Hourui Shi, Shuzhen Zhao, Liangqiong He, Changsheng Li, Jin Zhao, Jiaowen Pan, Guanghao Wang, Zhuqiang Han, Chuanzhi Zhao and Xiangli Yang

Genes 2023, 14(10), 1944; https://doi.org/10.3390/genes14101944 - 15 Oct 2023

Cited by 13 | Viewed by 2471

Abstract

Cytochrome P450s (CYPs) constitute extensive enzyme superfamilies in the plants, playing pivotal roles in a multitude of biosynthetic and detoxification pathways essential for growth and development, such as the flavonoid biosynthesis pathway. However, CYPs have not yet been systematically studied in the cultivated [...] Read more.

Cytochrome P450s (CYPs) constitute extensive enzyme superfamilies in the plants, playing pivotal roles in a multitude of biosynthetic and detoxification pathways essential for growth and development, such as the flavonoid biosynthesis pathway. However, CYPs have not yet been systematically studied in the cultivated peanuts (Arachis hypogaea L.), a globally significant cash crop. This study addresses this knowledge deficit through a comprehensive genome-wide analysis, leading to the identification of 589 AhCYP genes in peanuts. Through phylogenetic analysis, all AhCYPs were systematically classified into 9 clans, 43 gene families. The variability in the number of gene family members suggests specialization in biological functions. Intriguingly, both tandem duplication and fragment duplication events have emerged as pivotal drivers in the evolutionary expansion of the AhCYP superfamily. Ka/Ks analysis underscored the substantial influence of strong purifying selection on the evolution of AhCYPs. Furthermore, we selected 21 genes encoding 8 enzymes associated with the flavonoid pathway. The results of quantitative real-time PCR (qRT-PCR) experiments unveiled stage-specific expression patterns during the development of peanut testa, with discernible variations between pink and red testa. Importantly, we identified a direct correlation between gene expression levels and the accumulation of metabolites. These findings offer valuable insights into elucidating the comprehensive functions of AhCYPs and the underlying mechanisms governing the divergent accumulation of flavonoids in testa of different colors. Full article

(This article belongs to the Special Issue Peanut Genetic Breeding and Germplasm Innovation)

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11 pages, 2791 KiB

Open AccessEditor’s ChoiceCommunication

Genomic Scanning of Inbreeding Depression for Litter Size in Two Varieties of Iberian Pigs

by Carlos Hervás-Rivero, Houssemeddine Srihi, David López-Carbonell, Joaquim Casellas, Noelia Ibáñez-Escriche, Sara Negro and Luis Varona

Genes 2023, 14(10), 1941; https://doi.org/10.3390/genes14101941 - 15 Oct 2023

Cited by 2 | Viewed by 2032

Abstract

Inbreeding depression is expected to be more pronounced in fitness-related traits, such as pig litter size. Recent studies have suggested that the genetic determinism of inbreeding depression may be heterogeneous across the genome. Therefore, the objective of this study was to conduct a [...] Read more.

Inbreeding depression is expected to be more pronounced in fitness-related traits, such as pig litter size. Recent studies have suggested that the genetic determinism of inbreeding depression may be heterogeneous across the genome. Therefore, the objective of this study was to conduct a genomic scan of the whole pig autosomal genome to detect the genomic regions that control inbreeding depression for litter size in two varieties of Iberian pigs (Entrepelado and Retinto). The datasets consisted of 2069 (338 sows) and 2028 (327 sows) records of litter size (Total Number Born and Number Born Alive) for the Entrepelado and Retinto varieties. All sows were genotyped using the Geneseek GGP PorcineHD 70 K chip. We employed the Unfavorable Haplotype Finder software to extract runs of homozygosity (ROHs) and conducted a mixed-model analysis to identify highly significant differences between homozygous and heterozygous sows for each specific ROH. A total of eight genomic regions located on SSC2, SSC5, SSC7, SSC8, and SSC13 were significantly associated with inbreeding depression, housing some relevant genes such as FSHR, LHCGR, CORIN, AQP6, and CEP120. Full article

(This article belongs to the Special Issue Advances in Pig Breeding and Genetics (Volume II))

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11 pages, 1483 KiB

Open AccessEditor’s ChoiceArticle

The Mitochondrial Genome of Linichthys laticeps (Cypriniformes: Cyprinidae): Characterization and Phylogeny

by Renyi Zhang, Tingting Zhu, Hongmei Li and Lei Deng

Genes 2023, 14(10), 1938; https://doi.org/10.3390/genes14101938 - 14 Oct 2023

Cited by 5 | Viewed by 1776

Abstract

Mitochondrial genomes (mitogenomes) have been widely used in phylogenetic analysis and evolutionary biology. The Labeoninae is the largest subfamily of Cypriniformes and has great economic importance and ecological value. In this study, we sequenced, annotated, and characterized the complete mitogenome of Linichthys laticeps [...] Read more.

Mitochondrial genomes (mitogenomes) have been widely used in phylogenetic analysis and evolutionary biology. The Labeoninae is the largest subfamily of Cypriniformes and has great economic importance and ecological value. In this study, we sequenced, annotated, and characterized the complete mitogenome of Linichthys laticeps and then constructed the phylogenetic tree with previously published Labeoninae mitogenomes. The mitogenome of L. laticeps was 16,593 bp in length, with an A + T content of 57.1%. The mitogenome contained a standard set of 37 genes and a control region with the same order and orientation of genes as most fish mitogenomes. Each protein-coding gene (PCG) was initiated by an initial ATG codon, excluding COI, that began with a GTG codon. Furthermore, most of the PCGs were terminated by a conventional stop codon (TAA/TAG), while an incomplete termination codon (TA/T) was detected in 7 of the 13 PCGs. Most tRNA genes in L. laticeps were predicted to fold into the typical cloverleaf secondary structures. The K_a/K_s (ω) values for all PCGs were below one. The phylogenetic relationships of 96 Labeoninae mitogenomes indicated that Labeoninae was not a monophyletic group and L. laticeps was closely related to the genera Discogobio and Discocheilus. Overall, our study provided the first complete annotated mitogenome of L. laticeps, which filled a knowledge gap in Labeoninae and extended the understanding of the taxonomy and mitogenomic phylogeny of the subfamily Labeoninae. Full article

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

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23 pages, 434 KiB

Open AccessEditor’s ChoiceReview

The Human Microbiome and Its Role in Musculoskeletal Disorders

by Khaled Aboushaala, Arnold Y. L. Wong, Juan Nicolas Barajas, Perry Lim, Lena Al-Harthi, Ana Chee, Christopher B. Forsyth, Chun-do Oh, Sheila J. Toro, Frances M. K. Williams, Howard S. An and Dino Samartzis

Genes 2023, 14(10), 1937; https://doi.org/10.3390/genes14101937 - 14 Oct 2023

Cited by 8 | Viewed by 4268

Abstract

Musculoskeletal diseases (MSDs) are characterized as injuries and illnesses that affect the musculoskeletal system. MSDs affect every population worldwide and are associated with substantial global burden. Variations in the makeup of the gut microbiota may be related to chronic MSDs. There is growing [...] Read more.

Musculoskeletal diseases (MSDs) are characterized as injuries and illnesses that affect the musculoskeletal system. MSDs affect every population worldwide and are associated with substantial global burden. Variations in the makeup of the gut microbiota may be related to chronic MSDs. There is growing interest in exploring potential connections between chronic MSDs and variations in the composition of gut microbiota. The human microbiota is a complex community consisting of viruses, archaea, bacteria, and eukaryotes, both inside and outside of the human body. These microorganisms play crucial roles in influencing human physiology, impacting metabolic and immunological systems in health and disease. Different body areas host specific types of microorganisms, with facultative anaerobes dominating the gastrointestinal tract (able to thrive with or without oxygen), while strict aerobes prevail in the nasal cavity, respiratory tract, and skin surfaces (requiring oxygen for development). Together with the immune system, these bacteria have coevolved throughout time, forming complex biological relationships. Changes in the microbial ecology of the gut may have a big impact on health and can help illnesses develop. These changes are frequently impacted by lifestyle choices and underlying medical disorders. The potential for safety, expenses, and efficacy of microbiota-based medicines, even with occasional delivery, has attracted interest. They are, therefore, a desirable candidate for treating MSDs that are chronic and that may have variable progression patterns. As such, the following is a narrative review to address the role of the human microbiome as it relates to MSDs. Full article

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

12 pages, 1939 KiB

Open AccessEditor’s ChoiceArticle

Molecular Mechanisms Involved in MAFLD in Cholecystectomized Patients: A Cohort Study

by Shreya C. Pal, Stephany M. Castillo-Castañeda, Luis E. Díaz-Orozco, Mariana M. Ramírez-Mejía, Rita Dorantes-Heredia, Rogelio Alonso-Morales, Mohammed Eslam, Frank Lammert and Nahum Méndez-Sánchez

Genes 2023, 14(10), 1935; https://doi.org/10.3390/genes14101935 - 13 Oct 2023

Cited by 3 | Viewed by 2089

Abstract

Gallstone disease and metabolic dysfunction-associated fatty liver disease (MAFLD) share numerous common risk factors and progression determinants in that they both manifest as organ-specific consequences of metabolic dysfunction. Nevertheless, the precise molecular mechanisms underlying fibrosis development in cholecystectomized MAFLD patients remain inadequately defined. [...] Read more.

Gallstone disease and metabolic dysfunction-associated fatty liver disease (MAFLD) share numerous common risk factors and progression determinants in that they both manifest as organ-specific consequences of metabolic dysfunction. Nevertheless, the precise molecular mechanisms underlying fibrosis development in cholecystectomized MAFLD patients remain inadequately defined. This study aimed to investigate the involvement of farnesoid X receptor 1 (FXR1) and fibroblast growth factor receptor 4 (FGFR4) in the progression of fibrosis in cholecystectomized MAFLD patients. A meticulously characterized cohort of 12 patients diagnosed with MAFLD, who had undergone liver biopsies during programmed cholecystectomies, participated in this study. All enrolled patients underwent a follow-up regimen at 1, 3, and 6 months post-cholecystectomy, during which metabolic biochemical markers were assessed, along with elastography, which served as indirect indicators of fibrosis. Additionally, the hepatic expression levels of FGFR4 and FXR1 were quantified using quantitative polymerase chain reaction (qPCR). Our findings revealed a robust correlation between hepatic FGFR4 expression and various histological features, including the steatosis degree (r = 0.779, p = 0.023), ballooning degeneration (r = 0.764, p = 0.027), interphase inflammation (r = 0.756, p = 0.030), and steatosis activity score (SAS) (r = 0.779, p = 0.023). Conversely, hepatic FXR1 expression did not exhibit any significant correlations with these histological features. In conclusion, our study highlights a substantial correlation between FGFR4 expression and histological liver damage, emphasizing its potential role in lipid and glucose metabolism. These findings suggest that FGFR4 may play a crucial role in the progression of fibrosis in cholecystectomized MAFLD patients. Further research is warranted to elucidate the exact mechanisms through which FGFR4 influences metabolic dysfunction and fibrosis in this patient population. Full article

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

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17 pages, 1576 KiB

Open AccessEditor’s ChoiceArticle

Manifestation of Triploid Heterosis in the Root System after Crossing Diploid and Autotetraploid Energy Willow Plants

by Dénes Dudits, András Cseri, Katalin Török, Radomira Vankova, Petre I. Dobrev, László Sass, Gábor Steinbach, Ildikó Kelemen-Valkony, Zoltán Zombori, Györgyi Ferenc and Ferhan Ayaydin

Genes 2023, 14(10), 1929; https://doi.org/10.3390/genes14101929 - 12 Oct 2023

Cited by 6 | Viewed by 1851

Abstract

Successful use of woody species in reducing climatic and environmental risks of energy shortage and spreading pollution requires deeper understanding of the physiological functions controlling biomass productivity and phytoremediation efficiency. Targets in the breeding of energy willow include the size and the functionality [...] Read more.

Successful use of woody species in reducing climatic and environmental risks of energy shortage and spreading pollution requires deeper understanding of the physiological functions controlling biomass productivity and phytoremediation efficiency. Targets in the breeding of energy willow include the size and the functionality of the root system. For the combination of polyploidy and heterosis, we have generated triploid hybrids (THs) of energy willow by crossing autotetraploid willow plants with leading cultivars (Tordis and Inger). These novel Salix genotypes (TH3/12, TH17/17, TH21/2) have provided a unique experimental material for characterization of Mid-Parent Heterosis (MPH) in various root traits. Using a root phenotyping platform, we detected heterosis (TH3/12: MPH 43.99%; TH21/2: MPH 26.93%) in the size of the root system in soil. Triploid heterosis was also recorded in the fresh root weights, but it was less pronounced (MPH%: 9.63–19.31). In agreement with root growth characteristics in soil, the TH3/12 hybrids showed considerable heterosis (MPH: 70.08%) under in vitro conditions. Confocal microscopy-based imaging and quantitative analysis of root parenchyma cells at the division–elongation transition zone showed increased average cell diameter as a sign of cellular heterosis in plants from TH17/17 and TH21/2 triploid lines. Analysis of the hormonal background revealed that the auxin level was seven times higher than the total cytokinin contents in root tips of parental Tordis plants. In triploid hybrids, the auxin–cytokinin ratios were considerably reduced in TH3/12 and TH17/17 roots. In particular, the contents of cytokinin precursor, such as isopentenyl adenosine monophosphate, were elevated in all three triploid hybrids. Heterosis was also recorded in the amounts of active gibberellin precursor, GA₁₉, in roots of TH3/12 plants. The presented experimental findings highlight the physiological basics of triploid heterosis in energy willow roots. Full article

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

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9 pages, 682 KiB

Open AccessEditor’s ChoiceArticle

Effect of Supplementation with Curcuma longa and Rosmarinus officinalis Extract Mixture on Acute Phase Protein, Cathelicidin, Defensin and Cytolytic Protein Gene Expression in the Livers of Young Castrated Polish White Improved Bucks

by Daria M. Urbańska, Marek Pawlik, Agnieszka Korwin-Kossakowska, Michał Czopowicz, Karolina Rutkowska, Ewelina Kawecka-Grochocka, Marcin Mickiewicz, Jarosław Kaba and Emilia Bagnicka

Genes 2023, 14(10), 1932; https://doi.org/10.3390/genes14101932 - 12 Oct 2023

Cited by 2 | Viewed by 2037

Abstract

Goats are an excellent animal model for research on some physiological and pathophysiological processes in humans. The search for supplements that prevent homeostasis disorders and strengthen the immune system is necessary to reduce the risk of many diseases in both humans and animals. [...] Read more.

Goats are an excellent animal model for research on some physiological and pathophysiological processes in humans. The search for supplements that prevent homeostasis disorders and strengthen the immune system is necessary to reduce the risk of many diseases in both humans and animals. The aim of the study was to analyze the effect of supplementation with a mixture of dried extracts of Curcuma longa and Rosmarinus officinalis on the expression of acute-phase protein (SAA, HP, CRP, LALBA, AGP, CP, FGA, FGB, and FGG), cathelicidin (BAC5, BAC7.5, BAC3.4, MAP28, MAP34, and HEPC), beta-defensin-1 (GBD1, DEFB1), and beta-defensin-2, and cytolytic protein (LIZ and LF) genes in the livers of young castrated bucks of the Polish White Improved breed. The higher expression of LF in the control group suggests that it is important for the first line of hepatic immune defense and its expression is downregulated by the mixture of turmeric and rosemary extracts; thus, the spice–herb mixture mutes its activity. The lower expression of FGB and the higher expression of BAC5 genes in the livers of healthy, young castrated bucks who were administered the supplement suggest the silencing effects of the mixture on the acute-phase response and the stimulating effect on the antimicrobial activity of the immune system. Full article

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

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10 pages, 2104 KiB

Open AccessEditor’s ChoiceCommunication

STS and PUDP Deletion Identified by Targeted Panel Sequencing with CNV Analysis in X-Linked Ichthyosis: A Case Report and Literature Review

by Joonhong Park, Yong Gon Cho, Jin Kyu Kim and Hyun Ho Kim

Genes 2023, 14(10), 1925; https://doi.org/10.3390/genes14101925 - 10 Oct 2023

Cited by 3 | Viewed by 2322

Abstract

X-linked recessive ichthyosis (XLI) is clinically characterized by dark brown, widespread dryness with polygonal scales. We describe the identification of STS and PUDP deletions using targeted panel sequencing combined with copy-number variation (CNV) analysis in XLI. A 9-month-old infant was admitted for genetic [...] Read more.

X-linked recessive ichthyosis (XLI) is clinically characterized by dark brown, widespread dryness with polygonal scales. We describe the identification of STS and PUDP deletions using targeted panel sequencing combined with copy-number variation (CNV) analysis in XLI. A 9-month-old infant was admitted for genetic counseling. Since the second day after birth, the infant’s skin tended to be dry and polygonal scales had accumulated over the abdomen and upper extremities. The infant’s maternal uncle and brother (who had also exhibited similar skin symptoms from birth) presented with polygonal scales on their trunks. CNV analysis revealed a hemizygous deletion spanning 719.3 Kb on chromosome Xp22 (chrX:7,108,996–7,828,312), which included a segment of the STS gene and exhibited a Z ratio of −2 in the proband. Multiplex ligation-dependent probe amplification (MLPA) confirmed this interstitial Xp22.31 deletion. Our report underscores the importance of implementing CNV screening techniques, including sequencing data analysis and gene dosage assays such as MLPA, to detect substantial deletions that encompass the STS gene region of Xq22 in individuals suspected of having XLI. Full article

(This article belongs to the Special Issue Genetics of Skin Disorders (2.0 Edition))

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12 pages, 607 KiB

Open AccessEditor’s ChoiceReview

Emerging Opportunities to Study Mobile Element Insertions and Their Source Elements in an Expanding Universe of Sequenced Human Genomes

by Scott E. Devine

Genes 2023, 14(10), 1923; https://doi.org/10.3390/genes14101923 - 10 Oct 2023

Cited by 3 | Viewed by 3231

Abstract

Three mobile element classes, namely Alu, LINE-1 (L1), and SVA elements, remain actively mobile in human genomes and continue to produce new mobile element insertions (MEIs). Historically, MEIs have been discovered and studied using several methods, including: (1) Southern blots, (2) PCR [...] Read more.

Three mobile element classes, namely Alu, LINE-1 (L1), and SVA elements, remain actively mobile in human genomes and continue to produce new mobile element insertions (MEIs). Historically, MEIs have been discovered and studied using several methods, including: (1) Southern blots, (2) PCR (including PCR display), and (3) the detection of MEI copies from young subfamilies. We are now entering a new phase of MEI discovery where these methods are being replaced by whole genome sequencing and bioinformatics analysis to discover novel MEIs. We expect that the universe of sequenced human genomes will continue to expand rapidly over the next several years, both with short-read and long-read technologies. These resources will provide unprecedented opportunities to discover MEIs and study their impact on human traits and diseases. They also will allow the MEI community to discover and study the source elements that produce these new MEIs, which will facilitate our ability to study source element regulation in various tissue contexts and disease states. This, in turn, will allow us to better understand MEI mutagenesis in humans and the impact of this mutagenesis on human biology. Full article

(This article belongs to the Special Issue Mobile-Element-Related Genetic Variation)

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8 pages, 830 KiB

Open AccessEditor’s ChoiceBrief Report

Improving the Completeness of Chromosome-Level Assembly by Recalling Sequences from Lost Contigs

by Junyang Liu, Fang Liu and Weihua Pan

Genes 2023, 14(10), 1926; https://doi.org/10.3390/genes14101926 - 10 Oct 2023

Cited by 1 | Viewed by 1819

Abstract

For a long time, the construction of complete reference genomes for complex eukaryotic genomes has been hindered by the limitations of sequencing technologies. Recently, the Pacific Biosciences (PacBio) HiFi data and Oxford Nanopore Technologies (ONT) Ultra-Long data, leveraging their respective advantages in accuracy [...] Read more.

For a long time, the construction of complete reference genomes for complex eukaryotic genomes has been hindered by the limitations of sequencing technologies. Recently, the Pacific Biosciences (PacBio) HiFi data and Oxford Nanopore Technologies (ONT) Ultra-Long data, leveraging their respective advantages in accuracy and length, have provided an opportunity for generating complete chromosome sequences. Nevertheless, for the majority of genomes, the chromosome-level assemblies generated using existing methods still miss a high proportion of sequences due to losing small contigs in the step of assembly and scaffolding. To address this shortcoming, in this paper, we propose a novel method that is able to identify and fill the gaps in the chromosome-level assembly by recalling the sequences in the lost small contigs. Experimental results on both real and simulated datasets demonstrate that this method is able to improve the completeness of the chromosome-level assembly. Full article

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

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33 pages, 9826 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Identification and Expression Analysis of bZIP Family Genes in Stevia rebaudiana

by Mengyang Wu, Jinsong Chen, Weilin Tang, Yijie Jiang, Zhaoyong Hu, Dongbei Xu, Kai Hou, Yinyin Chen and Wei Wu

Genes 2023, 14(10), 1918; https://doi.org/10.3390/genes14101918 - 9 Oct 2023

Cited by 3 | Viewed by 2390

Abstract

The basic (region) leucine zippers (bZIPs) are evolutionarily conserved transcription factors widely distributed in eukaryotic organisms. In plants, they are not only involved in growth and development, defense and stress responses and regulation of physiological processes but also play a pivotal role in [...] Read more.

The basic (region) leucine zippers (bZIPs) are evolutionarily conserved transcription factors widely distributed in eukaryotic organisms. In plants, they are not only involved in growth and development, defense and stress responses and regulation of physiological processes but also play a pivotal role in regulating secondary metabolism. To explore the function related to the bZIP gene family in Stevia rebaudiana Bertoni, we identified 105 SrbZIP genes at the genome-wide level and classified them into 12 subfamilies using bioinformation methods. Three main classes of cis-acting elements were found in the SrbZIP promoter regions, including development-related elements, defense and stress-responsive elements and phytohormone-responsive elements. Through protein–protein interaction network of 105 SrbZIP proteins, SrbZIP proteins were mainly classified into four major categories: ABF2/ABF4/ABI5 (SrbZIP51/SrbZIP38/SrbZIP7), involved in phytohormone signaling, GBF1/GBF3/GBF4 (SrbZIP29/SrbZIP63/SrbZIP60) involved in environmental signaling, AREB3 (SrbZIP88), PAN (SrbZIP12), TGA1 (SrbZIP69), TGA4 (SrbZIP82), TGA7 (SrbZIP31), TGA9 (SrbZIP95), TGA10 (SrbZIP79) and HY5 (SrbZIP96) involved in cryptochrome signaling, and FD (SrbZIP72) promoted flowering. The transcriptomic data showed that SrbZIP genes were differentially expressed in six S. rebaudiana cultivars (‘023’, ‘110’, ‘B1188’, ‘11-14’, ‘GP’ and ‘GX’). Moreover, the expression levels of selected 15 SrbZIP genes in response to light, abiotic stress (low temperature, salt and drought), phytohormones (methyl jasmonate, gibberellic acid and salicylic acid) treatment and in different tissues were analyzed utilizing qRT-PCR. Some SrbZIP genes were further identified to be highly induced by factors affecting glycoside synthesis. Among them, three SrbZIP genes (SrbZIP54, SrbZIP63 and SrbZIP32) were predicted to be related to stress-responsive terpenoid synthesis in S. rebaudiana. The protein–protein interaction network expanded the potential functions of SrbZIP genes. This study firstly provided the comprehensive genome-wide report of the SrbZIP gene family, laying a foundation for further research on the evolution, function and regulatory role of the bZIP gene family in terpenoid synthesis in S. rebaudiana. Full article

(This article belongs to the Section Bioinformatics)

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14 pages, 2604 KiB

Open AccessEditor’s ChoiceArticle

Longitudinal Changes in Mitochondrial DNA Copy Number and Telomere Length in Patients with Parkinson’s Disease

by Alberto Ortega-Vázquez, Salvador Sánchez-Badajos, Miguel Ángel Ramírez-García, Diana Alvarez-Luquín, Marisol López-López, Laura Virginia Adalid-Peralta and Nancy Monroy-Jaramillo

Genes 2023, 14(10), 1913; https://doi.org/10.3390/genes14101913 - 7 Oct 2023

Cited by 8 | Viewed by 2413

Abstract

Parkinson’s disease (PD) pathophysiology includes mitochondrial dysfunction, neuroinflammation, and aging as its biggest risk factors. Mitochondrial DNA copy number (mtDNA-CN) and telomere length (TL) are biological aging markers with inconclusive results regarding their association with PD. A case–control study was used to measure [...] Read more.

Parkinson’s disease (PD) pathophysiology includes mitochondrial dysfunction, neuroinflammation, and aging as its biggest risk factors. Mitochondrial DNA copy number (mtDNA-CN) and telomere length (TL) are biological aging markers with inconclusive results regarding their association with PD. A case–control study was used to measure TL and mtDNA-CN using qPCR in PBMCs. PD patients were naive at baseline (T0) and followed-up at one (T1) and two (T2) years after the dopaminergic treatment (DRT). Plasmatic cytokines were determined by ELISA in all participants, along with clinical parameters of patients at T0. While TL was shorter in patients vs. controls at all time points evaluated (p < 0.01), mtDNA-CN showed no differences. An increase in mtDNA-CN and TL was observed in treated patients vs. naive ones (p < 0.001). Our statistical model analyzed both aging markers with covariates, showing a strong correlation between them (r = 0.57, p < 0.01), and IL-17A levels positively correlating with mtDNA-CN only in untreated patients (r = 0.45, p < 0.05). TL and mtDNA-CN could be useful markers for monitoring inflammation progression or treatment response in PD. DRT might modulate TL and mtDNA-CN, reflecting a compensatory mechanism to counteract mitochondrial dysfunction in PD, but this needs further investigation. Full article

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

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13 pages, 12854 KiB

Open AccessEditor’s ChoiceArticle

Comparative Analysis and Phylogenetic Insights of Cas14-Homology Proteins in Bacteria and Archaea

by Numan Ullah, Naisu Yang, Zhongxia Guan, Kuilin Xiang, Yali Wang, Mohamed Diaby, Cai Chen, Bo Gao and Chengyi Song

Genes 2023, 14(10), 1911; https://doi.org/10.3390/genes14101911 - 6 Oct 2023

Cited by 6 | Viewed by 2728

Abstract

Type-V-F Cas12f proteins, also known as Cas14, have drawn significant interest within the diverse CRISPR-Cas nucleases due to their compact size. This study involves analyzing and comparing Cas14-homology proteins in prokaryotic genomes through mining, sequence comparisons, a phylogenetic analysis, and an array/repeat analysis. [...] Read more.

Type-V-F Cas12f proteins, also known as Cas14, have drawn significant interest within the diverse CRISPR-Cas nucleases due to their compact size. This study involves analyzing and comparing Cas14-homology proteins in prokaryotic genomes through mining, sequence comparisons, a phylogenetic analysis, and an array/repeat analysis. In our analysis, we identified and mined a total of 93 Cas14-homology proteins that ranged in size from 344 aa to 843 aa. The majority of the Cas14-homology proteins discovered in this analysis were found within the Firmicutes group, which contained 37 species, representing 42% of all the Cas14-homology proteins identified. In archaea, the DPANN group had the highest number of species containing Cas14-homology proteins, a total of three species. The phylogenetic analysis results demonstrate the division of Cas14-homology proteins into three clades: Cas14-A, Cas14-B, and Cas14-U. Extensive similarity was observed at the C-terminal end (CTD) through a domain comparison of the three clades, suggesting a potentially shared mechanism of action due to the presence of cutting domains in that region. Additionally, a sequence similarity analysis of all the identified Cas14 sequences indicated a low level of similarity (18%) between the protein variants. The analysis of repeats/arrays in the extended nucleotide sequences of the identified Cas14-homology proteins highlighted that 44 out of the total mined proteins possessed CRISPR-associated repeats, with 20 of them being specific to Cas14. Our study contributes to the increased understanding of Cas14 proteins across prokaryotic genomes. These homologous proteins have the potential for future applications in the mining and engineering of Cas14 proteins. Full article

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

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13 pages, 2481 KiB

Open AccessEditor’s ChoiceArticle

GIP_HUMAN [22–51] Peptide Encoded by the Glucose-Dependent Insulinotropic Polypeptide (GIP) Gene Suppresses Insulin Expression and Secretion in INS-1E Cells and Rat Pancreatic Islets

by Emily Pusch, Małgorzata Krążek, Tatiana Wojciechowicz, Maciej Sassek, Paweł A. Kołodziejski, Mathias Z. Strowski, Krzysztof W. Nowak and Marek Skrzypski

Genes 2023, 14(10), 1910; https://doi.org/10.3390/genes14101910 - 5 Oct 2023

Cited by 2 | Viewed by 1985

Abstract

GIP_HUMAN [22–51] is a recently discovered peptide that shares the same precursor molecule with glucose-dependent insulinotropic polypeptide (GIP). In vivo, chronic infusion of GIP_HUMAN [22–51] in ApoE−/− mice enhanced the development of aortic atherosclerotic lesions and upregulated inflammatory and proatherogenic proteins. In the [...] Read more.

GIP_HUMAN [22–51] is a recently discovered peptide that shares the same precursor molecule with glucose-dependent insulinotropic polypeptide (GIP). In vivo, chronic infusion of GIP_HUMAN [22–51] in ApoE−/− mice enhanced the development of aortic atherosclerotic lesions and upregulated inflammatory and proatherogenic proteins. In the present study, we evaluate the effects of GIP_HUMAN [22–51] on insulin mRNA expression and secretion in insulin-producing INS-1E cells and isolated rat pancreatic islets. Furthermore, we characterize the influence of GIP_HUMAN [22–51] on cell proliferation and death and on Nf-kB nuclear translocation. Rat insulin-producing INS-1E cells and pancreatic islets, isolated from male Wistar rats, were used in this study. Gene expression was evaluated using real-time PCR. Cell proliferation was studied using a BrdU incorporation assay. Cell death was quantified by evaluating histone-complexed DNA fragments. Insulin secretion was determined using an ELISA test. Nf-kB nuclear translocation was detected using immunofluorescence. GIP_HUMAN [22–51] suppressed insulin (Ins1 and Ins2) in INS-1E cells and pancreatic islets. Moreover, GIP_HUMAN [22–51] promoted the translocation of NF-κB from cytoplasm to the nucleus. In the presence of a pharmacological inhibitor of NF-κB, GIP_HUMAN [22–51] was unable to suppress Ins2 mRNA expression. Moreover, GIP_HUMAN [22–51] downregulated insulin secretion at low (2.8 mmol/L) but not high (16.7 mmol/L) glucose concentration. By contrast, GIP_HUMAN [22–51] failed to affect cell proliferation and apoptosis. We conclude that GIP_HUMAN [22–51] suppresses insulin expression and secretion in pancreatic β cells without affecting β cell proliferation or apoptosis. Notably, the effects of GIP_HUMAN [22–51] on insulin secretion are glucose-dependent. Full article

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

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18 pages, 6383 KiB

Open AccessEditor’s ChoiceArticle

Sequence Characterization of Extra-Chromosomal Circular DNA Content in Multiple Blackgrass (Alopecurus myosuroides) Populations

by Wangfang Fu, Dana R. MacGregor, David Comont and Christopher A. Saski

Genes 2023, 14(10), 1905; https://doi.org/10.3390/genes14101905 - 4 Oct 2023

Cited by 5 | Viewed by 2793

Abstract

Alopecurus myosuroides (blackgrass) is a problematic weed of Western European winter wheat, and its success is largely due to widespread multiple-herbicide resistance. Previous analysis of F2 seed families derived from two distinct blackgrass populations exhibiting equivalent non-target site resistance (NTSR) phenotypes shows resistance [...] Read more.

Alopecurus myosuroides (blackgrass) is a problematic weed of Western European winter wheat, and its success is largely due to widespread multiple-herbicide resistance. Previous analysis of F2 seed families derived from two distinct blackgrass populations exhibiting equivalent non-target site resistance (NTSR) phenotypes shows resistance is polygenic and evolves from standing genetic variation. Using a CIDER-seq pipeline, we show that herbicide-resistant (HR) and herbicide-sensitive (HS) F3 plants from these F2 seed families as well as the parent populations they were derived from carry extra-chromosomal circular DNA (eccDNA). We identify the similarities and differences in the coding structures within and between resistant and sensitive populations. Although the numbers and size of detected eccDNAs varied between the populations, comparisons between the HR and HS blackgrass populations identified shared and unique coding content, predicted genes, and functional protein domains. These include genes related to herbicide detoxification such as Cytochrome P450s, ATP-binding cassette transporters, and glutathione transferases including AmGSTF1. eccDNA content was mapped to the A. myosuroides reference genome, revealing genomic regions at the distal end of chromosome 5 and the near center of chromosomes 1 and 7 as regions with a high number of mapped eccDNA gene density. Mapping to 15 known herbicide-resistant QTL regions showed that the eccDNA coding sequences matched twelve, with four QTL matching HS coding sequences; only one region contained HR coding sequences. These findings establish that, like other pernicious weeds, blackgrass has eccDNAs that contain homologs of chromosomal genes, and these may contribute genetic heterogeneity and evolutionary innovation to rapidly adapt to abiotic stresses, including herbicide treatment. Full article

(This article belongs to the Special Issue Identification and Innovation of Plant Genes)

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19 pages, 2303 KiB

Open AccessEditor’s ChoiceArticle

Enhancing Genetic Gains in Grain Yield and Efficiency of Testing Sites of Early-Maturing Maize Hybrids under Contrasting Environments

by Baffour Badu-Apraku, Adamu Masari Abubakar, Gloria Boakyewaa Adu, Abdoul-Madjidou Yacoubou, Samuel Adewale and Idris Ishola Adejumobi

Genes 2023, 14(10), 1900; https://doi.org/10.3390/genes14101900 - 30 Sep 2023

Cited by 2 | Viewed by 2118

Abstract

The major challenges of maize production and productivity in Sub-Saharan Africa (SSA) include Striga hermonthica infestation, recurrent drought, and low soil nitrogen (low N). This study assessed the following: (i) accelerated genetic advancements in grain yield and other measured traits of early-maturing maize [...] Read more.

The major challenges of maize production and productivity in Sub-Saharan Africa (SSA) include Striga hermonthica infestation, recurrent drought, and low soil nitrogen (low N). This study assessed the following: (i) accelerated genetic advancements in grain yield and other measured traits of early-maturing maize hybrids, (ii) ideal test environments for selecting early-maturing multiple-stress tolerant hybrids, and (iii) high-yielding and stable hybrids across multiple-stress and non-stress environments. Fifty-four hybrids developed during three periods of genetic enhancement (2008–2010, 2011–2013, and 2014–2016) were evaluated in Nigeria, The Republic of Benin, and Ghana under multiple stressors (Striga infestation, managed drought, and Low N) and non-stress environments from 2017 to 2019. Under multiple-stress and non-stress environments, annual genetic gains from selection in grain yield of 84.72 kg ha⁻¹ (4.05%) and 61 kg ha⁻¹ (1.56%), respectively, were recorded. Three mega-environments were identified across 14 stress environments. Abuja was identified as an ideal test environment for selecting superior hybrids. The hybrid TZdEI 352 × TZEI 355 developed during period 3 was the most outstanding under multiple-stress and non-stress environments. On-farm testing of this hybrid is required to verify its superior performance for commercialization in SSA. Considerable progress has been made in the genetic improvement of early-maturing maize hybrids for tolerance of multiple stressors and high yield. The identified core testing sites of this study could be used to enhance the testing and selection of promising hybrids. Full article

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

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18 pages, 3647 KiB

Open AccessEditor’s ChoiceArticle

Specific Gene Expression in Pseudomonas Putida U Shows New Alternatives for Cadaverine and Putrescine Catabolism

by Luis Getino, Alejandro Chamizo-Ampudia, José Luis Martín, José María Luengo, Carlos Barreiro and Elías R. Olivera

Genes 2023, 14(10), 1897; https://doi.org/10.3390/genes14101897 - 30 Sep 2023

Cited by 4 | Viewed by 2561

Abstract

Pseudomonas putida strain U can be grown using, as sole carbon sources, the biogenic amines putrescine or cadaverine, as well as their catabolic intermediates, ɣ-aminobutyrate or δ-aminovalerate, respectively. Several paralogs for the genes that encode some of the activities involved in the catabolism [...] Read more.

Pseudomonas putida strain U can be grown using, as sole carbon sources, the biogenic amines putrescine or cadaverine, as well as their catabolic intermediates, ɣ-aminobutyrate or δ-aminovalerate, respectively. Several paralogs for the genes that encode some of the activities involved in the catabolism of these compounds, such as a putrescine-pyruvate aminotransferase (spuC1 and spuC2 genes) and a ɣ-aminobutyrate aminotransferase (gabT1 and gabT2 genes) have been identified in this bacterium. When the expression pattern of these genes is analyzed by qPCR, it is drastically conditioned by supplying the carbon sources. Thus, spuC1 is upregulated by putrescine, whereas spuC2 seems to be exclusively induced by cadaverine. However, gabT1 increases its expression in response to different polyamines or aminated catabolic derivatives from them (i.e., ɣ-aminobutyrate or δ-aminovalerate), although gabT2 does not change its expression level concerning no-amine unrelated carbon sources (citrate). These results reveal differences between the mechanisms proposed for polyamine catabolism in P. aeruginosa and Escherichia coli concerning P. putida strain U, as well as allow a deeper understanding of the enzymatic systems used by this last strain during polyamine metabolism. Full article

(This article belongs to the Section Genes & Environments)

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17 pages, 2079 KiB

Open AccessEditor’s ChoiceArticle

Evaluation of Antioxidant Defence Systems and Inflammatory Status in Basketball Elite Athletes

by Alessandro Gentile, Carolina Punziano, Mariella Calvanese, Renato De Falco, Luca Gentile, Giovanni D’Alicandro, Ciro Miele, Filomena Capasso, Raffaela Pero, Cristina Mazzaccara, Barbara Lombardo, Giulia Frisso, Paola Borrelli, Cristina Mennitti, Olga Scudiero and Raffaella Faraonio

Genes 2023, 14(10), 1891; https://doi.org/10.3390/genes14101891 - 29 Sep 2023

Cited by 2 | Viewed by 1751

Abstract

Intense physical activity can induce metabolic changes that modify specific biochemical biomarkers. In this scenario, the purpose of our study was to evaluate how intense physical activity can affect oxidative metabolism. Following this, fifteen professional basketball players and fifteen sedentary controls were recruited [...] Read more.

Intense physical activity can induce metabolic changes that modify specific biochemical biomarkers. In this scenario, the purpose of our study was to evaluate how intense physical activity can affect oxidative metabolism. Following this, fifteen professional basketball players and fifteen sedentary controls were recruited and subjected to two samplings of serum and urine in the pre-season (September) and two months after the start of the competitive season (November). Our results have shown an increase in athletes compared to controls in CK and LDH in September (respectively, p-value 0.003 and p-value < 0.001) and in November (both p-value < 0.001), whereas ALT is increased only in November (p-value 0.09). GGT serum levels were decreased in athletes compared to controls in both months (in September p-value 0.001 and in November p-value < 0.001). A gene expression analysis, carried out using RT-PCR, has revealed that IL-2, IL-6, IL-8, xCT and GCLM are increased in athletes in both months (p-value < 0.0001), while IL-10 and CHAC1 are increased only in September if compared to the controls (respectively, p-value 0.040 and p-value < 0.001). In conclusion, physical activity creates an adaptation of the systems involved in oxidative metabolism but without causing damage to the liver or kidney. This information could be of help to sports doctors for the prevention of injuries and illnesses in professional athletes for the construction of the athlete’s passport. Full article

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

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11 pages, 1881 KiB

Open AccessEditor’s ChoiceArticle

Uncovering the Molecular Drivers of NHEJ DNA Repair-Implicated Missense Variants and Their Functional Consequences

by Raghad Al-Jarf, Malancha Karmakar, Yoochan Myung and David B. Ascher

Genes 2023, 14(10), 1890; https://doi.org/10.3390/genes14101890 - 29 Sep 2023

Cited by 4 | Viewed by 2309

Abstract

Variants in non-homologous end joining (NHEJ) DNA repair genes are associated with various human syndromes, including microcephaly, growth delay, Fanconi anemia, and different hereditary cancers. However, very little has been done previously to systematically record the underlying molecular consequences of NHEJ variants and [...] Read more.

Variants in non-homologous end joining (NHEJ) DNA repair genes are associated with various human syndromes, including microcephaly, growth delay, Fanconi anemia, and different hereditary cancers. However, very little has been done previously to systematically record the underlying molecular consequences of NHEJ variants and their link to phenotypic outcomes. In this study, a list of over 2983 missense variants of the principal components of the NHEJ system, including DNA Ligase IV, DNA-PKcs, Ku70/80 and XRCC4, reported in the clinical literature, was initially collected. The molecular consequences of variants were evaluated using in silico biophysical tools to quantitatively assess their impact on protein folding, dynamics, stability, and interactions. Cancer-causing and population variants within these NHEJ factors were statistically analyzed to identify molecular drivers. A comprehensive catalog of NHEJ variants from genes known to be mutated in cancer was curated, providing a resource for better understanding their role and molecular mechanisms in diseases. The variant analysis highlighted different molecular drivers among the distinct proteins, where cancer-driving variants in anchor proteins, such as Ku70/80, were more likely to affect key protein–protein interactions, whilst those in the enzymatic components, such as DNA-PKcs, were likely to be found in intolerant regions undergoing purifying selection. We believe that the information acquired in our database will be a powerful resource to better understand the role of non-homologous end-joining DNA repair in genetic disorders, and will serve as a source to inspire other investigations to understand the disease further, vital for the development of improved therapeutic strategies. Full article

(This article belongs to the Special Issue Bioinformatics and Computational Biology for Cancer Prediction and Prognosis)

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20 pages, 3264 KiB

Open AccessEditor’s ChoiceReview

The Role of IgLON Cell Adhesion Molecules in Neurodegenerative Diseases

by Marco Salluzzo, Clara Vianello, Sandra Abdullatef, Roberto Rimondini, Giovanni Piccoli and Lucia Carboni

Genes 2023, 14(10), 1886; https://doi.org/10.3390/genes14101886 - 28 Sep 2023

Cited by 11 | Viewed by 3964

Abstract

In the brain, cell adhesion molecules (CAMs) are critical for neurite outgrowth, axonal fasciculation, neuronal survival and migration, and synapse formation and maintenance. Among CAMs, the IgLON family comprises five members: Opioid Binding Protein/Cell Adhesion Molecule Like (OPCML or OBCAM), Limbic System Associated [...] Read more.

In the brain, cell adhesion molecules (CAMs) are critical for neurite outgrowth, axonal fasciculation, neuronal survival and migration, and synapse formation and maintenance. Among CAMs, the IgLON family comprises five members: Opioid Binding Protein/Cell Adhesion Molecule Like (OPCML or OBCAM), Limbic System Associated Membrane Protein (LSAMP), neurotrimin (NTM), Neuronal Growth Regulator 1 (NEGR1), and IgLON5. IgLONs exhibit three N-terminal C2 immunoglobulin domains; several glycosylation sites; and a glycosylphosphatidylinositol anchoring to the membrane. Interactions as homo- or heterodimers in cis and in trans, as well as binding to other molecules, appear critical for their functions. Shedding by metalloproteases generates soluble factors interacting with cellular receptors and activating signal transduction. The aim of this review was to analyse the available data implicating a role for IgLONs in neuropsychiatric disorders. Starting from the identification of a pathological role for antibodies against IgLON5 in an autoimmune neurodegenerative disease with a poorly understood mechanism of action, accumulating evidence links IgLONs to neuropsychiatric disorders, albeit with still undefined mechanisms which will require future thorough investigations. Full article

(This article belongs to the Special Issue Study on Genotypes and Phenotypes of Neurodegenerative Diseases)

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9 pages, 919 KiB

Open AccessEditor’s ChoiceArticle

A Spanish Family with Gordon Syndrome Due to a Variant in the Acidic Motif of WNK1

by Ramón Peces, Carlos Peces, Laura Espinosa, Rocío Mena, Carolina Blanco, Jair Tenorio-Castaño, Pablo Lapunzina and Julián Nevado

Genes 2023, 14(10), 1878; https://doi.org/10.3390/genes14101878 - 27 Sep 2023

Cited by 5 | Viewed by 1962

Abstract

(1) Background: Gordon syndrome (GS) or familial hyperkalemic hypertension is caused by pathogenic variants in the genes WNK1, WNK4, KLHL3, and CUL3. Patients presented with hypertension, hyperkalemia despite average glomerular filtration rate, hyperchloremic metabolic acidosis, and suppressed plasma renin (PR) [...] Read more.

(1) Background: Gordon syndrome (GS) or familial hyperkalemic hypertension is caused by pathogenic variants in the genes WNK1, WNK4, KLHL3, and CUL3. Patients presented with hypertension, hyperkalemia despite average glomerular filtration rate, hyperchloremic metabolic acidosis, and suppressed plasma renin (PR) activity with normal plasma aldosterone (PA) and sometimes failure to thrive. GS is a heterogeneous genetic syndrome, ranging from severe cases in childhood to mild and sometimes asymptomatic cases in mid-adulthood. (2) Methods: We report here a sizeable Spanish family of six patients (four adults and two children) with GS. (3) Results: They carry a novel heterozygous missense variant in exon 7 of WNK1 (p.Glu630Gly). The clinical presentation in the four adults consisted of hypertension (superimposed pre-eclampsia in two cases), hyperkalemia, short stature with low body weight, and isolated hyperkalemia in both children. All patients also presented mild hyperchloremic metabolic acidosis and low PR activity with normal PA levels. Abnormal laboratory findings and hypertension were normalized by dietary salt restriction and low doses of thiazide or indapamide retard. (4) Conclusions: This is the first Spanish family with GS with a novel heterozygous missense variant in WNK1 (p.Glu630Gly) in the region containing the highly conserved acidic motif, which is showing a relatively mild phenotype, and adults diagnosed in mild adulthood. These data support the importance of missense variants in the WNK1 acidic domain in electrolyte balance/metabolism. In addition, findings in this family also suggest that indapamide retard or thiazide may be an adequate long-standing treatment for GS. Full article

(This article belongs to the Special Issue Identifying the Molecular Basis of Rare Genetic Diseases)

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19 pages, 5016 KiB

Open AccessEditor’s ChoiceArticle

A Genome-Wide Identification and Comparative Analysis of the Heavy-Metal-Associated Gene Family in Cucurbitaceae Species and Their Role in Cucurbita pepo under Arsenic Stress

by Gerardo Flores-Iga, Carlos Lopez-Ortiz, Celeste Gracia-Rodriguez, Aldo Almeida, Padma Nimmakayala, Umesh K. Reddy and Nagamani Balagurusamy

Genes 2023, 14(10), 1877; https://doi.org/10.3390/genes14101877 - 27 Sep 2023

Cited by 10 | Viewed by 4080

Abstract

The heavy-metal-associated (HMA) proteins are a class of P_B1-type ATPases related to the intracellular transport and detoxification of metals. However, due to a lack of information regarding the HMA gene family in the Cucurbitaceae family, a comprehensive genome-wide analysis of the [...] Read more.

The heavy-metal-associated (HMA) proteins are a class of P_B1-type ATPases related to the intracellular transport and detoxification of metals. However, due to a lack of information regarding the HMA gene family in the Cucurbitaceae family, a comprehensive genome-wide analysis of the HMA family was performed in ten Cucurbitaceae species: Citrullus amarus, Citrullus colocynthis, Citrullus lanatus, Citrullus mucosospermus, Cucumis melo, Cucumis sativus, Cucurbita maxima, Cucurbita moschata, Cucurbita pepo, and Legenaria siceraria. We identified 103 Cucurbit HMA proteins with various members, ranging from 8 (Legenaria siceraria) to 14 (Cucurbita pepo) across species. The phylogenetic and structural analysis confirmed that the Cucurbitaceae HMA protein family could be further classified into two major clades: Zn/Co/Cd/Pb and Cu/Ag. The GO-annotation-based subcellular localization analysis predicted that all HMA gene family members were localized on membranes. Moreover, the analysis of conserved motifs and gene structure (intron/exon) revealed the functional divergence between clades. The interspecies microsynteny analysis demonstrated that maximum orthologous genes were found between species of the Citrullus genera. Finally, nine candidate HMA genes were selected, and their expression analysis was carried out via qRT-PCR in root, leaf, flower, and fruit tissues of C. pepo under arsenic stress. The expression pattern of the CpeHMA genes showed a distinct pattern of expression in root and shoot tissues, with a remarkable expression of CpeHMA6 and CpeHMA3 genes from the Cu/Ag clade. Overall, this study provides insights into the functional analysis of the HMA gene family in Cucurbitaceae species and lays down the basic knowledge to explore the role and mechanism of the HMA gene family to cope with arsenic stress conditions. Full article

(This article belongs to the Special Issue Genetics of Abiotic Stress Tolerance in Plants)

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22 pages, 2244 KiB

Open AccessEditor’s ChoiceReview

Tissue-Specific Tumour Suppressor and Oncogenic Activities of the Polycomb-like Protein MTF2

by Mzwanele Ngubo, Fereshteh Moradi, Caryn Y. Ito and William L. Stanford

Genes 2023, 14(10), 1879; https://doi.org/10.3390/genes14101879 - 27 Sep 2023

Cited by 4 | Viewed by 2722

Abstract

The Polycomb repressive complex 2 (PRC2) is a conserved chromatin-remodelling complex that catalyses the trimethylation of histone H3 lysine 27 (H3K27me3), a mark associated with gene silencing. PRC2 regulates chromatin structure and gene expression during organismal and tissue development and tissue homeostasis in [...] Read more.

The Polycomb repressive complex 2 (PRC2) is a conserved chromatin-remodelling complex that catalyses the trimethylation of histone H3 lysine 27 (H3K27me3), a mark associated with gene silencing. PRC2 regulates chromatin structure and gene expression during organismal and tissue development and tissue homeostasis in the adult. PRC2 core subunits are associated with various accessory proteins that modulate its function and recruitment to target genes. The multimeric composition of accessory proteins results in two distinct variant complexes of PRC2, PRC2.1 and PRC2.2. Metal response element-binding transcription factor 2 (MTF2) is one of the Polycomb-like proteins (PCLs) that forms the PRC2.1 complex. MTF2 is highly conserved, and as an accessory subunit of PRC2, it has important roles in embryonic stem cell self-renewal and differentiation, development, and cancer progression. Here, we review the impact of MTF2 in PRC2 complex assembly, catalytic activity, and spatiotemporal function. The emerging paradoxical evidence suggesting that MTF2 has divergent roles as either a tumour suppressor or an oncogene in different tissues merits further investigations. Altogether, our review illuminates the context-dependent roles of MTF2 in Polycomb group (PcG) protein-mediated epigenetic regulation. Its impact on disease paves the way for a deeper understanding of epigenetic regulation and novel therapeutic strategies. Full article

(This article belongs to the Special Issue Molecular Mechanisms of the Polycomb Repressive Complex 2 (PRC2) and Its Role in Human Cancer)

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21 pages, 391 KiB

Open AccessEditor’s ChoiceReview

Factors Influencing the Maturation and Developmental Competence of Yak (Bos grunniens) Oocytes In Vitro

by Luoyu Mo, Jun Ma, Yan Xiong, Xianrong Xiong, Daoliang Lan, Jian Li and Shi Yin

Genes 2023, 14(10), 1882; https://doi.org/10.3390/genes14101882 - 27 Sep 2023

Cited by 9 | Viewed by 2370

Abstract

The yak (Bos grunniens) is a unique breed living on the Qinghai–Tibet Plateau and its surrounding areas, providing locals with a variety of vital means of living and production. However, the yak has poor sexual maturity and low fertility. High-quality mature [...] Read more.

The yak (Bos grunniens) is a unique breed living on the Qinghai–Tibet Plateau and its surrounding areas, providing locals with a variety of vital means of living and production. However, the yak has poor sexual maturity and low fertility. High-quality mature oocytes are the basis of animal breeding technology. Recently, in vitro culturing of oocytes and embryo engineering technology have been applied to yak breeding. However, compared to those observed in vivo, the maturation rate and developmental capacity of in vitro oocytes are still low, which severely limits the application of in vitro fertilization and embryo production in yaks. This review summarizes the endogenous and exogenous factors affecting the in vitro maturation (IVM) and developmental ability of yak oocytes reported in recent years and provides a theoretical basis for obtaining high-quality oocytes for in vitro fertilization and embryo production in yaks. Full article

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

13 pages, 3449 KiB

Open AccessEditor’s ChoiceArticle

Association between DNA Methylation in the Core Promoter Region of the CUT-like Homeobox 1 (CUX1) Gene and Lambskin Pattern in Hu Sheep

by Xiaoyang Lv, Yue Li, Weihao Chen, Shanhe Wang, Xiukai Cao, Zehu Yuan, Tesfaye Getachew, Joram Mwacharo, Aynalem Haile, Yutao Li and Wei Sun

Genes 2023, 14(10), 1873; https://doi.org/10.3390/genes14101873 - 26 Sep 2023

Cited by 2 | Viewed by 1757

Abstract

CUT-like homeobox 1 (CUX1) has been proven to be a key regulator in sheep hair follicle development. In our previous study, CUX1 was identified as a differential expressed gene between Hu sheep lambskin with small wave patterns (SM) and straight wool [...] Read more.

CUT-like homeobox 1 (CUX1) has been proven to be a key regulator in sheep hair follicle development. In our previous study, CUX1 was identified as a differential expressed gene between Hu sheep lambskin with small wave patterns (SM) and straight wool patterns (ST); however, the exact molecular mechanism of CUX1 expression has been obscure. As DNA methylation can regulate the gene expression, the potential association between CUX1 core promotor region methylation and lambskin pattern in Hu sheep was explored in the present study. The results show that the core promoter region of CUX1 was present at (−1601–(−1) bp) upstream of the transcription start site. A repressive region (−1151–(−751) bp) was also detected, which had a strong inhibitory effect on CUX1 promoter activity. Bisulfite amplicon sequencing revealed that no significant difference was detected between the methylation levels of CUX1 core promoter region in SM tissues and ST tissues. Although the data demonstrated the differential expression of CUX1 between SM and ST probably has no association with DNA methylation, the identification of the core region and a potential repressive region of CUX1 promoter can enrich the role of CUX1 in Hu sheep hair follicle development. Full article

(This article belongs to the Special Issue Genetic Mechanism Analysis and Application of Important Economic Traits in Sheep and Goats)

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38 pages, 3439 KiB

Open AccessEditor’s ChoiceReview

Understanding Arrhythmogenic Cardiomyopathy: Advances through the Use of Human Pluripotent Stem Cell Models

by Christianne J. Chua, Justin Morrissette-McAlmon, Leslie Tung and Kenneth R. Boheler

Genes 2023, 14(10), 1864; https://doi.org/10.3390/genes14101864 - 25 Sep 2023

Cited by 12 | Viewed by 3764

Abstract

Cardiomyopathies (CMPs) represent a significant healthcare burden and are a major cause of heart failure leading to premature death. Several CMPs are now recognized to have a strong genetic basis, including arrhythmogenic cardiomyopathy (ACM), which predisposes patients to arrhythmic episodes. Variants in one [...] Read more.

Cardiomyopathies (CMPs) represent a significant healthcare burden and are a major cause of heart failure leading to premature death. Several CMPs are now recognized to have a strong genetic basis, including arrhythmogenic cardiomyopathy (ACM), which predisposes patients to arrhythmic episodes. Variants in one of the five genes (PKP2, JUP, DSC2, DSG2, and DSP) encoding proteins of the desmosome are known to cause a subset of ACM, which we classify as desmosome-related ACM (dACM). Phenotypically, this disease may lead to sudden cardiac death in young athletes and, during late stages, is often accompanied by myocardial fibrofatty infiltrates. While the pathogenicity of the desmosome genes has been well established through animal studies and limited supplies of primary human cells, these systems have drawbacks that limit their utility and relevance to understanding human disease. Human induced pluripotent stem cells (hiPSCs) have emerged as a powerful tool for modeling ACM in vitro that can overcome these challenges, as they represent a reproducible and scalable source of cardiomyocytes (CMs) that recapitulate patient phenotypes. In this review, we provide an overview of dACM, summarize findings in other model systems linking desmosome proteins with this disease, and provide an up-to-date summary of the work that has been conducted in hiPSC-cardiomyocyte (hiPSC-CM) models of dACM. In the context of the hiPSC-CM model system, we highlight novel findings that have contributed to our understanding of disease and enumerate the limitations, prospects, and directions for research to consider towards future progress. Full article

(This article belongs to the Special Issue Genetics and Mechanistic Basis of Cardiomyopathies)

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17 pages, 1493 KiB

Open AccessEditor’s ChoiceReview

Decoding Cancer Evolution: Integrating Genetic and Non-Genetic Insights

by Arghavan Ashouri, Chufan Zhang and Federico Gaiti

Genes 2023, 14(10), 1856; https://doi.org/10.3390/genes14101856 - 24 Sep 2023

Cited by 8 | Viewed by 5630

Abstract

The development of cancer begins with cells transitioning from their multicellular nature to a state akin to unicellular organisms. This shift leads to a breakdown in the crucial regulators inherent to multicellularity, resulting in the emergence of diverse cancer cell subpopulations that have [...] Read more.

The development of cancer begins with cells transitioning from their multicellular nature to a state akin to unicellular organisms. This shift leads to a breakdown in the crucial regulators inherent to multicellularity, resulting in the emergence of diverse cancer cell subpopulations that have enhanced adaptability. The presence of different cell subpopulations within a tumour, known as intratumoural heterogeneity (ITH), poses challenges for cancer treatment. In this review, we delve into the dynamics of the shift from multicellularity to unicellularity during cancer onset and progression. We highlight the role of genetic and non-genetic factors, as well as tumour microenvironment, in promoting ITH and cancer evolution. Additionally, we shed light on the latest advancements in omics technologies that allow for in-depth analysis of tumours at the single-cell level and their spatial organization within the tissue. Obtaining such detailed information is crucial for deepening our understanding of the diverse evolutionary paths of cancer, allowing for the development of effective therapies targeting the key drivers of cancer evolution. Full article

(This article belongs to the Special Issue The Genetics and Evolution of Multicellularity)

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15 pages, 2989 KiB

Open AccessEditor’s ChoiceArticle

Transcriptome and Metabolome Analyses Reveal the Mechanism of Corpus Luteum Cyst Formation in Pigs

by Jiage Dai, Jiabao Cai, Taipeng Zhang, Mingyue Pang, Xiaoling Xu, Jiahua Bai, Yan Liu and Yusheng Qin

Genes 2023, 14(10), 1848; https://doi.org/10.3390/genes14101848 - 23 Sep 2023

Cited by 2 | Viewed by 2606

Abstract

Corpus luteum cysts are a serious reproductive disorder that affects the reproductive performance of sows. In this study, transcriptome and metabolome datasets of porcine normal and cyst luteal granulosa cells were generated to explore the molecular mechanism of luteal cyst formation. We obtained [...] Read more.

Corpus luteum cysts are a serious reproductive disorder that affects the reproductive performance of sows. In this study, transcriptome and metabolome datasets of porcine normal and cyst luteal granulosa cells were generated to explore the molecular mechanism of luteal cyst formation. We obtained 28.9 Gb of high−quality transcriptome data from luteum tissue samples and identified 1048 significantly differentially expressed genes between the cyst and normal corpus luteum samples. Most of the differentially expressed genes were involved in cancer and immune signaling pathways. Furthermore, 22,622 information-containing positive and negative ions were obtained through gas chromatography−mass spectrometry, and 1106 metabolites were successfully annotated. Important differentially abundant metabolites and pathways were identified, among which abnormal lipid and choline metabolism were involved in the formation of luteal cysts. The relationships between granulosa cells of luteal cysts and cancer, immune-related signaling pathways, and abnormalities of lipid and choline metabolism were elaborated, providing new entry points for studying the pathogenesis of porcine luteal cysts. Full article

(This article belongs to the Special Issue Genetic Regulation of Animal Reproduction)

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19 pages, 2744 KiB

Open AccessEditor’s ChoiceArticle

Molecular Characterization of Complete Genome Sequence of an Avian Coronavirus Identified in a Backyard Chicken from Tanzania

by Henry M. Kariithi, Jeremy D. Volkening, Gaspar H. Chiwanga, Iryna V. Goraichuk, Peter L. M. Msoffe and David L. Suarez

Genes 2023, 14(10), 1852; https://doi.org/10.3390/genes14101852 - 23 Sep 2023

Cited by 2 | Viewed by 2171

Abstract

A complete genome sequence of an avian coronavirus (AvCoV; 27,663 bp excluding 3′ poly(A) tail) was determined using nontargeted next-generation sequencing (NGS) of an oropharyngeal swab from a backyard chicken in a live bird market in Arusha, Tanzania. The open reading frames (ORFs) [...] Read more.

A complete genome sequence of an avian coronavirus (AvCoV; 27,663 bp excluding 3′ poly(A) tail) was determined using nontargeted next-generation sequencing (NGS) of an oropharyngeal swab from a backyard chicken in a live bird market in Arusha, Tanzania. The open reading frames (ORFs) of the Tanzanian strain TZ/CA127/19 are organized as typical of gammaCoVs (Coronaviridae family): 5′UTR-[ORFs 1a/1b encoding replicase complex (Rep1ab) non-structural peptides nsp2-16]-[spike (S) protein]-[ORFs 3a/3b]-[small envelop (E) protein]-[membrane (M) protein]-[ORFs 4a/4c]-[ORFs 5a/5b]-[nucleocapsid (N) protein]-[ORF6b]-3′UTR. The structural (S, E, M and N) and Rep1ab proteins of TZ/CA127/19 contain features typically conserved in AvCoVs, including the cleavage sites and functional motifs in Rep1ab and S. Its genome backbone (non-spike region) is closest to Asian GI-7 and GI-19 infectious bronchitis viruses (IBVs) with 87.2–89.7% nucleotide (nt) identities, but it has a S gene closest (98.9% nt identity) to the recombinant strain ck/CN/ahysx-1/16. Its 3a, 3b E and 4c sequences are closest to the duck CoV strain DK/GD/27/14 at 99.43%, 100%, 99.65% and 99.38% nt identities, respectively. Whereas its S gene phylogenetically cluster with North American TCoVs and French guineafowl COVs, all other viral genes group monophyletically with Eurasian GI-7/GI-19 IBVs and Chinese recombinant AvCoVs. Detection of a 4445 nt-long recombinant fragment with breakpoints at positions 19,961 and 24,405 (C- and N-terminus of nsp16 and E, respectively) strongly suggested that TZ/CA127/19 acquired its genome backbone from an LX4-type (GI-19) field strain via recombination with an unknown AvCoV. This is the first report of AvCoV in Tanzania and leaves unanswered the questions of its emergence and the biological significance. Full article

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

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10 pages, 743 KiB

Open AccessEditor’s ChoiceArticle

Radiogenomic Features of GIMAP Family Genes in Clear Cell Renal Cell Carcinoma: An Observational Study on CT Images

by Federico Greco, Andrea Panunzio, Alessandro Tafuri, Caterina Bernetti, Vincenzo Pagliarulo, Bruno Beomonte Zobel, Arnaldo Scardapane and Carlo Augusto Mallio

Genes 2023, 14(10), 1832; https://doi.org/10.3390/genes14101832 - 22 Sep 2023

Cited by 9 | Viewed by 1986

Abstract

GTPases of immunity-associated proteins (GIMAP) genes include seven functional genes and a pseudogene. Most of the GIMAPs have a role in the maintenance and development of lymphocytes. GIMAPs could inhibit the development of tumors by increasing the amount and antitumor activity of infiltrating [...] Read more.

GTPases of immunity-associated proteins (GIMAP) genes include seven functional genes and a pseudogene. Most of the GIMAPs have a role in the maintenance and development of lymphocytes. GIMAPs could inhibit the development of tumors by increasing the amount and antitumor activity of infiltrating immunocytes. Knowledge of key factors that affect the tumor immune microenvironment for predicting the efficacy of immunotherapy and establishing new targets in ccRCC is of great importance. A computed tomography (CT)-based radiogenomic approach was used to detect the imaging phenotypic features of GIMAP family gene expression in ccRCC. In this retrospective study we enrolled 193 ccRCC patients divided into two groups: ccRCC patients with GIMAP expression (n = 52) and ccRCC patients without GIMAP expression (n = 141). Several imaging features were evaluated on preoperative CT scan. A statistically significant correlation was found with absence of endophytic growth pattern (p = 0.049), tumor infiltration (p = 0.005), advanced age (p = 0.018), and high Fuhrman grade (p = 0.024). This study demonstrates CT imaging features of GIMAP expression in ccRCC. These results could allow the collection of data on GIMAP expression through a CT-approach and could be used for the development of a targeted therapy. Full article

(This article belongs to the Special Issue Bioinformatics and Computational Biology for Cancer Prediction and Prognosis)

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15 pages, 8377 KiB

Open AccessEditor’s ChoiceArticle

Unlocking the Potential of the CA2, CA7, and ITM2C Gene Signatures for the Early Detection of Colorectal Cancer: A Comprehensive Analysis of RNA-Seq Data by Utilizing Machine Learning Algorithms

by Neha Shree Maurya, Sandeep Kushwaha, Ramesh Raju Vetukuri and Ashutosh Mani

Genes 2023, 14(10), 1836; https://doi.org/10.3390/genes14101836 - 22 Sep 2023

Cited by 9 | Viewed by 2763

Abstract

Colorectal cancer affects the colon or rectum and is a common global health issue, with 1.1 million new cases occurring yearly. The study aimed to identify gene signatures for the early detection of CRC using machine learning (ML) algorithms utilizing gene expression data. [...] Read more.

Colorectal cancer affects the colon or rectum and is a common global health issue, with 1.1 million new cases occurring yearly. The study aimed to identify gene signatures for the early detection of CRC using machine learning (ML) algorithms utilizing gene expression data. The TCGA-CRC and GSE50760 datasets were pre-processed and subjected to feature selection using the LASSO method in combination with five ML algorithms: Adaboost, Random Forest (RF), Logistic Regression (LR), Gaussian Naive Bayes (GNB), and Support Vector Machine (SVM). The important features were further analyzed for gene expression, correlation, and survival analyses. Validation of the external dataset GSE142279 was also performed. The RF model had the best classification accuracy for both datasets. A feature selection process resulted in the identification of 12 candidate genes, which were subsequently reduced to 3 (CA2, CA7, and ITM2C) through gene expression and correlation analyses. These three genes achieved 100% accuracy in an external dataset. The AUC values for these genes were 99.24%, 100%, and 99.5%, respectively. The survival analysis showed a significant logrank p-value of 0.044 for the final gene signatures. The analysis of tumor immunocyte infiltration showed a weak correlation with the expression of the gene signatures. CA2, CA7, and ITM2C can serve as gene signatures for the early detection of CRC and may provide valuable information for prognostic and therapeutic decision making. Further research is needed to fully understand the potential of these genes in the context of CRC. Full article

(This article belongs to the Special Issue Genetic and Genomics of Colorectal Cancer)

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13 pages, 2200 KiB

Open AccessEditor’s ChoiceArticle

Identification and Characterization of ABCG15—A Gene Required for Exocarp Color Differentiation in Pear

by Simeng Zhang, Jiayu Xu, Ying Zhang and Yufen Cao

Genes 2023, 14(9), 1827; https://doi.org/10.3390/genes14091827 - 21 Sep 2023

Cited by 1 | Viewed by 1508

Abstract

Exocarp color is a commercially essential quality for pear which can be divided into two types: green and russet. The occurrence of russet color is associated with deficiencies and defects in the cuticular and epidermal layers, which affect the structure of the cell [...] Read more.

Exocarp color is a commercially essential quality for pear which can be divided into two types: green and russet. The occurrence of russet color is associated with deficiencies and defects in the cuticular and epidermal layers, which affect the structure of the cell wall and the deposition of suberin. Until now, the genetic basics triggering this trait have not been well understood, and limited genes have been identified for the trait. To figure out the gene controlling the trait of exocarp color, we perform a comprehensive genome-wide association study, and we describe the candidate genes. One gene encoding the ABCG protein has been verified to be associated with the trait, using an integrative analysis of the metabolomic and transcriptomic data. This review covers a variety of omics resources, which provide a valuable resource for identifying gene-controlled traits of interest. The findings in this study help to elucidate the genetic components responsible for the trait of exocarp color in pear, and the implications of these findings for future pear breeding are evaluated. Full article

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

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15 pages, 2284 KiB

Open AccessEditor’s ChoiceArticle

The Chloroplast Genome of Endive (Cichorium endivia L.): Cultivar Structural Variants and Transcriptome Responses to Stress Due to Rain Extreme Events

by Giulio Testone, Michele Lamprillo, Maria Gonnella, Giuseppe Arnesi, Anatoly Petrovich Sobolev, Riccardo Aiese Cigliano and Donato Giannino

Genes 2023, 14(9), 1829; https://doi.org/10.3390/genes14091829 - 21 Sep 2023

Cited by 2 | Viewed by 1888

Abstract

The chloroplast (cp) genome diversity has been used in phylogeny studies, breeding, and variety protection, and its expression has been shown to play a role in stress response. Smooth- and curly-leafed endives (Cichorium endivia var. latifolium and var. crispum) are of [...] Read more.

The chloroplast (cp) genome diversity has been used in phylogeny studies, breeding, and variety protection, and its expression has been shown to play a role in stress response. Smooth- and curly-leafed endives (Cichorium endivia var. latifolium and var. crispum) are of nutritional and economic importance and are the target of ever-changing breeding programmes. A reference cp genome sequence was assembled and annotated (cultivar ‘Confiance’), which was 152,809 base pairs long, organized into the angiosperm-typical quadripartite structure, harboring two inverted repeats separated by the large- and short- single copy regions. The annotation included 136 genes, 90 protein-coding genes, 38 transfer, and 8 ribosomal RNAs and the sequence generated a distinct phyletic group within Asteraceae with the well-separated C. endivia and intybus species. SSR variants within the reference genome were mostly of tri-nucleotide type, and the cytosine to uracil (C/U) RNA editing recurred. The cp genome was nearly fully transcribed, hence sequence polymorphism was investigated by RNA-Seq of seven cultivars, and the SNP number was higher in smooth- than curly-leafed ones. All cultivars maintained C/U changes in identical positions, suggesting that RNA editing patterns were conserved; most cultivars shared SNPs of moderate impact on protein changes in the ndhD, ndhA, and psbF genes, suggesting that their variability may have a potential role in adaptive response. The cp transcriptome expression was investigated in leaves of plants affected by pre-harvest rainfall and rainfall excess plus waterlogging events characterized by production loss, compared to those of a cycle not affected by extreme rainfall. Overall, the analyses evidenced stress- and cultivar-specific responses, and further revealed that genes of the Cytochrome b6/f, and PSI-PSII systems were commonly affected and likely to be among major targets of extreme rain-related stress. Full article

(This article belongs to the Special Issue Plant Plastid Genome)

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9 pages, 235 KiB

Open AccessEditor’s ChoiceArticle

Aromatic L-Amino-Acid Decarboxylase Deficiency Screening by Analysis of 3-O-Methyldopa in Dried Blood Spots: Results of a Multicentric Study in Neurodevelopmental Disorders

by Susanna Rizzi, Carlotta Spagnoli, Melissa Bellini, Carlo Alberto Cesaroni, Elisabetta Spezia, Patrizia Bergonzini, Elisa Caramaschi, Luca Soliani, Emanuela Claudia Turco, Benedetta Piccolo, Laura Demuth, Duccio Maria Cordelli, Giacomo Biasucci, Daniele Frattini and Carlo Fusco

Genes 2023, 14(9), 1828; https://doi.org/10.3390/genes14091828 - 21 Sep 2023

Cited by 2 | Viewed by 1932

Abstract

Aromatic L-amino acid decarboxylase deficiency (AADCd) is a rare recessive metabolic disorder caused by pathogenic homozygous or compound heterozygous variants in the dopa decarboxylase (DDC) gene. Adeno-associated viral vector-mediated gene transfer of the human DDC gene injected into the putamen is available. The [...] Read more.

Aromatic L-amino acid decarboxylase deficiency (AADCd) is a rare recessive metabolic disorder caused by pathogenic homozygous or compound heterozygous variants in the dopa decarboxylase (DDC) gene. Adeno-associated viral vector-mediated gene transfer of the human DDC gene injected into the putamen is available. The typical presentation is characterized by early-onset hypotonia, severe developmental delay, movement disorders, and dysautonomia. Recently, mild and even atypical phenotypes have been reported, increasing the diagnostic challenge. The aim of this multicentric study is to identify the prevalence of AADCd in a population of patients with phenotypic clusters characterized by neurodevelopmental disorders (developmental delay/intellectual disability, and/or autism) by 3-O-methyldopa (3-OMD) detection in dried blood spots (DBS). It is essential to identify AADCd promptly, especially within non-typical phenotypic clusters, because better results are obtained when therapy is quickly started in mild-moderate phenotypes. Between 2021 and 2023, 390 patients with non-specific phenotypes possibly associated with AADCd were tested; none resulted in a positive result. This result highlights that the population to be investigated for AADCd should have more defined clinical characteristics: association with common signs (hypotonia) and/or pathognomonic symptoms (oculogyric crisis and dysautonomia). It is necessary to continue to screen selected clusters for reaching diagnosis and improving long-term outcomes through treatment initiation. This underscores the role of newborn screening in identifying AADCd. Full article

(This article belongs to the Section Neurogenomics)

10 pages, 554 KiB

Open AccessEditor’s ChoiceArticle

Association of Cognitive Polygenic Index and Cognitive Performance with Age in Cognitively Healthy Adults

by Angeliki Tsapanou, Margaret Gacheru, Seonjoo Lee, Niki Mourtzi, Yunglin Gazes, Christian Habeck, Daniel W. Belsky and Yaakov Stern

Genes 2023, 14(9), 1814; https://doi.org/10.3390/genes14091814 - 18 Sep 2023

Cited by 1 | Viewed by 2048

Abstract

Genome-wide association studies have discovered common genetic variants associated with cognitive performance. Polygenic scores that summarize these discoveries explain up to 10% of the variance in cognitive test performance in samples of adults. However, the role these genetics play in cognitive aging is [...] Read more.

Genome-wide association studies have discovered common genetic variants associated with cognitive performance. Polygenic scores that summarize these discoveries explain up to 10% of the variance in cognitive test performance in samples of adults. However, the role these genetics play in cognitive aging is not well understood. We analyzed data from 168 cognitively healthy participants aged 23–77 years old, with data on genetics, neuropsychological assessment, and brain-imaging measurements from two large ongoing studies, the Reference Abilities Neural Networks, and the Cognitive Reserve study. We tested whether a polygenic index previously related to cognition (Cog PGI) would moderate the relationship between age and measurements of the cognitive domains extracted from a neuropsychological evaluation: fluid reasoning, memory, vocabulary, and speed of processing. We further explored the relationship of Cog PGI and age on cognition using Johnson–Neyman intervals for two-way interactions. Sex, education, and brain measures of cortical thickness, total gray matter volume, and white matter hyperintensity were considered covariates. The analysis controlled for population structure-ancestry. There was a significant interaction effect of Cog PGI on the association between age and the domains of memory (Standardized coefficient = −0.158, p-value = 0.022), fluid reasoning (Standardized coefficient = −0.146, p-value = 0.020), and vocabulary (Standardized coefficient = −0.191, p-value = 0.001). Higher PGI strengthened the negative relationship between age and the domains of memory and fluid reasoning while PGI weakened the positive relationship between age and vocabulary. Based on the Johnson–Neyman intervals, Cog PGI was significantly associated with domains of memory, reasoning, and vocabulary for younger adults. There is a significant moderation effect of genetic predisposition for cognition for the association between age and cognitive performance. Genetics discovered in genome-wide association studies of cognitive performance show a stronger association in young and midlife older adults. Full article

(This article belongs to the Section Neurogenomics)

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7 pages, 2968 KiB

Open AccessEditor’s ChoiceReview

Exercise Does Not Independently Improve Histological Outcomes in Biopsy-Proven Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis

by George Chen, Bubu A. Banini, Albert Do, Craig Gunderson, Saif Zaman and Joseph K. Lim

Genes 2023, 14(9), 1811; https://doi.org/10.3390/genes14091811 - 17 Sep 2023

Cited by 10 | Viewed by 2212

Abstract

Introduction: The independent effect of exercise on liver histology in non-alcoholic fatty liver disease (NAFLD) remains unclear. As such, we conducted a systematic review and meta-analysis of the effect of exercise alone on histological endpoints in biopsy-proven NAFLD. Materials and Methods: A systematic [...] Read more.

Introduction: The independent effect of exercise on liver histology in non-alcoholic fatty liver disease (NAFLD) remains unclear. As such, we conducted a systematic review and meta-analysis of the effect of exercise alone on histological endpoints in biopsy-proven NAFLD. Materials and Methods: A systematic literature search was conducted to include controlled clinical trials investigating the effect of exercise alone on liver histology in biopsy-proven NAFLD. Meta-analysis was conducted for histological outcomes with available data from a minimum of three studies. Pooled estimates of the effect of exercise on histological endpoints were calculated using random-effects models. Results: We identified three controlled clinical trials that assessed the independent effect of exercise on histological outcomes in patients with biopsy-proven NAFLD. The studies consisted of 72 total participants, including 40 subjects in the exercise intervention and 32 individuals in the comparison group. Meta-analysis showed that exercise did not significantly improve Brunt grade, NAFLD activity score, and fibrosis in NAFLD. Discussion: Exercise alone may not lead to significant histopathological improvement in NAFLD. Future well-powered randomized controlled trials are needed to better characterize the impact of exercise on histological outcomes and clinical endpoints. Full article

(This article belongs to the Special Issue Liver Disease: Genetic Research and Clinical Diagnosis)

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22 pages, 9497 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Identification of BrCAX Genes and Functional Analysis of BrCAX1 Involved in Ca²⁺ Transport and Ca²⁺ Deficiency-Induced Tip-Burn in Chinese Cabbage (Brassica rapa L. ssp. pekinensis)

by Shuning Cui, Hong Liu, Yong Wu, Lugang Zhang and Shanshan Nie

Genes 2023, 14(9), 1810; https://doi.org/10.3390/genes14091810 - 17 Sep 2023

Cited by 4 | Viewed by 1980

Abstract

Calcium (Ca²⁺) plays essential roles in plant growth and development. Ca²⁺ deficiency causes a physiological disorder of tip-burn in Brassiceae crops and is involved in the regulation of cellular Ca²⁺ homeostasis. Although the functions of Ca²⁺/H⁺ [...] Read more.

Calcium (Ca²⁺) plays essential roles in plant growth and development. Ca²⁺ deficiency causes a physiological disorder of tip-burn in Brassiceae crops and is involved in the regulation of cellular Ca²⁺ homeostasis. Although the functions of Ca²⁺/H⁺ exchanger antiporters (CAXs) in mediating transmembrane transport of Ca²⁺ have been extensively characterized in multiple plant species, the potential roles of BrCAX genes remain unclear in Chinese cabbage. In this study, eight genes of the BrCAX family were genome-widely identified in Chinese cabbage. These BrCAX proteins contained conserved Na_Ca_ex domain and belonged to five members of the CAX family. Molecular evolutionary analysis and sequence alignment revealed the evolutionary conservation of BrCAX family genes. Expression profiling demonstrated that eight BrCAX genes exhibited differential expression in different tissues and under heat stress. Furthermore, Ca²⁺ deficiency treatment induced the typical symptoms of tip-burn in Chinese cabbage seedlings and a significant decrease in total Ca²⁺ content in both roots and leaves. The expression changes in BrCAX genes were related to the response to Ca²⁺ deficiency-induced tip-burn of Chinese cabbage. Specially, BrCAX1-1 and BrCAX1-2 genes were highly expressed gene members of the BrCAX family in the leaves and were significantly differentially expressed under Ca²⁺ deficiency stress. Moreover, overexpression of BrCAX1-1 and BrCAX1-2 genes in yeast and Chinese cabbage cotyledons exhibited a higher Ca²⁺ tolerance, indicating the Ca²⁺ transport capacity of BrCAX1-1 and BrCAX1-2. In addition, suppression expression of BrCAX1-1 and BrCAX1-2 genes reduced cytosolic Ca²⁺ levels in the root tips of Chinese cabbage. These results provide references for functional studies of BrCAX genes and to investigate the regulatory mechanisms underlying Ca²⁺ deficiency disorder in Brassiceae vegetables. Full article

(This article belongs to the Special Issue Genetics and Breeding of Horticulture Crops)

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18 pages, 2404 KiB

Open AccessEditor’s ChoiceArticle

Glucocorticoid Receptor Gene (NR3C1) Polymorphisms and Metabolic Syndrome: Insights from the Mennonite Population

by Kathleen Liedtke Kolb, Ana Luiza Sprotte Mira, Eduardo Delabio Auer, Isabela Dall’Oglio Bucco, Carla Eduarda de Lima e Silva, Priscila Ianzen dos Santos, Valéria Bumiller-Bini Hoch, Luana Caroline Oliveira, Aline Borsato Hauser, Jennifer Elisabeth Hundt, Alan R. Shuldiner, Fabiana Leão Lopes, Teide-Jens Boysen, Andre Franke, Luis Felipe Ribeiro Pinto, Sheila Coelho Soares-Lima, Gabriela Canalli Kretzschmar and Angelica Beate Winter Boldt

Genes 2023, 14(9), 1805; https://doi.org/10.3390/genes14091805 - 15 Sep 2023

Cited by 8 | Viewed by 4069

Abstract

The regulation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with polymorphisms and the methylation degree of the glucocorticoid receptor gene (NR3C1) and is potentially involved in the development of metabolic syndrome (MetS). In order to evaluate the association between MetS with [...] Read more.

The regulation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with polymorphisms and the methylation degree of the glucocorticoid receptor gene (NR3C1) and is potentially involved in the development of metabolic syndrome (MetS). In order to evaluate the association between MetS with the polymorphisms, methylation, and gene expression of the NR3C1 in the genetically isolated Brazilian Mennonite population, we genotyped 20 NR3C1 polymorphisms in 74 affected (MetS) and 138 unaffected individuals without affected first-degree relatives (Co), using exome sequencing, as well as five variants from non-exonic regions, in 70 MetS and 166 Co, using mass spectrometry. The methylation levels of 11 1F CpG sites were quantified using pyrosequencing (66 MetS and 141 Co), and the NR3C1 expression was evaluated via RT-qPCR (14 MetS and 25 Co). Age, physical activity, and family environment during childhood were associated with MetS. Susceptibility to MetS, independent of these factors, was associated with homozygosity for rs10482605*C (OR = 4.74, pcorr = 0.024) and the haplotype containing TTCGTTGATT (rs3806855*T_ rs3806854*T_rs10482605*C_rs10482614*G_rs6188*T_rs258813*T_rs33944801*G_rs34176759*A_rs17209258*T_rs6196*T, OR = 4.74, pcorr = 0.048), as well as for the CCT haplotype (rs41423247*C_ rs6877893*C_rs258763*T), OR = 6.02, pcorr = 0.030), but not to the differences in methylation or gene expression. Thus, NR3C1 polymorphisms seem to modulate the susceptibility to MetS in Mennonites, independently of lifestyle and early childhood events, and their role seems to be unrelated to DNA methylation and gene expression. Full article

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

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27 pages, 3063 KiB

Open AccessEditor’s ChoiceArticle

Sex Differences in Anderson–Fabry Cardiomyopathy: Clinical, Genetic, and Imaging Analysis in Women

by Denise Cristiana Faro, Valentina Losi, Margherita Stefania Rodolico, Elvira Mariateresa Torrisi, Paolo Colomba, Giovanni Duro and Ines Paola Monte

Genes 2023, 14(9), 1804; https://doi.org/10.3390/genes14091804 - 15 Sep 2023

Cited by 12 | Viewed by 2749

Abstract

Anderson–Fabry Disease (AFD) is a rare, systemic lysosomal storage disease triggered by mutations in the GLA gene, leading to α-galactosidase A (α-Gal A) deficiency. The disease’s X-linked inheritance leads to more severe, early-onset presentations in males, while females exhibit variable, often insidious, manifestations, [...] Read more.

Anderson–Fabry Disease (AFD) is a rare, systemic lysosomal storage disease triggered by mutations in the GLA gene, leading to α-galactosidase A (α-Gal A) deficiency. The disease’s X-linked inheritance leads to more severe, early-onset presentations in males, while females exhibit variable, often insidious, manifestations, notably impacting cardiac health. This study aims to examine gender-based AFD cardiac manifestations in correlation with the variant type: classical (CL), late-onset (LO), or variants of uncertain significance (VUS). We analyzed data from 72 AFD patients (53 females, 19 males) referred to the “G. Rodolico” University Hospital, employing enzyme activity measurements, genetic analysis, periodic lyso-Gb3 monitoring, comprehensive medical histories, and advanced cardiac imaging techniques. Statistical analysis was performed using SPSS version 26. Our AFD cohort, with an average age of 45 ± 16.1 years, comprised 12 individuals with hypertrophy (AFD-LVH) and 60 without (AFD-N). Women, representing about 75% of the subjects, were generally older than men (47.2 ± 16.2 vs. 38.8 ± 14.6, p = 0.046). In the female group, 17% had CL variants, 43.3% LO, and 39.6% had VUS, compared to 21.1%, 36.8%, and 31.6% in the male group, respectively. Females exhibited significantly higher α-Gal A values (median 7.9 vs. 1.8 nmol/mL/h, p < 0.001) and lower lyso-Gb3 levels (1.5 [IQR 1.1–1.7] vs. 1.9 [1.5–17.3] nmol/L, p = 0.02). Regarding the NYHA class distribution, 70% of women were in class I and 28% in class II, compared to 84% and 16% of men, respectively. Among women, 7.5% exhibited ventricular arrhythmias (10.5% in men), and 9.4% had atrial fibrillation (10.5% in men). Cardiac MRIs revealed fibrosis in 57% of examined women, compared to 87% of men. Even among patients without LVH, significant differences persisted in α-Gal A and lyso-Gb3 levels (p = 0.003 and 0.04), as well as LVMi (61.5 vs. 77.5 g/sqm, p = 0.008) and GLS values (−20% vs. −17%, p = 0.01). The analysis underscored older age, decreased lyso-Gb3 deposition, reduced hypertrophy, and lesser GLS compromise in females, suggesting later disease onset. Severe cardiac patterns were associated with classic variants, while more nuanced manifestations were noted in those with VUS. Early GLS impairment in males, irrespective of hypertrophy, emphasized the role of subclinical damage in AFD. Full article

(This article belongs to the Special Issue Diagnosis and Therapies for Genetic Diseases)

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