Genes

15 pages, 1920 KiB

Open AccessEditor’s ChoiceArticle

Whole Genome Analysis in Consanguineous Families Reveals New Loci for Speech Sound Disorder (SSD)

by Tahira Yasmin, Aatika Sadia, Laraib Nadeem, Muhammad Asim Raza Basra, Mabel L. Rice and Muhammad Hashim Raza

Genes 2024, 15(8), 1069; https://doi.org/10.3390/genes15081069 - 13 Aug 2024

Viewed by 1407

Abstract

Speech is the most common means of communication in humans. Any defect in accurate speech production ability results in the development of speech sound disorder (SSD), a condition that can significantly impair an individual’s academic performance, social interactions, and relationships with peers and [...] Read more.

Speech is the most common means of communication in humans. Any defect in accurate speech production ability results in the development of speech sound disorder (SSD), a condition that can significantly impair an individual’s academic performance, social interactions, and relationships with peers and adults. This study investigated the genetic basis of SSD in three Pakistani families. We performed family-based genome-wide parametric linkage analysis and homozygosity mapping in three consanguineous families with SSD from the Punjab province of Pakistan. The Test for Assessment of Articulation and Phonology in Urdu (TAAPU) was used to analyze the speech articulation data and determine the Percentage Correct Consonants (PCC) score. The PCC score defined the affected and unaffected individuals in each family. Parametric linkage analysis revealed a linkage to chromosome 5 (5q21.3-5q23.1) with a significant logarithm of the odds (LOD) score of 3.13 in a Pakistani family with specific language impairment-97 (PKSLI-97) under an autosomal recessive mode of inheritance. The other two families showed a suggestive linkage at 6p22.1, 14q12, and 16q12.1 under the recessive mode of inheritance. Interestingly, homozygosity mapping showed a loss of heterozygosity in the linkage region at 5q15-5q23.1, shared among seven affected (mostly in the younger generation) and one unaffected individual of PKSLI-97. Our analysis identified the 6p22 locus previously implicated in dyslexia, childhood apraxia of speech (CAS), and language impairment, confirming the role of KIAA0319 and DCDC2 in this locus. These findings provide statistical evidence for the genomic regions associated with articulation disorder and offer future opportunities to further the role of genes in speech production. Full article

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

► Show Figures

Figure 1

19 pages, 1079 KiB

Open AccessEditor’s ChoiceArticle

A Whole-Transcriptomic Analysis of Canine Oral Melanoma: A Chance to Disclose the Radiotherapy Effect and Outcome-Associated Gene Signature

by Greta Mucignat, Ludovica Montanucci, Ramy Elgendy, Mery Giantin, Paola Laganga, Marianna Pauletto, Franco Mutinelli, Marta Vascellari, Vito Ferdinando Leone, Mauro Dacasto and Anna Granato

Genes 2024, 15(8), 1065; https://doi.org/10.3390/genes15081065 - 13 Aug 2024

Viewed by 2224

Abstract

Oral melanoma (OM) is the most common malignant oral tumour among dogs and shares similarities with human mucosal melanoma (HMM), validating the role of canine species as an immunocompetent model for cancer research. In both humans and dogs, the prognosis is poor and [...] Read more.

Oral melanoma (OM) is the most common malignant oral tumour among dogs and shares similarities with human mucosal melanoma (HMM), validating the role of canine species as an immunocompetent model for cancer research. In both humans and dogs, the prognosis is poor and radiotherapy (RT) represents a cornerstone in the management of this tumour, either as an adjuvant or a palliative treatment. In this study, by means of RNA-seq, the effect of RT weekly fractionated in 9 Gray (Gy), up to a total dose of 36 Gy (4 weeks), was evaluated in eight dogs affected by OM. Furthermore, possible transcriptomic differences in blood and biopsies that might be associated with a longer overall survival (OS) were investigated. The immune response, glycosylation, cell adhesion, and cell cycle were the most affected pathways by RT, while tumour microenvironment (TME) composition and canonical and non-canonical WNT pathways appeared to be modulated in association with OS. Taking these results as a whole, this study improved our understanding of the local and systemic effect of RT, reinforcing the pivotal role of anti-tumour immunity in the control of canine oral melanoma (COM). Full article

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

► Show Figures

Figure 1

28 pages, 17168 KiB

Open AccessEditor’s ChoiceArticle

A Potential Role for the Amyloid Precursor Protein in the Regulation of Interferon Signaling, Cholesterol Homeostasis, and Tau Phosphorylation in Niemann–Pick Disease Type C

by Kayla L. Sanchez, Samuel D. Shin, Naren P. Rajagopal, Jacob B. White, Antonio Currais, David Soriano-Castell, Pamela Maher and Salvador Soriano

Genes 2024, 15(8), 1066; https://doi.org/10.3390/genes15081066 - 13 Aug 2024

Viewed by 1524

Abstract

Niemann–Pick disease type C (NPC) is a rare and fatal neurological disorder caused by mutations in Npc1 or Npc2, with Npc1 accounting for 95% of cases. These mutations result in the functional loss of their respective proteins, causing cellular abnormalities characterized by [...] Read more.

Niemann–Pick disease type C (NPC) is a rare and fatal neurological disorder caused by mutations in Npc1 or Npc2, with Npc1 accounting for 95% of cases. These mutations result in the functional loss of their respective proteins, causing cellular abnormalities characterized by disrupted lipid dysregulation, calcium dysfunction, elevated damage associated molecular patterns (DAMPs), and a pro-inflammatory environment. This cellular pathology ultimately triggers neurodegeneration, with the cerebellum being the earliest and most affected region. We have recently shown atypical activation of interferon signaling in the presymptomatic Npc1^−/− mouse cerebellum and, to a lesser extent, in the cerebral cortex. In addition, we reported that the Amyloid Precursor Protein (APP) is an NPC disease modifier. Loss of APP function leads to widespread neurodegeneration in the NPC brain, including exacerbated interferon signaling in the cerebellum. To better understand the role of APP as a disease modifier throughout the NPC brain, here we carried out a transcriptomic analysis of the cerebral cortex and cerebellum from 3-week-old Npc1^−/− mice as well as age-matched controls in the presence and absence of APP. We report differential effects of APP loss of function in the cerebral cortex and cerebellum, including cholesterol and tau dysregulation, in both brain regions. Our findings demonstrate a novel link between APP loss and early pathogenic mechanisms in NPC. Full article

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

► Show Figures

Figure 1

14 pages, 5350 KiB

Open AccessEditor’s ChoiceArticle

Optimization of Phycocyanobilin Synthesis in E. coli BL21: Biotechnological Insights and Challenges for Scalable Production

by Julia Esclapez, Laura Matarredona, Guillermo Zafrilla, Mónica Camacho, María-José Bonete and Basilio Zafrilla

Genes 2024, 15(8), 1058; https://doi.org/10.3390/genes15081058 - 12 Aug 2024

Viewed by 1829

Abstract

Phycocyanobilin (PCB) is a small chromophore found in certain phycobiliproteins, such as phycocyanins (PCs) and allophycocyanins (APCs). PCB, along with other phycobilins (PBs) and intermediates such as biliverdin (BV) or phycoerythrobilin (PEB), is attracting increasing biotechnological interest due to its fluorescent and medicinal [...] Read more.

Phycocyanobilin (PCB) is a small chromophore found in certain phycobiliproteins, such as phycocyanins (PCs) and allophycocyanins (APCs). PCB, along with other phycobilins (PBs) and intermediates such as biliverdin (BV) or phycoerythrobilin (PEB), is attracting increasing biotechnological interest due to its fluorescent and medicinal properties that allow potential applications in biomedicine and the food industry. This study aims to optimize PCB synthesis in Escherichia coli BL21 (DE3) and scale the process to a pre-industrial level. Parameters such as optimal temperature, inducer concentration, initial OD₆₀₀, and stirring speed were analyzed in shake flask cultures to maximize PCB production. The best results were obtained at a temperature of 28 °C, an IPTG concentration of 0.1 mM, an initial OD₆₀₀ of 0.5, and an orbital shaking speed of 260 rpm. Furthermore, the optimized protocol was scaled up into a 2 L bioreactor batch, achieving a maximum PCB concentration of 3.8 mg/L. Analysis of the results revealed that biosynthesis of exogenous PBs in Escherichia coli BL21 (DE3) is highly dependent on the metabolic burden of the host. Several scenarios, such as too rapid growth, high inducer concentration, or mechanical stress, can advance entry into the stationary phase. That progressively halts pigment synthesis, leading, in some cases, to its excretion into the growth media and ultimately triggering rapid degradation by the host. These conclusions provide a promising protocol for scalable PCB production and highlight the main biotechnological challenges to increase the yields of the process. Full article

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

► Show Figures

Figure 1

12 pages, 1172 KiB

Open AccessEditor’s ChoiceArticle

Association Analysis of METTL23 Gene Polymorphisms with Reproductive Traits in Kele Pigs

by Jie Sun, Chunyuan Wang, Yan Wu, Jin Xiang and Yiyu Zhang

Genes 2024, 15(8), 1061; https://doi.org/10.3390/genes15081061 - 12 Aug 2024

Cited by 1 | Viewed by 1199

Abstract

Methyltransferase-like 23 (METTL23) is a kind of RNA methyltransferase that catalyzes the methylation transfer to the N6-adenosine of RNA, serving as one of the key mediators in this process. However, the METTL23 gene has been poorly researched in pigs. In [...] Read more.

Methyltransferase-like 23 (METTL23) is a kind of RNA methyltransferase that catalyzes the methylation transfer to the N6-adenosine of RNA, serving as one of the key mediators in this process. However, the METTL23 gene has been poorly researched in pigs. In this study, we investigated the genetic effects of METTL23 single-nucleotide polymorphism(SNPs) on reproductive traits in Kele pigs. The DNA was extracted from 228 healthy multiparous Kele sows, and Sanger sequencing revealed three SNPs, g.4804958 G > T (intron 2), g.4805082 C > T (exon 2), and g.4806821 A > G (exon 3). The polymorphism information content (PIC) for each SNP was 0.264, 0.25, and 0.354, indicating moderate polymorphism (0.25 < PIC < 0.5) and providing genetic information. Linkage disequilibrium analysis showed no strong linkage disequilibrium between the three SNPs. The association analysis revealed that in the SNP g.4804958 G > T individuals with the GG genotype had a significantly higher number of piglets born alive, litter birth weight, number of weaned piglets, and weaning litter weight compared to those with the TT genotype (p < 0.05). Individuals with the GG genotype in the SNP g.4806821 A > G group had significantly higher litter birth weight and average birth weight than those with the AA genotype (p < 0.05). The H4H4 diplotype showed significant effects on the number of piglets born alive, litter birth weight, number of weaned piglets, weaning litter weight, and weaning weight (p < 0.05). Together, the METTL23 gene could be used as a candidate gene for the selection of reproductive traits in Kele pigs. Full article

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

► Show Figures

Figure 1

11 pages, 1098 KiB

Open AccessEditor’s ChoiceArticle

Effects of ACLY Inhibition on Body Weight Distribution: A Drug Target Mendelian Randomization Study

by Dipender Gill, Marie-Joe Dib, Rubinder Gill, Stefan R. Bornstein, Stephen Burgess and Andreas L. Birkenfeld

Genes 2024, 15(8), 1059; https://doi.org/10.3390/genes15081059 - 12 Aug 2024

Viewed by 2001

Abstract

Background: Adenosine triphosphate-citrate lyase (ACLY) inhibition has proven clinically efficacious for low-density lipoprotein cholesterol (LDL-c) lowering and cardiovascular disease (CVD) risk reduction. Clinical and genetic evidence suggests that some LDL-c lowering strategies, such as 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) inhibition with statin therapy increase [...] Read more.

Background: Adenosine triphosphate-citrate lyase (ACLY) inhibition has proven clinically efficacious for low-density lipoprotein cholesterol (LDL-c) lowering and cardiovascular disease (CVD) risk reduction. Clinical and genetic evidence suggests that some LDL-c lowering strategies, such as 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) inhibition with statin therapy increase body weight and the risk of developing type 2 diabetes mellitus (T2DM). However, whether ACLY inhibition affects metabolic risk factors is currently unknown. We aimed to investigate the effects of ACLY inhibition on glycaemic and anthropometric traits using Mendelian randomization (MR). Methods: As genetic instruments for ACLY inhibition, we selected weakly correlated single-nucleotide polymorphisms at the ACLY gene associated with lower ACLY gene expression in the eQTLGen study (N = 31,684) and lower LDL-c levels in the Global Lipid Genetic Consortium study (N = 1.65 million). Two-sample Mendelian randomization was employed to investigate the effects of ACLY inhibition on T2DM risk, and glycaemic and anthropometric traits using summary data from large consortia, with sample sizes ranging from 151,013 to 806,834 individuals. Findings for genetically predicted ACLY inhibition were compared to those obtained for genetically predicted HMGCR inhibition using the same instrument selection strategy and outcome data. Results: Primary MR analyses showed that genetically predicted ACLY inhibition was associated with lower waist-to-hip ratio (β per 1 standard deviation lower LDL-c: −1.17; 95% confidence interval (CI): −1.61 to −0.73; p < 0.001) but not with risk of T2DM (odds ratio (OR) per standard deviation lower LDL-c: 0.74, 95% CI = 0.25 to 2.19, p = 0.59). In contrast, genetically predicted HMGCR inhibition was associated with higher waist-to-hip ratio (β = 0.15; 95%CI = 0.04 to 0.26; p = 0.008) and T2DM risk (OR = 1.73, 95% CI = 1.27 to 2.36, p < 0.001). The MR analyses considering secondary outcomes showed that genetically predicted ACLY inhibition was associated with a lower waist-to-hip ratio adjusted for body mass index (BMI) (β = −1.41; 95%CI = −1.81 to −1.02; p < 0.001). In contrast, genetically predicted HMGCR inhibition was associated with higher HbA1c (β = 0.19; 95%CI = 0.23 to 0.49; p < 0.001) and BMI (β = 0.36; 95%CI = 0.23 to 0.49; p < 0.001). Conclusions: Human genetic evidence supports the metabolically favourable effects of ACLY inhibition on body weight distribution, in contrast to HMGCR inhibition. These findings should be used to guide and prioritize ongoing clinical development efforts. Full article

(This article belongs to the Special Issue Genetics and Epigenetics of Metabolic Diseases)

► Show Figures

Figure 1

23 pages, 10080 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Identification and Expression Analysis of Growth-Regulating Factor Family in Sweet Potato and Its Two Relatives

by Wenhui Huang, Xiongjian Lin, Zhenqin Li, Jinglin Mai, Mengqin Hu and Hongbo Zhu

Genes 2024, 15(8), 1064; https://doi.org/10.3390/genes15081064 - 12 Aug 2024

Viewed by 1433

Abstract

Growth-regulating factor (GRF) is a multi-gene family that plays an important role in plant growth and development and is widely present in plants. Currently, GRF gene members have been reported in many plants, but the GRF gene family has not been found in [...] Read more.

Growth-regulating factor (GRF) is a multi-gene family that plays an important role in plant growth and development and is widely present in plants. Currently, GRF gene members have been reported in many plants, but the GRF gene family has not been found in sweet potato. In this study, ten GRF genes were identified in sweet potato (Ipomoea batatas), twelve and twelve were identified in its two diploid relatives (Ipomoea trifida) and (Ipomoea triloba), which were unevenly distributed on nine different chromosomes. Subcellular localization analysis showed that GRF genes of sweet potato, I. trifida, and I. triloba were all located in the nucleus. The expression analysis showed that the expression of IbGRFs was diverse in different sweet potato parts, and most of the genes were upregulated and even had the highest expression in the vigorous growth buds. These findings provide molecular characterization of sweet potato and its two diploid relatives, the GRF families, further supporting functional characterization. Full article

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

► Show Figures

Figure 1

8 pages, 1940 KiB

Open AccessEditor’s ChoiceArticle

Hsa-miR-874-3p Reduces Endogenous Expression of RGS4-1 Isoform In Vitro

by Feng-Ling Xu and Bao-Jie Wang

Genes 2024, 15(8), 1057; https://doi.org/10.3390/genes15081057 - 11 Aug 2024

Cited by 1 | Viewed by 1383

Abstract

Background: The level of the regulator of G-protein signaling 4-1 (RGS4-1) isoform, the longest RGS4 isoform, is significantly reduced in the dorsolateral prefrontal cortex (DLPFC) of people with schizophrenia. However, the mechanism behind this has not been clarified. The 3′untranslated regions (3′UTRs) are [...] Read more.

Background: The level of the regulator of G-protein signaling 4-1 (RGS4-1) isoform, the longest RGS4 isoform, is significantly reduced in the dorsolateral prefrontal cortex (DLPFC) of people with schizophrenia. However, the mechanism behind this has not been clarified. The 3′untranslated regions (3′UTRs) are known to regulate the levels of their mRNA splice variants. Methods: We constructed recombinant pmir-GLO vectors with a truncated 3′ regulatory region of the RGS4 gene (3R1, 3R2, 3R3, 3R4, 3R5, and 3R6). The dual-luciferase reporter assay was conducted to find functional regions in HEK-293, SK-N-SH, and U87cells and then predicted miRNA binding to these regions. We performed a dual-luciferase reporter assay and a Western blot analysis after transiently transfecting the predicted miRNAs. Results: The dual-luciferase reporter assay found that regions +401–+789, +789–+1152, and +1562–+1990 (with the last base of the termination codon being +1) might be functional regions. Hsa-miR-874-3p, associated with many psychiatric disorders, might target the +789–+1152 region in the 3′UTR of the RGS4 gene. In the dual-luciferase reporter assay, the hsa-miR-874-3p mimic, co-transfected with 3R1, down-regulated the relative fluorescence intensities. However, this was reversed when the hsa-miR-874-3p mimic was co-transfected with m3R1 (deletion of +853–+859). The hsa-miR-874-3p mimic significantly decreased the endogenous expression of the RGS4-1 isoform in HEK-293 cells. Conclusions: Hsa-miR-874-3p inhibits the expression of the RGS4-1 isoform by targeting +853–+859. Full article

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

► Show Figures

Figure 1

11 pages, 2535 KiB

Open AccessEditor’s ChoiceArticle

Agouti-Signaling Protein and Melanocortin-1-Receptor Mutations Associated with Coat Color Phenotypes in Fallow Deer (Dama dama)

by Monika Reissmann, Evelin Ullrich, Uwe Bergfeld and Arne Ludwig

Genes 2024, 15(8), 1055; https://doi.org/10.3390/genes15081055 - 11 Aug 2024

Viewed by 1605

Abstract

Four dominant coat color phenotypes are found in fallow deer (Dama dama). Brown is the most common. Black, menil, and white occur with varying frequencies. In order to gain insights into the molecular genetic background of these phenotypes, 998 fallow animals [...] Read more.

Four dominant coat color phenotypes are found in fallow deer (Dama dama). Brown is the most common. Black, menil, and white occur with varying frequencies. In order to gain insights into the molecular genetic background of these phenotypes, 998 fallow animals (772 brown, 62 black, 126 menil, and 38 white) were examined for mutations in the ASIP, MC1R, TYR, and SLC45A2 genes. In ASIP, two mutations (ASIP-M-E2, located at the boundary from exon 2 to intron 2; and ASIP-M-E3, an InDel of five nucleotides) were found, leading to black fallow deer being either homozygous or heterozygous in combination. There were also two mutations found in MC1R. Whereby the mutation MC1R-M1 (leucine to proline, L48P) homozygous leads to a white coat, while the mutation MC1R-M2 (glycine to aspartic acid, G236D) homozygous is associated with the menil phenotype. When both mutations occur together in a heterozygous character state, it results in a menil coat. Since the mutations in the two genes are only present alternatively, 36 genotypes can be identified that form color clusters to which all animals can be assigned. No mutations were found in the TYR and SLC45A2 genes. Our investigations demonstrate that the four dominant coat colors in fallow deer can be explained by ASIP and MC1R mutations only. Full article

(This article belongs to the Special Issue Wildlife Genetic Diversity and Genomics)

► Show Figures

Figure 1

14 pages, 10544 KiB

Open AccessEditor’s ChoiceArticle

Bioinformatic Evaluation of KLF13 Genetic Variant: Implications for Neurodevelopmental and Psychiatric Symptoms

by Mirella Vinci, Donatella Greco, Simone Treccarichi, Valeria Chiavetta, Maria Grazia Figura, Antonino Musumeci, Vittoria Greco, Concetta Federico, Francesco Calì and Salvatore Saccone

Genes 2024, 15(8), 1056; https://doi.org/10.3390/genes15081056 - 11 Aug 2024

Cited by 1 | Viewed by 1618

Abstract

The Krüppel-like factor (KLF) family represents a group of transcription factors (TFs) performing different biological processes that are crucial for proper neuronal function, including neuronal development, synaptic plasticity, and neuronal survival. As reported, genetic variants within the KLF family have been associated with [...] Read more.

The Krüppel-like factor (KLF) family represents a group of transcription factors (TFs) performing different biological processes that are crucial for proper neuronal function, including neuronal development, synaptic plasticity, and neuronal survival. As reported, genetic variants within the KLF family have been associated with a wide spectrum of neurodevelopmental and psychiatric symptoms. In a patient exhibiting attention deficit hyperactivity disorder (ADHD) combined with both neurodevelopmental and psychiatric symptoms, whole-exome sequencing (WES) analysis revealed a de novo heterozygous variant within the Krüppel-like factor 13 (KLF13) gene, which belongs to the KLF family and regulates axonal growth, development, and regeneration in mice. Moreover, in silico analyses pertaining to the likely pathogenic significance of the variant and the impact of the mutation on the KLF13 protein structure suggested a potential deleterious effect. In fact, the variant was localized in correspondence to the starting residue of the N-terminal domain of KLF13, essential for protein–protein interactions, DNA binding, and transcriptional activation or repression. This study aims to highlight the potential involvement of the KLF13 gene in neurodevelopmental and psychiatric disorders. Nevertheless, we cannot rule out that excluded variants, those undetectable by WES, or the polygenic risk may have contributed to the patient’s phenotype given ADHD’s high polygenic risk. However, further functional studies are required to validate its potential contribution to these disorders. Full article

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

► Show Figures

Figure 1

11 pages, 276 KiB

Open AccessEditor’s ChoiceArticle

Gene Variants in Components of the microRNA Processing Pathway in Chronic Myeloid Leukemia

by Guillermina Chavaro-Francisco, Araceli Hernández-Zavala, Camila E. Bravo-Cidro, Sandybel Rios-Rodriguez, Mabel Muciño-Sánchez, Marisol López-López, Xóchitl H. Castro-Martínez, Irma Olarte-Carrillo, Anel Garcia-Laguna, Gilberto Barranco-Lampón, Adrián De la Cruz-Rosas, Adolfo Martínez-Tovar and Emilio J. Córdova

Genes 2024, 15(8), 1054; https://doi.org/10.3390/genes15081054 - 10 Aug 2024

Cited by 3 | Viewed by 1160

Abstract

Current therapy in chronic myeloid leukemia (CML) has improved patient life expectancy close to that of healthy individuals. However, molecular alterations other than BCR::ABL1 fusion gene in CML are barely known. MicroRNAs are important regulators of gene expression, and variants in some of [...] Read more.

Current therapy in chronic myeloid leukemia (CML) has improved patient life expectancy close to that of healthy individuals. However, molecular alterations other than BCR::ABL1 fusion gene in CML are barely known. MicroRNAs are important regulators of gene expression, and variants in some of the components of microRNA biosynthesis pathways have been associated with genetic susceptibility to different types of cancer. Thus, the aim of this study was to evaluate the association of variants located in genes involved in the biogenesis of microRNAs with susceptibility to CML. Fifteen variants in eight genes involved in the biogenesis of miRNAs were genotyped in 296 individuals with CML and 485 healthy participants using TaqMan probes. The association of gene variants with CML and clinical variables was evaluated by a Chi-square test, and odds ratios and 95% confidence intervals were estimated by logistic regression. The variant rs13078 in DICER1 was significantly higher among CML individuals than in healthy participants. In addition, the variants rs7813 and rs2740349 were significantly associated with worse prognosis, according to their Hasford scores, whereas the rs2740349 variant was also associated with a later age at diagnosis. These findings suggest that variants in components of the microRNA biogenesis pathway could be involved in CML genetic risk. Full article

(This article belongs to the Special Issue Cancer Risk and Gene Variations)

11 pages, 715 KiB

Open AccessEditor’s ChoiceReview

Selected Monogenic Genetic Diseases in Holstein Cattle—A Review

by Marta Gozdek, Sebastian Mucha, Adam Prostek and Tomasz Sadkowski

Genes 2024, 15(8), 1052; https://doi.org/10.3390/genes15081052 - 10 Aug 2024

Cited by 2 | Viewed by 1799

Abstract

Genetic disorders arise from alterations in the hereditary information encoded in DNA, leading to potential detrimental effects on the well-being and vitality of organisms. Within the bovine population, genetic conditions inherited in an autosomal recessive manner are frequently associated with particular breeds. In [...] Read more.

Genetic disorders arise from alterations in the hereditary information encoded in DNA, leading to potential detrimental effects on the well-being and vitality of organisms. Within the bovine population, genetic conditions inherited in an autosomal recessive manner are frequently associated with particular breeds. In recent years, several recessive haplotypes and a few causative mutations have been discovered in Holstein cattle: CDH (Holstein cholesterol deficiency), haplotypes with a homozygous deficiency in Holstein (HH1, HH3, HH4, HH5, HH6 and HH7), BLAD (bovine leukocyte adhesion deficiency) and DUMPS (deficiency of uridine monophosphate synthase). All of these diseases are inherited in an autosomal recessive manner. From a breeding perspective, recessive mutations specifically exhibit considerable detrimental effects and are a significant problem for breeders, exposing them to economic losses. Individual mutations can cause embryo death at any stage of pregnancy. Only genetic research and conscious selection of animals for mating will lead to a reduction in the number of carriers and elimination of mutations from the population. Full article

(This article belongs to the Collection Feature Papers in ‘Animal Genetics and Genomics’)

► Show Figures

Figure 1

17 pages, 1947 KiB

Open AccessEditor’s ChoiceArticle

Radiation-Tolerant Fibrivirga spp. from Rhizosphere Soil: Genome Insights and Potential in Agriculture

by Sathiyaraj Srinivasan

Genes 2024, 15(8), 1048; https://doi.org/10.3390/genes15081048 - 9 Aug 2024

Cited by 2 | Viewed by 1233

Abstract

The rhizosphere of plants contains a wide range of microorganisms that can be cultivated and used for the benefit of agricultural practices. From garden soil near the rhizosphere region, Strain ES10-3-2-2 was isolated, and the cells were Gram-negative, aerobic, non-spore-forming rods that were [...] Read more.

The rhizosphere of plants contains a wide range of microorganisms that can be cultivated and used for the benefit of agricultural practices. From garden soil near the rhizosphere region, Strain ES10-3-2-2 was isolated, and the cells were Gram-negative, aerobic, non-spore-forming rods that were 0.3–0.8 µm in diameter and 1.5–2.5 µm in length. The neighbor-joining method on 16S rDNA similarity revealed that the strain exhibited the highest sequence similarities with “Fibrivirga algicola JA-25” (99.2%) and Fibrella forsythia HMF5405^T (97.3%). To further explore its biotechnological potentialities, we sequenced the complete genome of this strain employing the PacBio RSII sequencing platform. The genome of Strain ES10-3-2-2 comprises a 6,408,035 bp circular chromosome with a 52.8% GC content, including 5038 protein-coding genes and 52 RNA genes. The sequencing also identified three plasmids measuring 212,574 bp, 175,683 bp, and 81,564 bp. Intriguingly, annotations derived from the NCBI-PGAP, eggnog, and KEGG databases indicated the presence of genes affiliated with radiation-resistance pathway genes and plant-growth promotor key/biofertilization-related genes regarding Fe acquisition, K and P assimilation, CO₂ fixation, and Fe solubilization, with essential roles in agroecosystems, as well as genes related to siderophore regulation. Additionally, T1SS, T6SS, and T9SS secretion systems are present in this species, like plant-associated bacteria. The inoculation of Strain ES10-3-2-2 to Arabidopsis significantly increases the fresh shoot and root biomass, thereby maintaining the plant quality compared to uninoculated controls. This work represents a link between radiation tolerance and the plant-growth mechanism of Strain ES10-3-2-2 based on in vitro experiments and bioinformatic approaches. Overall, the radiation-tolerant bacteria might enable the development of microbiological preparations that are extremely effective at increasing plant biomass and soil fertility, both of which are crucial for sustainable agriculture. Full article

(This article belongs to the Special Issue Feature Papers in Microbial Genetics in 2024)

► Show Figures

Figure 1

13 pages, 3303 KiB

Open AccessEditor’s ChoiceArticle

A Public Mid-Density Genotyping Platform for Hexaploid Sweetpotato (Ipomoea batatas [L.] Lam)

by Dongyan Zhao, Alexander M. Sandercock, Maria Katherine Mejia-Guerra, Marcelo Mollinari, Kasia Heller-Uszynska, Phillip A. Wadl, Seymour A. Webster, Craig T. Beil and Moira J. Sheehan

Genes 2024, 15(8), 1047; https://doi.org/10.3390/genes15081047 - 9 Aug 2024

Cited by 1 | Viewed by 1784

Abstract

Small public breeding programs focused on specialty crops have many barriers to adopting technology, particularly creating and using genetic marker panels for genomic-based decisions in selection. Here, we report the creation of a DArTag panel of 3120 loci distributed across the sweetpotato ( [...] Read more.

Small public breeding programs focused on specialty crops have many barriers to adopting technology, particularly creating and using genetic marker panels for genomic-based decisions in selection. Here, we report the creation of a DArTag panel of 3120 loci distributed across the sweetpotato (Ipomoea batatas [L.] Lam) genome for molecular-marker-assisted breeding and genomic prediction. The creation of this marker panel has the potential to bring cost-effective and rapid genotyping capabilities to sweetpotato breeding programs worldwide. The open access provided by this platform will allow the genetic datasets generated on the marker panel to be compared and joined across projects, institutions, and countries. This genotyping resource has the power to make routine genotyping a reality for any breeder of sweetpotato. Full article

(This article belongs to the Special Issue Advances in Genetic Breeding of Sweetpotato)

► Show Figures

Figure 1

13 pages, 1561 KiB

Open AccessEditor’s ChoiceArticle

Canine Histiocytic and Hemophagocytic Histiocytic Sarcomas Display KRAS and Extensive PTPN11/SHP2 Mutations and Respond In Vitro to MEK Inhibition by Cobimetinib

by Ya-Ting Yang, Alexander I. Engleberg, Ishana Kapoor, Keita Kitagawa, Sara A. Hilburger, Tuddow Thaiwong-Nebelung and Vilma Yuzbasiyan-Gurkan

Genes 2024, 15(8), 1050; https://doi.org/10.3390/genes15081050 - 9 Aug 2024

Cited by 1 | Viewed by 1876

Abstract

Histiocytic sarcoma (HS) is a rare and highly aggressive cancer in humans and dogs. In dogs, it has a high prevalence in certain breeds, such as Bernese mountain dogs (BMDs) and flat-coated retrievers. Hemophagocytic histiocytic sarcoma (HHS) is a unique form of HS [...] Read more.

Histiocytic sarcoma (HS) is a rare and highly aggressive cancer in humans and dogs. In dogs, it has a high prevalence in certain breeds, such as Bernese mountain dogs (BMDs) and flat-coated retrievers. Hemophagocytic histiocytic sarcoma (HHS) is a unique form of HS that presents with erythrophagocytosis. Due to its rareness, the study of HHS is very limited, and mutations in canine HHS patients have not been studied to date. In previous work, our research group identified two major PTPN11/SHP2 driver mutations, E76K and G503V, in HS in dogs. Here, we report additional mutations located in exon 3 of PTPN11/SHP2 in both HS and HHS cases, further supporting that this area is a mutational hotspot in dogs and that mutations in tumors and liquid biopsies should be evaluated utilizing comprehensive methods such as Sanger and NextGen sequencing. The overall prevalence of PTPN11/SHP2 mutations was 55.8% in HS and 46.2% in HHS. In addition, we identified mutations in KRAS, in about 3% of HS and 4% of HHS cases. These findings point to the shared molecular pathology of activation of the MAPK pathway in HS and HHS cases. We evaluated the efficacy of the highly specific MEK inhibitor, cobimetinib, in canine HS and HHS cell lines. We found that the IC₅₀ values ranged from 74 to 372 nM, which are within the achievable and tolerable ranges for cobimetinib. This finding positions cobimetinib as a promising potential candidate for future canine clinical trials and enhances our understanding of the molecular defects in these challenging cancers. Full article

(This article belongs to the Special Issue Animal Models, Genetic and Genomic Studies in Cancer and Its Therapy)

► Show Figures

Figure 1

23 pages, 4068 KiB

Open AccessEditor’s ChoiceArticle

Analyzing Runs of Homozygosity Reveals Patterns of Selection in German Brown Cattle

by Anna Wirth, Jürgen Duda, Reiner Emmerling, Kay-Uwe Götz, Franz Birkenmaier and Ottmar Distl

Genes 2024, 15(8), 1051; https://doi.org/10.3390/genes15081051 - 9 Aug 2024

Cited by 3 | Viewed by 1701

Abstract

An increasing trend in ancestral and classical inbreeding coefficients as well as inbreeding depression for longevity were found in the German Brown population. In addition, the proportion of US Brown Swiss genes is steadily increasing in German Browns. Therefore, the aim of the [...] Read more.

An increasing trend in ancestral and classical inbreeding coefficients as well as inbreeding depression for longevity were found in the German Brown population. In addition, the proportion of US Brown Swiss genes is steadily increasing in German Browns. Therefore, the aim of the present study was to analyze the presence and genomic localization of runs of homozygosity (ROH) in order to evaluate their associations with the proportion of US Brown Swiss genes and survival rates of cows to higher lactations. Genotype data were sampled in 2364 German Browns from 258 herds. The final data set included 49,693 autosomal SNPs. We identified on average 35.996 ± 7.498 ROH per individual with a mean length of 8.323 ± 1.181 Mb. The genomic inbreeding coefficient F_ROH was 0.122 ± 0.032 and it decreased to 0.074, 0.031 and 0.006, when genomic homozygous segments > 8 Mb (F_ROH>8), >16 Mb (F_ROH>16) and >32 Mb (F_ROH>32) were considered. New inbreeding showed the highest correlation with F_ROH>32, whereas ancestral inbreeding coefficients had the lowest correlations with F_ROH>32. The correlation between the classical inbreeding coefficient and F_ROH was 0.572. We found significantly lower F_ROH, F_ROH>4, F_ROH>8 and F_IS for US Brown Swiss proportions <60% compared to >80%. Cows surviving to the 2nd, 4th, 6th, 8th, and 10th lactation had lower genomic inbreeding for F_ROH and up to F_ROH>32, which was due to a lower number of ROH and a shorter average length of ROH. The strongest ROH island and consensus ROH shared by 50% of the animals was found on BTA 6 at 85–88 Mb. The genes located in this genomic region were associated with longevity (NPFFR2 and ADAMTS3), udder health and morphology (SLC4A4, NPFFR2, GC and RASSF6), milk production, milk protein percentage, coagulation properties of milk and milking speed (CSN3). On BTA 2, a ROH island was detected only in animals with <60% US Brown Swiss genes. Genes within this region are predominantly important for dual-purpose cattle breeds including Original Browns. For cows reaching more than 9 lactations, an exclusive ROH island was identified on BTA 7 with genes assumed to be associated with longevity. The analysis indicated that genomic homozygous regions important for Original Browns are still present and also ROH containing genes affecting longevity may have been identified. The breeding of German Browns should prevent any further increase in genomic inbreeding and run a breeding program with balanced weights on production, robustness and longevity. Full article

(This article belongs to the Special Issue Advances in Cattle, Sheep, and Goats Molecular Genetics and Breeding)

► Show Figures

Figure 1

15 pages, 5211 KiB

Open AccessEditor’s ChoiceArticle

Analysis of the miR482 Gene Family in Plants

by Wei Kuang, Danfeng Qin, Ying Huang, Yihua Liu, Xue Cao and Meng Xu

Genes 2024, 15(8), 1043; https://doi.org/10.3390/genes15081043 - 8 Aug 2024

Viewed by 1336

Abstract

MicroRNA482 (miR482) is a conserved microRNA family in plants, playing critical regulatory roles in different biological activities. Though the members of the miR482 gene family have been identified in plants, a systematic study has not been reported yet. In the present research, 140 [...] Read more.

MicroRNA482 (miR482) is a conserved microRNA family in plants, playing critical regulatory roles in different biological activities. Though the members of the miR482 gene family have been identified in plants, a systematic study has not been reported yet. In the present research, 140 mature sequences generated by 106 precursors were used for molecular characterization, phylogenetic analysis, and target gene prediction, and the competing endogenous RNA (ceRNA) network mediated by miR482 was summarized. The length of mature sequences ranged from 17 nt to 25 nt, with 22 nt being the most abundant, and the start and end of the mature sequences had a preference for uracil (U). By sequence multiplex comparison, it was found that the mature sequences of 5p were clustered into one group, and others were clustered into the other group. Phylogenetic analysis revealed that the 140 mature sequences were categorized into six groups. Meanwhile, all the precursor sequences formed a stable hairpin structure, and the 106 precursors were divided into five groups. However, the expression of miR482 varied significantly between different species and tissues. In total, 149 target genes were predicted and their functions focused on single-organism process, cellular process, and cell and cell part. The ceRNA network of miR482 in tomato, cotton, and peanut was summarized based on related publications. In conclusion, this research will provide a foundation for further understanding of the miR482 gene family. Full article

(This article belongs to the Special Issue RNAs in Biology)

► Show Figures

Figure 1

13 pages, 2756 KiB

Open AccessEditor’s ChoiceArticle

Impact of Long-Term Pyriproxyfen Exposure on the Genetic Structure and Diversity of Aedes aegypti and Aedes albopictus in Manaus, Amazonas, Brazil

by Lorena Ferreira de Oliveira Leles, Marcus Vinícius Niz Alvarez, Jose Joaquin Carvajal Cortes, Diego Peres Alonso, Paulo Eduardo Martins Ribolla and Sérgio Luiz Bessa Luz

Genes 2024, 15(8), 1046; https://doi.org/10.3390/genes15081046 - 8 Aug 2024

Viewed by 1602

Abstract

Aedes aegypti and Aedes albopictus are responsible for transmitting major human arboviruses such as Dengue, Zika, and Chikungunya, posing a global threat to public health. The lack of etiological treatments and efficient vaccines makes vector control strategies essential for reducing vector population density [...] Read more.

Aedes aegypti and Aedes albopictus are responsible for transmitting major human arboviruses such as Dengue, Zika, and Chikungunya, posing a global threat to public health. The lack of etiological treatments and efficient vaccines makes vector control strategies essential for reducing vector population density and interrupting the pathogen transmission cycle. This study evaluated the impact of long-term pyriproxyfen exposure on the genetic structure and diversity of Ae. aegypti and Ae. albopictus mosquito populations. The study was conducted in Manaus, Amazonas, Brazil, where pyriproxyfen dissemination stations have been monitored since 2014 up to the present day. Double digest restriction-site associated DNA sequencing was performed, revealing that despite significant local population reductions by dissemination stations with pyriproxyfen in various locations in Brazil, focal intervention has no significant impact on the population stratification of these vectors in urban scenarios. The genetic structuring level of Ae. aegypti suggests it is more stratified and directly affected by pyriproxyfen intervention, while for Ae. albopictus exhibits a more homogeneous and less structured population. The results suggest that although slight differences are observed among mosquito subpopulations, intervention focused on neighborhoods in a capital city is not efficient in terms of genetic structuring, indicating that larger-scale pyriproxyfen interventions should be considered for more effective urban mosquito control. Full article

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

► Show Figures

Figure 1

12 pages, 2213 KiB

Open AccessEditor’s ChoiceArticle

Molecular Cloning, Tissue Distribution and Antiviral Immune Response of Duck Src

by Jinlu Liu, Shuwen Luo, Guoyao Wang, Xuming Hu, Guohong Chen and Qi Xu

Genes 2024, 15(8), 1044; https://doi.org/10.3390/genes15081044 - 8 Aug 2024

Viewed by 1190

Abstract

As a founding member of the Src family of kinases, Src has been confirmed to participate in the regulation of immune responses, integrin signaling, and motility. Ducks are usually asymptomatic carriers of RNA viruses such as Newcastle disease virus and avian influenza virus, [...] Read more.

As a founding member of the Src family of kinases, Src has been confirmed to participate in the regulation of immune responses, integrin signaling, and motility. Ducks are usually asymptomatic carriers of RNA viruses such as Newcastle disease virus and avian influenza virus, which can be deadly to chickens. The beneficial role of Src in modulating the immune response remains largely unknown in ducks. Here, we characterized the duck Src and found that it contains a 192-base-pair 5′ untranslated region, a 1602-base-pair coding region, and a 2541-base-pair 3′ untranslated region, encoding 533 amino acid residues. Additionally, duSrc transcripts were significantly activated in duck tissues infected by Newcastle disease virus compared to controls. The duSrc transcripts were notably widespread in all tissues examined, and the expression level was higher in liver, blood, lung, pancreas, and thymus. Moreover, we found the expression levels of IFN-β, NF-κB, IRF3, and Src were significantly increased in DEFs after infection with 5′ppp dsRNA, but there was no significant difference before and after treatment in DF1 cells. Furthermore, overexpression of duSrc followed by stimulation with 5′ppp dsRNA led to an elevation of IFN-β levels. The SH3 and PTKc domains of duSrc contributed to promoting the activity of IFN-β and NF-κB in DEFs stimulated by 5′ppp dsRNA. Full article

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

► Show Figures

Figure 1

16 pages, 5266 KiB

Open AccessEditor’s ChoiceArticle

Integrated Analyses of Metabolome and RNA-seq Data Revealing Flower Color Variation in Ornamental Rhododendron simsii Planchon

by Zhiliang Li, Siduo Xu, Hongmei Wu, Xuchun Wan, Hanhan Lei, Jiaojun Yu, Jun Fu, Jialiang Zhang and Shuzhen Wang

Genes 2024, 15(8), 1041; https://doi.org/10.3390/genes15081041 - 7 Aug 2024

Cited by 3 | Viewed by 1370

Abstract

Rhododendron simsii Planchon is an important ornamental species in the northern hemisphere. Flower color is an important objective of Rhododendron breeding programs. However, information on anthocyanin synthesis in R. simsii is limited. In this research, the regulatory mechanism of anthocyanin biosynthesis in R. [...] Read more.

Rhododendron simsii Planchon is an important ornamental species in the northern hemisphere. Flower color is an important objective of Rhododendron breeding programs. However, information on anthocyanin synthesis in R. simsii is limited. In this research, the regulatory mechanism of anthocyanin biosynthesis in R. simsii was performed through the integrated analysis of metabolome and RNA-seq. A total of 805 and 513 metabolites were screened by positive and negative ionization modes, respectively, In total, 79 flavonoids contained seven anthocyanidins, 42 flavanones, 10 flavans, 13 flavones, and seven flavonols. Methylated and glycosylated derivatives took up the most. Differentially accumulated metabolites were mainly involved in “flavone and flavonol biosynthesis”, “cyanoamino acid metabolism”, “pyrimidine metabolism”, and “phenylalanine metabolism” pathways. For flavonoid biosynthesis, different expression of shikimate O-hydroxycinnamoyltransferase, caffeoyl-CoA O-methyltransferase, flavonoid 3′-monooxygenase, flavonol synthase, dihydroflavonol 4-reductase/flavanone 4-reductase, F3′5′H, chalcone synthase, leucoanthocyanidin reductase, and 5-O-(4-coumaroyl)-D-quinate 3′-monooxygenase genes ultimately led to different accumulations of quercetin, myricetin, cyanidin, and eriodictyol. In flavone and flavonol biosynthesis pathway, differential expression of F3′5′H, flavonoid 3′-monooxygenase and flavonol-3-O-glucoside/galactoside glucosyltransferase genes led to the differential accumulation of quercetin, isovitexin, and laricitrin. This research will provide a biochemical basis for further modification of flower color and genetic breeding in R. simsii and related Rhododendron species. Full article

(This article belongs to the Special Issue Molecular Genetics and Multi-omics in Medicinal Plants)

► Show Figures

Figure 1

10 pages, 2160 KiB

Open AccessEditor’s ChoiceArticle

Splice Variant of Spalax Heparanase Skipping Exon 12

by Nicola J. Nasser, Eviatar Nevo and Aaron Avivi

Genes 2024, 15(8), 1039; https://doi.org/10.3390/genes15081039 - 7 Aug 2024

Viewed by 1058

Abstract

The subterranean blind mole rat, Spalax, has evolved significantly over 47 million years to thrive in its underground habitat. A key enzyme in this adaptation is heparanase, which degrades heparan sulfate (HS) in the extracellular matrix (ECM), facilitating angiogenesis and releasing growth [...] Read more.

The subterranean blind mole rat, Spalax, has evolved significantly over 47 million years to thrive in its underground habitat. A key enzyme in this adaptation is heparanase, which degrades heparan sulfate (HS) in the extracellular matrix (ECM), facilitating angiogenesis and releasing growth factors for endothelial cells. Spalax heparanase has various splice variants influencing tumor growth and metastasis differently. We report a novel splice variant from a hypoxia-exposed kidney sample resulting from exon 12 skipping. This variant maintains the translation frame but lacks enzymatic activity, offering insights into Spalax’s unique adaptations. Full article

(This article belongs to the Special Issue Application of Animal Modeling in Cancer)

► Show Figures

Figure 1

13 pages, 2139 KiB

Open AccessEditor’s ChoiceArticle

Analysis of the Mitochondrial COI Gene and Genetic Diversity of Endangered Goose Breeds

by Hao Wu, Shangzong Qi, Suyu Fan, Haoyu Li, Yu Zhang, Yang Zhang, Qi Xu and Guohong Chen

Genes 2024, 15(8), 1037; https://doi.org/10.3390/genes15081037 - 6 Aug 2024

Cited by 1 | Viewed by 1672

Abstract

The mitochondrial cytochrome c oxidase subunit I (COI) genes of six endangered goose breeds (Xupu, Yangjiang, Yan, Wuzong, Baizi, and Lingxian) were sequenced and compared to assess the genetic diversity of endangered goose breeds. By constructing phylogenetic trees and evolutionary maps [...] Read more.

The mitochondrial cytochrome c oxidase subunit I (COI) genes of six endangered goose breeds (Xupu, Yangjiang, Yan, Wuzong, Baizi, and Lingxian) were sequenced and compared to assess the genetic diversity of endangered goose breeds. By constructing phylogenetic trees and evolutionary maps of genetic relationships, the affinities and degrees of genetic variations among the six different breeds were revealed. A total of 92 polymorphic sites were detected in the 741 bp sequence of the mtDNA COI gene after shear correction, and the GC content of the processed sequence (51.11%) was higher than that of the AT content (48.89%). The polymorphic loci within the populations of five of the six breeds (Xupu, Yangjiang, Yan, Baizi, and Lingxian) were more than 10, the haplotype diversity > 0.5, and the nucleotide diversity (Pi) > 0.005, with the Baizi geese being the exception. A total of 35 haplotypes were detected based on nucleotide variation among sequences, and the goose breed haplotypes showed a central star-shaped dispersion; the FST values were −0.03781 to 0.02645, The greatest genetic differentiation (FST = 0.02645) was observed in Yan and Wuzong breeds. The most frequent genetic exchange (Nm > 15.00) was between the Wuzong and Yangjiang geese. An analysis of molecular variance showed that the population genetic variation mainly came from within the population; the base mismatch differential distribution analysis of the goose breeds and the Tajima’s D and Fu’s Fs neutral detection of the historical occurrence dynamics of their populations were negative (p > 0.10). The distribution curve of the base mismatches showed a multimodal peak, which indicated that the population tended to be stabilised. These results provide important genetic information for the conservation and management of endangered goose breeds and a scientific basis for the development of effective conservation strategies. Full article

(This article belongs to the Special Issue Mitochondrial DNA Replication and Transcription)

► Show Figures

Figure 1

23 pages, 1609 KiB

Open AccessEditor’s ChoiceReview

A Comprehensive Review of Bioinformatics Tools for Genomic Biomarker Discovery Driving Precision Oncology

by Alexis J. Clark and James W. Lillard, Jr.

Genes 2024, 15(8), 1036; https://doi.org/10.3390/genes15081036 - 6 Aug 2024

Cited by 19 | Viewed by 11036

Abstract

The rapid advancement of high-throughput technologies, particularly next-generation sequencing (NGS), has revolutionized cancer research by enabling the investigation of genetic variations such as SNPs, copy number variations, gene expression, and protein levels. These technologies have elevated the significance of precision oncology, creating a [...] Read more.

The rapid advancement of high-throughput technologies, particularly next-generation sequencing (NGS), has revolutionized cancer research by enabling the investigation of genetic variations such as SNPs, copy number variations, gene expression, and protein levels. These technologies have elevated the significance of precision oncology, creating a demand for biomarker identification and validation. This review explores the complex interplay of oncology, cancer biology, and bioinformatics tools, highlighting the challenges in statistical learning, experimental validation, data processing, and quality control that underpin this transformative field. This review outlines the methodologies and applications of bioinformatics tools in cancer genomics research, encompassing tools for data structuring, pathway analysis, network analysis, tools for analyzing biomarker signatures, somatic variant interpretation, genomic data analysis, and visualization tools. Open-source tools and repositories like The Cancer Genome Atlas (TCGA), Genomic Data Commons (GDC), cBioPortal, UCSC Genome Browser, Array Express, and Gene Expression Omnibus (GEO) have emerged to streamline cancer omics data analysis. Bioinformatics has significantly impacted cancer research, uncovering novel biomarkers, driver mutations, oncogenic pathways, and therapeutic targets. Integrating multi-omics data, network analysis, and advanced ML will be pivotal in future biomarker discovery and patient prognosis prediction. Full article

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

► Show Figures

Figure 1

12 pages, 259 KiB

Open AccessEditor’s ChoiceArticle

Association of Very Rare NOTCH2 Variants with Clinical Features of Alagille Syndrome

by Martina Ferrandino, Giovanna Cardiero, Fabiola Di Dato, Ylenia Cerrato, Luigi Vitagliano, Claudia Mandato, Filomena Morisco, Maria Immacolata Spagnuolo, Raffaele Iorio, Maria Donata Di Taranto and Giuliana Fortunato

Genes 2024, 15(8), 1034; https://doi.org/10.3390/genes15081034 - 6 Aug 2024

Cited by 1 | Viewed by 2046

Abstract

Background. Alagille syndrome (ALGS) is a rare autosomal dominant genetic disease caused by pathogenic variants in two genes: Jagged Canonical Notch Ligand 1 (JAG1) and Notch Receptor 2 (NOTCH2). It is characterized by phenotypic variability and incomplete penetrance with [...] Read more.

Background. Alagille syndrome (ALGS) is a rare autosomal dominant genetic disease caused by pathogenic variants in two genes: Jagged Canonical Notch Ligand 1 (JAG1) and Notch Receptor 2 (NOTCH2). It is characterized by phenotypic variability and incomplete penetrance with multiorgan clinical signs. Methods. Using Next Generation Sequencing (NGS), we analyzed a panel of liver-disease-related genes in a population of 230 patients with cholestasis and hepatopathies. For the rare variants, bioinformatics predictions and pathogenicity classification were performed. Results. We identified eleven rare NOTCH2 variants in 10 patients, two variants being present in the same patient. Ten variants had never been described before in the literature. It was possible to classify only two null variants as pathogenic, whereas the most of variants were missense (8 out of 11) and were classified as uncertain significance variants (USVs). Among patients with ALGS suspicion, two carried null variants, two carried variants predicted to be pathogenic by bioinformatics, one carried a synonymous variant and variants in glycosylation-related genes, and two carried variants predicted as benign in the PEST domain. Conclusions. Our results increased the knowledge about NOTCH2 variants and the related phenotype, allowing us to improve the genetic diagnosis of ALGS. Full article

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

32 pages, 5113 KiB

Open AccessEditor’s ChoiceReview

Pediatric Hemispheric High-Grade Gliomas and H3.3-G34 Mutation: A Review of the Literature on Biological Features and New Therapeutic Strategies

by Marta Bonada, Matilde Pittarello, Emerson De Fazio, Alessandro Gans, Paolo Alimonti, Hasan Slika, Federico Legnani, Francesco Di Meco and Betty Tyler

Genes 2024, 15(8), 1038; https://doi.org/10.3390/genes15081038 - 6 Aug 2024

Cited by 1 | Viewed by 4070

Abstract

Pediatric high-grade glioma (pHGG) encompasses a wide range of gliomas with different genomic, epigenomic, and transcriptomic features. Almost 50% of pHGGs present a mutation in genes coding for histone 3, including the subtype harboring the H3.3-G34 mutation. In this context, histone mutations are [...] Read more.

Pediatric high-grade glioma (pHGG) encompasses a wide range of gliomas with different genomic, epigenomic, and transcriptomic features. Almost 50% of pHGGs present a mutation in genes coding for histone 3, including the subtype harboring the H3.3-G34 mutation. In this context, histone mutations are frequently associated with mutations in TP53 and ATRX, along with PDGFRA and NOTCH2NL amplifications. Moreover, the H3.3-G34 histone mutation induces epigenetic changes in immune-related genes and exerts modulatory functions on the microenvironment. Also, the functionality of the blood–brain barrier (BBB) has an impact on treatment response. The prognosis remains poor with conventional treatments, thus eliciting the investigation of additional and alternative therapies. Promising molecular targets include PDGFRA amplification, BRAF mutation, EGFR amplification, NF1 loss, and IDH mutation. Considering that pHGGs harboring the H3.3-G34R mutation appear to be more susceptible to immunotherapies (ITs), different options have been recently explored, including immune checkpoint inhibitors, antibody mediated IT, and Car-T cells. This review aims to summarize the knowledge concerning cancer biology and cancer-immune cell interaction in this set of pediatric gliomas, with a focus on possible therapeutic options. Full article

(This article belongs to the Special Issue Epigenetic Modifications for Cancer Therapy)

► Show Figures

Figure 1

13 pages, 946 KiB

Open AccessEditor’s ChoiceArticle

A Genotype/Phenotype Study of KDM5B-Associated Disorders Suggests a Pathogenic Effect of Dominantly Inherited Missense Variants

by Maria Carla Borroto, Coralie Michaud, Chloé Hudon, Pankaj B. Agrawal, Katherine Agre, Carolyn D. Applegate, Alan H. Beggs, Hans T. Bjornsson, Bert Callewaert, Mei-Jan Chen, Cynthia Curry, Orrin Devinsky, Tracy Dudding-Byth, Kelly Fagan, Candice R. Finnila, Ralitza Gavrilova, Casie A. Genetti, Susan M. Hiatt, Friedhelm Hildebrandt, Monica H. Wojcik, Tjitske Kleefstra, Caroline M. Kolvenbach, Bruce R. Korf, Paul Kruszka, Hong Li, Jessica Litwin, Julien Marcadier, Konrad Platzer, Patrick R. Blackburn, Margot R. F. Reijnders, Heiko Reutter, Ina Schanze, Joseph T. Shieh, Cathy A. Stevens, Zaheer Valivullah, Marie-José van den Boogaard, Eric W. Klee and Philippe M. Campeau Show full author list Hide full author list

Genes 2024, 15(8), 1033; https://doi.org/10.3390/genes15081033 - 6 Aug 2024

Cited by 2 | Viewed by 2972

Abstract

Bi-allelic disruptive variants (nonsense, frameshift, and splicing variants) in KDM5B have been identified as causative for autosomal recessive intellectual developmental disorder type 65. In contrast, dominant variants, usually disruptive as well, have been more difficult to implicate in a specific phenotype, since some [...] Read more.

Bi-allelic disruptive variants (nonsense, frameshift, and splicing variants) in KDM5B have been identified as causative for autosomal recessive intellectual developmental disorder type 65. In contrast, dominant variants, usually disruptive as well, have been more difficult to implicate in a specific phenotype, since some of them have been found in unaffected controls or relatives. Here, we describe individuals with likely pathogenic variants in KDM5B, including eight individuals with dominant missense variants. This study is a retrospective case series of 21 individuals with variants in KDM5B. We performed deep phenotyping and collected the clinical information and molecular data of these individuals’ family members. We compared the phenotypes according to variant type and to those previously described in the literature. The most common features were developmental delay, impaired intellectual development, behavioral problems, autistic behaviors, sleep disorders, facial dysmorphism, and overgrowth. DD, ASD behaviors, and sleep disorders were more common in individuals with dominant disruptive KDM5B variants, while individuals with dominant missense variants presented more frequently with renal and skin anomalies. This study extends our understanding of the KDM5B-related neurodevelopmental disorder and suggests the pathogenicity of certain dominant KDM5B missense variants. Full article

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

► Show Figures

Figure 1

14 pages, 4342 KiB

Open AccessEditor’s ChoiceArticle

Identification of Autophagy-Related Biomarkers and Diagnostic Model in Alzheimer’s Disease

by Wei Xu, Xi Su, Jing Qin, Ye Jin, Ning Zhang and Shasha Huang

Genes 2024, 15(8), 1027; https://doi.org/10.3390/genes15081027 - 5 Aug 2024

Cited by 1 | Viewed by 2248

Abstract

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease. Its accurate pathogenic mechanisms are incompletely clarified, and effective therapeutic treatments are still inadequate. Autophagy is closely associated with AD and plays multiple roles in eliminating harmful aggregated proteins and maintaining cell homeostasis. This [...] Read more.

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease. Its accurate pathogenic mechanisms are incompletely clarified, and effective therapeutic treatments are still inadequate. Autophagy is closely associated with AD and plays multiple roles in eliminating harmful aggregated proteins and maintaining cell homeostasis. This study identified 1191 differentially expressed genes (DEGs) based on the GSE5281 dataset from the GEO database, intersected them with 325 autophagy-related genes from GeneCards, and screened 26 differentially expressed autophagy-related genes (DEAGs). Subsequently, GO and KEGG enrichment analysis was performed and indicated that these DEAGs were primarily involved in autophagy–lysosomal biological process. Further, eight hub genes were determined by PPI construction, and experimental validation was performed by qRT-PCR on a SH-SY5Y cell model. Finally, three hub genes (TFEB, TOMM20, GABARAPL1) were confirmed to have potential application for biomarkers. A multigenic prediction model with good predictability (AUC = 0.871) was constructed in GSE5281 and validated in the GSE132903 dataset. Hub gene-targeted miRNAs closely associated with AD were also retrieved through the miRDB and HDMM database, predicting potential therapeutic agents for AD. This study provides new insights into autophagy-related genes in brain tissues of AD patients and offers more candidate biomarkers for AD mechanistic research as well as clinical diagnosis. Full article

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

► Show Figures

Figure 1

13 pages, 1900 KiB

Open AccessEditor’s ChoiceArticle

Validation of Molecular Markers for Low Kunitz Trypsin Inhibitor Content in European Soybean (Glycine max L. Merr.) Germplasm

by Miroslav Bukan, Zoe Andrijanić, Ivan Pejić, Marko Ključarić, Lucija Čižmek, Ivana Tomaz, Nina Buljević and Hrvoje Šarčević

Genes 2024, 15(8), 1028; https://doi.org/10.3390/genes15081028 - 5 Aug 2024

Cited by 1 | Viewed by 1526

Abstract

Trypsin inhibitors (TI) in raw soybean grain, mainly represented by the Kunitz trypsin inhibitor protein (KTI), prevent the normal activity of the digestive enzymes trypsin and chymotrypsin in humans and monogastric livestock. The inactivation of TI is achieved through costly and time-consuming heat [...] Read more.

Trypsin inhibitors (TI) in raw soybean grain, mainly represented by the Kunitz trypsin inhibitor protein (KTI), prevent the normal activity of the digestive enzymes trypsin and chymotrypsin in humans and monogastric livestock. The inactivation of TI is achieved through costly and time-consuming heat treatment. Thermal processing also impairs the solubility and availability of the soybean grain protein. Therefore, the genetic elimination of KTI has been proposed as a suitable alternative to heat treatment. The aim of this study was to screen the collection of European soybean cultivars with six genetic markers (one SSR marker and five SNP markers) previously proposed as tightly linked to the KTI3 gene encoding the major Kunitz trypsin inhibitor seed protein of soybean and validate their usability for marker-assisted selection (MAS). The six markers were validated on a subset of 38 cultivars with wide variability in KTI content and in the F₂ and F_3:5 progenies of two crosses between the known high- and low-KTI cultivars. Three genetic markers (SSR Satt228 and two SNP markers, Gm08_45317135_T/G and Gm08_45541906_A/C) were significantly associated with KTI content in a subset of 38 cultivars. Low-KTI alleles were detected in both low- and high-KTI genotypes and vice versa, high-KTI alleles were found in both high- and low-KTI genotypes, indicating a tight but not perfect association of these markers with the KTI3 gene. The genetic marker SSR Satt228 showed a significant association with KTI content in the F₂ progeny, while the SNP markers Gm08_45317135_T/G and Gm08_45541906_A/C allowed significant discrimination between progeny with high- vs. low-KTI progenies in the F_3:5 generation. These three markers could be applied in MAS for low-KTI content but not without the additional phenotyping step to extract the desired low-KTI genotypes. Full article

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

► Show Figures

Figure 1

17 pages, 2435 KiB

Open AccessEditor’s ChoiceArticle

Combined Analysis of Multi-Study miRNA and mRNA Expression Data Shows Overlap of Selected miRNAs Involved in West Nile Virus Infections

by Franz Leonard Böge, Sergej Ruff, Shamini Hemandhar Kumar, Michael Selle, Stefanie Becker and Klaus Jung

Genes 2024, 15(8), 1030; https://doi.org/10.3390/genes15081030 - 5 Aug 2024

Viewed by 1414

Abstract

The emerging zoonotic West Nile virus (WNV) has serious impact on public health. Thus, understanding the molecular basis of WNV infections in mammalian hosts is important to develop improved diagnostic and treatment strategies. In this context, the role of microRNAs (miRNAs) has been [...] Read more.

The emerging zoonotic West Nile virus (WNV) has serious impact on public health. Thus, understanding the molecular basis of WNV infections in mammalian hosts is important to develop improved diagnostic and treatment strategies. In this context, the role of microRNAs (miRNAs) has been analyzed by several studies under different conditions and with different outcomes. A systematic comparison is therefore necessary. Furthermore, additional information from mRNA target expression data has rarely been taken into account to understand miRNA expression profiles under WNV infections. We conducted a meta-analysis of publicly available miRNA expression data from multiple independent studies, and analyzed them in a harmonized way to increase comparability. In addition, we used gene-set tests on mRNA target expression data to further gain evidence about differentially expressed miRNAs. For this purpose, we also studied the use of target information from different databases. We detected a substantial number of miRNA that emerged as differentially expressed from several miRNA datasets, and from the mRNA target data analysis as well. When using mRNA target data, we found that the targetscan databases provided the most useful information. We demonstrated improved miRNA detection through research synthesis of multiple independent miRNA datasets coupled with mRNA target set testing, leading to the discovery of multiple miRNAs which should be taken into account for further research on the molecular mechanism of WNV infections. Full article

(This article belongs to the Special Issue Bioinformatics of Disease Research)

► Show Figures

Figure 1

15 pages, 3635 KiB

Open AccessEditor’s ChoiceArticle

Identification of QTNs and Their Candidate Genes for Boll Number and Boll Weight in Upland Cotton

by Xiaoshi Shi, Changhui Feng, Hongde Qin, Jingtian Wang, Qiong Zhao, Chunhai Jiao and Yuanming Zhang

Genes 2024, 15(8), 1032; https://doi.org/10.3390/genes15081032 - 5 Aug 2024

Viewed by 1158

Abstract

Genome-wide association study (GWAS) has identified numerous significant loci for boll number (BN) and boll weight (BW), which play an essential role in cotton (Gossypium spp.) yield. The North Carolina design II (NC II) genetic mating population exhibits a greater number of [...] Read more.

Genome-wide association study (GWAS) has identified numerous significant loci for boll number (BN) and boll weight (BW), which play an essential role in cotton (Gossypium spp.) yield. The North Carolina design II (NC II) genetic mating population exhibits a greater number of genetic variations than other populations, which may facilitate the identification of additional genes. Accordingly, the 3VmrMLM method was employed for the analysis of upland cotton (Gossypium hirsutum L.) in an incomplete NC II genetic mating population across three environments. A total of 204 quantitative trait nucleotides (QTNs) were identified, of which 25 (24.75%) BN and 30 (29.13%) BW QTNs were of small effect (<1%) and 24 (23.76%) BN and 20 (19.42%) BW QTNs were rare (<10%). In the vicinity of these QTNs, two BN-related genes and two BW-related genes reported in previous studies were identified, in addition to five BN candidate genes and six BW candidate genes, which were obtained using differential expression analysis, gene function annotation, and haplotype analysis. Among these, six candidate genes were identified as homologs of Arabidopsis genes. The present study addresses the limitation of heritability missing and uncovers several new candidate genes. The findings of this study can provide a basis for further research and marker-assisted selection in upland cotton. Full article

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

► Show Figures

Figure 1

11 pages, 2939 KiB

Open AccessEditor’s ChoiceArticle

A Novel Pathogenic TUBA1A Variant in a Croatian Infant Is Linked to a Severe Tubulinopathy with Walker–Warburg-like Features

by Akzam Saidin, Anet Papazovska Cherepnalkovski, Zeeshan Shaukat, Todor Arsov, Rashid Hussain, Ben J. Roberts, Marija Bucat, Klara Cogelja, Michael G. Ricos and Leanne M. Dibbens

Genes 2024, 15(8), 1031; https://doi.org/10.3390/genes15081031 - 5 Aug 2024

Viewed by 1421

Abstract

Tubulinopathies are associated with malformations of cortical development but not Walker–Warburg Syndrome. Intensive monitoring of a Croatian infant presenting as Walker–Warburg Syndrome in utero began at 21 weeks due to increased growth of cerebral ventricles and foetal biparietal diameter. Monitoring continued until Caesarean [...] Read more.

Tubulinopathies are associated with malformations of cortical development but not Walker–Warburg Syndrome. Intensive monitoring of a Croatian infant presenting as Walker–Warburg Syndrome in utero began at 21 weeks due to increased growth of cerebral ventricles and foetal biparietal diameter. Monitoring continued until Caesarean delivery at 34 weeks where the infant was eutrophic. Clinical assessment of a progressive neurological disorder of unknown aetiology found a macrocephalic head and markedly hypoplastic genitalia with a micropenis. Neurological examination showed generalized hypotonia with very rare spontaneous movements, hypotonia-induced respiratory insufficiency and ventilator dependence, and generalized myoclonus intensifying during manipulation. With clinical features of hypotonia, lissencephaly, and brain malformations, Walker–Warburg Syndrome was suspected; however, eye anomalies were absent. Genetic trio analysis via whole-exome sequencing only identified a novel de novo mutation in the TUBA1A gene (NM_006009.4:c.848A>G; NP_006000.2:p.His283Arg) in the infant, who died at 2 months of age, as the likely cause. We report a previously unpublished, very rare heterozygous TUBA1A mutation with clinical features of macrocephaly and hypoplastic genitalia which have not previously been associated with the gene. The absence of eye phenotypes or mutations in Walker–Warburg-associated genes confirm this as not a new presentation of Walker–Warburg Syndrome but a novel TUBA1A tubulinopathy for neonatologists to be aware of. Full article

(This article belongs to the Special Issue Genetics of Rare Monogenic Neurodevelopmental Syndromes)

► Show Figures

Figure 1

13 pages, 837 KiB

Open AccessEditor’s ChoiceReview

Exploring Candidate Gene Studies and Alexithymia: A Systematic Review

by Yazmín Hernández-Díaz, Alma Delia Genis-Mendoza, Thelma Beatriz González-Castro, Ana Fresán, Carlos Alfonso Tovilla-Zárate, María Lilia López-Narváez, Isela Esther Juárez-Rojop and Humberto Nicolini

Genes 2024, 15(8), 1025; https://doi.org/10.3390/genes15081025 - 4 Aug 2024

Viewed by 2379

Abstract

Background: Alexithymia is a trait involving difficulties in processing emotions. Genetic association studies have investigated candidate genes involved in alexithymia’s pathogenesis. Therefore, the aim of the present study was to perform a systematic review of the genetic background associated with alexithymia. Methods: A [...] Read more.

Background: Alexithymia is a trait involving difficulties in processing emotions. Genetic association studies have investigated candidate genes involved in alexithymia’s pathogenesis. Therefore, the aim of the present study was to perform a systematic review of the genetic background associated with alexithymia. Methods: A systematic review of genetic studies of people with alexithymia was conducted. Electronic databases including PubMed, Scopus, and Web of Science were searched for the study purpose. We used the words “Alexithymia”, “gene”, “genetics”, “variants”, and “biomarkers”. The present systematic review was performed following the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. We found only candidate gene studies. A total of seventeen studies met the eligibility criteria, which comprised 22,361 individuals. The candidate genes associated with alexithymia were the serotoninergic pathway genes solute carrier family 6 member 4 (SLC6A4), serotonin 1A receptor (HTR1A), and serotonin 1A receptor (HTR2A); the neurotransmitter metabolism genes dopamine receptor D2 (DRD2), ankyrin repeat and kinase domain containing 1 (ANKK1), catechol-o-methyltransferase (COMT), brain-derived neurotrophic factor (BDNF), and oxytocin receptor (OXTR); and other pathway genes, vitamin D-binding protein (VDBP), tumor protein P53 regulated apoptosis inducing protein 1 (TP53AIP1), Rho GTPase Activating Protein 32 (ARHGAP32), and transmembrane protein 88B (TMEM88B). Conclusion: The results of this study showed that only case–control gene studies have been performed in alexithymia. On the basis of our findings, the majority of alexithymia genes and polymorphisms in this study belong to the serotoninergic pathway and neurotransmitter metabolism genes. These data suggest a role of serotoninergic neurotransmission in alexithymia. Nevertheless, more and future research is required to learn about the role of these genes in alexithymia. Full article

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

► Show Figures

Figure 1

12 pages, 1548 KiB

Open AccessEditor’s ChoiceArticle

Aberrantly Expressed tRNA-Val Fragments Can Distinguish Canine Hepatocellular Carcinoma from Canine Hepatocellular Adenoma

by Saki Hashimoto, MD Nazmul Hasan, Mohammad Arif, Nobuhiro Nozaki, Al Asmaul Husna, Yu Furusawa, Takeshi Sogawa, Kaori Takahashi, Tomohide Kuramoto, Aki Noguchi, Masashi Takahashi, Osamu Yamato, Md Mahfuzur Rahman and Naoki Miura

Genes 2024, 15(8), 1024; https://doi.org/10.3390/genes15081024 - 4 Aug 2024

Viewed by 1612

Abstract

Hepatocellular adenoma (HCA) and hepatocellular carcinoma (HCC) can be difficult to differentiate but must be diagnosed correctly as treatment and prognosis for these tumors differ markedly. Relevant diagnostic biomarkers are thus needed, and those identified in dogs may have utility in human medicine [...] Read more.

Hepatocellular adenoma (HCA) and hepatocellular carcinoma (HCC) can be difficult to differentiate but must be diagnosed correctly as treatment and prognosis for these tumors differ markedly. Relevant diagnostic biomarkers are thus needed, and those identified in dogs may have utility in human medicine because of the similarities between human and canine HCA and HCC. A tRNA-derived fragment (tRF), tRNA-Val, is a promising potential biomarker for canine mammary gland tumors but has not previously been investigated in hepatic tumors. Accordingly, we aimed to elucidate the potential utility of tRNA-Val as a biomarker for canine HCA and HCC using clinical samples (tumor tissue and plasma extracellular vesicles [EVs]) and tumor cell lines with qRT-PCR assays. We also investigated relevant functions and signaling pathways with bioinformatic analyses (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes). tRNA-Val was markedly downregulated in HCC tumor tissue versus HCA tumor tissue and normal liver tissue, and a similar trend was shown in plasma EVs and HCC cell lines versus healthy controls. Based on areas under the receiver operating characteristic curves (AUCs), tRNA-Val significantly distinguished HCC (AUC = 1.00, p = 0.001) from healthy controls in plasma EVs and HCC from HCA (AUC = 0.950, p = 0.01). Bioinformatics analysis revealed that tRNA-Val may be primarily involved in DNA repair, mRNA processing, and splicing and may be linked to the N-glycan and ubiquitin-mediated proteasome pathways. This is the first report on the expression of tRNA-Val in canine HCC and HCA and its possible functions and signaling pathways. We suggest that tRNA-Val could be a promising novel biomarker to distinguish canine HCC from HCA. This study provides evidence for a greater understanding of the role played by tRNA-Val in the development of canine HCC. Full article

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

► Show Figures

Figure 1

11 pages, 2445 KiB

Open AccessEditor’s ChoiceArticle

Elucidating Scarab Divergence in an Evolutionary-Ecological Context through the Comprehensive Analysis of the Complete Mitogenome of Anomala

by Xianyi Wang, Shuchai Li and Tielong Xu

Genes 2024, 15(8), 1022; https://doi.org/10.3390/genes15081022 - 3 Aug 2024

Viewed by 1109

Abstract

Anomala Samouelle, 1819 is one of the specious genera of Coleoptera, with over 1000 known species, and includes some of the most destructive pests of crops or forests. Morphological convergence is a common phenomenon within this genus, making the identification of closely related [...] Read more.

Anomala Samouelle, 1819 is one of the specious genera of Coleoptera, with over 1000 known species, and includes some of the most destructive pests of crops or forests. Morphological convergence is a common phenomenon within this genus, making the identification of closely related species very difficult. To explore the phylogenetic placement of Anomalini and provide a basis for the classification and identification of Anomala, we comparatively analyzed the complete mitogenome of three Anomala species (A. exoleta, A. perplexa diana, and A. praecoxalis). Based on all accessible mitogenome data, we performed comparative mitochondrial genomics analysis of this genus and reconstructed the phylogenetic relationships of Scarabaeidae based on two datasets (protein-coding genes and amino acids) and two methods (Bayesian approach and maximum likelihood). The phylogenetic relationships found in this study highly support that the groups of Aphodiinae, Cetoniinae, Dynastinae, Rutelinae and Scarabaeinae are monophyletic. Interestingly, the phylogenetic clustering relationship was highly consistent with the Scarabaeidae diet, indicating that the herbivorous species and dung-eating species are clustered separately. The phylogenetic tree showed that the subfamily Melolonthinae and the genus Anomala are not monophyletic, suggesting that these two groups should be further revised with more data. Full article

(This article belongs to the Special Issue Molecular Evolution, Mitochondrial Genomics and Mitochondrial Genome Expression in Animals—2nd Edition)

► Show Figures

Figure 1

27 pages, 5317 KiB

Open AccessEditor’s ChoiceArticle

ARGONAUTE2 Localizes to Sites of Sporocysts in the Schistosome-Infected Snail, Biomphalaria glabrata

by Phong Phan, Conor E. Fogarty, Andrew L. Eamens, Mary G. Duke, Donald P. McManus, Tianfang Wang and Scott F. Cummins

Genes 2024, 15(8), 1023; https://doi.org/10.3390/genes15081023 - 3 Aug 2024

Cited by 3 | Viewed by 1947

Abstract

MicroRNAs (miRNAs) are a class of small regulatory RNA that are generated via core protein machinery. The miRNAs direct gene-silencing mechanisms to mediate an essential role in gene expression regulation. In mollusks, miRNAs have been demonstrated to be required to regulate gene expression [...] Read more.

MicroRNAs (miRNAs) are a class of small regulatory RNA that are generated via core protein machinery. The miRNAs direct gene-silencing mechanisms to mediate an essential role in gene expression regulation. In mollusks, miRNAs have been demonstrated to be required to regulate gene expression in various biological processes, including normal development, immune responses, reproduction, and stress adaptation. In this study, we aimed to establishment the requirement of the miRNA pathway as part of the molecular response of exposure of Biomphalaria glabrata (snail host) to Schistosoma mansoni (trematode parasite). Initially, the core pieces of miRNA pathway protein machinery, i.e., Drosha, DGCR8, Exportin-5, Ran, and Dicer, together with the central RNA-induced silencing complex (RISC) effector protein Argonaute2 (Ago2) were elucidated from the B. glabrata genome. Following exposure of B. glabrata to S. mansoni miracidia, we identified significant expression up-regulation of all identified pieces of miRNA pathway protein machinery, except for Exportin-5, at 16 h post exposure. For Ago2, we went on to show that the Bgl-Ago2 protein was localized to regions surrounding the sporocysts in the digestive gland of infected snails 20 days post parasite exposure. In addition to documenting elevated miRNA pathway protein machinery expression at the early post-exposure time point, a total of 13 known B. glabrata miRNAs were significantly differentially expressed. Of these thirteen B. glabrata miRNAs responsive to S. mansoni miracidia exposure, five were significantly reduced in their abundance, and correspondingly, these five miRNAs were determined to putatively target six genes with significantly elevated expression and that have been previously associated with immune responses in other animal species, including humans. In conclusion, this study demonstrates the central importance of a functional miRNA pathway in snails, which potentially forms a critical component of the immune response of snails to parasite exposure. Further, the data reported in this study provide additional evidence of the complexity of the molecular response of B. glabrata to S. mansoni infection: a molecular response that could be targeted in the future to overcome parasite infection and, in turn, human schistosomiasis. Full article

(This article belongs to the Special Issue Evolution of Non-coding Elements in Genome Biology)

► Show Figures

Figure 1

21 pages, 13456 KiB

Open AccessEditor’s ChoiceArticle

Tracking Ovine Pulmonary Adenocarcinoma Development Using an Experimental Jaagsiekte Sheep Retrovirus Infection Model

by Chris Cousens, James Meehan, David Collie, Steven Wright, Ziyuan Chang, Helen Todd, Jo Moore, Lynn Grant, Carola R. Daniel, Peter Tennant, Adrian Ritchie, James Nixon, Chris Proudfoot, Stefano Guido, Helen Brown, Calum D. Gray, Tom J. MacGillivray, R. Eddie Clutton, Stephen N. Greenhalgh, Rachael Gregson, David J. Griffiths, James Spivey, Nicole Storer, Chad E. Eckert and Mark Gray Show full author list Hide full author list

Genes 2024, 15(8), 1019; https://doi.org/10.3390/genes15081019 - 2 Aug 2024

Cited by 3 | Viewed by 1796

Abstract

Ovine pulmonary adenocarcinoma (OPA) is an infectious, neoplastic lung disease of sheep that causes significant animal welfare and economic issues throughout the world. Understanding OPA pathogenesis is key to developing tools to control its impact. Central to this need is the availability of [...] Read more.

Ovine pulmonary adenocarcinoma (OPA) is an infectious, neoplastic lung disease of sheep that causes significant animal welfare and economic issues throughout the world. Understanding OPA pathogenesis is key to developing tools to control its impact. Central to this need is the availability of model systems that can monitor and track events after Jaagsiekte sheep retrovirus (JSRV) infection. Here, we report the development of an experimentally induced OPA model intended for this purpose. Using three different viral dose groups (low, intermediate and high), localised OPA tumour development was induced by bronchoscopic JSRV instillation into the segmental bronchus of the right cardiac lung lobe. Pre-clinical OPA diagnosis and tumour progression were monitored by monthly computed tomography (CT) imaging and trans-thoracic ultrasound scanning. Post mortem examination and immunohistochemistry confirmed OPA development in 89% of the JSRV-instilled animals. All three viral doses produced a range of OPA lesion types, including microscopic disease and gross tumours; however, larger lesions were more frequently identified in the low and intermediate viral groups. Overall, 31% of JSRV-infected sheep developed localised advanced lesions. Of the sheep that developed localised advanced lesions, tumour volume doubling times (calculated using thoracic CT 3D reconstructions) were 14.8 ± 2.1 days. The ability of ultrasound to track tumour development was compared against CT; the results indicated a strong significant association between paired CT and ultrasound measurements at each time point (R² = 0.799, p < 0.0001). We believe that the range of OPA lesion types induced by this model replicates aspects of naturally occurring disease and will improve OPA research by providing novel insights into JSRV infectivity and OPA disease progression. Full article

(This article belongs to the Special Issue Application of Animal Modeling in Cancer)

► Show Figures

Figure 1

13 pages, 6087 KiB

Open AccessEditor’s ChoiceReview

Cardiac Phenotype and Gene Mutations in RASopathies

by Maria Felicia Faienza, Giovanni Meliota, Donatella Mentino, Romina Ficarella, Mattia Gentile, Ugo Vairo and Gabriele D’amato

Genes 2024, 15(8), 1015; https://doi.org/10.3390/genes15081015 - 2 Aug 2024

Cited by 1 | Viewed by 2145

Abstract

Cardiac involvement is a major feature of RASopathies, a group of phenotypically overlapping syndromes caused by germline mutations in genes encoding components of the RAS/MAPK (mitogen-activated protein kinase) signaling pathway. In particular, Noonan syndrome (NS) is associated with a wide spectrum of cardiac [...] Read more.

Cardiac involvement is a major feature of RASopathies, a group of phenotypically overlapping syndromes caused by germline mutations in genes encoding components of the RAS/MAPK (mitogen-activated protein kinase) signaling pathway. In particular, Noonan syndrome (NS) is associated with a wide spectrum of cardiac pathologies ranging from congenital heart disease (CHD), present in approximately 80% of patients, to hypertrophic cardiomyopathy (HCM), observed in approximately 20% of patients. Genotype–cardiac phenotype correlations are frequently described, and they are useful indicators in predicting the prognosis concerning cardiac disease over the lifetime. The aim of this review is to clarify the molecular mechanisms underlying the development of cardiac diseases associated particularly with NS, and to discuss the main morphological and clinical characteristics of the two most frequent cardiac disorders, namely pulmonary valve stenosis (PVS) and HCM. We will also report the genotype–phenotype correlation and its implications for prognosis and treatment. Knowing the molecular mechanisms responsible for the genotype–phenotype correlation is key to developing possible targeted therapies. We will briefly address the first experiences of targeted HCM treatment using RAS/MAPK pathway inhibitors. Full article

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

► Show Figures

Figure 1

17 pages, 5181 KiB

Open AccessEditor’s ChoiceArticle

Developing an Optimized Protocol for Regeneration and Transformation in Pepper

by Shamsullah Shams, Beenish Naeem, Lingling Ma, Rongxuan Li, Zhenghai Zhang, Yacong Cao, Hailong Yu, Xigang Feng, Yinhui Qiu, Huamao Wu and Lihao Wang

Genes 2024, 15(8), 1018; https://doi.org/10.3390/genes15081018 - 2 Aug 2024

Viewed by 2153

Abstract

Capsicum annuum L. is extensively cultivated in subtropical and temperate regions globally, respectively, when grown in a medium with 8 holding significant economic importance. Despite the availability of genome sequences and editing tools, gene editing in peppers is limited by the lack of [...] Read more.

Capsicum annuum L. is extensively cultivated in subtropical and temperate regions globally, respectively, when grown in a medium with 8 holding significant economic importance. Despite the availability of genome sequences and editing tools, gene editing in peppers is limited by the lack of a stable regeneration and transformation method. This study assessed regeneration and transformation protocols in seven chili pepper varieties, including CM334, Zunla-1, Zhongjiao6 (ZJ6), 0818, 0819, 297, and 348, in order to enhance genetic improvement efforts. Several explants, media compositions, and hormonal combinations were systematically evaluated to optimize the in vitro regeneration process across different chili pepper varieties. The optimal concentrations for shoot formation, shoot elongation, and rooting in regeneration experiments were determined as 5 mg/L of 6-Benzylaminopurine (BAP) with 5 mg/L of silver nitrate (AgNO₃), 0.5 mg/L of Gibberellic acid (GA₃), and 1 mg/L of Indole-3-butyric acid (IBA), respectively. The highest regeneration rate of 41% was observed from CM334 cotyledon explants. Transformation optimization established 300 mg/L of cefotaxime for bacterial control, with a 72-h co-cultivation period at OD₆₀₀ = 0.1. This study optimizes the protocols for chili pepper regeneration and transformation, thereby contributing to genetic improvement efforts. Full article

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

► Show Figures

Figure 1

10 pages, 228 KiB

Open AccessEditor’s ChoiceArticle

Alport Syndrome: Clinical Utility of Early Genetic Diagnosis in Children

by Vasileia Christodoulaki, Konstantina Kosma, Nikolaos M. Marinakis, Faidon-Nikolaos Tilemis, Nikolaos Stergiou, Afroditi Kampouraki, Charalampos Kapogiannis, Vasiliki Karava, Andromachi Mitsioni, Maria Mila, Christina Kanaka-Gantenbein, Periklis Makrythanasis, Maria Tzetis and Joanne Traeger-Synodinos

Genes 2024, 15(8), 1016; https://doi.org/10.3390/genes15081016 - 2 Aug 2024

Cited by 1 | Viewed by 1841

Abstract

Alport syndrome (AS) is a hereditary glomerulopathy due to pathogenic variants in COL4A3, COL4A4, and COL4A5. Treatment with Renin–Angiotensin–Aldosterone System (RAAS) inhibitors can delay progression to end stage renal disease (ESRD). From 2018 until today, we performed Whole Exome Sequencing (WES) [...] Read more.

Alport syndrome (AS) is a hereditary glomerulopathy due to pathogenic variants in COL4A3, COL4A4, and COL4A5. Treatment with Renin–Angiotensin–Aldosterone System (RAAS) inhibitors can delay progression to end stage renal disease (ESRD). From 2018 until today, we performed Whole Exome Sequencing (WES) in 19 patients with AS phenotype with or without positive family history. Fourteen of these patients were children. Genetic testing was extended to family members at risk. All patients received a genetic diagnosis of AS: five X-linked AS (XLAS) males, five X-linked AS (XLAS) females, six autosomal dominant AS (ADAS), and one autosomal recessive AS (ARAS). After cascade screening four XLAS males and eight XLAS females, six ADAS and three ARAS heterozygotes were added to our initial results. Fifteen patients were eligible to start treatment with RAAS inhibitors after their diagnosis. All XLAS female patients, ARAS heterozygotes, and ADAS have been advised to be followed up, so that therapeutic intervention can begin in the presence of microalbuminuria. Genetic diagnosis of AS ensures early therapeutic intervention and appropriate follow up to delay progression to chronic kidney disease, especially in thet pediatric population. Full article

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

29 pages, 1924 KiB

Open AccessEditor’s ChoiceReview

A Closer Look into White Adipose Tissue Biology and the Molecular Regulation of Stem Cell Commitment and Differentiation

by Presley D. Dowker-Key, Praveen Kumar Jadi, Nicholas B. Gill, Katelin N. Hubbard, Ahmed Elshaarrawi, Naba D. Alfatlawy and Ahmed Bettaieb

Genes 2024, 15(8), 1017; https://doi.org/10.3390/genes15081017 - 2 Aug 2024

Cited by 1 | Viewed by 3669

Abstract

White adipose tissue (WAT) makes up about 20–25% of total body mass in healthy individuals and is crucial for regulating various metabolic processes, including energy metabolism, endocrine function, immunity, and reproduction. In adipose tissue research, “adipogenesis” is commonly used to refer to the [...] Read more.

White adipose tissue (WAT) makes up about 20–25% of total body mass in healthy individuals and is crucial for regulating various metabolic processes, including energy metabolism, endocrine function, immunity, and reproduction. In adipose tissue research, “adipogenesis” is commonly used to refer to the process of adipocyte formation, spanning from stem cell commitment to the development of mature, functional adipocytes. Although, this term should encompass a wide range of processes beyond commitment and differentiation, to also include other stages of adipose tissue development such as hypertrophy, hyperplasia, angiogenesis, macrophage infiltration, polarization, etc.… collectively, referred to herein as the adipogenic cycle. The term “differentiation”, conversely, should only be used to refer to the process by which committed stem cells progress through distinct phases of subsequent differentiation. Recognizing this distinction is essential for accurately interpreting research findings on the mechanisms and stages of adipose tissue development and function. In this review, we focus on the molecular regulation of white adipose tissue development, from commitment to terminal differentiation, and examine key functional aspects of WAT that are crucial for normal physiology and systemic metabolic homeostasis. Full article

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

► Show Figures

Graphical abstract

14 pages, 1036 KiB

Open AccessEditor’s ChoiceArticle

Role of Selected Genetic Polymorphisms in the Development of Rheumatoid Arthritis in a British White Population

by Sarabjit Mastana, Ella Knight, Abigail Hampson, Liz Akam, David John Hunter, Anant Ghelani, Ash Samanta and Puneetpal Singh

Genes 2024, 15(8), 1009; https://doi.org/10.3390/genes15081009 - 1 Aug 2024

Cited by 1 | Viewed by 1631

Abstract

Background: Rheumatoid arthritis (RA) is a complex autoimmune disease that negatively affects synovial joints, leading to the deterioration of movement and mobility of patients. This chronic disease is considered to have a strong genetic inheritance, with genome-wide association studies (GWAS) highlighting many genetic [...] Read more.

Background: Rheumatoid arthritis (RA) is a complex autoimmune disease that negatively affects synovial joints, leading to the deterioration of movement and mobility of patients. This chronic disease is considered to have a strong genetic inheritance, with genome-wide association studies (GWAS) highlighting many genetic loci associated with the disease. Moreover, numerous confounding and non-genetic factors also contribute to the risk of the disease. Aims: This study investigates the association of selected genetic polymorphisms with rheumatoid arthritis risk and develops a polygenic risk score (PRS) based on selected genes. Methods: A case-control study recruited fully consenting participants from the East Midlands region of the UK. DNA samples were genotyped for a range of polymorphisms and genetic associations were calculated under several inheritance models. PRS was calculated at crude (unweighted) and weighted levels, and its associations with clinical parameters were determined. Results: There were significant associations with the risk of RA at six genetic markers and their associated risk alleles (TNRF2*G, TRAF1*A, PTPN22*T, HLA-DRB1*G, TNFα*A, and IL4-590*T). The TTG haplotype at the VDR locus increased the risk of RA with an OR of 3.05 (CI 1.33–6.98, p = 0.009). The GA haplotype of HLADRB1-TNFα-308 was a significant contributor to the risk of RA in this population (OR = 2.77, CI 1.23–6.28, p = 0.01), although linkage disequilibrium was low. The polygenic risk score was significantly higher in cases over controls in both unweighted (mean difference = 1.48, t₂₈₅ = 5.387, p < 0.001) and weighted (mean difference = 2.75, t₂₈₅ = 6.437, p < 0.001) results. Conclusion: Several genetic loci contribute to the increased risk of RA in the British White sample. The PRS is significantly higher in those with RA and can be used for clinical applications and personalised prevention of disease. Full article

(This article belongs to the Special Issue Advances in Human Genetics and Multi-omics)

► Show Figures

Figure 1

12 pages, 701 KiB

Open AccessEditor’s ChoiceArticle

Prevalence of the FMR1 Gene Premutation in Young Women with a Diminished Ovarian Reserve Included in an IVF Program: Implications for Clinical Practice

by Inés Agustí, Marta Méndez, Aina Borrás, Anna Goday, Marta Guimerà, Sara Peralta, Laura Ribera, Laia Rodriguez-Revenga and Dolors Manau

Genes 2024, 15(8), 1008; https://doi.org/10.3390/genes15081008 - 1 Aug 2024

Viewed by 1731

Abstract

The relationship between premature ovarian insufficiency (FXPOI) and premutation in the FMR1 gene is well established. In recent years, though, a potential relationship between the latter and a low ovarian reserve has been suggested. To explore it, we conducted a retrospective study in [...] Read more.

The relationship between premature ovarian insufficiency (FXPOI) and premutation in the FMR1 gene is well established. In recent years, though, a potential relationship between the latter and a low ovarian reserve has been suggested. To explore it, we conducted a retrospective study in an IVF program at a university tertiary referral center in Barcelona (Spain). Data were obtained retrospectively from a total of 385 women referred for FMR1 gene testing at our institution from January 2018 to December 2021. We compared the prevalence of FMR1 gene premutation between 93 of them, younger than 35 years, with a diminished ovarian reserve (DOR), characterized by levels of anti-Mullerian hormone < 1.1 ng/mL and antral follicle count < 5; and 132 egg donors screened by protocol that served as the controls. We found a higher prevalence of FMR1 premutation in the DOR group (seven patients (7.69%)) than in the control group (one patient (1.32%)), Fisher-exact test p-value = 0.012). We concluded that compared with the general population represented by young egg donors, the prevalence of FMR1 gene premutation is higher in young patients with a diminished ovarian reserve. Although these findings warrant further prospective validation in a larger cohort of patients within DOR, they suggest that, in clinical practice, FMR1 premutation should be determined in infertile young patients with DOR in order to give them adequate genetic counselling. Full article

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

► Show Figures

Figure 1

21 pages, 1436 KiB

Open AccessEditor’s ChoiceReview

Genome-Editing Products Line up for the Market: Will Europe Harvest the Benefits from Science and Innovation?

by Alexios Polidoros, Irini Nianiou-Obeidat, Nikolaos Tsakirpaloglou, Nestor Petrou, Eleftheria Deligiannidou and Nefeli-Maria Makri

Genes 2024, 15(8), 1014; https://doi.org/10.3390/genes15081014 - 1 Aug 2024

Cited by 1 | Viewed by 4162

Abstract

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technologies have revolutionized genome editing, significantly advancing the improvement of cultivated crop species. This review provides an overview of genome-edited crops that have either reached the market or received the necessary approvals but are not yet [...] Read more.

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technologies have revolutionized genome editing, significantly advancing the improvement of cultivated crop species. This review provides an overview of genome-edited crops that have either reached the market or received the necessary approvals but are not yet available to consumers. We analyze various genome-editing studies to understand the distribution of different genome-editing systems, the types of site-directed nucleases employed, and the geographical spread of these studies, with a specific focus on global and European contexts. Additionally, we examine the target crops involved. The review also outlines the multiple steps required for the legal acceptance of genome-edited crops within European jurisdictions. We conclude with suggestions for the future prospects of genome-editing research in Europe, aiming to streamline the approval process and enhance the development and adoption of genome-edited crops. Full article

(This article belongs to the Collection Feature Papers: 'Plant Genetics and Genomics' Section)

► Show Figures

Figure 1

13 pages, 1722 KiB

Open AccessEditor’s ChoiceArticle

Unique miRNA Expression Profile in MSI- and EMAST-Unstable Sporadic Colon Cancer

by Sonja Marinović, Kristina Vuković Đerfi, Anita Škrtić, Mirko Poljak and Sanja Kapitanović

Genes 2024, 15(8), 1007; https://doi.org/10.3390/genes15081007 - 1 Aug 2024

Viewed by 1480

Abstract

MicroRNAs (miRNAs) are critical post-transcriptional gene regulators and their involvement in sporadic colon cancer (CRC) tumorigenesis has been confirmed. In this study we investigated differences in miRNA expression in microsatellite stable (MSS/EMAST-S), microsatellite unstable marked by high elevated microsatellite alterations at selected tetranucleotide [...] Read more.

MicroRNAs (miRNAs) are critical post-transcriptional gene regulators and their involvement in sporadic colon cancer (CRC) tumorigenesis has been confirmed. In this study we investigated differences in miRNA expression in microsatellite stable (MSS/EMAST-S), microsatellite unstable marked by high elevated microsatellite alterations at selected tetranucleotide repeats (MSS/EMAST-H), and high microsatellite unstable (MSI-H/EMAST-H) tumor subgroups as well as in tumors with different clinicopathologic characteristics. An RT-qPCR analysis of miRNA expression was carried out on 45 colon cancer and adjacent normal tissue samples (15 of each group). Overall, we found three differentially expressed miRNAs between the subgroups. miR-92a-3p and miR-224-5p were significantly downregulated in MSI-H/EMAST-H tumors in comparison to other subgroups. miR-518c-3p was significantly upregulated in MSS/EMAST-H tumors in comparison to stable and highly unstable tumors. Furthermore, we showed that miR-143-3p and miR-145-5p were downregulated in tumors in comparison to normal tissues in all subgroups. In addition, we showed overexpression of miR-125b-5p in well-differentiated tumors and miR-451a in less advanced tumors. This is the first report on differences in miRNA expression profiles between MSS/EMAST-S, MSS/EMAST-H, and MSI-H/EMAST-H colorectal cancers. Our findings indicate that the miRNA expression signatures differ in CRC subgroups based on their instability status. Full article

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

► Show Figures

Figure 1

16 pages, 7285 KiB

Open AccessEditor’s ChoiceArticle

Interspecific and Intraspecific Transcriptomic Variations Unveil the Potential High-Altitude Adaptation Mechanisms of the Parnassius Butterfly Species

by Chen Ding, Chengyong Su, Yali Li, Youjie Zhao, Yunliang Wang, Ying Wang, Ruie Nie, Bo He, Junye Ma and Jiasheng Hao

Genes 2024, 15(8), 1013; https://doi.org/10.3390/genes15081013 - 1 Aug 2024

Cited by 1 | Viewed by 1533

Abstract

Parnassius butterflies have significantly advanced our understanding of biogeography, insect–plant interactions, and other fields of ecology and evolutionary biology. However, to date, little is known about the gene expression patterns related to the high-altitude adaptation of Parnassius species. In this study, we obtained [...] Read more.

Parnassius butterflies have significantly advanced our understanding of biogeography, insect–plant interactions, and other fields of ecology and evolutionary biology. However, to date, little is known about the gene expression patterns related to the high-altitude adaptation of Parnassius species. In this study, we obtained high-throughput RNA-seq data of 48 adult Parnassius individuals covering 10 species from 12 localities in China, and deciphered their interspecific and intraspecific expression patterns based on comparative transcriptomic analyses. Though divergent transcriptional patterns among species and populations at different altitudes were found, a series of pathways related to genetic information processing (i.e., recombination, repair, transcription, RNA processing, and ribosome biogenesis), energy metabolism (i.e., oxidative phosphorylation, thermogenesis, and the citrate cycle), and cellular homeostasis were commonly enriched, reflecting similar strategies to cope with the high-altitude environments by activating energy metabolism, enhancing immune defense, and concurrently inhibiting cell growth and development. These findings deepen our understanding about the molecular mechanisms of adaptative evolution to extreme environments, and provide us with some theoretical criteria for the biodiversity conservation of alpine insects. Full article

(This article belongs to the Special Issue Molecular Evolution, Mitochondrial Genomics and Mitochondrial Genome Expression in Animals—2nd Edition)

► Show Figures

Figure 1

17 pages, 2958 KiB

Open AccessEditor’s ChoiceArticle

Whole-Exome Analysis for Polish Caucasian Patients with Retinal Dystrophies and the Creation of a Reference Genomic Database for the Polish Population

by Ewa Matczyńska, Robert Szymańczak, Katarzyna Stradomska, Przemysław Łyszkiewicz, Maria Jędrzejowska, Karolina Kamińska, Marta Beć-Gajowniczek, Ewa Suchecka, Marek Zagulski, Marta Wiącek, Edward Wylęgała, Anna Machalińska, Małgorzata Mossakowska, Monika Puzianowska-Kuźnicka, Sławomir Teper and Anna Boguszewska-Chachulska

Genes 2024, 15(8), 1011; https://doi.org/10.3390/genes15081011 - 1 Aug 2024

Viewed by 1931

Abstract

We present the results of the first study of a large cohort of patients with inherited retinal dystrophies (IRD) performed for the Polish population using whole-exome sequencing (WES) in the years 2016–2019. Moreover, to facilitate such diagnostic analyses and enable future application of [...] Read more.

We present the results of the first study of a large cohort of patients with inherited retinal dystrophies (IRD) performed for the Polish population using whole-exome sequencing (WES) in the years 2016–2019. Moreover, to facilitate such diagnostic analyses and enable future application of gene therapy and genome editing for IRD patients, a Polish genomic reference database (POLGENOM) was created based on whole-genome sequences of healthy Polish Caucasian nonagenarians and centenarians. The newly constructed database served as a control, providing a comparison for variant frequencies in the Polish population. The diagnostic yield for the selected group of IRD patients reached 64.9%. The study uncovered the most common pathogenic variants in ABCA4 and USH2A in the European population, along with several novel causative variants. A significant frequency of the ABCA4 complex haplotype p.(Leu541Pro; Ala1038Val) was observed, as well as that of the p.Gly1961Glu variant. The first VCAN causative variant NM_004385.5:c.4004-2A>G in Poland was found and described. Moreover, one of the first patients with the RPE65 causative variants was identified, and, in consequence, could receive the dedicated gene therapy. The availability of the reference POLGENOM database enabled comprehensive variant characterisation during the NGS data analysis, confirming the utility of a population-specific genomic database for enhancing diagnostic accuracy. Study findings suggest the significance of genetic testing in elder patients with unclear aetiology of eye diseases. The combined approach of NGS and the reference genomic database can improve the diagnosis, management, and future treatment of IRDs. Full article

(This article belongs to the Special Issue Genetics of Eye Development and Diseases)

► Show Figures

Figure 1

46 pages, 4657 KiB

Open AccessEditor’s ChoiceArticle

Are There Barriers Separating the Pink River Dolphin Populations (Inia boliviensis, Iniidae, Cetacea) within the Mamoré–Iténez River Basins (Bolivia)? An Analysis of Its Genetic Structure by Means of Mitochondrial and Nuclear DNA Markers

by Manuel Ruiz-García, Pablo Escobar-Armel, María Martínez-Agüero, Magda Gaviria, Diana Álvarez, Myreya Pinedo and Joseph Mark Shostell

Genes 2024, 15(8), 1012; https://doi.org/10.3390/genes15081012 - 1 Aug 2024

Viewed by 1588

Abstract

The pink river dolphin, or bufeo, is one of the dolphins which lives in the rivers of the Orinoco and Amazon basins in South America. The Bolivian bufeo population is considered a differentiated species (Inia boliviensis) from the Amazon and Orinoco [...] Read more.

The pink river dolphin, or bufeo, is one of the dolphins which lives in the rivers of the Orinoco and Amazon basins in South America. The Bolivian bufeo population is considered a differentiated species (Inia boliviensis) from the Amazon and Orinoco species (Inia geoffrensis). Until now, no study has completed an extensive population genetics analysis of the bufeo in Bolivian rivers. We analyzed 82 bufeos from different rivers from the Mamoré and Iténez (Guaporé) river basins for the mt control region (CR), nuclear microsatellites, and DQB-1 gene sequences to determine if the inner rapids of these Bolivian river basins have some influence on the genetic structure of this species. The first relevant result was that the genetic diversity for CR, and the microsatellites were substantially lower in the Bolivian bufeos than in the dolphins studied in other areas of the Amazon and Orinoco. However, the DQB-1 gene sequences yielded similar genetic diversity to those found in other areas. The second relevant result is the existence of some significant genetic heterogeneity among the bufeo populations within Bolivia, although in a small degree, but this differentiation is independent of the inner rapids of the Bolivian rivers we sampled. The third relevant result was the existence of significant isolation by distance for the CR, but not for microsatellites and DQB-1 gene sequences. This was related to differential gene flow capacity of females (philopatric) and males (less philopatric and more migrants) and, possibly, to different selective patterns affecting the molecular markers studied. The fourth relevant result was related to diverse demographic changes of these bufeos. At least two or three bottleneck events and one or two population expansions have occurred in the Bolivian bufeo population. The major part of these events occurred during the Pleistocene. Full article

(This article belongs to the Special Issue New Phylogenetic and Phylogeography Insights and Molecular and Morphology Adaptive Evolution in Animals)

► Show Figures

Figure 1

25 pages, 4451 KiB

Open AccessEditor’s ChoiceArticle

Changes in the Transcriptome and Long Non-Coding RNAs but Not the Methylome Occur in Human Cells Exposed to Borrelia burgdorferi

by Anne Berthold and Vett K. Lloyd

Genes 2024, 15(8), 1010; https://doi.org/10.3390/genes15081010 - 1 Aug 2024

Viewed by 1765

Abstract

Lyme disease, caused by infection with members of the Lyme borreliosis group of Borrelia spirochete bacteria, is increasing in frequency and distribution worldwide. Epigenetic interactions between the mammalian host, tick, and bacterial pathogen are poorly understood. In this study, high-throughput next-generation sequencing (NGS) [...] Read more.

Lyme disease, caused by infection with members of the Lyme borreliosis group of Borrelia spirochete bacteria, is increasing in frequency and distribution worldwide. Epigenetic interactions between the mammalian host, tick, and bacterial pathogen are poorly understood. In this study, high-throughput next-generation sequencing (NGS) allowed for the in vitro study of the transcriptome, non-coding RNAs, and methylome in human host cells in response to Borrelia burgdorferi infection. We tested the effect of the Borrelia burgdorferi strain B31 on a human primary cell line (HUVEC) and an immortalized cell line (HEK-293) for 72 h, a long-duration time that might allow for epigenetic responses in the exposed human host cells. Differential gene expression was detected in both cell models in response to B. burgdorferi. More differentially expressed genes were found in HUVECs compared to HEK-293 cells. Borrelia burgdorferi exposure significantly induced genes in the interferon, in addition to cytokine and other immune response signaling in HUVECs. In HEK-293 cells, pre-NOTCH processing in Golgi was significantly downregulated in Borrelia-exposed cells. Other significantly altered gene expressions were found in genes involved in the extracellular matrix. No significant global methylation changes were detected in HUVECs or HEK-293 cells exposed to B. burgdorferi; however, two long non-coding RNAs and a pseudogene were deregulated in response to B. burgdorferi in HUVECs, suggesting that other epigenetic mechanisms may be initiated by infection. Full article

(This article belongs to the Special Issue Advances in Molecular Microbiology and Parasitology)

► Show Figures

Figure 1

12 pages, 1234 KiB

Open AccessEditor’s ChoiceArticle

Early-Life Sublethal Exposure to Thiacloprid Alters Adult Honeybee Gut Microbiota

by Bin Li, Xiasang Chen, Li Ke, Pingli Dai, Yuan Ge and Yong-Jun Liu

Genes 2024, 15(8), 1001; https://doi.org/10.3390/genes15081001 - 31 Jul 2024

Viewed by 1235

Abstract

Thiacloprid, a neonicotinoid pesticide, is known to affect the gut microbiome of honeybees, yet studies often focus on immediate alternations during exposure, overlooking long-term microbiological impacts post-exposure. This study investigates the influences of sublethal thiacloprid administered during the larval developmental stage of honeybees [...] Read more.

Thiacloprid, a neonicotinoid pesticide, is known to affect the gut microbiome of honeybees, yet studies often focus on immediate alternations during exposure, overlooking long-term microbiological impacts post-exposure. This study investigates the influences of sublethal thiacloprid administered during the larval developmental stage of honeybees on physiological changes and gut microbiota of adult honeybees. We found that thiacloprid exposure increased mortality and sugar intake in emerged honeybees. Using 16S rDNA sequencing, we analyzed intestinal microbial diversity of honeybees at one and six days post-emergence. Our findings reveal a significant but transient disruption in gut microbiota on day 1, with recovery from dysbiosis by day 6. This study emphasizes the importance of evaluating chronic sublethal exposure risks of thiacloprid to protect honeybee health. Full article

(This article belongs to the Special Issue Genetics and Epigenetics of Bees)

► Show Figures

Figure 1

3 pages, 154 KiB

Open AccessEditor’s ChoiceEditorial

Editorial for the “Genetics, Phylogeny, and Evolution of Insects” Special Issue

by Zhiteng Chen

Genes 2024, 15(8), 1000; https://doi.org/10.3390/genes15081000 - 30 Jul 2024

Viewed by 1095

Abstract

The rapid advancement of sequencing technologies has revolutionized our understanding of the phylogeny and evolution of insects, enabling researchers to generate extensive molecular data with unprecedented detail [...] Full article

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

Journal Menu

Journal Browser

Editor’s Choice Articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI