Genes

13 pages, 3101 KiB

Open AccessArticle

Genetic Polymorphism of Y-Chromosome in Turkmen Population from Turkmenistan

by Maxat Zhabagin, Assel Tashkarayeva, Alizhan Bukayev, Aigul Zhunussova, Georgy Ponomarev, Saltanat Tayshanova, Albina Maxutova, Dmitry Adamov, Elena Balanovska and Zhaxylyk Sabitov

Genes 2024, 15(12), 1501; https://doi.org/10.3390/genes15121501 - 22 Nov 2024

Abstract

This study investigates the Y-chromosome genetic diversity of the Turkmen population in Turkmenistan, analyzing 23 Y-STR loci for the first time in a sample of 100 individuals. Combined with comparative data from Turkmen populations in Afghanistan, Iran, Iraq, Russia, and Uzbekistan, this analysis [...] Read more.

This study investigates the Y-chromosome genetic diversity of the Turkmen population in Turkmenistan, analyzing 23 Y-STR loci for the first time in a sample of 100 individuals. Combined with comparative data from Turkmen populations in Afghanistan, Iran, Iraq, Russia, and Uzbekistan, this analysis offers insights into the genetic structure and relationships among Turkmen populations across regions across Central Asia and the Near East. High haplotype diversity in the Turkmen of Turkmenistan is shaped by founder effects (lineage expansions) from distinct haplogroups, with haplogroups Q and R1a predominating. Subhaplogroups Q1a and Q1b identified in Turkmenistan trace back to ancient Y-chromosome lineages from the Bronze Age. Comparative analyses, including genetic distance (RST), median-joining network, and multidimensional scaling (MDS), highlight the genetic proximity of the Turkmen in Turkmenistan to those in Afghanistan and Iran, while Iraqi Turkmen display unique characteristics, aligning with Near Eastern populations. This study underscores the Central Asian genetic affinity across most Turkmen populations. It demonstrates the value of deep-sequencing Y-chromosome data in tracing the patrilineal history of Central Asia for future studies. These findings contribute to a more comprehensive understanding of Turkmen genetic ancestry and add new data to the ongoing study of Central Asian population genetics. Full article

(This article belongs to the Special Issue The Genetic Diversification of Human Populations)

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13 pages, 532 KiB

Open AccessArticle

Targeted Transcriptome Analysis of Beef Cattle Persistently Infected with Bovine Viral Diarrhea Virus

by Morgan Adkins, Sonia Moisa, Jon Beever and Andrea Lear

Genes 2024, 15(12), 1500; https://doi.org/10.3390/genes15121500 - 22 Nov 2024

Abstract

Background: Bovine viral diarrhea virus (BVDV) is an endemic virus of North American cattle populations with significant economic and animal health impacts. While BVDV infection has a myriad of clinical manifestations, a unique and problematic outcome is the establishment of a persistently infected [...] Read more.

Background: Bovine viral diarrhea virus (BVDV) is an endemic virus of North American cattle populations with significant economic and animal health impacts. While BVDV infection has a myriad of clinical manifestations, a unique and problematic outcome is the establishment of a persistently infected (PI) animal following in utero viral infection. While it is well established that PI animals serve as a constant reservoir of BVDV, the mechanism for the maintained infection remains unknown despite multiple theories. Objective: The purpose of this study was to use transcriptome analysis to investigate the long-term immune status of adult PI cattle and offer insight into the potential mechanistic establishment of persistent BVDV infection. Methods: Peripheral blood mononuclear cells were collected from PI beef cattle (N = 6) and controls (N = 6) for targeted RNAseq analysis using 54 immune-related genes followed by pathway enrichment analysis. Results: Analysis revealed 29 differentially expressed genes (FDR < 0.05, fold change ≥ 2), representing 14 significant KEGG pathways between groups (FDR < 0.05). Transcriptome changes indicated chronic upregulation of interferon-gamma (IFNG) with an unexpected expression of related genes. Conclusions: These results provide novel insight into understanding the adult PI immune system and indicate maintained stimulation resulting from virus-mediated dysregulation. Full article

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

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12 pages, 14712 KiB

Open AccessBrief Report

Targeted Genetic Education in Dentistry in the Era of Genomics

by Farah Asa’ad, Anne Nørremølle, Qalbi Khan, Lena Larsson, Niels Tommerup, Nuno Vibe Hermann and Asli Silahtaroglu

Genes 2024, 15(12), 1499; https://doi.org/10.3390/genes15121499 - 22 Nov 2024

Abstract

Background: The growing body of knowledge on the human genome and its variants points towards the significance of genetic factors in oral health and disease. Since the dental curricula have historically prioritized clinically oriented subjects, this focus has resulted in insufficient coverage of [...] Read more.

Background: The growing body of knowledge on the human genome and its variants points towards the significance of genetic factors in oral health and disease. Since the dental curricula have historically prioritized clinically oriented subjects, this focus has resulted in insufficient coverage of genetics. To leverage this knowledge in patient care, dental education must equip students with an understanding of the principles of genetics. Method: We have established “Genetic Educators Network in Dentistry” (GEN-Dent) to identify common concerns regarding genetics in dental education and work for a greater emphasis on genetics in future dental programs to make sure that professionals in dentistry are well-prepared to navigate the complexities of the evolving “human genome era”. Results: Here, GEN-Dent proposes specific learning goals for medical genetics in dentistry and provides supporting teaching material addressing each learning goal. The five life-like case studies exemplify different dental conditions and introduce important concepts of genetics, inspiring other educators. Conclusions: Opportunities in Scandinavian countries can be an advantage in increasing global awareness of the importance of genetics in dentistry. The integration of genetics into dental education not only aims to improve patient care but also seeks to inspire a new generation of basic scientists with clinical backgrounds in dentistry. We expect that using life-like patient cases will significantly motivate dental students when learning medical genetics. Full article

(This article belongs to the Special Issue Genetic, Epigenetic and Environmental Factors in Dental Development and Pathologies: Genes, Interactions and Dental Development)

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15 pages, 1935 KiB

Open AccessArticle

Genomic Regions Associated with Spontaneous Abortion in Holstein Heifers

by Emaly M. Suarez, Victoria C. Kelson, Jennifer N. Kiser, Kimberly M. Davenport, Brenda M. Murdoch and Holly L. Neibergs

Genes 2024, 15(12), 1498; https://doi.org/10.3390/genes15121498 - 22 Nov 2024

Abstract

Background/Objectives: The dairy industry relies on reproductive efficiency to maintain efficient milk production. Spontaneous abortion (SA), defined as pregnancy loss between gestation days 42 and 260, occurred in 4.5% of the artificially inseminated (AI) Holstein heifers and 31.6% of the embryo transfer (ET) [...] Read more.

Background/Objectives: The dairy industry relies on reproductive efficiency to maintain efficient milk production. Spontaneous abortion (SA), defined as pregnancy loss between gestation days 42 and 260, occurred in 4.5% of the artificially inseminated (AI) Holstein heifers and 31.6% of the embryo transfer (ET) recipient Holstein heifers that received in vitro-produced frozen embryos on a single dairy farm in Idaho. Methods: A genome-wide association analysis (GWAA) was performed to identify the associations (FDR p < 0.05) with SA in heifers that were bred by AI (1351 controls that delivered at term and 63 cases that aborted) that conceived following the first insemination, as well as in 59 controls and 273 cases of ET recipient heifers pregnant from the first ET. Results: There were 216 loci and 413 positional candidate genes associated (FDR p < 0.05) with SA in the heifers bred by AI in a recessive model and no loci associated with SA in the ET recipients. Conclusions: The identification of loci associated with SA in the heifers bred by AI may be used to reduce fetal loss through genomic selection. Full article

(This article belongs to the Special Issue Functional Genomics and Breeding of Animals)

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17 pages, 1410 KiB

Open AccessArticle

Leveraging Bioinformatics and Machine Learning for Identifying Prognostic Biomarkers and Predicting Clinical Outcomes in Lung Adenocarcinoma

by Kaida Cai, Wenzhi Fu, Hanwen Liu, Xiaofang Yang, Zhengyan Wang and Xin Zhao

Genes 2024, 15(12), 1497; https://doi.org/10.3390/genes15121497 - 21 Nov 2024

Abstract

Background/Objectives: There exist significant challenges for lung adenocarcinoma (LUAD) due to its poor prognosis and limited treatment options, particularly in the advanced stages. It is crucial to identify genetic biomarkers for improving outcome predictions and guiding personalized therapies. Methods: In this study, we [...] Read more.

Background/Objectives: There exist significant challenges for lung adenocarcinoma (LUAD) due to its poor prognosis and limited treatment options, particularly in the advanced stages. It is crucial to identify genetic biomarkers for improving outcome predictions and guiding personalized therapies. Methods: In this study, we utilize a multi-step approach that combines principled sure independence screening, penalized regression methods and information gain to identify the key genetic features of the ultra-high dimensional RNA-sequencing data from LUAD patients. We then evaluate three methods of survival analysis: the Cox model, survival tree, and random survival forests (RSFs), to compare their predictive performance. Additionally, a protein–protein interaction network is used to explore the biological significance of identified genes. Results: DKK1 and TNS4 are consistently selected as significant predictors across all feature selection methods. The Kaplan–Meier method shows that high expression levels of these genes are strongly correlated with poorer survival outcomes, suggesting their potential as prognostic biomarkers. RSF outperforms Cox and survival tree methods, showing higher AUC and C-index values. The protein–protein interaction network highlights key nodes such as VEGFC and LAMA3, which play central roles in LUAD progression. Conclusions: Our findings provide valuable insights into the genetic mechanisms of LUAD. These results contribute to the development of more accurate prognostic tools and personalized treatment strategies for LUAD. Full article

(This article belongs to the Section Bioinformatics)

15 pages, 4589 KiB

Open AccessArticle

Unraveling the Anthocyanin Regulatory Mechanisms of White Mutation in Verbena stricta by Integrative Transcriptome and Metabolome Analysis

by Shengyue Chai, Jiaming Yang, Xiaofei Zhang, Xuwen Shang and Lixin Lang

Genes 2024, 15(12), 1496; https://doi.org/10.3390/genes15121496 - 21 Nov 2024

Abstract

Background: Verbena stricta is a perennial herb of the Verbenaceae family, known for its medicinal properties, wide adaptability, and high resistance. Methods: This research investigated the metabolic pathways of flower color change by combining transcriptome and metabolomics analyses. Results: In [...] Read more.

Background: Verbena stricta is a perennial herb of the Verbenaceae family, known for its medicinal properties, wide adaptability, and high resistance. Methods: This research investigated the metabolic pathways of flower color change by combining transcriptome and metabolomics analyses. Results: In purple flowers and white variants, a total of 118 differentially accumulated metabolites (DAMs), including 20 anthocyanins, and 7627 differentially expressed genes (DEGs) were found. The downregulation of delphinidin-3-O-galactoside, delphinidin-3-O-glucoside, and delphinidin-3-O-(6″-O-p-coumaroyl) glucoside, along with the absence of petunidin and malvidin derivatives, may explain the loss of pigmentation in the white-flower mutant. Fourteen candidate genes involved in anthocyanin biosynthesis were identified, among which the expression of Flavonoid 3′, 5′-hydroxylase (F3′5′H) was significantly downregulated, notably limiting flux through the delphinidin pathway and reducing delphinidin accumulation. This limitation in upstream reactions, coupled with the multi-shunt process in downstream reactions, completely blocked the production of petunidin and malvidin. Conclusions: These findings offer new opinions on the anthocyanin metabolites and key genes responsible for the floral pigmentation in V. stricta. Additionally, the white variant provides a valuable platform for future research into the ornamental flower color of the Verbenaceae family. Full article

(This article belongs to the Special Issue 5Gs in Crop Genetic and Genomic Improvement: 2nd Edition)

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16 pages, 717 KiB

Open AccessReview

Tailoring Genomic Selection for Bos taurus indicus: A Comprehensive Review of SNP Arrays and Reference Genomes

by Adebisi R. Ogunbawo, Henrique A. Mulim, Gabriel S. Campos, Allan P. Schinckel and Hinayah Rojas de Oliveira

Genes 2024, 15(12), 1495; https://doi.org/10.3390/genes15121495 - 21 Nov 2024

Abstract

Background: Advances in SNP arrays and reference genome assemblies have significantly transformed cattle genomics, particularly for Bos taurus indicus (Zebu cattle). Many commercial SNP arrays were originally designed for Bos taurus taurus, leading to ascertainment bias and the exclusion of crucial SNPs [...] Read more.

Background: Advances in SNP arrays and reference genome assemblies have significantly transformed cattle genomics, particularly for Bos taurus indicus (Zebu cattle). Many commercial SNP arrays were originally designed for Bos taurus taurus, leading to ascertainment bias and the exclusion of crucial SNPs specific to Zebu populations. This review assesses progress in SNP array and reference genome development, with a focus on efforts tailored to Zebu populations and their impact on genomic selection and breeding efficiency. Methods: We reviewed the relevant literature on the development of SNP arrays, reference genome assemblies, and SNP genotyping techniques used for Zebu cattle. Emphasis was placed on SNP arrays specifically designed for Zebu breeds, evaluating their contributions to genomic evaluations and identifying limitations in prediction accuracy. Results: Recent advancements, such as GeneSeek’s low- and high-density SNP panels, have aimed to reduce ascertainment bias and include key SNPs for Zebu populations by providing breed-specific panels. These panels have been instrumental in identifying genomic regions associated with economically important traits in Nellore cattle. Studies show that tailored SNP arrays and breed-specific reference genomes can enhance genetic diversity assessment and improve genomic predictions, supporting more effective breeding programs for Zebu cattle. Conclusions: Improved SNP arrays and breed-specific reference genomes are crucial for accurate genomic selection in Zebu cattle. Future efforts should prioritize expanding de novo genome assemblies, reducing ascertainment bias, and developing cost-effective genotyping solutions tailored to Zebu populations. Targeted genomic tools will ultimately enable more efficient breeding practices and enhance genomic selection for economically important traits in B. t. indicus cattle. Full article

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

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11 pages, 3329 KiB

Open AccessArticle

Effect of IGF1 on Myogenic Proliferation and Differentiation of Bovine Skeletal Muscle Satellite Cells Through PI3K/AKT Signaling Pathway

by Xin Li, Yang Cao, Yu Liu, Wenwen Fang, Cheng Xiao, Yang Cao and Yumin Zhao

Genes 2024, 15(12), 1494; https://doi.org/10.3390/genes15121494 - 21 Nov 2024

Abstract

Background: Cultivated meat, an alternative to conventional meat, has substantial potential for alleviating environmental and ethical concerns. This method of manufacturing meat involves the isolation of skeletal muscle satellite cells (SMSCs) from donor animals, after which they proliferate in vitro and differentiate [...] Read more.

Background: Cultivated meat, an alternative to conventional meat, has substantial potential for alleviating environmental and ethical concerns. This method of manufacturing meat involves the isolation of skeletal muscle satellite cells (SMSCs) from donor animals, after which they proliferate in vitro and differentiate into primitive muscle fibers. The aim of this research was to evaluate how the insulin-like growth factor 1 (IGF1) gene regulates the myogenic differentiation of bovine skeletal muscle satellite cells (bSMSCs). Methods: bSMSCs isolated from newborn calves were cultured to the third generation in vitro and differentiated into myoblasts via the serum withdrawal method. An overexpression lentivirus and siRNA targeting the IGF1 gene were constructed and transduced into bSMSCs, which were subsequently analyzed via real-time fluorescence quantitative PCR(qRT–PCR) and Western blots. The mRNA and protein levels of the myogenic differentiation markers myosin heavy chain (MyHC) and myogenin (MyoG) were determined. Results: The results revealed that the lentivirus overexpressing the IGF1 gene significantly increased the expression of MyHC and MyoG, whereas the expression of both the MyHC and MyoG mRNAs and proteins was strongly reduced by si-IGF1. Conclusions: IGF1 positively regulates the myogenic differentiation of bSMSCs. This study provides a reference for further elucidating the molecular mechanism by which the IGF1 gene regulates the myogenic differentiation of bSMSCs via the PI3K/Akt signaling pathway and lays a foundation for establishing a regulatory network of bovine muscle growth and development. Full article

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

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11 pages, 1000 KiB

Open AccessArticle

Genome Insights and Identification of Sex Determination Region and Sex Markers in Argyrosomus japonicus

by Yike Liu, Wanbo Li, Dinaer Yekefenhazi, Xianfeng Yang, Qihui Zhu, Kun Ye, Fang Han and Dongdong Xu

Genes 2024, 15(12), 1493; https://doi.org/10.3390/genes15121493 - 21 Nov 2024

Abstract

Background: Argyrosomus japonicus, a member of the Sciaenidae family, is widely distributed across the sea areas near China, Japan, Australia, and South Africa. The aim of this study is to provide a high-quality genome with new technology and to understand the sex [...] Read more.

Background: Argyrosomus japonicus, a member of the Sciaenidae family, is widely distributed across the sea areas near China, Japan, Australia, and South Africa. The aim of this study is to provide a high-quality genome with new technology and to understand the sex determination mechanism of this species. Methods: We generated a high-quality chromosome-level genome for Argyrosomus japonicus using PacBio HiFi and Hi-C sequencing technologies. To map the sex determination region, we employed re-sequencing data from 38 A. japonicus and conducted genome-wide association studies (GWASs) on sex phenotypes. Results: Utilizing Hifiasm, we assembled a 708.8 Mb genome with a contig N50 length of 30 Mb. Based on Hi-C data, these contigs were organized into 24 chromosomes. The completeness of the assembly was assessed to be 99% using BUSCO, and over 98% according to Merqury. We identified a total of 174.57 Mb of repetitive elements and annotated 24,726 protein-coding genes in the genome. We mapped a 2.8 Mb sex determination region on chromosome 9, within which we found two sex-linked markers. Furthermore, we confirmed that the XX-XY sex determination system is adopted in A. japonicus. Conclusions: The findings of this study provide significant insights into genetic breeding, genome evolution research, and sex control breeding in A. japonicus. Full article

(This article belongs to the Special Issue Omic Study and Genes in Fish Sex Determination and Differentiation)

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11 pages, 774 KiB

Open AccessReview

Application of CRISPR/Cas9 Technology in Rice Germplasm Innovation and Genetic Improvement

by Jijin Chen, Zhening Miao, Deyan Kong, Anning Zhang, Feiming Wang, Guolan Liu, Xinqiao Yu, Lijun Luo and Yi Liu

Genes 2024, 15(11), 1492; https://doi.org/10.3390/genes15111492 - 20 Nov 2024

Abstract

Improving the efficiency of germplasm innovation has always been the aim of rice breeders. Traditional hybrid breeding methods for variety selection rarely meet the practical needs of rice production. The emergence of genome-editing technologies, such as CRISPR/Cas9, provides a new approach to the [...] Read more.

Improving the efficiency of germplasm innovation has always been the aim of rice breeders. Traditional hybrid breeding methods for variety selection rarely meet the practical needs of rice production. The emergence of genome-editing technologies, such as CRISPR/Cas9, provides a new approach to the genetic improvement of crops such as rice. The number of published scientific papers related to “gene editing” and “CRISPR/Cas9” retrievable on websites both from China and other countries exhibited an increasing trend, year by year, from 2014 to 2023. Research related to gene editing in rice accounts for 33.4% and 12.3% of all the literature on gene editing published in China and other countries, respectively, much higher than that on maize and wheat. This article reviews recent research on CRISPR/Cas9 gene-editing technology in rice, especially germplasm innovation and genetic improvement of commercially promoted varieties with improved traits such as disease, insect, and herbicide resistance, salt tolerance, quality, nutrition, and safety. The aim is to provide a reference for the precise and efficient development of new rice cultivars that meet market demand. Full article

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

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10 pages, 893 KiB

Open AccessArticle

MIR27A rs895819 CC Genotype Severely Reduces miR-27a Plasma Expression Levels

by Georgia Ragia, Myria Pallikarou, Chrysoula Michou and Vangelis G. Manolopoulos

Genes 2024, 15(11), 1491; https://doi.org/10.3390/genes15111491 - 20 Nov 2024

Abstract

Background/Objectives: MIR27A rs895819 polymorphism has emerged as a potential additional pharmacogenomic marker of fluoropyrimidine response. Current evidence on its potential effect on miR-27a expression, which represses DPD activity, leading to DPD deficiency and increased fluoropyrimidine-associated toxicity risk, is scarce and inconsistent. We [...] Read more.

Background/Objectives: MIR27A rs895819 polymorphism has emerged as a potential additional pharmacogenomic marker of fluoropyrimidine response. Current evidence on its potential effect on miR-27a expression, which represses DPD activity, leading to DPD deficiency and increased fluoropyrimidine-associated toxicity risk, is scarce and inconsistent. We have analyzed the effect of MIR27A rs895819 polymorphism on miR-27a-3p plasma expression levels under different models of inheritance to contribute further evidence on its plausible biological role in miR-27a expression. Methods: A total of 59 individuals with no medical history of cancer were included in this study. MIR27A rs895819 genotyping and miR-27a-3p expression were analyzed by using predesigned TaqMan assays. Results: The frequency of TT, TC, and CC genotypes was present at a prevalence of 50.8%, 44.1%, and 5.1%, respectively. Individuals carrying the CC genotype presented with decreased miR-27a-3p expression (0.422 fold-change versus TT, p = 0.041; 0.461 fold-change versus TC, p = 0.064), whereas no differences were present between TT and TC individuals (1.092 fold-change, p = 0.718). miR-27a-3p expression was decreased in CC individuals under a recessive model of inheritance (0.440 fold-change, p = 0.047). No differences were found in dominant (TT vs. TC+CC, 0.845 fold-change, p = 0.471) or over dominant (TT+CC vs. TC, 0.990 fold-change, p = 0.996) models of inheritance. Conclusions: MIR27A rs895819CC genotype leads to severely reduced miR-27a-3p expression in plasma. Further study of this association is warranted in cancer patients to apply MIR27A genotyping in therapeutics to identify fluoropyrimidine-treated patients who are at a decreased risk of experiencing fluoropyrimidine-induced severe toxicity. Full article

(This article belongs to the Special Issue MicroRNA in Cancers)

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Graphical abstract

10 pages, 3169 KiB

Open AccessCase Report

Multiple Osteochondritis Dissecans as Main Manifestation of Multiple Epiphyseal Dysplasia Caused by a Novel Cartilage Oligomeric Matrix Protein Pathogenic Variant: A Clinical Report

by Antonio Mazzotti, Elena Artioli, Evelise Brizola, Alice Moroni, Morena Tremosini, Alessia Di Cecco, Salvatore Gallone, Cesare Faldini, Luca Sangiorgi and Maria Gnoli

Genes 2024, 15(11), 1490; https://doi.org/10.3390/genes15111490 - 20 Nov 2024

Abstract

Background: Multiple epiphyseal dysplasia (MED) is a clinically and genetically heterogeneous group of skeletal diseases characterized by epiphyseal abnormalities associated with mild short stature. The clinical variability is wide, and the first clinical manifestations still occur in childhood with joint pain and stiffness [...] Read more.

Background: Multiple epiphyseal dysplasia (MED) is a clinically and genetically heterogeneous group of skeletal diseases characterized by epiphyseal abnormalities associated with mild short stature. The clinical variability is wide, and the first clinical manifestations still occur in childhood with joint pain and stiffness that evolve into degenerative joint disease. MED, caused by mutations in the Cartilage Oligomeric Matrix Protein (COMP) gene, is the most common form of the disease. COMP-MED usually shows significant involvement of the capital femoral epiphyses and irregular acetabulum; instead, COL9A1-, COL9A2-, and COL9A3-MED appear to have more severe knee involvement than hips, resulting in a milder presentation than COMP-MED cases. Other complications have been reported, in particular osteochondritis dissecans (OCD), which has been described in two large COL9A2-related MED families associated with myopathy. Methods: Here, we report the case of a 24-year-old man affected by COMP-MED with a positive family history for the disease and a clinical presentation that interestingly is characterized by the presence of multiple OCD. Results: To our knowledge, this is the first case of COMP mutations related to multiple OCD as the main clinical feature. Conclusions: This report can expand the clinical phenotype related to the pathogenic variants of the COMP gene, as it shows that multiple OCD can also be present in COMP-related MED as well as in COL9A2-related MED. Full article

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

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18 pages, 1651 KiB

Open AccessReview

An Updated Analysis of Exon-Skipping Applicability for Duchenne Muscular Dystrophy Using the UMD-DMD Database

by Jamie Leckie, Abdullah Zia and Toshifumi Yokota

Genes 2024, 15(11), 1489; https://doi.org/10.3390/genes15111489 - 20 Nov 2024

Abstract

Background/Objectives: Antisense oligonucleotide (ASO)-mediated exon-skipping is an effective approach to restore the disrupted reading frame of the dystrophin gene for the treatment of Duchenne muscular dystrophy (DMD). Currently, four FDA-approved ASOs can target three different exons, but these therapies are mutation-specific and only [...] Read more.

Background/Objectives: Antisense oligonucleotide (ASO)-mediated exon-skipping is an effective approach to restore the disrupted reading frame of the dystrophin gene for the treatment of Duchenne muscular dystrophy (DMD). Currently, four FDA-approved ASOs can target three different exons, but these therapies are mutation-specific and only benefit a subset of patients. Understanding the broad applicability of exon-skipping approaches is essential for prioritizing the development of additional therapies with the greatest potential impact on the DMD population. This review offers an updated analysis of all theoretical exon-skipping strategies and their applicability across the patient population, with a specific focus on DMD-associated mutations documented in the UMD-DMD database. Unlike previous studies, this approach leverages the inclusion of phenotypic data for each mutation, providing a more comprehensive and clinically relevant perspective. Methods: The theoretical applicability of all single and double exon-skipping strategies, along with multi exon-skipping strategies targeting exons 3–9 and 45–55, was evaluated for all DMD mutations reported in the UMD-DMD database. Results: Single and double exon-skipping approaches were applicable for 92.8% of large deletions, 93.7% of small lesions, 72.4% of duplications, and 90.3% of all mutations analyzed. Exon 51 was the most relevant target and was applicable for 10.6% of all mutations and 17.2% of large deletions. Additionally, two multi-exon-skipping approaches, targeting exons 45–55 and 3–9, were relevant for 70.6% of large deletions and 19.2% of small lesions. Conclusions: Current FDA-approved ASOs were applicable to 27% of the UMD-DMD population analyzed, leaving a significant portion of patients without access to exon-skipping therapies. The clinical translation of alternative approaches is critical to expanding the accessibility of these therapies for the DMD population. Full article

(This article belongs to the Section Bioinformatics)

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20 pages, 7102 KiB

Open AccessArticle

Characterization and Phylogenetic Analysis of the First Complete Chloroplast Genome of Shizhenia pinguicula (Orchidaceae: Orchideae)

by Yuan Chen, Yanlin Zhao, Quan Yan, Wei Wu, Qingqing Lin, Guoqiang Chen, Yanfang Zheng, Mingqing Huang, Shiming Fan and Yanxiang Lin

Genes 2024, 15(11), 1488; https://doi.org/10.3390/genes15111488 - 20 Nov 2024

Abstract

Background: Genomic analysis is crucial for better understanding the evolutionary history of species and for their conservation. Shizhenia pinguicula is a rare medicinal plant endemic to China. However, the complete chloroplast genome of this species has not been reported to date. Insufficient genomic [...] Read more.

Background: Genomic analysis is crucial for better understanding the evolutionary history of species and for their conservation. Shizhenia pinguicula is a rare medicinal plant endemic to China. However, the complete chloroplast genome of this species has not been reported to date. Insufficient genomic research on S. pinguicula has hindered effective conservation efforts for this valuable plant. Methods: In this study, we sequenced and assembled the first complete chloroplast genome of S. pinguicula using Illumina sequencing technology. We conducted a comparative analysis of its chloroplast genome with related species and reconstructed phylogenetic relationships. Results: The chloroplast genome of S. pinguicula exhibited a typical quadripartite structure with a length of 158,658 bp. A total of 123 genes, 118 simple sequence repeats, and 51 dispersed repetitive sequences were identified. The inverted repeat boundaries were significantly expanded, along with the pseudogenization and loss of multiple NDH genes. Codon usage bias is primarily influenced by natural selection and other factors, with the ycf3 gene under positive selection. Additionally, 10 hypervariable regions were detected for species identification and evolutionary studies. Phylogenetic analysis indicated that Ponerorchis gracilis and Hemipilia yajiangensis form a clade, with S. pinguicula as their sister species, located at the basal position of the Ponerorchis-Hemipilia alliance. Conclusions: The chloroplast genome structure and gene content of S. pinguicula exhibit certain degrees of variation compared to other species within the Orchidinae subtribe. This genome should be useful for further investigations into the biology of Shizhenia and the development of biodiversity conservation strategies. Full article

(This article belongs to the Special Issue Advances in Evolution of Plant Organelle Genome—2nd Edition)

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14 pages, 2404 KiB

Open AccessArticle

Prognostic Relevance of Copy Number Losses in Ovarian Cancer

by Andrea Jemma, Alessandra Ardizzoia, Serena Redaelli, Angela Bentivegna, Marialuisa Lavitrano and Donatella Conconi

Genes 2024, 15(11), 1487; https://doi.org/10.3390/genes15111487 - 19 Nov 2024

Abstract

Background/Objectives: Aneuploidy is a prevalent cancer feature that occurs in many solid tumors. For example, high-grade serous ovarian cancer shows a high level of copy number alterations and genomic rearrangements. This makes genomic variants appealing as diagnostic or prognostic biomarkers, as well as [...] Read more.

Background/Objectives: Aneuploidy is a prevalent cancer feature that occurs in many solid tumors. For example, high-grade serous ovarian cancer shows a high level of copy number alterations and genomic rearrangements. This makes genomic variants appealing as diagnostic or prognostic biomarkers, as well as for their easy detection. In this study, we focused on copy number (CN) losses shared by ovarian cancer stem cells (CSCs) to identify chromosomal regions that may be important for CSC features and, in turn, for patients’ prognosis. Methods: Array-CGH and bioinformatic analyses on three CSCs subpopulations were performed. Results: Pathway and gene ontology analyses on genes involved in copy number loss in all CSCs revealed a significant decrease in mRNA surveillance pathway, as well as miRNA-mediated gene silencing. Then, starting from these CN losses, we validated their potential prognostic relevance by analyzing the TCGA cohort. Notably, losses of 4q34.3-q35.2, 8p21.2-p21.1, and 18q12.2-q23 were linked to increased genomic instability. Loss of 18q12.2-q23 was also related to a higher tumor stage and poor prognosis. Finally, specific genes mapping in these regions, such as PPP2R2A and TPGS2A, emerged as potential biomarkers. Conclusions: Our findings highlight the importance of genomic alterations in ovarian cancer and their impact on tumor progression and patients’ prognosis, offering advance in understanding of the application of numerical aberrations as prognostic ovarian cancer biomarkers. Full article

(This article belongs to the Special Issue Molecular Diagnostic and Prognostic Markers of Human Cancers)

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14 pages, 2487 KiB

Open AccessArticle

S100A9 Affects Milk Protein Content by Regulating Amino Acid Transporters and the PI3K-Akt, WNT, and mTOR Signaling Pathways

by Xinyi Zhang, Jun Teng, Zhujun Chen, Changheng Zhao, Li Jiang and Qin Zhang

Genes 2024, 15(11), 1486; https://doi.org/10.3390/genes15111486 - 19 Nov 2024

Abstract

Background: Calgranulin B (S100A9) was found to be strongly associated with milk protein percentage in dairy cattle in our previous genome-wide association study. Methods: SNPs in S100A9 were identified via pooled sequencing, and genotyping of 1054 cows was performed individually using [...] Read more.

Background: Calgranulin B (S100A9) was found to be strongly associated with milk protein percentage in dairy cattle in our previous genome-wide association study. Methods: SNPs in S100A9 were identified via pooled sequencing, and genotyping of 1054 cows was performed individually using MassArray with MALDI-TOFMS technology. Association analyses between the S100A9 SNPs and five milk production traits were conducted using SAS 9.2 software. Functional studies of S100A9 were conducted using quantitative PCR, Western blot, CCK-8, and immunofluorescence assays. Results: In the present study, we further verified that two SNPs in S100A9, g.17115387 C>A and g.17115176 C>A, were significantly associated with milk protein percentage. We found that S100A9 could affect the expressions of caseins CSN1S1, CSN2, and CSN3 in MAC-T cells by regulating the expressions of amino acid transporter genes. We investigated the effects of S100A9 on the PI3K-Akt, WNT, and mTOR pathways, which are well known to play important roles in mammary gland development and milk protein synthesis. Our results suggest that S100A9 regulates the expressions of the relevant genes in these pathways, and thus potentially influences the protein synthesis in the mammary gland. Conclusions: This study demonstrates the important role of the S100A9 gene in the milk protein trait of dairy cattle and provides new insights into the molecular mechanism of milk protein content. Full article

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

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24 pages, 6742 KiB

Open AccessArticle

SNP Polymorphisms Are Associated with Environmental Factors in Sockeye Salmon Populations Across the Northwest Pacific: Insights from Redundancy Analysis

by Anastasia M. Khrustaleva

Genes 2024, 15(11), 1485; https://doi.org/10.3390/genes15111485 - 19 Nov 2024

Abstract

The SNP variation in sockeye salmon across the Asian part of its range was studied in 23 samples from 16 lake–river systems of the West Pacific Coast to improve understanding of genetic adaptation in response to spawning watersheds conditions. Identification of candidate SNPs [...] Read more.

The SNP variation in sockeye salmon across the Asian part of its range was studied in 23 samples from 16 lake–river systems of the West Pacific Coast to improve understanding of genetic adaptation in response to spawning watersheds conditions. Identification of candidate SNPs and environmental factors that can contribute to local adaptations in sockeye salmon populations was carried out using redundancy analysis (RDA), a powerful tool for landscape genetics proven to be effective in genotype–environment association studies. Climatic and hydrographic indices (7 indices in total), reflecting abiotic conditions in freshwater habitats of sockeye salmon and characterizing the temperature regime in the river basin, its variability during the year, the amount of precipitation, as well as the height of the maximum tide in the estuary, were used as predictor factors. Among the 45 analyzed SNPs, several loci (ALDOB-135, HGFA, and RAG3-93) correlated with predictors gradients along the northwest Pacific coast were identified. The putative candidate loci localized in genes involved in the immune and inflammatory responses, as well as genes encoding temperature-sensitive enzymes and some hormones regulating ion homeostasis in fish during the anadromous migration and smoltification, were potentially associated with environmental conditions in natal rivers. The findings could have implications for aquaculture, conservation, and resource management in the context of global climate change. Full article

(This article belongs to the Special Issue Genetic Studies of Fish)

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17 pages, 9643 KiB

Open AccessArticle

Comparative Chloroplast Genome Study of Zingiber in China Sheds Light on Plastome Characterization and Phylogenetic Relationships

by Maoqin Xia, Dongzhu Jiang, Wuqin Xu, Xia Liu, Shanshan Zhu, Haitao Xing, Wenlin Zhang, Yong Zou and Hong-Lei Li

Genes 2024, 15(11), 1484; https://doi.org/10.3390/genes15111484 - 19 Nov 2024

Abstract

Background: Zingiber Mill., a morphologically diverse herbaceous perennial genus of Zingiberaceae, is distributed mainly in tropical to warm-temperate Asia. In China, species of Zingiber have crucial medicinal, edible, and horticultural values; however, their phylogenetic relationships remain unclear. Methods: To address this issue, the [...] Read more.

Background: Zingiber Mill., a morphologically diverse herbaceous perennial genus of Zingiberaceae, is distributed mainly in tropical to warm-temperate Asia. In China, species of Zingiber have crucial medicinal, edible, and horticultural values; however, their phylogenetic relationships remain unclear. Methods: To address this issue, the complete plastomes of the 29 Zingiber accessions were assembled and characterized. Comparative plastome analysis and phylogenetic analysis were conducted to develop genomic resources and elucidate the intraspecific phylogeny of Zingiber. Results: The newly reported plastomes ranged from 161,495 to 163,880 bp in length with highly conserved structure. Results of comparative analysis suggested that IR expansions/contractions and changes of repeats were the main reasons that influenced the genome size of the Zingiber plastome. A large number of SSRs and six highly variable regions (rpl20, clpP, ycf1, petA-psbJ, rbcL-accD, and rpl32-trnL) have been identified, which could serve as potential DNA markers for future population genetics or phylogeographic studies on this genus. The well-resolved plastome phylogeny suggested that Zingiber could be divided into three clades, corresponding to sect. Pleuranthesis (sect. Zingiber + sect. Dymczewiczia) and sect. Cryptanthium. Conclusions: Overall, this study provided a robust phylogeny of Zingiber plants in China, and the newly reported plastome data and plastome-derived markers will be of great significance for the accurate identification, protection, and agricultural management of Zingiber resources in the future. Full article

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

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12 pages, 4363 KiB

Open AccessCase Report

Small Complex Rearrangement in HINT1-Related Axonal Neuropathy

by Alessandra Tessa, Mariapaola Schifino, Eliana Salvo, Rosanna Trovato, Luca Cesana, Silvia Frosini, Rosa Pasquariello, Giada Sgherri, Roberta Battini, Maria Clara Bonaglia, Filippo Maria Santorelli and Guja Astrea

Genes 2024, 15(11), 1483; https://doi.org/10.3390/genes15111483 - 19 Nov 2024

Abstract

Background: Autosomal recessive inherited pathogenetic variants in the histidine triad nucleotide-binding protein 1 (HINT1) gene are responsible for an axonal Charcot-Marie-Tooth neuropathy associated with neuromyotonia, a phenomenon resulting from peripheral nerve hyperexcitability that causes a spontaneous muscle activity such as persistent [...] Read more.

Background: Autosomal recessive inherited pathogenetic variants in the histidine triad nucleotide-binding protein 1 (HINT1) gene are responsible for an axonal Charcot-Marie-Tooth neuropathy associated with neuromyotonia, a phenomenon resulting from peripheral nerve hyperexcitability that causes a spontaneous muscle activity such as persistent muscle contraction, impaired relaxation and myokymias. Methods: Herein, we describe two brothers in whom biallelic HINT1 variants were identified following a multidisciplinary approach. Results: The younger brother came to our attention for clinical evaluation of moderate intellectual disability, language developmental delay, and some behavioral issues. His elder brother presented mild intellectual disability, hyperactivity, tiptoe walking, and gait ataxia. At first evaluation, motor impairment with frequent falls, pes cavus, and distal hyposthenia with reduced osteotendinous reflexes were found in both. Grip myotonic phenomenon was also noted. Blood tests revealed mildly elevated creatine kinase, and neurophysiology investigations revealed predominantly axonal polyneuropathy. Muscle MRI highlighted fibro-adipose infiltration, prevalent in the lower limbs. Gene panel testing detected a heterozygous HINT1 variant (c.355C>T/p.(Arg119Trp)) on the paternal allele. A further in-depth analysis using Integrative Genomics Viewer and Optical Genome Mapping led us to identify an additional variant in HINT1 represented by a complex rearrangement located in the region 5′UTR-exon 1-intron 1, not previously described. Conclusions: This complex rearrangement could have been overlooked if the clinical picture had not been evaluated as a whole (from a clinical, neurophysiological, and neuroimaging point of view). Neuropsychiatric manifestations (intellectual disability, hyperactivity, etc.) are part of the picture of HINT1-related neuromyotonia. Full article

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

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