Genes

12 pages, 2241 KiB

Open AccessArticle

Molecular Phylogeny, DNA Barcoding, and ITS2 Secondary Structure Predictions in the Medicinally Important Eryngium Genotypes of East Coast Region of India

by Gobinda Chandra Acharya, Sansuta Mohanty, Madhumita Dasgupta, Supriya Sahu, Satyapriya Singh, Ayyagari V. V. Koundinya, Meenu Kumari, Ponnam Naresh and Manas Ranjan Sahoo

Genes 2022, 13(9), 1678; https://doi.org/10.3390/genes13091678 - 19 Sep 2022

Cited by 8 | Viewed by 3695

Abstract

Commercial interest in the culinary herb, Eryngium foetidum L., has increased worldwide due to its typical pungency, similar to coriander or cilantro, with immense pharmaceutical components. The molecular delimitation and taxonomic classification of this lesser-known medicinal plant are restricted to conventional phenotyping and [...] Read more.

Commercial interest in the culinary herb, Eryngium foetidum L., has increased worldwide due to its typical pungency, similar to coriander or cilantro, with immense pharmaceutical components. The molecular delimitation and taxonomic classification of this lesser-known medicinal plant are restricted to conventional phenotyping and DNA-based marker evaluation, which hinders accurate identification, genetic conservation, and safe utilization. This study focused on species discrimination using DNA sequencing with chloroplast–plastid genes (matK, Kim matK, and rbcL) and the nuclear ITS2 gene in two Eryngium genotypes collected from the east coast region of India. The results revealed that matK discriminated between two genotypes, however, Kim matK, rbcL, and ITS2 identified these genotypes as E. foetidum. The ribosomal nuclear ITS2 region exhibited significant inter- and intra-specific divergence, depicted in the DNA barcodes and the secondary structures derived based on the minimum free energy. Although the efficiency of matK genes is better in species discrimination, ITS2 demonstrated polyphyletic phylogeny, and could be used as a reliable marker for genetic divergence studies understanding the mechanisms of RNA molecules. The results of this study provide insights into the scientific basis of species identification, genetic conservation, and safe utilization of this important medicinal plant species. Full article

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

► Show Figures

Graphical abstract

15 pages, 1231 KiB

Open AccessArticle

Gene Polymorphism and Total Genetic Score in Martial Arts Athletes with Different Athletic Qualifications

by Anna Vostrikova, Victoria Pechenkina, Maria Danilova, Svetlana Boronnikova and Ruslan Kalendar

Genes 2022, 13(9), 1677; https://doi.org/10.3390/genes13091677 - 19 Sep 2022

Cited by 1 | Viewed by 2553

Abstract

The personalized approach in sports genetics implies considering the allelic variants of genes in polymorphic loci when adjusting the training process of athletes. The personalized approach is used both in sports genetics and in medicine to identify the influence of genotype on the [...] Read more.

The personalized approach in sports genetics implies considering the allelic variants of genes in polymorphic loci when adjusting the training process of athletes. The personalized approach is used both in sports genetics and in medicine to identify the influence of genotype on the manifestations of human physical qualities that allow to achieve high sports results or to assess the impact of genotype on the development and course of diseases. The impact of genes of the renin-angiotensin and kinin-bradykinin systems in the development of cardiovascular disease in athletes has not been defined. This study aims to determine the polymorphisms of four genes (ACE, BDKRB2, PPARGC1A and NOS3) and the total genetic score to reveal the predisposition to the formation of physical qualities in martial arts athletes with different athletic abilities. The products of these four genes are involved in the control of blood pressure. The allelic variants of these genes are associated with the development of the physical quality “endurance” and have an indirect influence on the formation of speed and power qualities. The total genetic score (TGS: from 0 to 100 arbitrary units) was calculated from the genotype score in each polymorphism. The athletes were divided into Group I with high and Group II with low qualifications depending on their sports success. Single nucleotide polymorphisms (SNPs) are identified through restriction endonucleases cleavage for PCR amplicons for discriminating between alleles of the target genes ACE (rs4646994), BDKRB2 (rs5810761), PPARGC1A (rs8192673) and NOS3 (rs1799983). Significant differences between the allelic variants of target genes and athletic ability were found between Group I and Group II for genotype G/G of NOS3 gene and genotypes Gly/Gly and Gly/Ser of PPARGC1A gene. The data obtained confirm that athletes with unfavourable genotypes are excluded in the screening phase because their endurance is not fully developed to the required level in martial arts. Martial arts athletes with the highest TGS have the highest skill level. Polymorphic loci of four genes whose products are involved in blood pressure control (ACE, BDKRB2, NOS3 and PPARGC1A) can be used in martial arts not only to determine predisposition to cardiovascular disease but also to predispose to the development of speed and power qualities and endurance. The total genetic score can serve as a tool for predicting athletic success. Full article

(This article belongs to the Special Issue Personalized Diagnostic Tools and Methods to Assess Genetic Predisposition in Human Diseases 2023)

► Show Figures

Figure 1

24 pages, 24302 KiB

Open AccessArticle

Gene Regulation during Carapacial Ridge Development of Mauremys reevesii: The Development of Carapacial Ridge, Ribs and Scutes

by Jiayu Yang, Yingying Xia, Shaohu Li, Tingting Chen, Jilong Zhang, Zhiyuan Weng, Huiwei Zheng, Minxuan Jin, Chuanhe Bao, Shiping Su, Yangyang Liang and Jun Zhang

Genes 2022, 13(9), 1676; https://doi.org/10.3390/genes13091676 - 19 Sep 2022

Cited by 2 | Viewed by 1985

Abstract

The unique topological structure of a turtle shell, including the special ribs–scapula relationship, is an evolutionarily novelty of amniotes. The carapacial ridge is a key embryonic tissue for inducing turtle carapace morphologenesis. However, the gene expression profiles and molecular regulatory mechanisms that occur [...] Read more.

The unique topological structure of a turtle shell, including the special ribs–scapula relationship, is an evolutionarily novelty of amniotes. The carapacial ridge is a key embryonic tissue for inducing turtle carapace morphologenesis. However, the gene expression profiles and molecular regulatory mechanisms that occur during carapacial ridge development, including the regulation mechanism of rib axis arrest, the development mechanism of the carapacial ridge, and the differentiation between soft-shell turtles and hard-shell turtles, are not fully understood. In this study, we obtained genome-wide gene expression profiles during the carapacial ridge development of Mauremys reevesii using RNA-sequencing by using carapacial ridge tissues from stage 14, 15 and 16 turtle embryos. In addition, a differentially expressed genes (DEGs) analysis and a gene set enrichment analysis (GSEA) of three comparison groups were performed. Furthermore, a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was used to analyze the pathway enrichment of the differentially expressed genes of the three comparative groups. The result displayed that the Wnt signaling pathway was substantially enriched in the CrTK14 vs. the CrTK15 comparison group, while the Hedgehog signaling pathway was significantly enriched in the CrTK15 vs. the CrTK16 group. Moreover, the regulatory network of the Wnt signaling pathway showed that Wnt signaling pathways might interact with Fgfs, Bmps, and Shh to form a regulatory network to regulate the carapacial ridge development. Next, WGCNA was used to cluster and analyze the expression genes during the carapacial ridge development of M. reevesii and P. sinensis. Further, a KEGG functional enrichment analysis of the carapacial ridge correlation gene modules was performed. Interesting, these results indicated that the Wnt signaling pathway and the MAPK signaling pathway were significantly enriched in the gene modules that were highly correlated with the stage 14 and stage 15 carapacial ridge samples of the two species. The Hedgehog signaling pathway was significantly enriched in the modules that were strongly correlated with the stage 16 carapacial ridge samples of M. reevesii, however, the PI3K-Akt signaling and the TGF-β signaling pathways were significantly enriched in the modules that were strongly correlated with the stage 16 carapacial ridge samples of P. sinensis. Furthermore, we found that those modules that were strongly correlated with the stage 14 carapacial ridge samples of M. reevesii and P. sinensis contained Wnts and Lef1. While the navajo white 3 module which was strongly correlated with the stage 16 carapacial ridge samples of M. reevesii contained Shh and Ptchs. The dark green module strongly correlated with the stage 16 carapacial ridge samples of P. sinensis which contained Col1a1, Col1a2, and Itga8. Consequently, this study systematically revealed the signaling pathways and genes that regulate the carapacial ridge development of M. reevesii and P. sinensis, which provides new insights for revealing the molecular mechanism that is underlying the turtle’s body structure. Full article

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

► Show Figures

Figure 1

9 pages, 276 KiB

Open AccessReview

The Genetic Architecture of Non-Syndromic Rhegmatogenous Retinal Detachment

by Malik Moledina, David G. Charteris and Aman Chandra

Genes 2022, 13(9), 1675; https://doi.org/10.3390/genes13091675 - 19 Sep 2022

Viewed by 1899

Abstract

Rhegmatogenous retinal detachment (RRD) is the most common form of retinal detachment (RD), affecting 1 in 10,000 patients per year. The condition has significant ocular morbidity, with a sizeable proportion of patients obtaining poor visual outcomes. Despite this, the genetics underpinning Idiopathic Retinal [...] Read more.

Rhegmatogenous retinal detachment (RRD) is the most common form of retinal detachment (RD), affecting 1 in 10,000 patients per year. The condition has significant ocular morbidity, with a sizeable proportion of patients obtaining poor visual outcomes. Despite this, the genetics underpinning Idiopathic Retinal Detachment (IRD) remain poorly understood; this is likely due to small sample sizes in relevant studies. The majority of research pertains to the well-characterised Mende lian syndromes, such as Sticklers and Wagners, associated with RRD. Nevertheless, in recent years, there has been an increasing body of literature identifying the common genetic mutations and mechanisms associated with IRD. Several recent Genomic Wide Association Studies (GWAS) studies have identified a number of genetic loci related to the development of IRD. Our review aims to provide an up-to-date summary of the significant genetic mechanisms and associations of Idiopathic RRD. Full article

(This article belongs to the Special Issue Genetics in Stickler Syndrome)

46 pages, 2037 KiB

Open AccessArticle

Survival Analysis with High-Dimensional Omics Data Using a Threshold Gradient Descent Regularization-Based Neural Network Approach

by Yu Fan, Sanguo Zhang and Shuangge Ma

Genes 2022, 13(9), 1674; https://doi.org/10.3390/genes13091674 - 19 Sep 2022

Cited by 3 | Viewed by 2240

Abstract

Analysis of data with a censored survival response and high-dimensional omics measurements is now common. Most of the existing analyses are based on specific (semi)parametric models, in particular the Cox model. Such analyses may be limited by not having sufficient flexibility, for example, [...] Read more.

Analysis of data with a censored survival response and high-dimensional omics measurements is now common. Most of the existing analyses are based on specific (semi)parametric models, in particular the Cox model. Such analyses may be limited by not having sufficient flexibility, for example, in accommodating nonlinearity. For categorical and continuous responses, neural networks (NNs) have provided a highly competitive alternative. Comparatively, NNs for censored survival data remain limited. Omics measurements are usually high-dimensional, and only a small subset is expected to be survival-associated. As such, regularized estimation and selection are needed. In the existing NN studies, this is usually achieved via penalization. In this article, we propose adopting the threshold gradient descent regularization (TGDR) technique, which has competitive performance (for example, when compared to penalization) and unique advantages in regression analysis, but has not been adopted with NNs. The TGDR-based NN has a highly sensible formulation and an architecture different from the unregularized and penalization-based ones. Simulations show its satisfactory performance. Its practical effectiveness is further established via the analysis of two cancer omics datasets. Overall, this study can provide a practical and useful new way in the NN paradigm for survival analysis with high-dimensional omics measurements. Full article

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

► Show Figures

Figure 1

17 pages, 4839 KiB

Open AccessArticle

Comparative Analysis of Chloroplast Genomes within Saxifraga (Saxifragaceae) Takes Insights into Their Genomic Evolution and Adaption to the High-Elevation Environment

by Zhuyifu Chen, Xiaolei Yu, Yujiao Yang, Pei Wei, Wencai Zhang, Xinzhong Li, Chenlai Liu, Shuqi Zhao, Xiaoyan Li and Xing Liu

Genes 2022, 13(9), 1673; https://doi.org/10.3390/genes13091673 - 19 Sep 2022

Cited by 12 | Viewed by 2289

Abstract

Saxifraga species are widely distributed in alpine and arctic regions in the Northern hemisphere. Highly morphological diversity within this genus brings great difficulties for species identification, and their typical highland living properties make it interesting how they adapt to the extreme environment. Here, [...] Read more.

Saxifraga species are widely distributed in alpine and arctic regions in the Northern hemisphere. Highly morphological diversity within this genus brings great difficulties for species identification, and their typical highland living properties make it interesting how they adapt to the extreme environment. Here, we newly generated the chloroplast (cp) genomes of two Saxifraga species and compared them with another five Saxifraga cp genomes to understand the characteristics of cp genomes and their potential roles in highland adaptation. The genome size, structure, gene content, GC content, and codon usage pattern were found to be highly similar. Cp genomes ranged from 146,549 bp to 151,066 bp in length, most of which comprised 130 predicted genes. Yet, due to the expansion of IR regions, the second copy of rps19 in Saxifraga stolonifera was uniquely kept. Through sequence divergence analysis, we identified seven hypervariable regions and detected some signatures of regularity associated with genetic distance. We also identified 52 to 89 SSRs and some long repeats among seven Saxifraga species. Both ML and BI phylogenetic analyses confirmed that seven Saxifraga species formed a monophyletic clade in the Saxifragaceae family, and their intragenus relationship was also well supported. Additionally, the ndhI and ycf1 genes were considered under positive selection in species inhabiting relatively high altitudes. Given the conditions of intense light and low CO₂ concentration in the highland, the products of these two genes might participate in the adaptation to the extreme environment. Full article

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

► Show Figures

Figure 1

14 pages, 1454 KiB

Open AccessArticle

The Relationships between Dopaminergic, Glutamatergic, and Cognitive Functioning in 22q11.2 Deletion Syndrome: A Cross-Sectional, Multimodal ¹H-MRS and ¹⁸F-Fallypride PET Study

by Carmen F. M. van Hooijdonk, Desmond H. Y. Tse, Julia Roosenschoon, Jenny Ceccarini, Jan Booij, Therese A. M. J. van Amelsvoort and Claudia Vingerhoets

Genes 2022, 13(9), 1672; https://doi.org/10.3390/genes13091672 - 19 Sep 2022

Cited by 1 | Viewed by 2259

Abstract

Background: Individuals with 22q11.2 deletion syndrome (22q11DS) are at increased risk of developing psychosis and cognitive impairments, which may be related to dopaminergic and glutamatergic abnormalities. Therefore, in this exploratory study, we examined the association between dopaminergic and glutamatergic functioning in 22q11DS. Additionally, [...] Read more.

Background: Individuals with 22q11.2 deletion syndrome (22q11DS) are at increased risk of developing psychosis and cognitive impairments, which may be related to dopaminergic and glutamatergic abnormalities. Therefore, in this exploratory study, we examined the association between dopaminergic and glutamatergic functioning in 22q11DS. Additionally, the associations between glutamatergic functioning and brain volumes in 22q11DS and healthy controls (HC), as well as those between dopaminergic and cognitive functioning in 22q11DS, were also examined. Methods: In this cross-sectional, multimodal imaging study, glutamate, glutamine, and their combined concentration (Glx) were assessed in the anterior cingulate cortex (ACC) and striatum in 17 22q11DS patients and 20 HC using 7T proton magnetic resonance spectroscopy. Ten 22q11DS patients also underwent ¹⁸F-fallypride positron emission tomography to measure dopamine D_2/3 receptor (D_2/3R) availability in the ACC and striatum. Cognitive performance was assessed with the Cambridge Neuropsychological Test Automated Battery. Results: No significant associations were found between ACC or striatal (1) glutamate, glutamine, or Glx concentrations and (2) D_2/3R availability. In HC but not in 22q11DS patients, we found a significant relationship between ACC volume and ACC glutamate, glutamine, and Glx concentration. In addition, some aspects of cognitive functioning were significantly associated with D_2/3R availability in 22q11DS. However, none of the associations remained significant after Bonferroni correction. Conclusions: Although our results did not reach statistical significance, our findings suggest an association between glutamatergic functioning and brain volume in HC but not in 22q11DS. Additionally, D_2/3R availability seems to be related to cognitive functioning in 22q11DS. Studies in larger samples are needed to further elucidate our findings. Full article

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

► Show Figures

Figure 1

15 pages, 12864 KiB

Open AccessArticle

Blood Transcriptome Analysis of Beef Cow with Different Parity Revealed Candidate Genes and Gene Networks Regulating the Postpartum Diseases

by Yanda Yang, Chencheng Chang, Batu Baiyin, Zaixia Liu, Lili Guo, Le Zhou, Bin Liu, Caixia Shi and Wenguang Zhang

Genes 2022, 13(9), 1671; https://doi.org/10.3390/genes13091671 - 19 Sep 2022

Cited by 2 | Viewed by 2177

Abstract

Maternal parity is an important physiological factor influencing beef cow reproductive performance. However, there are few studies on the influence of different calving periods on early growth and postpartum diseases. Here, we conducted blood transcriptomic analysis on cows of different parities for gene [...] Read more.

Maternal parity is an important physiological factor influencing beef cow reproductive performance. However, there are few studies on the influence of different calving periods on early growth and postpartum diseases. Here, we conducted blood transcriptomic analysis on cows of different parities for gene discovery. We used Short Time Series Expression Miner (STEM) analysis to determine gene expression levels in cows of various parities and divided multiple parities into three main periods (nulliparous, primiparous, and multiparous) for subsequent analysis. Furthermore, the top 15,000 genes with the lowest median absolute deviation (MAD) were used to build a co-expression network using weighted correlation network analysis (WGCNA), and six independent modules were identified. Combing with Exon Wide Selection Signature (EWSS) and protein-protein interaction (PPI) analysis revealed that TPCN2, KIF22, MICAL3, RUNX2, PDE4A, TESK2, GPM6A, POLR1A, and KLHL6 involved in early growth and postpartum diseases. The GO and KEGG enrichment showed that the Parathyroid hormone synthesis, secretion, and action pathway and stem cell differentiation function-related pathways were enriched. Collectively, our study revealed candidate genes and gene networks regulating the early growth and postpartum diseases and provided new insights into the potential mechanism of reproduction advantages of different parity selection. Full article

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

► Show Figures

Graphical abstract

8 pages, 996 KiB

Open AccessEditor’s ChoiceArticle

Variation in Ovine DGAT1 and Its Association with Carcass Muscle Traits in Southdown Sheep

by Rong Dai, Huitong Zhou, Qian Fang, Ping Zhou, Yang Yang, Shuang Jiang and Jonathan G. H. Hickford

Genes 2022, 13(9), 1670; https://doi.org/10.3390/genes13091670 - 19 Sep 2022

Cited by 5 | Viewed by 2125

Abstract

Diacylglycerol O-acyltransferase 1 (DGAT1) is a microsomal enzyme that plays a key role in the synthesis of triglycerides. Its gene (DGAT1) is regarded as a candidate gene for variation in milk and meat traits in cattle. The objective of this study [...] Read more.

Diacylglycerol O-acyltransferase 1 (DGAT1) is a microsomal enzyme that plays a key role in the synthesis of triglycerides. Its gene (DGAT1) is regarded as a candidate gene for variation in milk and meat traits in cattle. The objective of this study was to use a PCR single-strand conformation polymorphism approach to explore sequence variation in two regions of ovine DGAT1 and to assess its effect on meat traits in New Zealand Southdown sheep. Three variant nucleotide sequences were identified in each region, with two single nucleotide polymorphisms (SNPs) and one nucleotide deletion being detected in intron 1 and two SNPs being found in exon 17. The effect of the exon 17 variation was not investigated due to one variant being predominant and the other two variants occurring at low frequencies. In intron 1, one variant (B₁) was found to be associated with increase loin meat yield, suggesting that this may have value as a gene marker for improving meat traits. Full article

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

► Show Figures

Figure 1

14 pages, 2089 KiB

Open AccessArticle

LncRNA HULC and miR-122 Expression Pattern in HCC-Related HCV Egyptian Patients

by Dalia A. Gaber, Olfat Shaker, Alaa Tarek Younis and Mohamed El-Kassas

Genes 2022, 13(9), 1669; https://doi.org/10.3390/genes13091669 - 18 Sep 2022

Cited by 6 | Viewed by 2030

Abstract

Hepatocellular carcinoma (HCC) is a highly prevalent malignancy. It is a common type of cancer in Egypt due to chronic virus C infection (HCV). Currently, the frequently used lab test is serum α-fetoprotein. However, its diagnostic value is challenging due to its low [...] Read more.

Hepatocellular carcinoma (HCC) is a highly prevalent malignancy. It is a common type of cancer in Egypt due to chronic virus C infection (HCV). Currently, the frequently used lab test is serum α-fetoprotein. However, its diagnostic value is challenging due to its low sensitivity and specificity. Genetic biomarkers have recently provided new insights for cancer diagnostics. Herein, we quantified Lnc HULC and miR-122 gene expression to test their potential in diagnosis. Both biomarkers were tested in the sera of 60 HCC patients and 60 with chronic HCV using real-time RT-PCR. miR-122 was highly expressed in HCV patients with a significant difference from the HCC group (p = 0.004), which points towards its role in prognosis value as a predictor of HCC in patients with chronic HCV. HULC was more highly expressed in HCC patients than in the HCV group (p = 0.018), indicating its potential use in screening and the early diagnosis of HCC. The receiver operating characteristic (ROC) curve analysis showed their reliable sensitivity and specificity. Our results reveal that miR-122 can act as a prognostic tool for patients with chronic HCV. Furthermore, it is an early predictor of HCC. LncRNA HULC can be used as an early diagnostic tool for HCC. Full article

(This article belongs to the Section RNA)

► Show Figures

Figure 1

11 pages, 1563 KiB

Open AccessArticle

A Novel Non-Allelic Homologous Recombination Event in a Parent with an 11;22 Reciprocal Translocation Leading to 22q11.2 Deletion Syndrome

by Steven Pastor, Oanh Tran, Daniel E. McGinn, T. Blaine Crowley, Elaine H. Zackai, Donna M. McDonald-McGinn and Beverly S. Emanuel

Genes 2022, 13(9), 1668; https://doi.org/10.3390/genes13091668 - 17 Sep 2022

Viewed by 2839

Abstract

The most prevalent microdeletion in the human population occurs at 22q11.2, a region rich in chromosome-specific low copy repeats (LCR22s). The structure of this region has eluded characterization due to a combination of size, regional complexity, and haplotype diversity. To further complicate matters, [...] Read more.

The most prevalent microdeletion in the human population occurs at 22q11.2, a region rich in chromosome-specific low copy repeats (LCR22s). The structure of this region has eluded characterization due to a combination of size, regional complexity, and haplotype diversity. To further complicate matters, it is not well represented in the human reference genome. Most individuals with 22q11.2 deletion syndrome (22q11.2DS) carry a de novo, hemizygous deletion approximately 3 Mbp in size occurring by non-allelic homologous recombination (NAHR) mediated by the LCR22s. The ability to fully delineate an individual’s 22q11.2 regional structure will likely be important for studies designed to assess an unaffected individual’s risk for generating rearrangements in germ cells, potentially leading to offspring with 22q11.2DS. Towards understanding these risk factors, optical mapping has been previously employed to successfully elucidate the structure and variation of LCR22s across 30 families affected by 22q11.2DS. The father in one of these families carries a t(11;22)(q23;q11) translocation. Surprisingly, it was determined that he is the parent-of-deletion-origin. NAHR, which occurred between his der(22) and intact chromosome 22, led to a 22q11.2 deletion in his affected child. The unaffected sibling of the proband with 22q11.2DS inherited the father’s normal chromosome 22, which did not aberrantly recombine. This unexpected observation definitively shows that haplotypes that engage in NAHR can also be inherited intact. This study is the first to identify all structures involving a rearranged chromosome 22 that also participates in NAHR leading to a 22q11.2 deletion. Full article

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

► Show Figures

Figure 1

9 pages, 452 KiB

Open AccessCase Report

A Novel Nonsense Variant in GRM1 Causes Autosomal Recessive Spinocerebellar Ataxia 13 in a Consanguineous Pakistani Family

by Hammad Yousaf, Ambrin Fatima, Zafar Ali, Shahid M. Baig, Mathias Toft and Zafar Iqbal

Genes 2022, 13(9), 1667; https://doi.org/10.3390/genes13091667 - 17 Sep 2022

Cited by 8 | Viewed by 4679

Abstract

Background and objectives: Autosomal recessive spinocerebellar ataxia-13 (SCAR13) is an ultra-rare disorder characterized by slowly progressive cerebellar ataxia, cognitive deficiencies, and skeletal and oculomotor abnormalities. The objective of this case report is to expand the clinical and molecular spectrum of SCAR13. Methods: We [...] Read more.

Background and objectives: Autosomal recessive spinocerebellar ataxia-13 (SCAR13) is an ultra-rare disorder characterized by slowly progressive cerebellar ataxia, cognitive deficiencies, and skeletal and oculomotor abnormalities. The objective of this case report is to expand the clinical and molecular spectrum of SCAR13. Methods: We investigated a consanguineous Pakistani family with four patients partially presenting with clinical features of SCAR13 using whole exome sequencing. Segregation analysis was performed by Sanger sequencing in all the available individuals of the family. Results: Patients presented with quadrupedal gait, delayed developmental milestones, non-progressive peripheral neuropathy, and cognitive impairment. Whole exome sequencing identified a novel pathogenic nonsense homozygous variant, Gly240*, in the gene GRM1 as a cause of SCAR13 that segregates with the recessive disease. Discussion: We report a novel homozygous nonsense variant in the GRM1 gene in four Pakistani patients presenting with clinical features that partially overlap with the already reported phenotype of SCAR13. In addition, the family presented quadrupedal gait and non-progressive symptoms, manifestations which have not been recognized previously. So far, only four variants in GRM1 have been reported, in families of Roma, Iranian, and Tunisian origins. The current study adds to the mutation spectrum of GRM1 and provides a rare presentation of SCAR13, the first from the Pakistani population. Full article

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

► Show Figures

Figure 1

9 pages, 1079 KiB

Open AccessArticle

The Impact of the COVID-19 Pandemic on School-Aged Children with Fragile X Syndrome

by Hailey Silver, Hilary Rosselot, Rebecca Shaffer and Reymundo Lozano

Genes 2022, 13(9), 1666; https://doi.org/10.3390/genes13091666 - 17 Sep 2022

Cited by 2 | Viewed by 2127

Abstract

The pandemic caused by the spread of the coronavirus disease (COVID-19), beginning in early 2020, had an impact beyond anything experienced in recent history. People with Fragile X Syndrome (FXS), the leading known heritable cause of ASD and intellectual disability, were uniquely vulnerable [...] Read more.

The pandemic caused by the spread of the coronavirus disease (COVID-19), beginning in early 2020, had an impact beyond anything experienced in recent history. People with Fragile X Syndrome (FXS), the leading known heritable cause of ASD and intellectual disability, were uniquely vulnerable to pandemic-related changes. This study surveyed parent perspectives of the impact on 33 school-aged children with FXS across daily living skills, education, therapies, behaviors, health visits, and mask wearing. Academic performance was perceived to have decreased in most of the children (58%). Students in online school had the most reports of decline and those in person had the most reported improvement. Parents were significantly more satisfied with services that remained in person compared to those delivered online or in hybrid settings. Additionally, depression (75%), sleep problems (80%), attention problems (73%), and social skills (61%) were reported to have worsened the most. Parents reported that in addition to continuing with a structured schedule, the most helpful strategies were increasing face-to-face social interactions and outdoor activities. Future research should explore strategies to help online interventions and education to be more successful with individuals with FXS, given this may become a resource for families not geographically able to access in-person resources. Full article

(This article belongs to the Special Issue Epigenetics of Fragile X and Other Neurodevelopmental Disorders)

► Show Figures

Figure 1

11 pages, 1743 KiB

Open AccessArticle

G-quadruplexes Mark Sites of Methylation Instability Associated with Ageing and Cancer

by Jonas Rauchhaus, Jenna Robinson, Ludovica Monti and Marco Di Antonio

Genes 2022, 13(9), 1665; https://doi.org/10.3390/genes13091665 - 17 Sep 2022

Cited by 6 | Viewed by 3554

Abstract

Regulation of the epigenome is critical for healthy cell function but can become disrupted with age, leading to aberrant epigenetic profiles including altered DNA methylation. Recent studies have indicated that DNA methylation homeostasis can be compromised by the formation of DNA secondary structures [...] Read more.

Regulation of the epigenome is critical for healthy cell function but can become disrupted with age, leading to aberrant epigenetic profiles including altered DNA methylation. Recent studies have indicated that DNA methylation homeostasis can be compromised by the formation of DNA secondary structures known as G-quadruplexes (G4s), which form in guanine-rich regions of the genome. G4s can be recognised and bound by certain methylation-regulating enzymes, and in turn perturb the surrounding methylation architecture. However, the effect G4 formation has on DNA methylation at critical epigenetic sites remains elusive and poorly explored. In this work, we investigate the association between G4 sequences and prominent DNA methylation sites, termed ‘ageing clocks’, that act as bona fide dysregulated regions in aged and cancerous cells. Using a combination of in vitro (G4-seq) and in cellulo (BG4-ChIP) G4 distribution maps, we show that ageing clocks sites are significantly enriched with G4-forming sequences. The observed enrichment also varies across species and cell lines, being least significant in healthy cells and more pronounced in tumorigenic cells. Overall, our results suggest a biological significance of G4s in the realm of DNA methylation, which may be important for further deciphering the driving forces of diseases characterised by epigenetic abnormality, including ageing. Full article

(This article belongs to the Special Issue Investigation of the Importance of Non-B DNA Structures at the Interface between Chemistry and Biology)

► Show Figures

Figure 1

21 pages, 3980 KiB

Open AccessArticle

Expression Profile of New Gene Markers Involved in Differentiation of Canine Adipose-Derived Stem Cells into Chondrocytes

by Maurycy Jankowski, Mariusz Kaczmarek, Grzegorz Wąsiatycz, Aneta Konwerska, Claudia Dompe, Dorota Bukowska, Paweł Antosik, Paul Mozdziak and Bartosz Kempisty

Genes 2022, 13(9), 1664; https://doi.org/10.3390/genes13091664 - 16 Sep 2022

Viewed by 2976

Abstract

The interest in stem cell research continuously increased over the last decades, becoming one of the most important trends in the 21st century medicine. Stem cell-based therapies have a potential to become a solution for a range of currently untreatable diseases, such as [...] Read more.

The interest in stem cell research continuously increased over the last decades, becoming one of the most important trends in the 21st century medicine. Stem cell-based therapies have a potential to become a solution for a range of currently untreatable diseases, such as spinal cord injuries, type I diabetes, Parkinson’s disease, heart disease, stroke, and osteoarthritis. Hence, this study, based on canine material, aims to investigate the molecular basis of adipose-derived stem cell (ASC) differentiation into chondrocytes, to serve as a transcriptomic reference for further research aiming to introduce ASC into treatment of bone and cartilage related diseases, such as osteoarthritis in veterinary medicine. Adipose tissue samples were harvested from a canine specimen subjected to a routine ovariohysterecromy procedure at an associated veterinary clinic. The material was treated for ASC isolation and chondrogenic differentiation. RNA samples were isolated at day 1 of culture, day 30 of culture in unsupplemented culture media, and day 30 of culture in chondrogenic differentiation media. The resulting RNA was analyzed using RNAseq assays, with the results validated by RT-qPCR. Between differentiated chondrocytes, early and late cultures, most up- and down-regulated genes in each comparison were selected for further analysis., there are several genes (e.g., MMP12, MPEG1, CHI3L1, and CD36) that could be identified as new markers of chondrogenesis and the influence of long-term culture conditions on ASCs. The results of the study prove the usefulness of the in vitro culture model, providing further molecular insight into the processes associated with ASC culture and differentiation. Furthermore, the knowledge obtained could be used as a molecular reference for future in vivo and clinical studies. Full article

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

► Show Figures

Figure 1

39 pages, 5179 KiB

Open AccessReview

Telomeres and Their Neighbors

by Leon P. Jenner, Vratislav Peska, Jana Fulnečková and Eva Sýkorová

Genes 2022, 13(9), 1663; https://doi.org/10.3390/genes13091663 - 16 Sep 2022

Cited by 8 | Viewed by 4060

Abstract

Telomeres are essential structures formed from satellite DNA repeats at the ends of chromosomes in most eukaryotes. Satellite DNA repeat sequences are useful markers for karyotyping, but have a more enigmatic role in the eukaryotic cell. Much work has been done to investigate [...] Read more.

Telomeres are essential structures formed from satellite DNA repeats at the ends of chromosomes in most eukaryotes. Satellite DNA repeat sequences are useful markers for karyotyping, but have a more enigmatic role in the eukaryotic cell. Much work has been done to investigate the structure and arrangement of repetitive DNA elements in classical models with implications for species evolution. Still more is needed until there is a complete picture of the biological function of DNA satellite sequences, particularly when considering non-model organisms. Celebrating Gregor Mendel’s anniversary by going to the roots, this review is designed to inspire and aid new research into telomeres and satellites with a particular focus on non-model organisms and accessible experimental and in silico methods that do not require specialized equipment or expensive materials. We describe how to identify telomere (and satellite) repeats giving many examples of published (and some unpublished) data from these techniques to illustrate the principles behind the experiments. We also present advice on how to perform and analyse such experiments, including details of common pitfalls. Our examples are a selection of recent developments and underexplored areas of research from the past. As a nod to Mendel’s early work, we use many examples from plants and insects, especially as much recent work has expanded beyond the human and yeast models traditional in telomere research. We give a general introduction to the accepted knowledge of telomere and satellite systems and include references to specialized reviews for the interested reader. Full article

(This article belongs to the Special Issue Satellite DNA Genomics)

► Show Figures

Graphical abstract

17 pages, 1027 KiB

Open AccessEditor’s ChoiceArticle

Clustering of Genetic Anomalies of Cilia Outer Dynein Arm and Central Apparatus in Patients with Transposition of the Great Arteries

by Marlon De Ita, Javier Gaytán-Cervantes, Bulmaro Cisneros, María Antonieta Araujo, Juan Carlos Huicochea-Montiel, Alan Cárdenas-Conejo, Charles César Lazo-Cárdenas, César Iván Ramírez-Portillo, Carina Feria-Kaiser, Leoncio Peregrino-Bejarano, Lucelli Yáñez-Gutiérrez, Carolina González-Torres and Haydeé Rosas-Vargas

Genes 2022, 13(9), 1662; https://doi.org/10.3390/genes13091662 - 16 Sep 2022

Cited by 4 | Viewed by 2746

Abstract

Transposition of the great arteries (TGA) is a congenital heart defect with a complex pathogenesis that has not been fully elucidated. In this study, we performed whole-exome sequencing (WES) in isolated TGA-diagnosed patients and analyzed genes of motile and non-motile cilia ciliogenesis and [...] Read more.

Transposition of the great arteries (TGA) is a congenital heart defect with a complex pathogenesis that has not been fully elucidated. In this study, we performed whole-exome sequencing (WES) in isolated TGA-diagnosed patients and analyzed genes of motile and non-motile cilia ciliogenesis and ciliary trafficking, as well as genes previously associated with this heart malformation. Deleterious missense and splicing variants of genes DNAH9, DNAH11, and ODAD4 of cilia outer dynein arm and central apparatus, HYDIN, were found in our TGA patients. Remarkable, there is a clustering of deleterious genetic variants in cilia genes, suggesting it could be an oligogenic disease. Our data evidence the genetic diversity and etiological complexity of TGA and point out that population allele determination and genetic aggregation studies are required to improve genetic counseling. Full article

(This article belongs to the Special Issue Genetics of Complex Human Disease)

► Show Figures

Graphical abstract

14 pages, 2067 KiB

Open AccessArticle

Coyotes in New York City Carry Variable Genomic Dog Ancestry and Influence Their Interactions with Humans

by Anthony Caragiulo, Stephen J. Gaughran, Neil Duncan, Christopher Nagy, Mark Weckel and Bridgett M. vonHoldt

Genes 2022, 13(9), 1661; https://doi.org/10.3390/genes13091661 - 16 Sep 2022

Cited by 5 | Viewed by 4531

Abstract

Coyotes are ubiquitous on the North American landscape as a result of their recent expansion across the continent. They have been documented in the heart of some of the most urbanized cities, such as Chicago, Los Angeles, and New York City. Here, we [...] Read more.

Coyotes are ubiquitous on the North American landscape as a result of their recent expansion across the continent. They have been documented in the heart of some of the most urbanized cities, such as Chicago, Los Angeles, and New York City. Here, we explored the genomic composition of 16 coyotes in the New York metropolitan area to investigate genomic demography and admixture for urban-dwelling canids in Queens County, New York. We identified moderate-to-high estimates of relatedness among coyotes living in Queens (r = 0.0–0.5) and adjacent neighborhoods, suggestive of a relatively small population. Although we found low background levels of domestic-dog ancestry across most coyotes in our sample (5%), we identified a male suspected to be a first-generation coyote–dog hybrid with 46% dog ancestry, as well as his two putative backcrossed offspring that carried approximately 25% dog ancestry. The male coyote–dog hybrid and one backcrossed offspring each carried two transposable element insertions that are associated with human-directed hypersociability in dogs and gray wolves. An additional, unrelated coyote with little dog ancestry also carried two of these insertions. These genetic patterns suggest that gene flow from domestic dogs may become an increasingly important consideration as coyotes continue to inhabit metropolitan regions. Full article

(This article belongs to the Special Issue Advances in Canine Genetics)

► Show Figures

Figure 1

17 pages, 2510 KiB

Open AccessArticle

Observable Symptoms of Anxiety in Individuals with Fragile X Syndrome: Parent and Caregiver Perspectives

by Reymundo Lozano, Talia Thompson, Jayne Dixon-Weber, Craig A. Erickson, Elizabeth Berry-Kravis, Sara Williams, Elizabeth Smith, Jean A. Frazier, Hilary Rosselot, Cristan Farmer and David Hessl

Genes 2022, 13(9), 1660; https://doi.org/10.3390/genes13091660 - 16 Sep 2022

Cited by 9 | Viewed by 2796

Abstract

Caregiver reports, clinical observations, and diagnostic assessments indicate that most individuals with fragile X syndrome experience high levels of chronic anxiety. However, anxiety is a challenging endpoint for outcome measurement in FXS because most individuals cannot reliably report internal emotional or body states. [...] Read more.

Caregiver reports, clinical observations, and diagnostic assessments indicate that most individuals with fragile X syndrome experience high levels of chronic anxiety. However, anxiety is a challenging endpoint for outcome measurement in FXS because most individuals cannot reliably report internal emotional or body states. A comprehensive survey of the presence, frequency, and duration of anxiety-related symptoms and questions to elicit open-ended responses was completed by caregivers of 456 individuals with FXS, ages 2–81 years (87 female, 369 male) and 24 female and 2 male FXS self-advocates ages 15–66 years. Caregivers reported classic behavioral indicators of anxiety, such as avoidance, irritability, motor agitation, and physiological symptoms, as well as behavioral features in FXS such as repetitive behavior, aggression, and self-injury. Self-advocate accounts largely paralleled caregiver data. Factor analyses yielded four factors: (1) increased irritability, aggression, and self-injury; (2) increased physical movement, nervous activity, and restlessness; (3) physical and physiological features of anxiety; and (4) internalizing and gastrointestinal symptoms. Caregivers are capable of observing and reporting behaviors that are valid indicators of anxious states that are usually reported in self-report standardized assessments. These results support the development of an anxiety measure for FXS that minimizes problems with rater inference. Full article

(This article belongs to the Special Issue Fragile X Syndrome Genetics)

► Show Figures

Figure 1

17 pages, 1909 KiB

Open AccessReview

SR Splicing Factors Promote Cancer via Multiple Regulatory Mechanisms

by Ledong Wan, Min Deng and Honghe Zhang

Genes 2022, 13(9), 1659; https://doi.org/10.3390/genes13091659 - 16 Sep 2022

Cited by 9 | Viewed by 3721

Abstract

Substantial emerging evidence supports that dysregulated RNA metabolism is associated with tumor initiation and development. Serine/Arginine-Rich proteins (SR) are a number of ultraconserved and structurally related proteins that contain a characteristic RS domain rich in arginine and serine residues. SR proteins perform a [...] Read more.

Substantial emerging evidence supports that dysregulated RNA metabolism is associated with tumor initiation and development. Serine/Arginine-Rich proteins (SR) are a number of ultraconserved and structurally related proteins that contain a characteristic RS domain rich in arginine and serine residues. SR proteins perform a critical role in spliceosome assembling and conformational transformation, contributing to precise alternative RNA splicing. Moreover, SR proteins have been reported to participate in multiple other RNA-processing-related mechanisms than RNA splicing, such as genome stability, RNA export, and translation. The dysregulation of SR proteins has been reported to contribute to tumorigenesis through multiple mechanisms. Here we reviewed the different biological roles of SR proteins and strategies for functional rectification of SR proteins that may serve as potential therapeutic approaches for cancer. Full article

(This article belongs to the Special Issue RNA Splicing in Cancer and Targeted Therapies)

► Show Figures

Figure 1

16 pages, 2911 KiB

Open AccessArticle

Probabilistic Genotyping of Single Cell Replicates from Mixtures Involving First-Degree Relatives Prevents the False Inclusions of Non-Donor Relatives

by Kaitlin Huffman and Jack Ballantyne

Genes 2022, 13(9), 1658; https://doi.org/10.3390/genes13091658 - 15 Sep 2022

Cited by 6 | Viewed by 2162

Abstract

Analysis of complex DNA mixtures comprised of related individuals requires a great degree of care due to the increased risk of falsely including non-donor first-degree relatives. Although alternative likelihood ratio (LR) propositions that may aid in the analysis of these difficult cases can [...] Read more.

Analysis of complex DNA mixtures comprised of related individuals requires a great degree of care due to the increased risk of falsely including non-donor first-degree relatives. Although alternative likelihood ratio (LR) propositions that may aid in the analysis of these difficult cases can be employed, the prior information required for their use is not always known, nor do these alternative propositions always prevent false inclusions. For example, with a father/mother/child mixture, conditioning the mixture on the presence of one of the parents is recommended. However, the definitive presence of the parent(s) is not always known and an assumption of their presence in the mixture may not be objectively justifiable. Additionally, the high level of allele sharing seen with familial mixtures leads to an increased risk of underestimating the number of contributors (NOC) to a mixture. Therefore, fully resolving and identifying each of the individuals present in familial mixtures and excluding related non-donors is an important goal of the mixture deconvolution process and can be of great investigative value. Here, firstly, we further investigated and confirmed the problems encountered with standard bulk analysis of familial mixtures and demonstrated the ability of single cell analysis to fully distinguish first-degree relatives (FDR). Then, separation of each of the individual donors via single cell analysis was carried out by a combination of direct single cell subsampling (DSCS), enhanced DNA typing, and probabilistic genotyping, and applied to three complex familial 4-person mixtures resulting in a probative gain of LR for all donors and an accurate determination of the NOC. Significantly, non-donor first-degree relatives that were falsely included (LRs > 10²–10⁸) by a standard bulk sampling and analysis approach were no longer falsely included using DSCS. Full article

(This article belongs to the Special Issue Improved Methods in Forensic DNA Analysis)

► Show Figures

Graphical abstract

10 pages, 467 KiB

Open AccessReview

Recommendations for Interpreting and Reporting Silent Carrier and Disease-Modifying Variants in SMA Testing Workflows

by John N. Milligan, Laura Blasco-Pérez, Mar Costa-Roger, Marta Codina-Solà and Eduardo F. Tizzano

Genes 2022, 13(9), 1657; https://doi.org/10.3390/genes13091657 - 15 Sep 2022

Cited by 10 | Viewed by 4747

Abstract

Genetic testing for SMA diagnosis, newborn screening, and carrier screening has become a significant public health interest worldwide, driven largely by the development of novel and effective molecular therapies for the treatment of spinal muscular atrophy (SMA) and the corresponding updates to testing [...] Read more.

Genetic testing for SMA diagnosis, newborn screening, and carrier screening has become a significant public health interest worldwide, driven largely by the development of novel and effective molecular therapies for the treatment of spinal muscular atrophy (SMA) and the corresponding updates to testing guidelines. Concurrently, understanding of the underlying genetics of SMA and their correlation with a broad range of phenotypes and risk factors has also advanced, particularly with respect to variants that modulate disease severity or impact residual carrier risks. While testing guidelines are beginning to emphasize the importance of these variants, there are no clear guidelines on how to utilize them in a real-world setting. Given the need for clarity in practice, this review summarizes several clinically relevant variants in the SMN1 and SMN2 genes, including how they inform outcomes for spinal muscular atrophy carrier risk and disease prognosis. Full article

(This article belongs to the Special Issue Advances in Genetics of Motor Neuron Diseases)

► Show Figures

Figure 1

18 pages, 3384 KiB

Open AccessArticle

Nonsense-Mediated Decay Targeted RNA (ntRNA): Proposal of a ntRNA–miRNA–lncRNA Triple Regulatory Network Usable as Biomarker of Prognostic Risk in Patients with Kidney Cancer

by Zhiyue Zhou, Fuyan Hu, Dan Huang, Qingjia Chi and Nelson L. S. Tang

Genes 2022, 13(9), 1656; https://doi.org/10.3390/genes13091656 - 15 Sep 2022

Viewed by 2488

Abstract

The most prevalent subtype of renal cell carcinoma (RCC), kidney renal clear cell carcinoma (KIRC) may be associated with a poor prognosis in a high number of cases, with a stage-specific prognostic stratification currently in use. No reliable biomarkers have been utilized so [...] Read more.

The most prevalent subtype of renal cell carcinoma (RCC), kidney renal clear cell carcinoma (KIRC) may be associated with a poor prognosis in a high number of cases, with a stage-specific prognostic stratification currently in use. No reliable biomarkers have been utilized so far in clinical practice despite the efforts in biomarker research in the last years. Nonsense-mediated mRNA decay (NMD) is a critical safeguard against erroneous transcripts, particularly mRNA transcripts containing premature termination codons (called nonsense-mediated decay targeted RNA, ntRNA). In this study, we first characterized 296 differentially expressed ntRNAs that were independent of the corresponding gene, 261 differentially expressed miRNAs, and 4653 differentially expressed lncRNAs. Then, we constructed a hub ntRNA–miRNA–lncRNA triple regulatory network associated with the prognosis of KIRC. Moreover, the results of immune infiltration analysis indicated that this network may influence the changes of the tumor immune microenvironment. A prognostic model derived from the genes and immune cells associated with the network was developed to distinguish between high- and low-risk patients, which was a better prognostic than other models, constructed using different biomarkers. Additionally, correlation of methylation and ntRNAs in the network suggested that some ntRNAs were regulated by methylation, which is helpful to further study the causes of abnormal expression of ntRNAs. In conclusion, this study highlighted the possible clinical implications of ntRNA functions in KIRC, proposing potential significant biomarkers that could be utilized to define the prognosis and design personalized treatment plans in kidney cancer management in the next future. Full article

(This article belongs to the Section Bioinformatics)

► Show Figures

Graphical abstract

9 pages, 254 KiB

Open AccessReview

SLC13A5 Deficiency Disorder: From Genetics to Gene Therapy

by Kimberly Goodspeed, Judy S. Liu, Kimberly L. Nye, Suyash Prasad, Chanchal Sadhu, Fatemeh Tavakkoli, Deborah A. Bilder, Berge A. Minassian and Rachel M. Bailey

Genes 2022, 13(9), 1655; https://doi.org/10.3390/genes13091655 - 15 Sep 2022

Cited by 8 | Viewed by 3672

Abstract

Epileptic encephalopathies may arise from single gene variants. In recent years, next-generation sequencing technologies have enabled an explosion of gene identification in monogenic epilepsies. One such example is the epileptic encephalopathy SLC13A5 deficiency disorder, which is caused by loss of function pathogenic variants [...] Read more.

Epileptic encephalopathies may arise from single gene variants. In recent years, next-generation sequencing technologies have enabled an explosion of gene identification in monogenic epilepsies. One such example is the epileptic encephalopathy SLC13A5 deficiency disorder, which is caused by loss of function pathogenic variants to the gene SLC13A5 that results in deficiency of the sodium/citrate cotransporter. Patients typically experience seizure onset within the first week of life and have developmental delay and intellectual disability. Current antiseizure medications may reduce seizure frequency, yet more targeted treatments are needed to address the epileptic and non-epileptic features of SLC13A5 deficiency disorder. Gene therapy may offer hope to these patients and better clinical outcomes than current available treatments. Here, we discuss SLC13A5 genetics, natural history, available treatments, potential outcomes and assessments, and considerations for translational medical research for an AAV9-based gene replacement therapy. Full article

(This article belongs to the Special Issue Genetics of Epileptic Encephalopathies: From Gene Discovery to Clinical Diagnosis and Management Implications of Genetic Diagnoses)

13 pages, 960 KiB

Open AccessArticle

Exploring Parents’ Concerns Regarding Long-Term Support and Living Arrangements for Their Children with Fragile X Syndrome

by Kaylynn Shuleski, Laura Zalles and Reymundo Lozano

Genes 2022, 13(9), 1654; https://doi.org/10.3390/genes13091654 - 15 Sep 2022

Cited by 2 | Viewed by 2199

Abstract

Given limited data regarding future planning specific to Fragile X Syndrome (FXS) individuals and the growing population of individuals within this community, this study sought to explore the concerns and challenges caregivers of individuals affected by FXS encounter when considering long-term support plans. [...] Read more.

Given limited data regarding future planning specific to Fragile X Syndrome (FXS) individuals and the growing population of individuals within this community, this study sought to explore the concerns and challenges caregivers of individuals affected by FXS encounter when considering long-term support plans. This involved identifying the reasons individuals with FXS continue to reside with family and the reservations caregivers have regarding future supports and living arrangements. We administered an anonymous online survey consisting of 34 questions assessing eligibility, living arrangements/supports, and future concerns. We found that most individuals with FXS were affected with moderate Intellectual and Developmental Disabilities (IDD) and co-occurring behavioral conditions but had overall good health. The majority of individuals with FXS currently resided with family due to parental desire, their own desire, and the inability to live independently. For one-third of caregivers, the plan for future living arrangements is to continue residing with family members long-term. A large proportion of caregivers had not considered alternative arrangements or were unsure. More than 70% of caregivers of individuals with FXS are concerned about multiple aspects of the individual’s future. Caregivers of younger individuals are the most concerned, but also believe they have time before they need to plan or are unable to currently assess the future need for support. Full article

(This article belongs to the Special Issue Fragile X Syndrome Genetics)

► Show Figures

Figure 1

10 pages, 608 KiB

Open AccessArticle

Vasovagal Syncope Is Associated with Variants in Genes Involved in Neurohumoral Signaling Pathways

by Boris Titov, Natalya Matveeva, Olga Kulakova, Natalia Baulina, Elizaveta Bazyleva, Grigory Kheymets, Anatolii Rogoza, Alexander Pevzner and Olga Favorova

Genes 2022, 13(9), 1653; https://doi.org/10.3390/genes13091653 - 15 Sep 2022

Cited by 4 | Viewed by 1763

Abstract

Vasovagal syncope (VVS) is the most common cause of sudden loss of consciousness. VVS results from cerebral hypoperfusion, due to abnormal autonomic control of blood circulation, leading to arterial hypotension. It is a complex disease, and its development is largely associated with genetic [...] Read more.

Vasovagal syncope (VVS) is the most common cause of sudden loss of consciousness. VVS results from cerebral hypoperfusion, due to abnormal autonomic control of blood circulation, leading to arterial hypotension. It is a complex disease, and its development is largely associated with genetic susceptibility. Since abnormal neurohumoral regulation plays an important role in VVS development, we analyzed the association of VVS with polymorphic variants of ADRA1A, ADRB1, HTR1A, ADORA2A, COMT, and NOS3 genes, the products of which are involved in neurohumoral signaling, in patients with a confirmed VVS diagnosis (157 subjects) and individuals without a history of syncope (161 subjects). We were able to identify the associations between VVS and alleles/genotypes ADRA1A rs1048101, ADRB1 rs1801253, ADORA2A rs5751876, and COMT rs4680, as well as NOS3 rs2070744 in biallelic combination with COMT rs4680. Thus, we are the first to observe, within a single study, the role of the genes that encode α- and β-adrenergic receptors, catechol-O-methyltransferase, adenosine receptors and nitric oxide synthase in VVS development. These findings demonstrate that the genes involved in neurohumoral signaling pathways contribute to the formation of a genetic susceptibility to VVS. Full article

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

► Show Figures

Figure 1

12 pages, 752 KiB

Open AccessArticle

Slow RNAPII Transcription Elongation Rate, Low Levels of RNAPII Pausing, and Elevated Histone H1 Content at Promoters Associate with Higher m6A Deposition on Nascent mRNAs

by Alicia Gallego, José Miguel Fernández-Justel, Sara Martín-Vírgala, Magdalena M. Maslon and María Gómez

Genes 2022, 13(9), 1652; https://doi.org/10.3390/genes13091652 - 14 Sep 2022

Cited by 2 | Viewed by 2871

Abstract

N6-methyladenosine modification (m6A) fine-tunes RNA fate in a variety of ways, thus regulating multiple fundamental biological processes. m6A writers bind to chromatin and interact with RNA polymerase II (RNAPII) during transcription. To evaluate how the dynamics of the transcription process impact m6A deposition, [...] Read more.

N6-methyladenosine modification (m6A) fine-tunes RNA fate in a variety of ways, thus regulating multiple fundamental biological processes. m6A writers bind to chromatin and interact with RNA polymerase II (RNAPII) during transcription. To evaluate how the dynamics of the transcription process impact m6A deposition, we studied RNAPII elongation rates in mouse embryonic stem cells with altered chromatin configurations, due to reductions in linker histone H1 content. We found that genes transcribed at slow speed are preferentially methylated and display unique signatures at their promoter region, namely high levels of histone H1, together with marks of bivalent chromatin and low RNAPII pausing. They are also highly susceptible to m6A loss upon histone H1 reduction. These results indicate that RNAPII velocity links chromatin structure and the deposition of m6A, highlighting the intricate relationship between different regulatory layers on nascent mRNA molecules. Full article

(This article belongs to the Special Issue Epigenomics and Epitranscriptomics Crosstalk)

► Show Figures

Graphical abstract

15 pages, 4474 KiB

Open AccessArticle

Grp94 Inhibitor HCP1 Inhibits Human Dermal Fibroblast Senescence

by Xiaoling Cui, Xuxiao Hao, Jie Wen, Shangli Zhang, Baoxiang Zhao and Junying Miao

Genes 2022, 13(9), 1651; https://doi.org/10.3390/genes13091651 - 14 Sep 2022

Cited by 4 | Viewed by 2290

Abstract

Researchers are paying more and more attention to aging, especially skin aging. Therefore, it is urgent to find an effective way to inhibit aging. Here, we report a small chemical molecule, HCP1, that inhibited the senescence of human dermal fibroblasts (HDFs). First, we [...] Read more.

Researchers are paying more and more attention to aging, especially skin aging. Therefore, it is urgent to find an effective way to inhibit aging. Here, we report a small chemical molecule, HCP1, that inhibited the senescence of human dermal fibroblasts (HDFs). First, we performed morphological experiment and found that HCP1-treated HDFs were no longer elongated and flat compared to DMSO-treated groups. Next, we found that the number of β-gal positive cells decreased compared to DMSO-treated groups. Through flow cytometry, western blot, and immunofluorescence, we found that HCP1 could inhibit the senescence of HDFs. In the study of the mechanism, we found that HCP1 could regulate the AMPK/mTOR signal pathway through glucose-regulated protein 94 (Grp94). In addition, we found that HCP1 could promote the interaction between Grp94 and lysosomes, which led to an increase in the activity of lysosomes and inhibited the senescence of HDFs. At the same time, we found that HCP1 decreased the concentration of Ca²⁺ in mitochondria, inhibiting the senescence of HCP1. Therefore, we propose that HCP1 is a potential aging-inhibiting compound, and provide a new idea for the development of senescence-inhibiting drugs. Full article

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

► Show Figures

Graphical abstract

16 pages, 10149 KiB

Open AccessArticle

A Transformation and Genome Editing System for Cassava Cultivar SC8

by Ya-Jie Wang, Xiao-Hua Lu, Xing-Hou Zhen, Hui Yang, Yan-Nian Che, Jing-Yi Hou, Meng-Ting Geng, Jiao Liu, Xin-Wen Hu, Rui-Mei Li, Jian-Chun Guo and Yuan Yao

Genes 2022, 13(9), 1650; https://doi.org/10.3390/genes13091650 - 14 Sep 2022

Cited by 15 | Viewed by 3536

Abstract

Cassava starch is a widely used raw material for industrial production. South Chinese cassava cultivar 8 (Manihot esculenta Crantz cv. SC8) is one of the main locally planted cultivars. In this study, an efficient transformation system for cassava SC8 mediated with Agrobacterium [...] Read more.

Cassava starch is a widely used raw material for industrial production. South Chinese cassava cultivar 8 (Manihot esculenta Crantz cv. SC8) is one of the main locally planted cultivars. In this study, an efficient transformation system for cassava SC8 mediated with Agrobacterium strain LBA4404 was presented for the first time. Cassava friable embryogenic calli (FECs) were transformed through the binary vector pCAMBIA1304 harboring GUS- and GFP-fused genes driven by the CaMV35S promoter. The transformation efficiency was increased in the conditions of Agrobacterium strain cell infection density (OD₆₀₀ = 0.65), 250 µM acetosyringone induction, and agro-cultivation with wet FECs for 3 days in dark. Based on the optimized transformation protocol, approximately 120–140 independent transgenic lines per mL settled cell volume (SCV) of FECs were created by gene transformation in approximately 5 months, and 45.83% homozygous mono-allelic mutations of the MePDS gene with a YAO promoter-driven CRISPR/Cas9 system were generated. This study will open a more functional avenue for the genetic improvement of cassava SC8. Full article

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

► Show Figures

Figure 1

7 pages, 747 KiB

Open AccessCase Report

TBX3 and EFNA4 Variant in a Family with Ulnar-Mammary Syndrome and Sagittal Craniosynostosis

by Moon Ley Tung, Bharatendu Chandra, Jaclyn Kotlarek, Marcelo Melo, Elizabeth Phillippi, Cristina M. Justice, Anthony Musolf, Simeon A. Boyadijev, Paul A. Romitti, Benjamin Darbro and Hatem El-Shanti

Genes 2022, 13(9), 1649; https://doi.org/10.3390/genes13091649 - 14 Sep 2022

Cited by 1 | Viewed by 2011

Abstract

Ulnar-mammary syndrome (UMS) is a rare, autosomal dominant disorder characterized by anomalies affecting the limbs, apocrine glands, dentition, and genital development. This syndrome is caused by haploinsufficiency in the T-Box3 gene (TBX3), with considerable variability in the clinical phenotype being observed [...] Read more.

Ulnar-mammary syndrome (UMS) is a rare, autosomal dominant disorder characterized by anomalies affecting the limbs, apocrine glands, dentition, and genital development. This syndrome is caused by haploinsufficiency in the T-Box3 gene (TBX3), with considerable variability in the clinical phenotype being observed even within families. We describe a one-year-old female with unilateral, postaxial polydactyly, and bilateral fifth fingernail duplication. Next-generation sequencing revealed a novel, likely pathogenic, variant predicted to affect the canonical splice site in intron 3 of the TBX3 gene (c.804 + 1G > A, IVS3 + 1G > A). This variant was inherited from the proband’s father who was also diagnosed with UMS with the additional clinical finding of congenital, sagittal craniosynostosis. Subsequent whole genome analysis in the proband’s father detected a variant in the EFNA4 gene (c.178C > T, p.His60Tyr), which has only been reported to be associated with sagittal craniosynostosis in one patient prior to this report but reported in other cranial suture synostosis. The findings in this family extend the genotypic spectrum of UMS, as well as the phenotypic spectrum of EFNA4-related craniosynostosis. Full article

(This article belongs to the Collection Genotype-Phenotype Study in Disease)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Genes, Volume 13, Issue 9 (September 2022) – 178 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI