Genes

11 pages, 1718 KiB

Open AccessArticle

pcPromoter-CNN: A CNN-Based Prediction and Classification of Promoters

by Muhammad Shujaat, Abdul Wahab, Hilal Tayara and Kil To Chong

Genes 2020, 11(12), 1529; https://doi.org/10.3390/genes11121529 - 21 Dec 2020

Cited by 41 | Viewed by 5140

A promoter is a small region within the DNA structure that has an important role in initiating transcription of a specific gene in the genome. Different types of promoters are recognized by their different functions. Due to the importance of promoter functions, computational [...] Read more.

A promoter is a small region within the DNA structure that has an important role in initiating transcription of a specific gene in the genome. Different types of promoters are recognized by their different functions. Due to the importance of promoter functions, computational tools for the prediction and classification of a promoter are highly desired. Promoters resemble each other; therefore, their precise classification is an important challenge. In this study, we propose a convolutional neural network (CNN)-based tool, the pcPromoter-CNN, for application in the prediction of promotors and their classification into subclasses σ70, σ54, σ38, σ32, σ28 and σ24. This CNN-based tool uses a one-hot encoding scheme for promoter classification. The tools architecture was trained and tested on a benchmark dataset. To evaluate its classification performance, we used four evaluation metrics. The model exhibited notable improvement over that of existing state-of-the-art tools. Full article

(This article belongs to the Special Issue Computational Methods for the Analysis of Genomic Data and Biological Processes (II))

► Show Figures

Figure 1

35 pages, 20853 KiB

Open AccessReview

Chromosome Instability in Fanconi Anemia: From Breaks to Phenotypic Consequences

by Benilde García-de-Teresa, Alfredo Rodríguez and Sara Frias

Genes 2020, 11(12), 1528; https://doi.org/10.3390/genes11121528 - 21 Dec 2020

Cited by 48 | Viewed by 12836

Abstract

Fanconi anemia (FA), a chromosomal instability syndrome, is caused by inherited pathogenic variants in any of 22 FANC genes, which cooperate in the FA/BRCA pathway. This pathway regulates the repair of DNA interstrand crosslinks (ICLs) through homologous recombination. In FA proper repair of [...] Read more.

Fanconi anemia (FA), a chromosomal instability syndrome, is caused by inherited pathogenic variants in any of 22 FANC genes, which cooperate in the FA/BRCA pathway. This pathway regulates the repair of DNA interstrand crosslinks (ICLs) through homologous recombination. In FA proper repair of ICLs is impaired and accumulation of toxic DNA double strand breaks occurs. To repair this type of DNA damage, FA cells activate alternative error-prone DNA repair pathways, which may lead to the formation of gross structural chromosome aberrations of which radial figures are the hallmark of FA, and their segregation during cell division are the origin of subsequent aberrations such as translocations, dicentrics and acentric fragments. The deficiency in DNA repair has pleiotropic consequences in the phenotype of patients with FA, including developmental alterations, bone marrow failure and an extreme risk to develop cancer. The mechanisms leading to the physical abnormalities during embryonic development have not been clearly elucidated, however FA has features of premature aging with chronic inflammation mediated by pro-inflammatory cytokines, which results in tissue attrition, selection of malignant clones and cancer onset. Moreover, chromosomal instability and cell death are not exclusive of the somatic compartment, they also affect germinal cells, as evidenced by the infertility observed in patients with FA. Full article

(This article belongs to the Special Issue Causes and Consequences of Chromosomal Aberrations)

► Show Figures

Figure 1

15 pages, 4299 KiB

Open AccessArticle

The Complete Genome of Probiotic Lactobacillus sakei Derived from Plateau Yak Feces

by Kun Li, Juanjuan Liu, Zhibo Zeng, Muhammad Fakhar-e-Alam Kulyar, Yaping Wang, Aoyun Li, Zeeshan Ahmad Bhutta, Amjad Islam Aqib, Muhammad Shahzad, Jiakui Li and Desheng Qi

Genes 2020, 11(12), 1527; https://doi.org/10.3390/genes11121527 - 21 Dec 2020

Cited by 9 | Viewed by 2997

Abstract

Probiotic bacteria are receiving increased attention due to the potential benefits to their hosts. Plateau yaks have resistance against diseases and stress, which is potentially related to their inner probiotics. To uncover the potential functional genes of yak probiotics, we sequenced the whole [...] Read more.

Probiotic bacteria are receiving increased attention due to the potential benefits to their hosts. Plateau yaks have resistance against diseases and stress, which is potentially related to their inner probiotics. To uncover the potential functional genes of yak probiotics, we sequenced the whole genome of Lactobacillus sakei (L. sakei). The results showed that the genome length of L. sakei was 1.99 Mbp, with 1943 protein coding genes (21 rRNA, 65 tRNA, and 1 tmRNA). There were three plasmids found in this bacteria, with 88 protein coding genes. EggNOG annotation uncovered that the L. sakei genes were found to belong to J (translation, ribosomal structure, and biogenesis), L (replication, recombination, and repair), G (carbohydrate transport and metabolism), and K (transcription). GO annotation showed that most of the L. sakei genes were related to cellular processes, metabolic processes, biological regulation, localization, response to stimulus, and organization or biogenesis of cellular components. CAZy annotation found that there were 123 CAZys in the L. sakei genome, with glycosyl transferases and glycoside hydrolases. Our results revealed the genome characteristics of L. sakei, which may give insight into the future employment of this probiotic bacterium for its functional benefits. Full article

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

► Show Figures

Figure 1

20 pages, 3277 KiB

Open AccessArticle

Transcriptional Regulation of CD40 Expression by 4 Ribosomal Proteins via a Functional SNP on a Disease-Associated CD40 Locus

by Meijuan Zou, Xiaoyu Zhang, Danli Jiang, Yihan Zhao, Ting Wu, Qiaoke Gong, Hang Su, Di Wu, Larry Moreland and Gang Li

Genes 2020, 11(12), 1526; https://doi.org/10.3390/genes11121526 - 21 Dec 2020

Cited by 7 | Viewed by 3485

Abstract

Previously, using FREP-MS, we identified a protein complex including eight proteins that specifically bind to the functional SNP (fSNP) rs6032664 at a CD40 locus associated with autoimmune diseases. Among these eight proteins, four are ribosomal proteins RPL26, RPL4, RPL8, and RPS9 that normally [...] Read more.

Previously, using FREP-MS, we identified a protein complex including eight proteins that specifically bind to the functional SNP (fSNP) rs6032664 at a CD40 locus associated with autoimmune diseases. Among these eight proteins, four are ribosomal proteins RPL26, RPL4, RPL8, and RPS9 that normally make up the ribosomal subunits involved in the cellular process of protein translation. So far, no publication has shown these ribosomal proteins function as transcriptional regulators. In this work, we demonstrate that four ribosomal proteins: RPL26, RPL4, RPL8, and RPS9 are bona fide CD40 transcriptional regulators via binding to rs6032664. In addition, we show that suppression of CD40 expression by RPL26 RNAi knockdown inactivates NF-κB p65 by dephosphorylation via NF-κB signaling pathway in fibroblast-like synoviocytes (FLS), which further reduces the transcription of disease-associated risk genes such as STAT4, CD86, TRAF1 and ICAM1 as the direct targets of NF-κB p65. Based on these findings, a disease-associated risk gene transcriptional regulation network (TRN) is generated, in which decreased expression of, at least, RPL26 results in the downregulation of risk genes: STAT4, CD86, TRAF1 and ICAM1, as well as the two proinflammatory cytokines: IL1β and IL6 via CD40-induced NF-κB signaling. We believe that further characterization of this disease-associated TRN in the CD40-induced NF-κB signaling by identifying both the upstream and downstream regulators will potentially enable us to identify the best targets for drug development. Full article

(This article belongs to the Special Issue Autoimmune Disease Genetics)

► Show Figures

Figure 1

2 pages, 156 KiB

Open AccessEditorial

The Different Roads to Maintain Telomeres in Cancer Cells

by Rosario Perona

Genes 2020, 11(12), 1525; https://doi.org/10.3390/genes11121525 - 21 Dec 2020

Viewed by 1630

Abstract

Telomeres are the protective structures at the ends of linear chromosomes that progressively shorten each time that a cell divides, which is in part caused by the end-replication problem [...] Full article

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

12 pages, 1277 KiB

Open AccessArticle

RAM-PGK: Prediction of Lysine Phosphoglycerylation Based on Residue Adjacency Matrix

by Abel Avitesh Chandra, Alok Sharma, Abdollah Dehzangi and Tatushiko Tsunoda

Genes 2020, 11(12), 1524; https://doi.org/10.3390/genes11121524 - 20 Dec 2020

Cited by 7 | Viewed by 2965

Abstract

Background: Post-translational modification (PTM) is a biological process that is associated with the modification of proteome, which results in the alteration of normal cell biology and pathogenesis. There have been numerous PTM reports in recent years, out of which, lysine phosphoglycerylation has emerged [...] Read more.

Background: Post-translational modification (PTM) is a biological process that is associated with the modification of proteome, which results in the alteration of normal cell biology and pathogenesis. There have been numerous PTM reports in recent years, out of which, lysine phosphoglycerylation has emerged as one of the recent developments. The traditional methods of identifying phosphoglycerylated residues, which are experimental procedures such as mass spectrometry, have shown to be time-consuming and cost-inefficient, despite the abundance of proteins being sequenced in this post-genomic era. Due to these drawbacks, computational techniques are being sought to establish an effective identification system of phosphoglycerylated lysine residues. The development of a predictor for phosphoglycerylation prediction is not a first, but it is necessary as the latest predictor falls short in adequately detecting phosphoglycerylated and non-phosphoglycerylated lysine residues. Results: In this work, we introduce a new predictor named RAM-PGK, which uses sequence-based information relating to amino acid residues to predict phosphoglycerylated and non-phosphoglycerylated sites. A benchmark dataset was employed for this purpose, which contained experimentally identified phosphoglycerylated and non-phosphoglycerylated lysine residues. From the dataset, we extracted the residue adjacency matrix pertaining to each lysine residue in the protein sequences and converted them into feature vectors, which is used to build the phosphoglycerylation predictor. Conclusion: RAM-PGK, which is based on sequential features and support vector machine classifiers, has shown a noteworthy improvement in terms of performance in comparison to some of the recent prediction methods. The performance metrics of the RAM-PGK predictor are: 0.5741 sensitivity, 0.6436 specificity, 0.0531 precision, 0.6414 accuracy, and 0.0824 Mathews correlation coefficient. Full article

(This article belongs to the Special Issue Selected Papers from the 19th International Conference on Bioinformatics (InCoB 2020))

► Show Figures

Figure 1

13 pages, 3893 KiB

Open AccessArticle

OSmfs: An Online Interactive Tool to Evaluate Prognostic Markers for Myxofibrosarcoma

by Huimin Li, Longxiang Xie, Qiang Wang, Yifang Dang, Xiaoxiao Sun, Lu Zhang, Yali Han, Zhongyi Yan, Huan Dong, Hong Zheng, Yongqiang Li, Wan Zhu and Xiangqian Guo

Genes 2020, 11(12), 1523; https://doi.org/10.3390/genes11121523 - 19 Dec 2020

Cited by 4 | Viewed by 2570

Abstract

Myxofibrosarcoma is a complex genetic disease with poor prognosis. However, more effective biomarkers that forebode poor prognosis in Myxofibrosarcoma remain to be determined. Herein, utilizing gene expression profiling data and clinical follow-up data of Myxofibrosarcoma cases in three independent cohorts with a total [...] Read more.

Myxofibrosarcoma is a complex genetic disease with poor prognosis. However, more effective biomarkers that forebode poor prognosis in Myxofibrosarcoma remain to be determined. Herein, utilizing gene expression profiling data and clinical follow-up data of Myxofibrosarcoma cases in three independent cohorts with a total of 128 Myxofibrosarcoma samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we constructed an easy-to-use web tool, named Online consensus Survival analysis for Myxofibrosarcoma (OSmfs) to analyze the prognostic value of certain genes. Through retrieving the database, users generate a Kaplan–Meier plot with log-rank test and hazard ratio (HR) to assess prognostic-related genes or discover novel Myxofibrosarcoma prognostic biomarkers. The effectiveness and availability of OSmfs were validated using genes in ever reports predicting the prognosis of Myxofibrosarcoma patients. Furthermore, utilizing the cox analysis data and transcriptome data establishing OSmfs, seven genes were selected and considered as more potentially prognostic biomarkers through overlapping and ROC analysis. In conclusion, OSmfs is a promising web tool to evaluate the prognostic potency and reliability of genes in Myxofibrosarcoma, which may significantly contribute to the enrichment of novelly potential prognostic biomarkers and therapeutic targets for Myxofibrosarcoma. Full article

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

► Show Figures

Figure 1

8 pages, 636 KiB

Open AccessCommunication

Fourier-Transform Infrared Spectroscopy of Skeletal Muscle Tissue: Expanding Biomarkers in Primary Mitochondrial Myopathies

by Jacopo Gervasoni, Aniello Primiano, Federico Marini, Andrea Sabino, Alessandra Biancolillo, Riccardo Calvani, Anna Picca, Emanuele Marzetti, Silvia Persichilli, Andrea Urbani, Serenella Servidei and Guido Primiano

Genes 2020, 11(12), 1522; https://doi.org/10.3390/genes11121522 - 19 Dec 2020

Cited by 6 | Viewed by 2360

Abstract

Primary mitochondrial myopathies (PMM) are a group of mitochondrial disorders characterized by a predominant skeletal muscle involvement. The aim of this study was to evaluate whether the biochemical profile determined by Fourier-transform infrared (FTIR) spectroscopic technique would allow to distinguish among patients affected [...] Read more.

Primary mitochondrial myopathies (PMM) are a group of mitochondrial disorders characterized by a predominant skeletal muscle involvement. The aim of this study was to evaluate whether the biochemical profile determined by Fourier-transform infrared (FTIR) spectroscopic technique would allow to distinguish among patients affected by progressive external ophthalmoplegia (PEO), the most common PMM presentation, oculopharyngeal muscular dystrophy (OPMD), and healthy controls. Thirty-four participants were enrolled in the study. FTIR spectroscopy was found to be a sensitive and specific diagnostic marker for PEO. In particular, FTIR spectroscopy was able to distinguish PEO patients from those affected by OPMD, even in the presence of histological findings similar to mitochondrial myopathy. At the same time, FTIR spectroscopy differentiated single mtDNA deletion and mutations in POLG, the most common nuclear gene associated with mitochondrial diseases, with high sensitivity and specificity. In conclusion, our data suggest that FTIR spectroscopy is a valuable biodiagnostic tool for the differential diagnosis of PEO with a high ability to also distinguish between single mtDNA deletion and mutations in POLG gene based on specific metabolic transitions. Full article

(This article belongs to the Special Issue Genetics of Mitochondrial Diseases: From Laboratory to the Clinic)

► Show Figures

Figure 1

12 pages, 1447 KiB

Open AccessReview

The Reproductive Journey in the Genomic Era: From Preconception to Childhood

by Sandra Garcia-Herrero, Blanca Simon and Javier Garcia-Planells

Genes 2020, 11(12), 1521; https://doi.org/10.3390/genes11121521 - 19 Dec 2020

Cited by 7 | Viewed by 4455

Abstract

It is estimated that around 10–15% of the population have problems achieving a pregnancy. Assisted reproduction techniques implemented and enforced by personalized genomic medicine have paved the way for millions of infertile patients to become parents. Nevertheless, having a baby is just the [...] Read more.

It is estimated that around 10–15% of the population have problems achieving a pregnancy. Assisted reproduction techniques implemented and enforced by personalized genomic medicine have paved the way for millions of infertile patients to become parents. Nevertheless, having a baby is just the first challenge to overcome in the reproductive journey, the most important is to obtain a healthy baby free of any genetic condition that can be prevented. Prevention of congenital anomalies throughout the lifespan of the patient must be a global health priority. Congenital disorders can be defined as structural or functional anomalies that occur during intrauterine life and can be identified prenatally, at birth, or sometimes may only be detected later during childhood. It is considered a frequent group of disorders, affecting 3–6% of the population, and one of the leading causes of morbidity and mortality. Congenital anomalies can represent up to 30–50% of infant mortality in developed countries. Genetics plays a substantial role in the pathogenesis of congenital anomalies. This becomes especially important in some ethnic communities or populations where the incidence and levels of consanguinity are higher. The impact of genetic disorders during childhood is high, representing 20–30% of all infant deaths and 11.1% of pediatric hospital admissions. With these data, obtaining a precise genetic diagnosis is one of the main aspects of a preventive medicine approach in developed countries. The field of reproductive health has changed dramatically from traditional non-molecular visual microscope-based techniques (i.e., fluorescence in situ hybridization (FISH) or G-banding karyotype), to the latest molecular high-throughput techniques such as next-generation sequencing (NGS). Genome-wide technologies are applied along the different stages of the reproductive health lifecycle from preconception carrier screening and pre-implantation genetic testing, to prenatal and postnatal testing. The aim of this paper is to assess the new horizon opened by technologies such as next-generation sequencing (NGS), in new strategies, as a genomic precision diagnostic tool to understand the mechanisms underlying genetic conditions during the “reproductive journey”. Full article

(This article belongs to the Special Issue EmbryoGenetics)

► Show Figures

Figure 1

18 pages, 3070 KiB

Open AccessArticle

Analysis of Whole Transcriptome RNA-seq Data Reveals Many Alternative Splicing Events in Soybean Roots under Drought Stress Conditions

by Li Song, Zhenzhi Pan, Lin Chen, Yi Dai, Jinrong Wan, Heng Ye, Henry T. Nguyen, Guozheng Zhang and Huatao Chen

Genes 2020, 11(12), 1520; https://doi.org/10.3390/genes11121520 - 19 Dec 2020

Cited by 22 | Viewed by 3987

Abstract

Alternative splicing (AS) is a common post-transcriptional regulatory mechanism that modulates gene expression to increase proteome diversity. Increasing evidence indicates that AS plays an important role in regulating plant stress responses. However, the mechanism by which AS coordinates with transcriptional regulation to regulate [...] Read more.

Alternative splicing (AS) is a common post-transcriptional regulatory mechanism that modulates gene expression to increase proteome diversity. Increasing evidence indicates that AS plays an important role in regulating plant stress responses. However, the mechanism by which AS coordinates with transcriptional regulation to regulate drought responses in soybean remains poorly understood. In this study, we performed a genome-wide analysis of AS events in soybean (Glycine max) roots grown under various drought conditions using the high-throughput RNA-sequencing method, identifying 385, 989, 1429, and 465 AS events that were significantly differentially spliced under very mild drought stress, mild drought stress, severe drought stress, and recovery after severe drought conditions, respectively. Among them, alternative 3′ splice sites and skipped exons were the major types of AS. Overall, 2120 genes that experienced significant AS regulation were identified from these drought-treated root samples. Gene Ontology term analysis indicated that the AS regulation of binding activity has vital roles in the drought response of soybean root. Notably, the genes encoding splicing regulatory factors in the spliceosome pathway and mRNA surveillance pathway were enriched according to the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Splicing regulatory factor-related genes in soybean root also responded to drought stress and were alternatively spliced under drought conditions. Taken together, our data suggest that drought-responsive AS acts as a direct or indirect mode to regulate drought response of soybean roots. With further in-depth research of the function and mechanism of AS in the process of abiotic stress, these results will provide a new strategy for enhancing stress tolerance of plants. Full article

(This article belongs to the Special Issue Root Development and Architecture in Relation to Environmental Conditions)

► Show Figures

Figure 1

8 pages, 1628 KiB

Open AccessCase Report

The First Case of Congenital Myasthenic Syndrome Caused by a Large Homozygous Deletion in the C-Terminal Region of COLQ (Collagen Like Tail Subunit of Asymmetric Acetylcholinesterase) Protein

by Nicola Laforgia, Lucrezia De Cosmo, Orazio Palumbo, Carlotta Ranieri, Michela Sesta, Donatella Capodiferro, Antonino Pantaleo, Pierluigi Iapicca, Patrizia Lastella, Manuela Capozza, Federico Schettini, Nenad Bukvic, Rosanna Bagnulo and Nicoletta Resta

Genes 2020, 11(12), 1519; https://doi.org/10.3390/genes11121519 - 18 Dec 2020

Cited by 8 | Viewed by 2869

Abstract

Congenital myasthenic syndromes (CMSs) are caused by mutations in genes that encode proteins involved in the organization, maintenance, function, or modification of the neuromuscular junction. Among these, the collagenic tail of endplate acetylcholinesterase protein (COLQ; MIM 603033) has a crucial role in anchoring [...] Read more.

Congenital myasthenic syndromes (CMSs) are caused by mutations in genes that encode proteins involved in the organization, maintenance, function, or modification of the neuromuscular junction. Among these, the collagenic tail of endplate acetylcholinesterase protein (COLQ; MIM 603033) has a crucial role in anchoring the enzyme into the synaptic basal lamina. Here, we report on the first case of a patient with a homozygous deletion affecting the last exons of the COLQ gene in a CMS patient born to consanguineous parents of Pakistani origin. Electromyography (EMG), electroencephalography (EEG), clinical exome sequencing (CES), and single nucleotide polymorphism (SNP) array analyses were performed. The subject was born at term after an uneventful pregnancy and developed significant hypotonia and dystonia, clinical pseudoseizures, and recurring respiratory insufficiency with a need for mechanical ventilation. CES analysis of the patient revealed a homozygous deletion of the COLQ gene located on the 3p25.1 chromosome region. The SNP-array confirmed the presence of deletion that extended from exon 11 to the last exon 17 with a size of 19.5 Kb. Our results add new insights about the underlying pathogenetic mechanisms expanding the spectrum of causative COLQ mutations. It is relevant, considering the therapeutic implications, to apply suitable molecular approaches so that no type of mutation is missed: “each lost mutation means a baby treated improperly”. Full article

(This article belongs to the Special Issue Genetic Basis of Sensory and Neurological Disorders)

► Show Figures

Figure 1

11 pages, 5743 KiB

Open AccessArticle

Distribution of the Warmblood Fragile Foal Syndrome Type 1 Mutation (PLOD1 c.2032G>A) in Different Horse Breeds from Europe and the United States

by Simone Reiter, Barbara Wallner, Gottfried Brem, Elisabeth Haring, Ludwig Hoelzle, Monika Stefaniuk-Szmukier, Bogusława Długosz, Katarzyna Piórkowska, Katarzyna Ropka-Molik, Julia Malvick, Maria Cecilia T. Penedo and Rebecca R. Bellone

Genes 2020, 11(12), 1518; https://doi.org/10.3390/genes11121518 - 18 Dec 2020

Cited by 12 | Viewed by 7273

Abstract

Warmblood fragile foal syndrome (WFFS) is an autosomal recessive disorder caused by a single nucleotide variant in the procollagen-lysine-2-oxoglutarate-5-dioxygenase 1 gene (PLOD1:c.2032G>A, p.Gly678Arg). Homozygosity for the PLOD1 variant causes an Ehler-Danlos-like syndrome, which has to date only been reported in warmblood breeds but [...] Read more.

Warmblood fragile foal syndrome (WFFS) is an autosomal recessive disorder caused by a single nucleotide variant in the procollagen-lysine-2-oxoglutarate-5-dioxygenase 1 gene (PLOD1:c.2032G>A, p.Gly678Arg). Homozygosity for the PLOD1 variant causes an Ehler-Danlos-like syndrome, which has to date only been reported in warmblood breeds but the WFFS allele has been also detected in the Thoroughbred. To investigate the breed distribution of the WFFS allele, 4081 horses belonging to 38 different breeds were screened. In total, 4.9% of the horses representing 21 breeds carried the WFFS allele. The affected breeds were mainly warmbloods, with carrier frequency as high as 17% in the Hanoverian and Danish Warmblood. The WFFS allele was not detected in most non-warmblood breeds. Exceptions include WFFS carriers in the Thoroughbred (17/716), Haflinger (2/48), American Sport Pony (1/12), and Knabstrupper (3/46). The origin of the WFFS allele remains unknown. The Arabian breed and specifically the stallion Bairactar Or. Ar. (1813), whose offspring were reported to have a similar phenotype in the 19th century, were hypothesized as the origin. DNA from a museum sample of Bairactar Or. Ar. showed that he did not carry the mutated allele. This result, together with the genotypes of 302 Arabians, all homozygous for the reference allele, does not support an Arabian origin of the WFFS allele. Our extensive survey shows the WFFS allele to be of moderate frequency and concern in warmbloods and also in breeds where it may not be expected. Full article

(This article belongs to the Special Issue Marker-Assisted Selection in the Equine)

► Show Figures

Figure 1

10 pages, 1414 KiB

Open AccessArticle

Bi-Allelic Pathogenic Variations in MERTK Including Deletions Are Associated with an Early Onset Progressive Form of Retinitis Pigmentosa

by Cathrine Jespersgaard, Mette Bertelsen, Farah Arif, Helene Gry Gellert-Kristensen, Mingyan Fang, Hanne Jensen, Thomas Rosenberg, Zeynep Tümer, Lisbeth Birk Møller, Karen Brøndum-Nielsen and Karen Grønskov

Genes 2020, 11(12), 1517; https://doi.org/10.3390/genes11121517 - 18 Dec 2020

Cited by 8 | Viewed by 2249

Abstract

Bi-allelic pathogenic variants in MERTK cause retinitis pigmentosa (RP). Since deletions of more than one exon have been reported repeatedly for MERTK, CNV (copy number variation) analysis of next-generation sequencing (NGS) data has proven important in molecular genetic diagnostics of MERTK. [...] Read more.

Bi-allelic pathogenic variants in MERTK cause retinitis pigmentosa (RP). Since deletions of more than one exon have been reported repeatedly for MERTK, CNV (copy number variation) analysis of next-generation sequencing (NGS) data has proven important in molecular genetic diagnostics of MERTK. CNV analysis was performed on NGS data of 677 individuals with inherited retinal diseases (IRD) and confirmed by quantitative RT-PCR analysis. Clinical evaluation was based on retrospective records. Clinical re-examination included visual field examination, dark adaption, scotopic and photopic full-field electroretinograms (ffERG), multifocal ERG (mfERG) and optic coherence tomography (OCT). Fourteen variants were detected in MERTK in six individuals, three of which were deletions of more than one exon. Clinical examinations of five out of six individuals revealed a severe phenotype with early-onset generalized retinal dystrophy with night blindness and progressive visual field loss; however, one individual had a milder phenotype. Three individuals had hearing impairments. We show that deletions represent a substantial part of the causative variants in MERTK and emphasize that CNV analysis should be included in the molecular genetic diagnostics of IRDs. Full article

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

► Show Figures

Figure 1

15 pages, 1328 KiB

Open AccessArticle

Carriage and Gene Content Variability of the pESI-Like Plasmid Associated with Salmonella Infantis Recently Established in United States Poultry Production

by Elizabeth A. McMillan, Jamie L. Wasilenko, Kaitlin A. Tagg, Jessica C. Chen, Mustafa Simmons, Sushim K. Gupta, Glenn E. Tillman, Jason Folster, Charlene R. Jackson and Jonathan G. Frye

Genes 2020, 11(12), 1516; https://doi.org/10.3390/genes11121516 - 18 Dec 2020

Cited by 29 | Viewed by 4968

Abstract

Salmonella Infantis carrying extended spectrum β-lactamase bla_CTX-M-65 on a pESI-like megaplasmid has recently emerged in United States poultry. In order to determine the carriage rate and gene content variability of this plasmid in U.S. Salmonella Infantis, whole genome sequences of Salmonella isolates [...] Read more.

Salmonella Infantis carrying extended spectrum β-lactamase bla_CTX-M-65 on a pESI-like megaplasmid has recently emerged in United States poultry. In order to determine the carriage rate and gene content variability of this plasmid in U.S. Salmonella Infantis, whole genome sequences of Salmonella isolates from humans and animals in the U.S. and internationally containing the pESI-like plasmid were analyzed. The U.S. Department of Agriculture Food Safety and Inspection Service (FSIS) identified 654 product sampling isolates containing pESI-like plasmids through hazard analysis and critical control point (HACCP) verification testing in 2017 and 2018. The Centers for Disease Control and Prevention identified 55 isolates with pESI-like plasmids in 2016–2018 through the National Antimicrobial Resistance Monitoring System. Approximately 49% of pESI-like plasmids from FSIS verification isolates and 71% from CDC NARMS contained bla_CTX-M-65. Pan-plasmid genome analysis was also performed. All plasmids contained traN and more than 95% contained 172 other conserved genes; 61% contained bla_CTX-M-65. In a hierarchical clustering analysis, some plasmids from U.S. animal sources clustered together and some plasmids from South America clustered together, possibly indicating multiple plasmid lineages. However, most plasmids contained similar genes regardless of origin. Carriage of the pESI-like plasmid in U.S. appears to be limited to Salmonella Infantis and carriage rates increased from 2017 to 2018. Full article

(This article belongs to the Special Issue Genetics and Genomics of Zoonotic Foodborne Pathogens)

► Show Figures

Figure 1

13 pages, 1949 KiB

Open AccessArticle

Latitudinal Cline in Chromosome Numbers of Ice Cod A. glacialis (Gadidae) from Northeast Greenland

by Laura Ghigliotti, Jørgen S. Christiansen, Erica Carlig, Davide Di Blasi and Eva Pisano

Genes 2020, 11(12), 1515; https://doi.org/10.3390/genes11121515 - 18 Dec 2020

Cited by 6 | Viewed by 2429

Abstract

The ice cod Arctogadus glacialis (Peters, 1872) is one of the few fish species endemic to the Arctic. With a circumpolar distribution, the species is confined to the fjords and shelves of the Arctic seas. Biological information on A. glacialis is scarce, with [...] Read more.

The ice cod Arctogadus glacialis (Peters, 1872) is one of the few fish species endemic to the Arctic. With a circumpolar distribution, the species is confined to the fjords and shelves of the Arctic seas. Biological information on A. glacialis is scarce, with genomic information restricted to microsatellites. Within the frame of the TUNU-Programme: Arctic Ocean Fishes—Diversity, Adaptation and Conservation, we studied A. glacialis at the chromosomal level to explore fish diversity and evolutionary aspects. The analysis of over 50 individuals from the Northeast Greenland fjords between latitudes 71°09′ N and 76°42′ N revealed a remarkable intraspecific diversity epitomized by chromosome numbers spanning from 28 to 33, the occurrence of putative B chromosomes, and diversified patterns of distribution of heterochromatin and rDNAs. The number of B chromosomes followed a latitudinal gradient from 0–2 in the north to 2–5 in the south. Considering the benthic and rather stationary life history of this species, the observed chromosomal differences might have arisen independently, possibly driven and/or fostered by the dynamics of repetitive sequences, and are being fixed in relatively isolated fjord populations. The resulting latitudinal cline we observe today might have repercussions on the fate of local populations facing the ongoing climate-driven environmental changes. Full article

(This article belongs to the Special Issue Fish Cytogenetics: Present and Future)

► Show Figures

Figure 1

16 pages, 267 KiB

Open AccessReview

Genetic Variants behind Cardiovascular Diseases and Dementia

by Wei-Min Ho, Yah-Yuan Wu and Yi-Chun Chen

Genes 2020, 11(12), 1514; https://doi.org/10.3390/genes11121514 - 18 Dec 2020

Cited by 10 | Viewed by 4151

Abstract

Cardiovascular diseases (CVDs) and dementia are the leading causes of disability and mortality. Genetic connections between cardiovascular risk factors and dementia have not been elucidated. We conducted a scoping review and pathway analysis to reveal the genetic associations underlying both CVDs and dementia. [...] Read more.

Cardiovascular diseases (CVDs) and dementia are the leading causes of disability and mortality. Genetic connections between cardiovascular risk factors and dementia have not been elucidated. We conducted a scoping review and pathway analysis to reveal the genetic associations underlying both CVDs and dementia. In the PubMed database, literature was searched using keywords associated with diabetes mellitus, hypertension, dyslipidemia, white matter hyperintensities, cerebral microbleeds, and covert infarctions. Gene lists were extracted from these publications to identify shared genes and pathways for each group. This included high penetrance genes and single nucleotide polymorphisms (SNPs) identified through genome wide association studies. Most risk SNPs to both diabetes and dementia participate in the phospholipase C enzyme system and the downstream nositol 1,4,5-trisphosphate and diacylglycerol activities. Interestingly, AP-2 (TFAP2) transcription factor family and metabolism of vitamins and cofactors were associated with genetic variants that were shared by white matter hyperintensities and dementia, and by microbleeds and dementia. Variants shared by covert infarctions and dementia were related to VEGF ligand–receptor interactions and anti-inflammatory cytokine pathways. Our review sheds light on future investigations into the causative relationships behind CVDs and dementia, and can be a paradigm of the identification of dementia treatments. Full article

(This article belongs to the Special Issue Cardiovascular Genetics)

21 pages, 1704 KiB

Open AccessArticle

You Had Me at “MAGIC”!: Four Barley MAGIC Populations Reveal Novel Resistance QTL for Powdery Mildew

by Fluturë Novakazi, Lene Krusell, Jens Due Jensen, Jihad Orabi, Ahmed Jahoor, Therése Bengtsson and on behalf of the PPP Barley Consortium

Genes 2020, 11(12), 1512; https://doi.org/10.3390/genes11121512 - 18 Dec 2020

Cited by 12 | Viewed by 4669

Abstract

Blumeria graminis f. sp. hordei (Bgh), the causal agent of barley powdery mildew (PM), is one of the most important barley leaf diseases and is prevalent in most barley growing regions. Infection decreases grain quality and yields on average by 30%. [...] Read more.

Blumeria graminis f. sp. hordei (Bgh), the causal agent of barley powdery mildew (PM), is one of the most important barley leaf diseases and is prevalent in most barley growing regions. Infection decreases grain quality and yields on average by 30%. Multi-parent advanced generation inter-cross (MAGIC) populations combine the advantages of bi-parental and association panels and offer the opportunity to incorporate exotic alleles into adapted material. Here, four barley MAGIC populations consisting of six to eight founders were tested for PM resistance in field trials in Denmark. Principle component and STRUCTURE analysis showed the populations were unstructured and genome-wide linkage disequilibrium (LD) decay varied between 14 and 38 Mbp. Genome-wide association studies (GWAS) identified 11 regions associated with PM resistance located on chromosomes 1H, 2H, 3H, 4H, 5H and 7H, of which three regions are putatively novel resistance quantitative trait locus/loci (QTL). For all regions high-confidence candidate genes were identified that are predicted to be involved in pathogen defense. Haplotype analysis of the significant SNPs revealed new allele combinations not present in the founders and associated with high resistance levels. Full article

(This article belongs to the Special Issue Powdery Mildew Resistance Genetics)

► Show Figures

Figure 1

15 pages, 2040 KiB

Open AccessArticle

Exon-Trapping Assay Improves Clinical Interpretation of COL11A1 and COL11A2 Intronic Variants in Stickler Syndrome Type 2 and Otospondylomegaepiphyseal Dysplasia

by Lucia Micale, Silvia Morlino, Annalisa Schirizzi, Emanuele Agolini, Grazia Nardella, Carmela Fusco, Stefano Castellana, Vito Guarnieri, Roberta Villa, Maria Francesca Bedeschi, Paola Grammatico, Antonio Novelli and Marco Castori

Genes 2020, 11(12), 1513; https://doi.org/10.3390/genes11121513 - 17 Dec 2020

Cited by 10 | Viewed by 3174

Abstract

Stickler syndrome (SS) is a hereditary connective tissue disorder affecting bones, eyes, and hearing. Type 2 SS and the SS variant otospondylomegaepiphyseal dysplasia (OSMED) are caused by deleterious variants in COL11A1 and COL11A2, respectively. In both genes, available database information indicates a [...] Read more.

Stickler syndrome (SS) is a hereditary connective tissue disorder affecting bones, eyes, and hearing. Type 2 SS and the SS variant otospondylomegaepiphyseal dysplasia (OSMED) are caused by deleterious variants in COL11A1 and COL11A2, respectively. In both genes, available database information indicates a high rate of potentially deleterious intronic variants, but published evidence of their biological effect is usually insufficient for a definite clinical interpretation. We report four previously unpublished intronic variants in COL11A1 (c.2241 + 5G>T, c.2809 − 2A>G, c.3168 + 5G>C) and COL11A2 (c.4392 + 1G>A) identified in type 2 SS/OSMED individuals. The pathogenic effect of these variants was first predicted in silico and then investigated by an exon-trapping assay. We demonstrated that all variants can induce exon in-frame deletions, which lead to the synthesis of shorter collagen XI α1 or 2 chains. Lacking residues are located in the α-triple helical region, which has a crucial role in regulating collagen fibrillogenesis. In conclusion, this study suggests that these alternative COL11A1 and COL11A2 transcripts might result in aberrant triple helix collagen. Our approach may help to improve the diagnostic molecular pathway of COL11-related disorders. Full article

(This article belongs to the Collection Genetics and Genomics of Hereditary Disorders of Connective Tissue)

► Show Figures

Figure 1

19 pages, 4141 KiB

Open AccessArticle

Two Separate Cases: Complex Chromosomal Abnormality Involving Three Chromosomes and Small Supernumerary Marker Chromosome in Patients with Impaired Reproductive Function

by Tatyana V. Karamysheva, Tatyana A. Gayner, Vladimir V. Muzyka, Konstantin E. Orishchenko and Nikolay B. Rubtsov

Genes 2020, 11(12), 1511; https://doi.org/10.3390/genes11121511 - 17 Dec 2020

Cited by 3 | Viewed by 3380

Abstract

For medical genetic counseling, estimating the chance of a child being born with chromosome abnormality is crucially important. Cytogenetic diagnostics of parents with a balanced karyotype are a special case. Such chromosome rearrangements cannot be detected with comprehensive chromosome screening. In the current [...] Read more.

For medical genetic counseling, estimating the chance of a child being born with chromosome abnormality is crucially important. Cytogenetic diagnostics of parents with a balanced karyotype are a special case. Such chromosome rearrangements cannot be detected with comprehensive chromosome screening. In the current paper, we consider chromosome diagnostics in two cases of chromosome rearrangement in patients with balanced karyotype and provide the results of a detailed analysis of complex chromosomal rearrangement (CCR) involving three chromosomes and a small supernumerary marker chromosome (sSMC) in a patient with impaired reproductive function. The application of fluorescent in situ hybridization, microdissection, and multicolor banding allows for describing analyzed karyotypes in detail. In the case of a CCR, such as the one described here, the probability of gamete formation with a karyotype, showing a balance of chromosome regions, is extremely low. Recommendation for the family in genetic counseling should take into account the obtained result. In the case of an sSMC, it is critically important to identify the original chromosome from which the sSMC has been derived, even if the euchromatin material is absent. Finally, we present our view on the optimal strategy of identifying and describing sSMCs, namely the production of a microdissectional DNA probe from the sSMC combined with a consequent reverse painting. Full article

(This article belongs to the Special Issue Chromosome-Centric View of the Genome Organization and Evolution)

► Show Figures

Graphical abstract

15 pages, 530 KiB

Open AccessArticle

A Revised Model of Anatomically Modern Human Expansions Out of Africa through a Machine Learning Approximate Bayesian Computation Approach

by Maria Teresa Vizzari, Andrea Benazzo, Guido Barbujani and Silvia Ghirotto

Genes 2020, 11(12), 1510; https://doi.org/10.3390/genes11121510 - 16 Dec 2020

Cited by 4 | Viewed by 3919

Abstract

There is a wide consensus in considering Africa as the birthplace of anatomically modern humans (AMH), but the dispersal pattern and the main routes followed by our ancestors to colonize the world are still matters of debate. It is still an open question [...] Read more.

There is a wide consensus in considering Africa as the birthplace of anatomically modern humans (AMH), but the dispersal pattern and the main routes followed by our ancestors to colonize the world are still matters of debate. It is still an open question whether AMH left Africa through a single process, dispersing almost simultaneously over Asia and Europe, or in two main waves, first through the Arab Peninsula into southern Asia and Australo-Melanesia, and later through a northern route crossing the Levant. The development of new methodologies for inferring population history and the availability of worldwide high-coverage whole-genome sequences did not resolve this debate. In this work, we test the two main out-of-Africa hypotheses through an Approximate Bayesian Computation approach, based on the Random-Forest algorithm. We evaluated the ability of the method to discriminate between the alternative models of AMH out-of-Africa, using simulated data. Once assessed that the models are distinguishable, we compared simulated data with real genomic variation, from modern and archaic populations. This analysis showed that a model of multiple dispersals is four-fold as likely as the alternative single-dispersal model. According to our estimates, the two dispersal processes may be placed, respectively, around 74,000 and around 46,000 years ago. Full article

(This article belongs to the Special Issue Ancient and Archaic Genomes)

► Show Figures

Figure 1

24 pages, 755 KiB

Open AccessReview

Distinct Effects of Inflammation on Cytochrome P450 Regulation and Drug Metabolism: Lessons from Experimental Models and a Potential Role for Pharmacogenetics

by Laura M. de Jong, Wim Jiskoot, Jesse J. Swen and Martijn L. Manson

Genes 2020, 11(12), 1509; https://doi.org/10.3390/genes11121509 - 16 Dec 2020

Cited by 68 | Viewed by 7035

Abstract

Personalized medicine strives to optimize drug treatment for the individual patient by taking into account both genetic and non-genetic factors for drug response. Inflammation is one of the non-genetic factors that has been shown to greatly affect the metabolism of drugs—primarily through inhibition [...] Read more.

Personalized medicine strives to optimize drug treatment for the individual patient by taking into account both genetic and non-genetic factors for drug response. Inflammation is one of the non-genetic factors that has been shown to greatly affect the metabolism of drugs—primarily through inhibition of cytochrome P450 (CYP450) drug-metabolizing enzymes—and hence contribute to the mismatch between the genotype predicted drug response and the actual phenotype, a phenomenon called phenoconversion. This review focuses on inflammation-induced drug metabolism alterations. In particular, we discuss the evidence assembled through human in-vitro models on the effect of inflammatory mediators on clinically relevant CYP450 isoform levels and their metabolizing capacity. We also present an overview of the current understanding of the mechanistic pathways via which inflammation in hepatocytes may modulate hepatic functions that are critical for drug metabolism. Furthermore, since large inter-individual variability in response to inflammation is observed in human in-vitro models and clinical studies, we evaluate the potential role of pharmacogenetic variability in the inflammatory signaling cascade and how this can modulate the outcome of inflammation on drug metabolism and response. Full article

(This article belongs to the Special Issue Pharmacogenomic Determinants of Interindividual Drug Response Variability: From Discovery to Implementation)

► Show Figures

Figure 1

18 pages, 471 KiB

Open AccessArticle

Resolving the Phylogeny of the Olive Family (Oleaceae): Confronting Information from Organellar and Nuclear Genomes

by Julia Dupin, Pauline Raimondeau, Cynthia Hong-Wa, Sophie Manzi, Myriam Gaudeul and Guillaume Besnard

Genes 2020, 11(12), 1508; https://doi.org/10.3390/genes11121508 - 16 Dec 2020

Cited by 26 | Viewed by 5484

Abstract

The olive family, Oleaceae, is a group of woody plants comprising 28 genera and ca. 700 species, distributed on all continents (except Antarctica) in both temperate and tropical environments. It includes several genera of major economic and ecological importance such as olives, ash [...] Read more.

The olive family, Oleaceae, is a group of woody plants comprising 28 genera and ca. 700 species, distributed on all continents (except Antarctica) in both temperate and tropical environments. It includes several genera of major economic and ecological importance such as olives, ash trees, jasmines, forsythias, osmanthuses, privets and lilacs. The natural history of the group is not completely understood yet, but its diversification seems to be associated with polyploidisation events and the evolution of various reproductive and dispersal strategies. In addition, some taxonomical issues still need to be resolved, particularly in the paleopolyploid tribe Oleeae. Reconstructing a robust phylogenetic hypothesis is thus an important step toward a better comprehension of Oleaceae’s diversity. Here, we reconstructed phylogenies of the olive family using 80 plastid coding sequences, 37 mitochondrial genes, the complete nuclear ribosomal cluster and a small multigene family encoding phytochromes (phyB and phyE) of 61 representative species. Tribes and subtribes were strongly supported by all phylogenetic reconstructions, while a few Oleeae genera are still polyphyletic (Chionanthus, Olea, Osmanthus, Nestegis) or paraphyletic (Schrebera, Syringa). Some phylogenetic relationships among tribes remain poorly resolved with conflicts between topologies reconstructed from different genomic regions. The use of nuclear data remains an important challenge especially in a group with ploidy changes (both paleo- and neo-polyploids). This work provides new genomic datasets that will assist the study of the biogeography and taxonomy of the whole Oleaceae. Full article

(This article belongs to the Special Issue Oleaceae Genetics)

► Show Figures

Figure 1

14 pages, 1531 KiB

Open AccessArticle

A Comprehensive Transcriptional Profiling of Pepper Responses to Root-Knot Nematode

by Weiming Hu, Krista Kingsbury, Shova Mishra and Peter DiGennaro

Genes 2020, 11(12), 1507; https://doi.org/10.3390/genes11121507 - 15 Dec 2020

Cited by 7 | Viewed by 2892

Abstract

Genetic resistance remains a key component in integrated pest management systems. The cosmopolitan root-knot nematode (RKN; Meloidogyne spp.) proves a significant management challenge as virulence and pathogenicity vary among and within species. RKN greatly reduces commercial bell pepper yield, and breeding programs continuously [...] Read more.

Genetic resistance remains a key component in integrated pest management systems. The cosmopolitan root-knot nematode (RKN; Meloidogyne spp.) proves a significant management challenge as virulence and pathogenicity vary among and within species. RKN greatly reduces commercial bell pepper yield, and breeding programs continuously develop cultivars to emerging nematode threats. However, there is a lack of knowledge concerning the nature and forms of nematode resistance. Defining how resistant and susceptible pepper cultivars mount defenses against RKN attacks can help inform breeding programs. Here, we characterized the transcriptional responses of the highly related resistant (Charleston Belle) and susceptible (Keystone Resistance Giant) pepper cultivars throughout early nematode infection stages. Comprehensive transcriptomic sequencing of resistant and susceptible cultivar roots with or without Meloidogyneincognita infection over three-time points; covering early penetration (1-day), through feeding site maintenance (7-days post-inoculation), produced > 300 million high quality reads. Close examination of chromosome P9, on which nematode resistance hotspots are located, showed more differentially expressed genes were upregulated in resistant cultivar at day 1 when compared to the susceptible cultivar. Our comprehensive approach to transcriptomic profiling of pepper resistance revealed novel insights into how RKN causes disease and the plant responses mounted to counter nematode attack. This work broadens the definition of resistance from a single loci concept to a more complex array of interrelated pathways. Focus on these pathways in breeding programs may provide more sustainable and enduring forms of resistance. Full article

(This article belongs to the Special Issue Genomics of Plant-Nematode Interactions)

► Show Figures

Figure 1

13 pages, 261 KiB

Open AccessArticle

Genetics of Hearing Impairment in North-Eastern Romania—A Cost-Effective Improved Diagnosis and Literature Review

by Irina Resmerita, Romica Sebastian Cozma, Roxana Popescu, Luminita Mihaela Radulescu, Monica Cristina Panzaru, Lacramioara Ionela Butnariu, Lavinia Caba, Ovidiu-Dumitru Ilie, Eva-Cristiana Gavril, Eusebiu Vlad Gorduza and Cristina Rusu

Genes 2020, 11(12), 1506; https://doi.org/10.3390/genes11121506 - 15 Dec 2020

Cited by 9 | Viewed by 3318

Abstract

Background: We have investigated the main genetic causes for non-syndromic hearing impairment (NSHI) in the hearing impairment individuals from the North-Eastern Romania and proposed a cost-effective diagnosis protocol. Methods: MLPA followed by Sanger Sequencing were used for all 291 patients included in this [...] Read more.

Background: We have investigated the main genetic causes for non-syndromic hearing impairment (NSHI) in the hearing impairment individuals from the North-Eastern Romania and proposed a cost-effective diagnosis protocol. Methods: MLPA followed by Sanger Sequencing were used for all 291 patients included in this study. Results: MLPA revealed abnormal results in 141 cases (48.45%): 57 (40.5%) were c.35delG homozygous, 26 (18.44%) were c.35delG heterozygous, 14 (9.93%) were compound heterozygous and 16 (11.35%) had other types of variants. The entire coding region of GJB2 was sequenced and out of 150 patients with normal results at MLPA, 29.33% had abnormal results: variants in heterozygous state: c.71G>A (28%), c.457G>A (20%), c.269T>C (12%), c.109G>A (12%), c.100A>T (12%), c.551G>C (8%). Out of 26 patients with c.35delG in heterozygous state, 38.46% were in fact compound heterozygous. Conclusions: We identified two variants: c.109G>A and c.100A>T that have not been reported in any study from Romania. MLPA is an inexpensive, rapid and reliable technique that could be a cost-effective diagnosis method, useful for patients with hearing impairment. It can be adaptable for the mutation spectrum in every population and followed by Sanger sequencing can provide a genetic diagnosis for patients with different degrees of hearing impairment. Full article

(This article belongs to the Special Issue Genetics of Hearing Impairment)

11 pages, 271 KiB

Open AccessArticle

Association of Long Non-Coding RNA Polymorphisms with Gastric Cancer and Atrophic Gastritis

by Vytenis Petkevicius, Greta Streleckiene, Kotryna Balciute, Alexander Link, Marcis Leja, Peter Malfertheiner, Jurgita Skieceviciene and Juozas Kupcinskas

Genes 2020, 11(12), 1505; https://doi.org/10.3390/genes11121505 - 15 Dec 2020

Cited by 20 | Viewed by 2372

Abstract

Long non-coding RNAs (lncRNA) play an important role in the carcinogenesis of various tumours, including gastric cancer. This study aimed to assess the associations of lncRNA ANRIL, H19, MALAT1, MEG3, HOTAIR single-nucleotide polymorphisms (SNPs) with gastric cancer and atrophic gastritis. SNPs were analyzed [...] Read more.

Long non-coding RNAs (lncRNA) play an important role in the carcinogenesis of various tumours, including gastric cancer. This study aimed to assess the associations of lncRNA ANRIL, H19, MALAT1, MEG3, HOTAIR single-nucleotide polymorphisms (SNPs) with gastric cancer and atrophic gastritis. SNPs were analyzed in 613 gastric cancer patients, 118 patients with atrophic gastritis and 476 controls from three tertiary centers in Germany, Lithuania and Latvia. Genomic DNA was extracted from peripheral blood leukocytes. SNPs were genotyped by the real-time polymerase chain reaction. Results showed that carriers of MALAT1 rs3200401 CT genotype had the significantly higher odds of atrophic gastritis than those with CC genotype (OR-1.81; 95% CI 1.17–2.80, p = 0.0066). Higher odds of AG were found in a recessive model (CC vs. TT + CT) for ANRIL rs1333045 (OR-1.88; 95% CI 1.19–2.95, p = 0.0066). Carriers of ANRIL (rs17694493) GG genotype had higher odds of gastric cancer (OR-4.93; 95% CI 1.28–19.00) and atrophic gastritis (OR-5.11; 95% CI 1.10–23.80) compared with the CC genotype, and carriers of HOTAIR rs17840857 TG genotype had higher odds of atrophic gastritis (OR-1.61 95% CI 1.04–2.50) compared with the TT genotype; however, the ORs did not reach the adjusted significance threshold (p < 0.007). In summary, our data provide novel evidence for a possible link between lncRNA SNPs and premalignant condition of gastric cancer, suggesting the involvement of lncRNAs in gastric cancer development. Full article

(This article belongs to the Special Issue Non-coding RNAs: Variety of Roles and Applications in Human Diseases)

17 pages, 2573 KiB

Open AccessArticle

Genomic Investigation into the Virulome, Pathogenicity, Stress Response Factors, Clonal Lineages, and Phylogenetic Relationship of Escherichia coli Strains Isolated from Meat Sources in Ghana

by Frederick Adzitey, Jonathan Asante, Hezekiel M. Kumalo, Rene B. Khan, Anou M. Somboro and Daniel G. Amoako

Genes 2020, 11(12), 1504; https://doi.org/10.3390/genes11121504 - 14 Dec 2020

Cited by 8 | Viewed by 2669

Abstract

Escherichia coli are among the most common foodborne pathogens associated with infections reported from meat sources. This study investigated the virulome, pathogenicity, stress response factors, clonal lineages, and the phylogenomic relationship of E. coli isolated from different meat sources in Ghana using whole-genome [...] Read more.

Escherichia coli are among the most common foodborne pathogens associated with infections reported from meat sources. This study investigated the virulome, pathogenicity, stress response factors, clonal lineages, and the phylogenomic relationship of E. coli isolated from different meat sources in Ghana using whole-genome sequencing. Isolates were screened from five meat sources (beef, chevon, guinea fowl, local chicken, and mutton) and five areas (Aboabo, Central market, Nyorni, Victory cinema, and Tishegu) based in the Tamale Metropolis, Ghana. Following microbial identification, the E. coli strains were subjected to whole-genome sequencing. Comparative visualisation analyses showed different DNA synteny of the strains. The isolates consisted of diverse sequence types (STs) with the most common being ST155 (n = 3/14). Based Upon Related Sequence Types (eBURST) analyses of the study sequence types identified four similar clones, five single-locus variants, and two satellite clones (more distantly) with global curated E. coli STs. All the isolates possessed at least one restriction-modification (R-M) and CRISPR defence system. Further analysis revealed conserved stress response mechanisms (detoxification, osmotic, oxidative, and periplasmic stress) in the strains. Estimation of pathogenicity predicted a higher average probability score (P_score ≈ 0.937), supporting their pathogenic potential to humans. Diverse virulence genes that were clonal-specific were identified. Phylogenomic tree analyses coupled with metadata insights depicted the high genetic diversity of the E. coli isolates with no correlation with their meat sources and areas. The findings of this bioinformatic analyses further our understanding of E. coli in meat sources and are broadly relevant to the design of contamination control strategies in meat retail settings in Ghana. Full article

(This article belongs to the Special Issue Genetics and Genomics of Zoonotic Foodborne Pathogens)

► Show Figures

Figure 1

28 pages, 1999 KiB

Open AccessArticle

Seascape Genomics of the Sugar Kelp Saccharina latissima along the North Eastern Atlantic Latitudinal Gradient

by Jaromir Guzinski, Paolo Ruggeri, Marion Ballenghien, Stephane Mauger, Bertrand Jacquemin, Chloe Jollivet, Jerome Coudret, Lucie Jaugeon, Christophe Destombe and Myriam Valero

Genes 2020, 11(12), 1503; https://doi.org/10.3390/genes11121503 - 13 Dec 2020

Cited by 20 | Viewed by 4991

Abstract

Temperature is one of the most important range-limiting factors for many seaweeds. Driven by the recent climatic changes, rapid northward shifts of species’ distribution ranges can potentially modify the phylogeographic signature of Last Glacial Maximum. We explored this question in detail in the [...] Read more.

Temperature is one of the most important range-limiting factors for many seaweeds. Driven by the recent climatic changes, rapid northward shifts of species’ distribution ranges can potentially modify the phylogeographic signature of Last Glacial Maximum. We explored this question in detail in the cold-tolerant kelp species Saccharina latissima, using microsatellites and double digest restriction site-associated DNA sequencing ( ddRAD-seq) derived single nucleotide polymorphisms (SNPs) to analyze the genetic diversity and structure in 11 sites spanning the entire European Atlantic latitudinal range of this species. In addition, we checked for statistical correlation between genetic marker allele frequencies and three environmental proxies (sea surface temperature, salinity, and water turbidity). Our findings revealed that genetic diversity was significantly higher for the northernmost locality (Spitsbergen) compared to the southern ones (Northern Iberia), which we discuss in light of the current state of knowledge on phylogeography of S. latissima and the potential influence of the recent climatic changes on the population structure of this species. Seven SNPs and 12 microsatellite alleles were found to be significantly associated with at least one of the three environmental variables. We speculate on the putative adaptive functions of the genes associated with the outlier markers and the importance of these markers for successful conservation and aquaculture strategies for S. latissima in this age of rapid global change. Full article

(This article belongs to the Special Issue Genetic Diversity of Marine Populations)

► Show Figures

Figure 1

15 pages, 6423 KiB

Open AccessArticle

Establishment and Preliminary Characterization of Three Astrocytic Cells Lines Obtained from Primary Rat Astrocytes by Sub-Cloning

by Fabio Caradonna, Gabriella Schiera, Carlo Maria Di Liegro, Vincenzo Vitale, Ilenia Cruciata, Tiziana Ferrara, Pietro D’Oca, Riccardo Mormino, Simona Maria Angela Rizzo and Italia Di Liegro

Genes 2020, 11(12), 1502; https://doi.org/10.3390/genes11121502 - 13 Dec 2020

Cited by 6 | Viewed by 2707

Abstract

Gliomas are complex and heterogeneous tumors that originate from the glial cells of the brain. The malignant cells undergo deep modifications of their metabolism, and acquire the capacity to invade the brain parenchyma and to induce epigenetic modifications in the other brain cell [...] Read more.

Gliomas are complex and heterogeneous tumors that originate from the glial cells of the brain. The malignant cells undergo deep modifications of their metabolism, and acquire the capacity to invade the brain parenchyma and to induce epigenetic modifications in the other brain cell types. In spite of the efforts made to define the pathology at the molecular level, and to set novel approaches to reach the infiltrating cells, gliomas are still fatal. In order to gain a better knowledge of the cellular events that accompany astrocyte transformation, we developed three increasingly transformed astrocyte cell lines, starting from primary rat cortical astrocytes, and analyzed them at the cytogenetic and epigenetic level. In parallel, we also studied the expression of the differentiation-related H1.0 linker histone variant to evaluate its possible modification in relation with transformation. We found that the most modified astrocytes (A-FC6) have epigenetic and chromosomal alterations typical of cancer, and that the other two clones (A-GS1 and A-VV5) have intermediate properties. Surprisingly, the differentiation-specific somatic histone H1.0 steadily increases from the normal astrocytes to the most transformed ones. As a whole, our results suggest that these three cell lines, together with the starting primary cells, constitute a potential model for studying glioma development. Full article

(This article belongs to the Special Issue Genes at Ten)

► Show Figures

Figure 1

16 pages, 2251 KiB

Open AccessArticle

Genome-Wide Analysis of Off-Target CRISPR/Cas9 Activity in Single-Cell-Derived Human Hematopoietic Stem and Progenitor Cell Clones

by Richard H. Smith, Yun-Ching Chen, Fayaz Seifuddin, Daniel Hupalo, Camille Alba, Robert Reger, Xin Tian, Daisuke Araki, Clifton L. Dalgard, Richard W. Childs, Mehdi Pirooznia and Andre Larochelle

Genes 2020, 11(12), 1501; https://doi.org/10.3390/genes11121501 - 13 Dec 2020

Cited by 15 | Viewed by 5976

Abstract

CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9)-mediated genome editing holds remarkable promise for the treatment of human genetic diseases. However, the possibility of off-target Cas9 activity remains a concern. To address this issue using clinically relevant target cells, we electroporated Cas9 [...] Read more.

CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9)-mediated genome editing holds remarkable promise for the treatment of human genetic diseases. However, the possibility of off-target Cas9 activity remains a concern. To address this issue using clinically relevant target cells, we electroporated Cas9 ribonucleoprotein (RNP) complexes (independently targeted to two different genomic loci, the CXCR4 locus on chromosome 2 and the AAVS1 locus on chromosome 19) into human mobilized peripheral blood-derived hematopoietic stem and progenitor cells (HSPCs) and assessed the acquisition of somatic mutations in an unbiased, genome-wide manner via whole genome sequencing (WGS) of single-cell-derived HSPC clones. Bioinformatic analysis identified >20,000 total somatic variants (indels, single nucleotide variants, and structural variants) distributed among Cas9-treated and non-Cas9-treated control HSPC clones. Statistical analysis revealed no significant difference in the number of novel non-targeted indels among the samples. Moreover, data analysis showed no evidence of Cas9-mediated indel formation at 623 predicted off-target sites. The median number of novel single nucleotide variants was slightly elevated in Cas9 RNP-recipient sample groups compared to baseline, but did not reach statistical significance. Structural variants were rare and demonstrated no clear causal connection to Cas9-mediated gene editing procedures. We find that the collective somatic mutational burden observed within Cas9 RNP-edited human HSPC clones is indistinguishable from naturally occurring levels of background genetic heterogeneity. Full article

(This article belongs to the Special Issue CRISPR-Cas: Interactions with Genome and Physiological Maintenance)

► Show Figures

Figure 1

19 pages, 2950 KiB

Open AccessArticle

Global Profiling of lncRNAs Expression Responsive to Allopolyploidization in Cucumis

by Panqiao Wang, Xiaqing Yu, Zaobing Zhu, Yufei Zhai, Qinzheng Zhao, Ya Meng, Ji Li, Qunfeng Lou and Jinfeng Chen

Genes 2020, 11(12), 1500; https://doi.org/10.3390/genes11121500 - 12 Dec 2020

Cited by 6 | Viewed by 2903

Abstract

Long non-coding RNAs (lncRNAs) play critical regulatory roles in various biological processes. However, the presence of lncRNAs and how they function in plant polyploidy are still largely unknown. Hence, we examined the profile of lncRNAs in a nascent allotetraploid Cucumis hytivus (S₁₄ [...] Read more.

Long non-coding RNAs (lncRNAs) play critical regulatory roles in various biological processes. However, the presence of lncRNAs and how they function in plant polyploidy are still largely unknown. Hence, we examined the profile of lncRNAs in a nascent allotetraploid Cucumis hytivus (S₁₄), its diploid parents, and the F₁ hybrid, to reveal the function of lncRNAs in plant-interspecific hybridization and whole genome duplication. Results showed that 2206 lncRNAs evenly transcribed from all 19 chromosomes were identified in C. hytivus, 44.6% of which were from intergenic regions. Based on the expression trend in allopolyploidization, we found that a high proportion of lncRNAs (94.6%) showed up-regulated expression to varying degrees following hybridization. However, few lncRNAs (33, 2.1%) were non-additively expressed after genome duplication, suggesting the significant effect of hybridization on lncRNAs, rather than genome duplication. Furthermore, 253 cis-regulated target genes were predicted for these differentially expressed lncRNAs in S₁₄, which mainly participated in chloroplast biological regulation (e.g., chlorophyll synthesis and light harvesting system). Overall, this study provides new insight into the function of lncRNAs during the processes of hybridization and polyploidization in plant evolution. Full article

(This article belongs to the Special Issue Molecular Evolutionary and Comparative Genomics Analyses in Plants)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Genes, Volume 11, Issue 12 (December 2020) – 140 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI