Genes

15 pages, 4942 KiB

Open AccessEditor’s ChoiceArticle

Reduced OPA1, Mitochondrial Fragmentation and Increased Susceptibility to Apoptosis in Granular Corneal Dystrophy Type 2 Corneal Fibroblasts

by Seung-Il Choi, Ga-Hyun Lee, Jong-Hwan Woo, Ikhyun Jun and Eung Kweon Kim

Genes 2023, 14(3), 566; https://doi.org/10.3390/genes14030566 - 24 Feb 2023

Cited by 2 | Viewed by 2716

Abstract

The progressive degeneration of granular corneal dystrophy type 2 (GCD2) corneal fibroblasts is associated with altered mitochondrial function, but the underlying mechanisms are incompletely understood. We investigated whether an imbalance of mitochondrial dynamics contributes to mitochondrial dysfunction of GCD2 corneal fibroblasts. Transmission electron [...] Read more.

The progressive degeneration of granular corneal dystrophy type 2 (GCD2) corneal fibroblasts is associated with altered mitochondrial function, but the underlying mechanisms are incompletely understood. We investigated whether an imbalance of mitochondrial dynamics contributes to mitochondrial dysfunction of GCD2 corneal fibroblasts. Transmission electron microscopy revealed several small, structurally abnormal mitochondria with altered cristae morphology in GCD2 corneal fibroblasts. Confocal microscopy showed enhanced mitochondrial fission and fragmented mitochondrial tubular networks. Western blotting revealed higher levels of MFN1, MFN2, and pDRP1 and decreased levels of OPA1 and FIS1 in GCD2. OPA1 reduction by short hairpin RNA (shRNA) resulted in fragmented mitochondrial tubular networks and increased susceptibility to mitochondrial stress-induced apoptosis. A decrease in the mitochondrial biogenesis-related transcription factors NRF1 and PGC1α was observed, while there was an increase in the mitochondrial membrane proteins TOM20 and TIM23. Additionally, reduced levels of mitochondrial DNA (mtDNA) were exhibited in GCD2 corneal fibroblasts. These observations suggest that altered mitochondrial fission/fusion and biogenesis are the critical molecular mechanisms that cause mitochondrial dysfunction contributing to the degeneration of GCD2 corneal fibroblasts. Full article

(This article belongs to the Special Issue Ophthalmic Genetics, Epigenetics, and Disease)

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18 pages, 2360 KiB

Open AccessEditor’s ChoiceArticle

Reconstruction of a Comprehensive Interactome and Experimental Data Analysis of FRA10AC1 May Provide Insights into Its Biological Role in Health and Disease

by Theologia Sarafidou, Eleni Galliopoulou, Despina Apostolopoulou, Georgios A. Fragkiadakis and Nicholas K. Moschonas

Genes 2023, 14(3), 568; https://doi.org/10.3390/genes14030568 - 24 Feb 2023

Cited by 2 | Viewed by 2611

Abstract

FRA10AC1, the causative gene for the manifestation of the FRA10A fragile site, encodes a well-conserved nuclear protein characterized as a non-core spliceosomal component. Pre-mRNA splicing perturbations have been linked with neurodevelopmental diseases. FRA10AC1 variants have been, recently, causally linked with severe neuropathological [...] Read more.

FRA10AC1, the causative gene for the manifestation of the FRA10A fragile site, encodes a well-conserved nuclear protein characterized as a non-core spliceosomal component. Pre-mRNA splicing perturbations have been linked with neurodevelopmental diseases. FRA10AC1 variants have been, recently, causally linked with severe neuropathological and growth retardation phenotypes. To further elucidate the participation of FRA10AC1 in spliceosomal multiprotein complexes and its involvement in neurological phenotypes related to splicing, we exploited protein–protein interaction experimental data and explored network information and information deduced from transcriptomics. We confirmed the direct interaction of FRA10AC1with ESS2, a non-core spliceosomal protein, mapped their interacting domains, and documented their tissue co-localization and physical interaction at the level of intracellular protein stoichiometries. Although FRA10AC1 and SF3B2, a major core spliceosomal protein, were shown to interact under in vitro conditions, the endogenous proteins failed to co-immunoprecipitate. A reconstruction of a comprehensive, strictly binary, protein–protein interaction network of FRA10AC1 revealed dense interconnectivity with many disease-associated spliceosomal components and several non-spliceosomal regulatory proteins. The topological neighborhood of FRA10AC1 depicts an interactome associated with multiple severe monogenic and multifactorial neurodevelopmental diseases mainly referring to spliceosomopathies. Our results suggest that FRA10AC1 involvement in pre-mRNA processing might be strengthened by interconnecting splicing with transcription and mRNA export, and they propose the broader role(s) of FRA10AC1 in cell pathophysiology. Full article

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

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12 pages, 2919 KiB

Open AccessEditor’s ChoiceArticle

Accumulation of STR-Loci Aberrations in Subclones of Jurkat Cell Line as a Model of Tumor Clonal Evolution

by Natalya Risinskaya, Olga Glinshchikova, Tatiana Makarik, Yana Kozhevnikova, Julia Chabaeva and Sergey Kulikov

Genes 2023, 14(3), 571; https://doi.org/10.3390/genes14030571 - 24 Feb 2023

Cited by 2 | Viewed by 2405

Abstract

Many genetic markers are known to distinguish tumor cells from normal. Genetic lesions found at disease onset often belong to a predominant tumor clone, and further observation makes it possible to assess the fate of this clone during therapy. However, minor clones escape [...] Read more.

Many genetic markers are known to distinguish tumor cells from normal. Genetic lesions found at disease onset often belong to a predominant tumor clone, and further observation makes it possible to assess the fate of this clone during therapy. However, minor clones escape monitoring and become unidentified, leading to relapses. Here we report the results of in vitro study of clonal evolution in cultured tumor cell line (Jurkat) compared to the cell line of non-tumor origin (WIL2-S). Cell lines were cultured and cloned by limiting dilutions. Subclones were tested by short tandem repeats (STR) profiling. Spontaneous STR aberrations in cells of non-tumor origin occur in less than 1 of 100 cultured cells. While in the cells of tumor origin, new aberrations appear in 1 or even more of 3 cultured cells. At the same time, a significant relationship was found between the accumulation of aberrations in the pool of subclones and the rate of cell growth. One can speculate that this approach could be applied for the analysis of primary patient tumor cell culture to obtain information concerning the evolutionary potential of the tumor cells that may be useful for the selection of a therapy approach. Full article

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

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10 pages, 443 KiB

Open AccessEditor’s ChoiceArticle

The Role of Glutamatergic Gene Polymorphisms in the Clinical Phenotypes of Schizophrenia

by Evgeniya G. Poltavskaya, Elena G. Kornetova, Maxim B. Freidin, Ivan V. Pozhidaev, Diana Z. Paderina, Anna V. Bocharova, Arkadiy V. Semke, Nikolay A. Bokhan, Svetlana A. Ivanova and Olga Y. Fedorenko

Genes 2023, 14(3), 575; https://doi.org/10.3390/genes14030575 - 24 Feb 2023

Cited by 4 | Viewed by 2473

Abstract

Background: Personal variations in genetic risk for schizophrenia relate to its phenotypic heterogeneity—both in disorder development and clinical manifestations. Abnormal glutamatergic neurotransmitter system functioning is integrated in the pathogenesis of schizophrenia. Methods: A sample of 805 Russian schizophrenia patients from the Siberian Federal [...] Read more.

Background: Personal variations in genetic risk for schizophrenia relate to its phenotypic heterogeneity—both in disorder development and clinical manifestations. Abnormal glutamatergic neurotransmitter system functioning is integrated in the pathogenesis of schizophrenia. Methods: A sample of 805 Russian schizophrenia patients from the Siberian Federal region was investigated. We examined the association of 39 single nucleotide polymorphisms in eight genes (GRIN2A, GRIN2B, SLC1A2, SLC1A3, SLC17A7, GRM3, GRM7, and GRM8) involved in the glutamatergic system with the development of clinical heterogeneity of schizophrenia. The MassARRAY Analyzer 4 was used for genotyping. Results: GRIN2A rs11644461, rs8057394 and GRIN2B rs7313149 are associated with the continuous type of schizophrenia. The GRIN2A rs8057394*G allele is a relative risk factor (p = 0.019) for developing the continuous type of schizophrenia. We found a nominally significant association between negative symptoms of schizophrenia and SLC17A7 rs62126236. The SLC17A7 rs62126236*T allele has a protective effect (p = 0.039) against predominant negative symptoms in schizophrenia. The total Positive and Negative Syndrome Scale (PANSS) scores were significantly associated with GRIN2A rs9788936 after adjusting for multiple testing (p = 0.001). Conclusions: In this study the contribution of the glutamatergic gene polymorphisms to the clinical heterogeneity of schizophrenia has been demonstrated. Full article

(This article belongs to the Special Issue Advances in Genetics of Psychiatric Disorder)

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17 pages, 3138 KiB

Open AccessEditor’s ChoiceArticle

Childhood Hearing Impairment in Senegal

by Yacouba Dia, Birame Loum, Yaay Joor Koddu Biigé Dieng, Jean Pascal Demba Diop, Samuel Mawuli Adadey, Elvis Twumasi Aboagye, Seydi Abdoul Ba, Abdoul Aziz Touré, Fallou Niang, Pierre Diaga Sarr, Cheikh Ahmed Tidiane Ly, Andrea Regina Gnilane Sène, Carmen De Kock, Rhiyana Bassier, Kalinka Popel, Rokhaya Ndiaye Diallo, Ambroise Wonkam and Bay Karim Diallo

Genes 2023, 14(3), 562; https://doi.org/10.3390/genes14030562 - 23 Feb 2023

Cited by 3 | Viewed by 2934

Abstract

We recently showed that variants in GJB2 explained Hearing Impairment (HI) in 34.1% (n = 15/44) of multiplex families in Senegal. The present study aimed to use community-based nationwide recruitment to determine the etiologies and the clinical profiles of childhood HI in [...] Read more.

We recently showed that variants in GJB2 explained Hearing Impairment (HI) in 34.1% (n = 15/44) of multiplex families in Senegal. The present study aimed to use community-based nationwide recruitment to determine the etiologies and the clinical profiles of childhood HI in Senegal. Participants with early onset HI were included after clinical examination, including audiological assessment by pure tone audiometry and/or auditory brainstem response. We investigated a total of 406 participants from 295 families, recruited from 13/14 administrative regions of Senegal. Male/female ratio was 1.33 (232/174). Prelingual HI was the most common type of HI and accounted for 80% (n = 325 individuals). The mean age at medical diagnosis for congenital HI was computed at 3.59 ± 2.27 years. Audiological evaluation showed sensorineural HI as the most frequently observed HI (89.16%; n = 362 individuals). Pedigree analysis suggested autosomal recessive inheritance in 61.2% (63/103) of multiplex families and sporadic cases in 27 families (26.2%; 27/103), with a consanguinity rate estimated at 93% (84/90 families). Genetic factors were likely involved in 52.7% (214/406) of the cases, followed by environmental causes (29.57%; 120/406). In 72 cases (17.73%), the etiology was unknown. Clinically, non-syndromic HI was the most common type of HI (90.6%; n = 194/214 individuals). Among families segregating syndromic cases, type 2 Waardenburg syndrome was the most common (36.3%; 4/11 families). This study revealed putative genetic factors, mostly associated with high consanguinity rate, as the leading causes of early-onset HI in Senegal. The high consanguinity could provide a good opportunity to identify variants in known and novel genes involved in childhood HI. Full article

(This article belongs to the Special Issue New Advances in Genetic Research on Hearing Loss)

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8 pages, 1379 KiB

Open AccessEditor’s ChoiceCommunication

Prenatal Detection of a FOXF1 Deletion in a Fetus with ACDMPV and Hydronephrosis

by Katarzyna Bzdęga, Anna Kutkowska-Kaźmierczak, Gail H. Deutsch, Izabela Plaskota, Marta Smyk, Magdalena Niemiec, Artur Barczyk, Ewa Obersztyn, Jan Modzelewski, Iwona Lipska, Paweł Stankiewicz, Marzena Gajecka, Małgorzata Rydzanicz, Rafał Płoski, Tomasz Szczapa and Justyna A. Karolak

Genes 2023, 14(3), 563; https://doi.org/10.3390/genes14030563 - 23 Feb 2023

Cited by 5 | Viewed by 2538

Abstract

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by the arrest of fetal lung formation, resulting in neonatal death due to acute respiratory failure and pulmonary arterial hypertension. Heterozygous single-nucleotide variants or copy-number variant (CNV) [...] Read more.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by the arrest of fetal lung formation, resulting in neonatal death due to acute respiratory failure and pulmonary arterial hypertension. Heterozygous single-nucleotide variants or copy-number variant (CNV) deletions involving the FOXF1 gene and/or its lung-specific enhancer are found in the vast majority of ACDMPV patients. ACDMPV is often accompanied by extrapulmonary malformations, including the gastrointestinal, cardiac, or genitourinary systems. Thus far, most of the described ACDMPV patients have been diagnosed post mortem, based on histologic evaluation of the lung tissue and/or genetic testing. Here, we report a case of a prenatally detected de novo CNV deletion (~0.74 Mb) involving the FOXF1 gene in a fetus with ACDMPV and hydronephrosis. Since ACDMPV is challenging to detect by ultrasound examination, the more widespread implementation of prenatal genetic testing can facilitate early diagnosis, improve appropriate genetic counselling, and further management. Full article

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

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16 pages, 4003 KiB

Open AccessEditor’s ChoiceArticle

Exposure to Juvenile Stress Induces Epigenetic Alterations in the GABAergic System in Rats

by Gil Ben David, Yam Amir, Kuldeep Tripathi, Lital Sharvit, Amir Benhos, Rachel Anunu, Gal Richter-Levin and Gil Atzmon

Genes 2023, 14(3), 565; https://doi.org/10.3390/genes14030565 - 23 Feb 2023

Cited by 1 | Viewed by 2507

Abstract

Epigenetics is a gene–environment interaction mechanism, manifested mostly through changes in regulatory gene expression. Stress is an established environmental factor known to induce epigenetic changes. This study aimed to assess the long-term effect of stress as juveniles, or juvenile and adult stress, on [...] Read more.

Epigenetics is a gene–environment interaction mechanism, manifested mostly through changes in regulatory gene expression. Stress is an established environmental factor known to induce epigenetic changes. This study aimed to assess the long-term effect of stress as juveniles, or juvenile and adult stress, on alterations in glutamic acid decarboxylase genes (GAD65, GAD67). We assessed DNA methylation and RNA expression in four rat groups: (1) control group, (2) juvenile stress group sacrificed two days following stress exposure (JSe) (RNA only), (3) juvenile stress group sacrificed as adults (JS), and (4) juvenile and adult stress group (JS + AS). Three different areas of the brain were examined in each group: the dorsal dentate gyrus (dDG), the dorsal CA1 (dCA1), and the basolateral amygdala (BLA). A significantly low methylation level of GAD65 in the BLA was observed among the JS group, followed by almost complete recovery among the JS + AS group. However, in dDG, an opposite trend was captured, and higher GAD65 methylation was found in JS. In addition, RNA levels were found to be decreased in JS compared to JSe and JS + AS. These findings can point to a possible mechanism: while juvenile stress may enhance a better coping strategy with life challenges, additional stress in adulthood may trigger a contradictory response, either beneficial or harmful. Full article

(This article belongs to the Special Issue Advances in Genetics of Psychiatric Disorder)

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11 pages, 2017 KiB

Open AccessEditor’s ChoiceArticle

Re-Evaluation of Genotyping Methodologies in Cattle: The Proficiency of Imputation

by Moran Gershoni, Andrey Shirak, Yehoshav Ben-Meir, Ariel Shabtay, Miri Cohen-Zinder and Eyal Seroussi

Genes 2023, 14(3), 547; https://doi.org/10.3390/genes14030547 - 22 Feb 2023

Viewed by 2038

Abstract

In dairy cattle, identifying polymorphisms that contribute to complex economical traits such as residual feed intake (RFI) is challenging and demands accurate genotyping. In this study, we compared imputed genotypes (n = 192 cows) to those obtained using the TaqMan and high-resolution [...] Read more.

In dairy cattle, identifying polymorphisms that contribute to complex economical traits such as residual feed intake (RFI) is challenging and demands accurate genotyping. In this study, we compared imputed genotypes (n = 192 cows) to those obtained using the TaqMan and high-resolution melting (HRM) methods (n = 114 cows), for mutations in the FABP4 gene that had been suggested to have a large effect on RFI. Combining the whole genome sequence (n = 19 bulls) and the cows’ BovineHD BeadChip allowed imputing genotypes for these mutations that were verified by Sanger sequencing, whereas, an error rate of 11.6% and 10.7% were encountered for HRM and TaqMan, respectively. We show that this error rate seriously affected the linkage-disequilibrium analysis that supported this gene candidacy over other BTA14 gene candidates. Thus, imputation produced superior genotypes and should also be regarded as a method of choice to validate the reliability of the genotypes obtained by other methodologies that are prone to genotyping errors due to technical conditions. These results support the view that RFI is a complex trait and that searching for the causative sequence variation underlying cattle RFI should await the development of statistical methods suitable to handle additive and epistatic interactions. Full article

(This article belongs to the Special Issue From QTL Mapping to QTG and QTN Identification)

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15 pages, 4188 KiB

Open AccessEditor’s ChoiceArticle

A Comparative Analysis of the Chloroplast Genomes of Three Lonicera Medicinal Plants

by Chenju Yang, Ni Zhang, Shaoxiong Wu, Chunyan Jiang, Lian Xie, Feng Yang and Zhengwen Yu

Genes 2023, 14(3), 548; https://doi.org/10.3390/genes14030548 - 22 Feb 2023

Cited by 10 | Viewed by 2439

Abstract

Both Lonicerae japonicae flos and Lonicerae similis flos are important components in traditional Chinese medicine (TCM) with precious medicinal value. However, the absence of studies on their chloroplast genomes and chromatography has considerably hindered the study of their evolutionary and phylogenetic relationships. In [...] Read more.

Both Lonicerae japonicae flos and Lonicerae similis flos are important components in traditional Chinese medicine (TCM) with precious medicinal value. However, the absence of studies on their chloroplast genomes and chromatography has considerably hindered the study of their evolutionary and phylogenetic relationships. In this study, the complete chloroplast (cp) genomes of Lonicera acuminata Wall. and Lonicera similis Hemsl. were sequenced using the Illumina sequencing platform and compared with that of Lonicera japonica Thunb., which has been previously reported. Furthermore, the chromatographic fingerprints of the three plants were constructed using HPLC and the content of quality marker (Q-Marker) was calculated. The annotation results showed that the two chloroplast genomes were typical quadripartite structures with lengths of 155,330 bp (L. acuminata) and 155,207 bp (L. similis). A total of 126 different genes were annotated, containing 82 protein-coding genes, 36 tRNA genes, and 8 rRNA genes. The expansion and contraction of the inverted repeat (IR) regions suggested that the boundary regions of IR/SC were comparatively conserved in the three species, and six regions (trnH-GUG-psbA, rps2-rpoC2, rbcL-psaI, trnN-GUU-ndhF, rps15-ycf1, and infA) with nucleotide diversity values (Pi) of variable sites higher than 1% were identified. Phylogenetic relation indicated that L. similis had a closer genetic relationship with L. japonica than L. acuminata. Additionally, the chromatographic fingerprints showed that the characteristic peaks of the three medicinal plants were similar, including Neochlorogenic acid, Chlorogenic acid, 4-Dicaffeoylquinic acid, Sweroside, Secoxyloganin, Luteoloside, Isochlorogenic acid A, Isochlorogenic acid B, and Isochlorogenic acid C. The content of chlorogenic acid and total phenolic acid in L. acuminata (7.4633 ± 0.4461%, 14.8953 ± 0.0728%) and L. similis (14.1055 ± 0.2566%, 21.9782 ± 0.1331%) was much higher than that of L. japonica (3.9729 ± 0.0928%, 6.0964 ± 0.1228%), respectively. This study provides appropriate information for species identification, phylogeny, quality assessment, and rational use of three medicinal plants of the genus Lonicera. Full article

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

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14 pages, 3681 KiB

Open AccessEditor’s ChoiceReview

Roles of Local Soluble Factors in Maintaining the Growth Plate: An Update

by Yiqian Zhang, Xenab Ahmadpoor and Hang Lin

Genes 2023, 14(3), 534; https://doi.org/10.3390/genes14030534 - 21 Feb 2023

Cited by 2 | Viewed by 4589

Abstract

The growth plate is a cartilaginous tissue found at the ends of growing long bones, which contributes to the lengthening of bones during development. This unique structure contains at least three distinctive layers, including resting, proliferative, and hypertrophic chondrocyte zones, maintained by a [...] Read more.

The growth plate is a cartilaginous tissue found at the ends of growing long bones, which contributes to the lengthening of bones during development. This unique structure contains at least three distinctive layers, including resting, proliferative, and hypertrophic chondrocyte zones, maintained by a complex regulatory network. Due to its soft tissue nature, the growth plate is the most susceptible tissue of the growing skeleton to injury in childhood. Although most growth plate damage in fractures can heal, some damage can result in growth arrest or disorder, impairing leg length and resulting in deformity. In this review, we re-visit previously established knowledge about the regulatory network that maintains the growth plate and integrate current research displaying the most recent progress. Next, we highlight local secretary factors, such as Wnt, Indian hedgehog (Ihh), and parathyroid hormone-related peptide (PTHrP), and dissect their roles and interactions in maintaining cell function and phenotype in different zones. Lastly, we discuss future research topics that can further our understanding of this unique tissue. Given the unmet need to engineer the growth plate, we also discuss the potential of creating particular patterns of soluble factors and generating them in vitro. Full article

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

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11 pages, 545 KiB

Open AccessEditor’s ChoiceArticle

Genetic Lesions in Russian CLL Patients with the Most Common Stereotyped Antigen Receptors

by Bella V. Biderman, Ekaterina B. Likold, Nataliya A. Severina, Tatiana N. Obukhova and Andrey B. Sudarikov

Genes 2023, 14(2), 532; https://doi.org/10.3390/genes14020532 - 20 Feb 2023

Cited by 1 | Viewed by 2117

Abstract

Chronic lymphocytic leukemia (CLL) is one of the most common B-cell malignancies in Western countries. IGHV mutational status is the most important prognostic factor for this disease. CLL is characterized by an extreme narrowing of the IGHV genes repertoire and the existence of [...] Read more.

Chronic lymphocytic leukemia (CLL) is one of the most common B-cell malignancies in Western countries. IGHV mutational status is the most important prognostic factor for this disease. CLL is characterized by an extreme narrowing of the IGHV genes repertoire and the existence of subgroups of quasi-identical stereotyped antigenic receptors (SAR). Some of these subgroups have already been identified as independent prognostic factors for CLL. Here, we report the frequencies of TP53, NOTCH1, and SF3B1 gene mutations and chromosomal aberrations assessed by NGS and FISH in 152 CLL patients with the most common SAR in Russia. We noted these lesions to be much more common in patients with certain SAR than average in CLL. The profile of these aberrations differs between the subgroups of SAR, despite the similarity of their structure. For most of these subgroups mutations prevailed in a single gene, except for CLL#5 with all three genes affected by mutations. It should be noted that our data concerning the mutation frequency in some SAR groups differ from that obtained previously, which could be due to the population differences between patient cohorts. The research in this area should be important for better understanding the pathogenesis of CLL and therapy optimization. Full article

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

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14 pages, 4421 KiB

Open AccessEditor’s ChoiceArticle

Phylogenetic Relationships among TnpB-Containing Mobile Elements in Six Bacterial Species

by Yali Wang, Mengke Guo, Naisu Yang, Zhongxia Guan, Han Wu, Numan Ullah, Emmanuel Asare, Shasha Shi, Bo Gao and Chengyi Song

Genes 2023, 14(2), 523; https://doi.org/10.3390/genes14020523 - 19 Feb 2023

Cited by 2 | Viewed by 3200

Abstract

Some families of mobile elements in bacterial genomes encode not only a transposase but also an accessory TnpB gene. This gene has been shown to encode an RNA-guided DNA endonuclease, co-evolving with Y1 transposase and serine recombinase in mobile elements IS605 and IS607 [...] Read more.

Some families of mobile elements in bacterial genomes encode not only a transposase but also an accessory TnpB gene. This gene has been shown to encode an RNA-guided DNA endonuclease, co-evolving with Y1 transposase and serine recombinase in mobile elements IS605 and IS607. In this paper, we reveal the evolutionary relationships among TnpB-containing mobile elements (TCMEs) in well-assembled genomes of six bacterial species: Bacillus cereus, Clostridioides difficile, Deinococcus radiodurans, Escherichia coli, Helicobacter pylori and Salmonella enterica. In total, 9996 TCMEs were identified in 4594 genomes. They belonged to 39 different insertion sequences (ISs). Based on their genetic structures and sequence identities, the 39 TCMEs were classified into three main groups and six subgroups. According to our phylogenetic analysis, TnpBs include two main branches (TnpB-A and TnpB-B) and two minor branches (TnpB-C and TnpB-D). The key TnpB motifs and the associated Y1 and serine recombinases were highly conserved across species, even though their overall sequence identities were low. Substantial variation was observed for the rate of invasion across bacterial species and strains. Over 80% of the genomes of B. cereus, C. difficile, D. radiodurans and E. coli contained TCMEs; however, only 64% of the genomes of H. pylori and 44% of S. enterica genomes contained TCMEs. IS605 showed the largest rate of invasion in these species, while IS607 and IS1341 had a relatively narrow distribution. Co-invasions of IS605, IS607 and IS1341 elements were observed in various genomes. The largest average copy number was observed for IS605b elements in C. difficile. The average copy numbers of most other TCMEs were smaller than four. Our findings have important implications for understanding the co-evolution of TnpB-containing mobile elements and their biological roles in host genome evolution. Full article

(This article belongs to the Special Issue Co-evolution of Mobilome and Genome)

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15 pages, 1286 KiB

Open AccessEditor’s ChoiceReview

Genetic Ethnic Differences in Human 2′-5′-Oligoadenylate Synthetase and Disease Associations: A Systematic Review

by Anmol Gokul, Thilona Arumugam and Veron Ramsuran

Genes 2023, 14(2), 527; https://doi.org/10.3390/genes14020527 - 19 Feb 2023

Cited by 6 | Viewed by 3303

Abstract

Recently, several studies have highlighted a skewed prevalence of infectious diseases within the African continent. Furthermore, a growing number of studies have demonstrated unique genetic variants found within the African genome are one of the contributing factors to the disease severity of infectious [...] Read more.

Recently, several studies have highlighted a skewed prevalence of infectious diseases within the African continent. Furthermore, a growing number of studies have demonstrated unique genetic variants found within the African genome are one of the contributing factors to the disease severity of infectious diseases within Africa. Understanding the host genetic mechanisms that offer protection against infectious diseases provides an opportunity to develop unique therapeutic interventions. Over the past two decades, several studies have linked the 2′-5′-oligoadenylate synthetase (OAS) family with a range of infectious diseases. More recently, the OAS-1 gene has also been associated with disease severity caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which led to a global pandemic. The OAS family serves as an antiviral factor through the interaction with Ribonuclease-Latent (RNase-L). This review explores the genetic variants observed within the OAS genes and the associations with various viral infections and how previously reported ethnic-specific polymorphisms drive clinical significance. This review provides an overview of OAS genetic association studies with a particular focus on viral diseases affecting individuals of African descent. Full article

(This article belongs to the Special Issue Host Genetics and Infectious Disease)

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15 pages, 668 KiB

Open AccessFeature PaperEditor’s ChoiceReview

An Introduction and Overview of RON Receptor Tyrosine Kinase Signaling

by Brian G. Hunt, Levi H. Fox, James C. Davis, Angelle Jones, Zhixin Lu and Susan E. Waltz

Genes 2023, 14(2), 517; https://doi.org/10.3390/genes14020517 - 17 Feb 2023

Cited by 13 | Viewed by 4448

Abstract

RON is a receptor tyrosine kinase (RTK) of the MET receptor family that is canonically involved in mediating growth and inflammatory signaling. RON is expressed at low levels in a variety of tissues, but its overexpression and activation have been associated with malignancies [...] Read more.

RON is a receptor tyrosine kinase (RTK) of the MET receptor family that is canonically involved in mediating growth and inflammatory signaling. RON is expressed at low levels in a variety of tissues, but its overexpression and activation have been associated with malignancies in multiple tissue types and worse patient outcomes. RON and its ligand HGFL demonstrate cross-talk with other growth receptors and, consequentially, positions RON at the intersection of numerous tumorigenic signaling programs. For this reason, RON is an attractive therapeutic target in cancer research. A better understanding of homeostatic and oncogenic RON activity serves to enhance clinical insights in treating RON-expressing cancers. Full article

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

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11 pages, 4568 KiB

Open AccessEditor’s ChoiceArticle

Insights into the Genetic Determination of the Autotetraploid Potato Plant Height

by Long Zhao, Meiling Zou, Sirong Jiang, Xiaorui Dong, Ke Deng, Tiancang Na, Jian Wang, Zhiqiang Xia and Fang Wang

Genes 2023, 14(2), 507; https://doi.org/10.3390/genes14020507 - 16 Feb 2023

Cited by 4 | Viewed by 2883

Abstract

Plant height is an important characteristic, the modification of which can improve the ability of stress adaptation as well as the yield. In this study, genome-wide association analysis was performed for plant height traits in 370 potato cultivars using the tetraploid potato genome [...] Read more.

Plant height is an important characteristic, the modification of which can improve the ability of stress adaptation as well as the yield. In this study, genome-wide association analysis was performed for plant height traits in 370 potato cultivars using the tetraploid potato genome as a reference. A total of 92 significant single nucleotide polymorphism (SNP) loci for plant height were obtained, which were particularly significant in haplotypes A3 and A4 on chromosome 1 and A1, A2, and A4 on chromosome 5. Thirty-five candidate genes were identified that were mainly involved in the gibberellin and brassinolide signal transduction pathways, including the FAR1 gene, methyltransferase, ethylene response factor, and ubiquitin protein ligase. Among them, PIF3 and GID1a were only present on chromosome 1, with PIF3 in all four haplotypes and GID1a in haplotype A3. This could lead to more effective genetic loci for molecular marker-assisted selection breeding as well as more precise localization and cloning of genes for plant height traits in potatoes. Full article

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

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20 pages, 1068 KiB

Open AccessEditor’s ChoiceArticle

Attention-Based Graph Neural Network for Label Propagation in Single-Cell Omics

by Rahul Bhadani, Zhuo Chen and Lingling An

Genes 2023, 14(2), 506; https://doi.org/10.3390/genes14020506 - 16 Feb 2023

Cited by 8 | Viewed by 2820

Abstract

Single-cell data analysis has been at forefront of development in biology and medicine since sequencing data have been made available. An important challenge in single-cell data analysis is the identification of cell types. Several methods have been proposed for cell-type identification. However, these [...] Read more.

Single-cell data analysis has been at forefront of development in biology and medicine since sequencing data have been made available. An important challenge in single-cell data analysis is the identification of cell types. Several methods have been proposed for cell-type identification. However, these methods do not capture the higher-order topological relationship between different samples. In this work, we propose an attention-based graph neural network that captures the higher-order topological relationship between different samples and performs transductive learning for predicting cell types. The evaluation of our method on both simulation and publicly available datasets demonstrates the superiority of our method, scAGN, in terms of prediction accuracy. In addition, our method works best for highly sparse datasets in terms of F1 score, precision score, recall score, and Matthew’s correlation coefficients as well. Further, our method’s runtime complexity is consistently faster compared to other methods. Full article

(This article belongs to the Special Issue Machine Learning Applications in Genetics)

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15 pages, 322 KiB

Open AccessEditor’s ChoicePerspective

Challenges and Opportunities for Clinical Cytogenetics in the 21st Century

by Eric Heng, Sanjana Thanedar and Henry H. Heng

Genes 2023, 14(2), 493; https://doi.org/10.3390/genes14020493 - 15 Feb 2023

Cited by 19 | Viewed by 7193

Abstract

The powerful utilities of current DNA sequencing technology question the value of developing clinical cytogenetics any further. By briefly reviewing the historical and current challenges of cytogenetics, the new conceptual and technological platform of the 21st century clinical cytogenetics is presented. Particularly, the [...] Read more.

The powerful utilities of current DNA sequencing technology question the value of developing clinical cytogenetics any further. By briefly reviewing the historical and current challenges of cytogenetics, the new conceptual and technological platform of the 21st century clinical cytogenetics is presented. Particularly, the genome architecture theory (GAT) has been used as a new framework to emphasize the importance of clinical cytogenetics in the genomic era, as karyotype dynamics play a central role in information-based genomics and genome-based macroevolution. Furthermore, many diseases can be linked to elevated levels of genomic variations within a given environment. With karyotype coding in mind, new opportunities for clinical cytogenetics are discussed to integrate genomics back into cytogenetics, as karyotypic context represents a new type of genomic information that organizes gene interactions. The proposed research frontiers include: 1. focusing on karyotypic heterogeneity (e.g., classifying non-clonal chromosome aberrations (NCCAs), studying mosaicism, heteromorphism, and nuclear architecture alteration-mediated diseases), 2. monitoring the process of somatic evolution by characterizing genome instability and illustrating the relationship between stress, karyotype dynamics, and diseases, and 3. developing methods to integrate genomic data and cytogenomics. We hope that these perspectives can trigger further discussion beyond traditional chromosomal analyses. Future clinical cytogenetics should profile chromosome instability-mediated somatic evolution, as well as the degree of non-clonal chromosomal aberrations that monitor the genomic system’s stress response. Using this platform, many common and complex disease conditions, including the aging process, can be effectively and tangibly monitored for health benefits. Full article

(This article belongs to the Special Issue Advances in Clinical Cytogenetics)

11 pages, 2608 KiB

Open AccessEditor’s ChoiceArticle

Differential Repeat Accumulation in the Bimodal Karyotype of Agave L.

by Lamonier Chaves Ramos, Mariana Báez, Joerg Fuchs, Andreas Houben, Reginaldo Carvalho and Andrea Pedrosa-Harand

Genes 2023, 14(2), 491; https://doi.org/10.3390/genes14020491 - 15 Feb 2023

Cited by 4 | Viewed by 2900

Abstract

The genus Agave presents a bimodal karyotype with x = 30 (5L, large, +25S, small chromosomes). Bimodality within this genus is generally attributed to allopolyploidy in the ancestral form of Agavoideae. However, alternative mechanisms, such as the preferential accumulation of repetitive elements at [...] Read more.

The genus Agave presents a bimodal karyotype with x = 30 (5L, large, +25S, small chromosomes). Bimodality within this genus is generally attributed to allopolyploidy in the ancestral form of Agavoideae. However, alternative mechanisms, such as the preferential accumulation of repetitive elements at the macrochromosomes, could also be important. Aiming to understand the role of repetitive DNA within the bimodal karyotype of Agave, genomic DNA from the commercial hybrid 11648 (2n = 2x = 60, 6.31 Gbp) was sequenced at low coverage, and the repetitive fraction was characterized. In silico analysis showed that ~67.6% of the genome is mainly composed of different LTR retrotransposon lineages and one satellite DNA family (AgSAT171). The satellite DNA localized at the centromeric regions of all chromosomes; however, stronger signals were observed for 20 of the macro- and microchromosomes. All transposable elements showed a dispersed distribution, but not uniform across the length of the chromosomes. Different distribution patterns were observed for different TE lineages, with larger accumulation at the macrochromosomes. The data indicate the differential accumulation of LTR retrotransposon lineages at the macrochromosomes, probably contributing to the bimodality. Nevertheless, the differential accumulation of the satDNA in one group of macro- and microchromosomes possibly reflects the hybrid origin of this Agave accession. Full article

(This article belongs to the Special Issue Commemorating the Launch of the Section "Cytogenomics")

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12 pages, 1727 KiB

Open AccessEditor’s ChoiceBrief Report

The Coding Mitogenome of the Freshwater Crayfish Pontastacus leptodactylus (Decapoda:Astacidea:Astacidae) from Lake Vegoritida, Greece and Its Taxonomic Classification

by Maria V. Alvanou, Apostolos P. Apostolidis, Athanasios Lattos, Basile Michaelidis and Ioannis A. Giantsis

Genes 2023, 14(2), 494; https://doi.org/10.3390/genes14020494 - 15 Feb 2023

Cited by 9 | Viewed by 2466

Abstract

Pontastacus leptodactylus (Eschscholtz, 1823) (Decapoda:Astacidea:Astacidae) constitutes an ecologically and economically highly important species. In the present study, the mitochondrial genome of the freshwater crayfish P. leptodactylus from Greece is analyzed for the first time, using 15 newly designed primer pairs based on available [...] Read more.

Pontastacus leptodactylus (Eschscholtz, 1823) (Decapoda:Astacidea:Astacidae) constitutes an ecologically and economically highly important species. In the present study, the mitochondrial genome of the freshwater crayfish P. leptodactylus from Greece is analyzed for the first time, using 15 newly designed primer pairs based on available sequences of closely related species. The analyzed coding part of the mitochondrial genome of P. leptodactylus consists of 15,050 base pairs including 13 protein-coding genes (PCGs), 2 ribosomal RNA gene (rRNAs), and 22 transfer RNA genes (tRNAs). These newly designed primers may be particularly useful in future studies for analyzing different mitochondrial DNA segments. Based on the entire mitochondrial genome sequence, compared to other haplotypes from related species belonging in the same family (Astacidae) available in the GenBank database, a phylogenetic tree was constructed depicting the phylogenetic relationships of P. leptodactylus. Based on the results, the genetic distance between Astacus astacus and P. leptodactylus is smaller than the genetic distance between Austropotamobius pallipes and Austropotamobius torrentium, despite the fact that the latter two are classified within the same genus, questioning the phylogenetic position of A. astacus as a different genus than P. leptodactylus. In addition, the sample from Greece seems genetically distant compared with a conspecific haplotype available in the GenBank database, possibly implying a genetic distinction of P. leptodactylus from Greece. Full article

(This article belongs to the Special Issue Aquaculture Genetics: Latest Advances and Prospects)

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17 pages, 1322 KiB

Open AccessEditor’s ChoiceReview

Phase Separation: Direct and Indirect Driving Force for High-Order Chromatin Organization

by Xiaoli Li, Ziyang An, Wenqing Zhang and Feifei Li

Genes 2023, 14(2), 499; https://doi.org/10.3390/genes14020499 - 15 Feb 2023

Cited by 11 | Viewed by 5691

Abstract

The multi-level spatial chromatin organization in the nucleus is closely related to chromatin activity. The mechanism of chromatin organization and remodeling attract much attention. Phase separation describes the biomolecular condensation which is the basis for membraneless compartments in cells. Recent research shows that [...] Read more.

The multi-level spatial chromatin organization in the nucleus is closely related to chromatin activity. The mechanism of chromatin organization and remodeling attract much attention. Phase separation describes the biomolecular condensation which is the basis for membraneless compartments in cells. Recent research shows that phase separation is a key aspect to drive high-order chromatin structure and remodeling. In addition, chromatin functional compartmentalization in the nucleus which is formed by phase separation also plays an important role in overall chromatin structure. In this review, we summarized the latest work about the role of phase separation in spatial chromatin organization, focusing on direct and indirect effects of phase separation on 3D chromatin organization and its impact on transcription regulation. Full article

(This article belongs to the Special Issue Dynamics of 3D Genome Organization)

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12 pages, 1102 KiB

Open AccessEditor’s ChoiceArticle

Sequence Characterization of ITS Regions of Immortelle Helichrysum italicum (Roth) G. Don from the East Adriatic Coast

by Matjaž Hladnik, Alenka Baruca Arbeiter and Dunja Bandelj

Genes 2023, 14(2), 480; https://doi.org/10.3390/genes14020480 - 14 Feb 2023

Cited by 2 | Viewed by 1736

Abstract

The immortelle (Helichrysum italicum (Roth) G. Don) is a typical perennial plant of natural vegetation in the Mediterranean region, and due to secondary metabolites with several biological properties (anti-inflammatory, antioxidant, antimicrobial, and anti-proliferative), it has become an important species for essential oil [...] Read more.

The immortelle (Helichrysum italicum (Roth) G. Don) is a typical perennial plant of natural vegetation in the Mediterranean region, and due to secondary metabolites with several biological properties (anti-inflammatory, antioxidant, antimicrobial, and anti-proliferative), it has become an important species for essential oil production, especially in the cosmetic industry. To increase the production of highly priced essential oils, it has been moved to cultivated fields. However, due to the lack of highly characterized planting material, there is a great need for genotype identification, and to provide a link with chemical profiles and geographic origin as a basis for the identification of local superior genotypes. The aims of the study were to characterize the ITS (ribosomal internal transcribed spacer) regions, ITS1 and ITS2, in samples from the East Adriatic region to determine the possibility of using these regions for plant genetic resources identification. Genetic variation was observed when comparing the ITS sequence variants of samples from the North-East Adriatic and the South-East Adriatic. Some rare and unique ITS sequence variants can be helpful for identifying specific populations from different geographical regions. Full article

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

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7 pages, 231 KiB

Open AccessEditor’s ChoiceCase Report

Coexistence of Genetic Diseases Is a New Clinical Challenge: Three Unrelated Cases of Dual Diagnosis

by Anna Paola Capra, Maria Angela La Rosa, Sara Briguori, Rosa Civa, Chiara Passarelli, Emanuele Agolini, Antonio Novelli and Silvana Briuglia

Genes 2023, 14(2), 484; https://doi.org/10.3390/genes14020484 - 14 Feb 2023

Cited by 9 | Viewed by 2290

Abstract

Technological advancements in molecular genetics and cytogenetics have led to the diagnostic definition of complex or atypical clinical pictures. In this paper, a genetic analysis identifies multimorbidities, one due to either a copy number variant or a chromosome aneuploidy, and a second due [...] Read more.

Technological advancements in molecular genetics and cytogenetics have led to the diagnostic definition of complex or atypical clinical pictures. In this paper, a genetic analysis identifies multimorbidities, one due to either a copy number variant or a chromosome aneuploidy, and a second due to biallelic sequence variants in a gene associated with an autosomal recessive disorder. We diagnosed the simultaneous presence of these conditions, which co-occurred by chance, in three unrelated patients: a 10q11.22q11.23 microduplication and a homozygous variant, c.3470A>G (p.Tyr1157Cys), in the WDR19 gene associated with autosomal recessive ciliopathy; down syndrome and two variants, c.850G>A; p.(Gly284Arg) and c.5374G>T; p.(Glu1792*), in the LAMA2 gene associated with merosin-deficient congenital muscular dystrophy type 1A (MDC1A); and a de novo 16p11.2 microdeletion syndrome and homozygous variant, c.2828G>A (p.Arg943Gln), in the ABCA4 gene associated with Stargardt disease 1 (STGD1). The possibility of being affected by two relatively common or rare inherited genetic conditions would be suspected when signs and symptoms are incoherent with the primary diagnosis. All this could have important implications for improving genetic counseling, determining the correct prognosis, and, consequently, organizing the best long-term follow-up. Full article

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

15 pages, 2780 KiB

Open AccessEditor’s ChoiceArticle

A Chemoptogenetic Tool for Spatiotemporal Induction of Oxidative DNA Lesions In Vivo

by Suhao Han, Austin Sims, Anthony Aceto, Brigitte F. Schmidt, Marcel P. Bruchez and Aditi U. Gurkar

Genes 2023, 14(2), 485; https://doi.org/10.3390/genes14020485 - 14 Feb 2023

Viewed by 2398

Abstract

Oxidative nuclear DNA damage increases in all tissues with age in multiple animal models, as well as in humans. However, the increase in DNA oxidation varies from tissue to tissue, suggesting that certain cells/tissues may be more vulnerable to DNA damage than others. [...] Read more.

Oxidative nuclear DNA damage increases in all tissues with age in multiple animal models, as well as in humans. However, the increase in DNA oxidation varies from tissue to tissue, suggesting that certain cells/tissues may be more vulnerable to DNA damage than others. The lack of a tool that can control dosage and spatiotemporal induction of oxidative DNA damage, which accumulates with age, has severely limited our ability to understand how DNA damage drives aging and age-related diseases. To overcome this, here we developed a chemoptogenetic tool that produces 8-oxoguanine (8-oxoG) at DNA in a whole organism, Caenorhabditis elegans. This tool uses di-iodinated malachite green (MG-2I) photosensitizer dye that generates singlet oxygen, ¹O₂, upon fluorogen activating peptide (FAP) binding and excitation with far-red light. Using our chemoptogenetic tool, we are able to control generation of singlet oxygen ubiquitously or in a tissue-specific manner, including in neurons and muscle cells. To induce oxidative DNA damage, we targeted our chemoptogenetic tool to histone, his-72, that is expressed in all cell types. Our results show that a single exposure to dye and light is able to induce DNA damage, promote embryonic lethality, lead to developmental delay, and significantly reduce lifespan. Our chemoptogenetic tool will now allow us to assess the cell autonomous versus non-cell autonomous role of DNA damage in aging, at an organismal level. Full article

(This article belongs to the Topic Recent Advances in Healthy Ageing)

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23 pages, 1197 KiB

Open AccessEditor’s ChoiceReview

Impact of Advanced Paternal Age on Fertility and Risks of Genetic Disorders in Offspring

by Aris Kaltsas, Efthalia Moustakli, Athanasios Zikopoulos, Ioannis Georgiou, Fotios Dimitriadis, Evangelos N. Symeonidis, Eleftheria Markou, Theologos M. Michaelidis, Dung Mai Ba Tien, Ioannis Giannakis, Eleni Maria Ioannidou, Athanasios Papatsoris, Panagiota Tsounapi, Atsushi Takenaka, Nikolaos Sofikitis and Athanasios Zachariou

Genes 2023, 14(2), 486; https://doi.org/10.3390/genes14020486 - 14 Feb 2023

Cited by 77 | Viewed by 25117

Abstract

The average age of fathers at first pregnancy has risen significantly over the last decade owing to various variables, including a longer life expectancy, more access to contraception, later marriage, and other factors. As has been proven in several studies, women over 35 [...] Read more.

The average age of fathers at first pregnancy has risen significantly over the last decade owing to various variables, including a longer life expectancy, more access to contraception, later marriage, and other factors. As has been proven in several studies, women over 35 years of age have an increased risk of infertility, pregnancy problems, spontaneous abortion, congenital malformations, and postnatal issues. There are varying opinions on whether a father’s age affects the quality of his sperm or his ability to father a child. First, there is no single accepted definition of old age in a father. Second, much research has reported contradictory findings in the literature, particularly concerning the most frequently examined criteria. Increasing evidence suggests that the father’s age contributes to his offspring’s higher vulnerability to inheritable diseases. Our comprehensive literature evaluation shows a direct correlation between paternal age and decreased sperm quality and testicular function. Genetic abnormalities, such as DNA mutations and chromosomal aneuploidies, and epigenetic modifications, such as the silencing of essential genes, have all been linked to the father’s advancing years. Paternal age has been shown to affect reproductive and fertility outcomes, such as the success rate of in vitro fertilisation (IVF), intracytoplasmic sperm injection (ICSI), and premature birth rate. Several diseases, including autism, schizophrenia, bipolar disorders, and paediatric leukaemia, have been linked to the father’s advanced years. Therefore, informing infertile couples of the alarming correlations between older fathers and a rise in their offspring’s diseases is crucial, so that they can be effectively guided through their reproductive years. Full article

(This article belongs to the Special Issue Male Infertility: From Genes to Genomes 2022)

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12 pages, 7126 KiB

Open AccessEditor’s ChoiceArticle

Characterization of the MMP9 Gene and Its Association with Cryptocaryon irritans Resistance Traits in Trachinotus ovatus (Linnaeus, 1758)

by Jun Liu, Ke-Cheng Zhu, Jin-Min Pan, Hua-Yang Guo, Bao-Suo Liu, Nan Zhang, Jing-Wen Yang and Dian-Chang Zhang

Genes 2023, 14(2), 475; https://doi.org/10.3390/genes14020475 - 13 Feb 2023

Cited by 8 | Viewed by 3018

Abstract

The MMPs are endogenous proteolytic enzymes that require zinc and calcium as cofactors. MMP9 is one of the most complex matrix metalloproteinases in the gelatinase family and has many biological functions. In mammals, mmp9 is thought to be closely associated with cancer. However, [...] Read more.

The MMPs are endogenous proteolytic enzymes that require zinc and calcium as cofactors. MMP9 is one of the most complex matrix metalloproteinases in the gelatinase family and has many biological functions. In mammals, mmp9 is thought to be closely associated with cancer. However, studies in fish have rarely been reported. In this study, to understand the expression pattern of the ToMMP9 gene and its association with the resistance of Trachinotus ovatus to Cryptocaryon irritans, the sequence of the MMP9 gene was obtained from the genome database. The expression profiles were measured by qRT–PCR, the SNPs were screened by direct sequencing, and genotyping was performed. The ToMMP9 gene contained a 2058 bp ORF encoding a putative amino acid sequence of 685 residues. The homology of the ToMMP9 in teleosts was more than 85%, and the genome structure of ToMMP9 was conserved in chordates. The ToMMP9 gene was expressed in different tissues of healthy individuals and was highly expressed in the fin, the gill, the liver and the skin tissues. The ToMMP9 expression in the skin of the infected site and its adjacent sites increased significantly after C. irritans infection. Two SNPs were identified in the ToMMP9 gene, and the SNP (+400A/G) located in the first intron was found to be significantly associated with the susceptibility/resistance to C. irritans. These findings suggest that ToMMP9 may play an important role in the immune response of T. ovatus against C. irritans. Full article

(This article belongs to the Special Issue Genetic Breeding of Aquaculture)

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14 pages, 3706 KiB

Open AccessEditor’s ChoiceArticle

Glucosinolate Biosynthetic Genes of Cabbage: Genome-Wide Identification, Evolution, and Expression Analysis

by Peng Wang, Wenxue Cao, Limei Yang, Yangyong Zhang, Zhiyuan Fang, Mu Zhuang, Honghao Lv, Yong Wang, Shanhan Cheng and Jialei Ji

Genes 2023, 14(2), 476; https://doi.org/10.3390/genes14020476 - 13 Feb 2023

Cited by 4 | Viewed by 2686

Abstract

Cabbage (Brassica oleracea var. capitata) is a vegetable rich in glucosinolates (GSLs) that have proven health benefits. To gain insights into the synthesis of GSLs in cabbage, we systematically analyzed GSLs biosynthetic genes (GBGs) in the entire cabbage genome. In total, [...] Read more.

Cabbage (Brassica oleracea var. capitata) is a vegetable rich in glucosinolates (GSLs) that have proven health benefits. To gain insights into the synthesis of GSLs in cabbage, we systematically analyzed GSLs biosynthetic genes (GBGs) in the entire cabbage genome. In total, 193 cabbage GBGs were identified, which were homologous to 106 GBGs in Arabidopsis thaliana. Most GBGs in cabbage have undergone negative selection. Many homologous GBGs in cabbage and Chinese cabbage differed in expression patterns indicating the unique functions of these homologous GBGs. Spraying five exogenous hormones significantly altered expression levels of GBGs in cabbage. For example, MeJA significantly upregulated side chain extension genes BoIPMILSU1-1 and BoBCAT-3-1, and the expression of core structure construction genes BoCYP83A1 and BoST5C-1, while ETH significantly repressed the expression of side chain extension genes such as BoIPMILSU1-1, BoCYP79B2-1, and BoMAMI-1, and some transcription factors, namely BoMYB28-1, BoMYB34-1, BoMYB76-1, BoCYP79B2-1, and BoMAMI-1. Phylogenetically, the CYP83 family and CYP79B and CYP79F subfamilies may only be involved in GSL synthesis in cruciferous plants. Our unprecedented identification and analysis of GBGs in cabbage at the genome-wide level lays a foundation for the regulation of GSLs synthesis through gene editing and overexpression. Full article

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

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14 pages, 2247 KiB

Open AccessEditor’s ChoiceArticle

Genotype–Phenotype Correlations in 2q37-Deletion Syndrome: An Update of the Clinical Spectrum and Literature Review

by Eva-Cristiana Gavril, Irina Nucă, Monica-Cristina Pânzaru, Anca Viorica Ivanov, Cosmin-Teodor Mihai, Lucian-Mihai Antoci, Cristian-Gabriel Ciobanu, Cristina Rusu and Roxana Popescu

Genes 2023, 14(2), 465; https://doi.org/10.3390/genes14020465 - 11 Feb 2023

Cited by 7 | Viewed by 4881

Abstract

2q37 microdeletion/deletion syndrome (2q37DS) is one of the most common subtelomeric deletion disorders, caused by a 2q37 deletion of variable size. The syndrome is characterized by a broad and diverse spectrum of clinical findings: characteristic facial dysmorphism, developmental delay/intellectual disability (ID), brachydactyly type [...] Read more.

2q37 microdeletion/deletion syndrome (2q37DS) is one of the most common subtelomeric deletion disorders, caused by a 2q37 deletion of variable size. The syndrome is characterized by a broad and diverse spectrum of clinical findings: characteristic facial dysmorphism, developmental delay/intellectual disability (ID), brachydactyly type E, short stature, obesity, hypotonia in infancy, and abnormal behavior with autism spectrum disorder. Although numerous cases have been described so far, the exact mapping of the genotype and phenotype have not yet been achieved. Materials and Methods: In this study we analyzed nine newly diagnosed cases with 2q37 deletion (3 male/6 female, aged between 2 and 30 years old), and followed up at the Iasi Regional Medical Genetics Centre. All patients were tested first with MLPA using combined kits P036/P070 subtelomeric screening mix and follow-up mix P264; after, the deletion size and location were confirmed via CGH-array. We compared our findings with the data of other cases reported in the literature. Results: From nine cases, four had pure 2q37 deletions of variable sizes, and five presented deletion/duplication rearrangements (with chromosomes 2q, 9q, and 11p). In most cases, characteristic phenotypic aspects were observed: 9/9 facial dysmorphism, 8/9 global developmental delay and ID, 6/9 hypotonia, 5/9 behavior disorders, and 8/9 skeletal anomalies—especially brachydactyly type E. Two cases had obesity, one case had craniosynostosis, and four had heart defects. Other features found in our cases included translucent skin and telangiectasias (6/9), and a hump of fat on the upper thorax (5/9). Conclusions: Our study enriches the literature data by describing new clinical features associated with 2q37 deletion, and possible genotype–phenotype correlations. Full article

(This article belongs to the Special Issue Genetic and Phenotypic Correlation: Gene-Disease Validation)

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14 pages, 3613 KiB

Open AccessEditor’s ChoiceArticle

Complete Chloroplast Genome Sequence of the Long Blooming Cultivar Camellia ‘Xiari Qixin’: Genome Features, Comparative and Phylogenetic Analysis

by Yufen Xu, Yanju Liu, Zhaoyan Yu and Xiaocheng Jia

Genes 2023, 14(2), 460; https://doi.org/10.3390/genes14020460 - 10 Feb 2023

Cited by 4 | Viewed by 2278

Abstract

The camellia flower is a famous woody plant with a long-cultivated history and high ornamental value. It is extensively planted and utilized around the world and owns a massive germplasm resource. Camellia ‘Xiari Qixin’ belongs to one of the typical cultivars in the [...] Read more.

The camellia flower is a famous woody plant with a long-cultivated history and high ornamental value. It is extensively planted and utilized around the world and owns a massive germplasm resource. Camellia ‘Xiari Qixin’ belongs to one of the typical cultivars in the four seasons camellia hybrids series. Due to its long flowering period, this kind of cultivar is identified as a precious resource of camellia flowers. In this study, the complete chloroplast genome sequence of C. ‘Xiari Qixin’ was first reported. Its whole chloroplast genome is 157,039 bp in length with an overall GC content of 37.30%, composed of a large single copy region (LSC, 86,674 bp), a small single copy region (SSC, 18,281 bp), and a pair of inverted repeat regions (IRs, 26,042 bp each). A total of 134 genes were predicted in this genome, including 8 ribosomal RNA genes, 37 transfer RNA genes, and 89 protein-coding genes. In addition, 50 simple sequence repeats (SSRs) and 36 long repeat sequences were detected. By comparing C. ‘Xiari Qixin’ and seven Camellia species on the chloroplast genome, seven mutation hotspot regions were identified, including psbK, trnS (GCU)-trnG(GCC), trnG(GCC), petN-psbM, trnF(GAA)-ndhJ, trnP(UGG)-psaJ, and ycf1. Phylogenetic analysis of 30 chloroplast genomes showed that the genetic relationship between C. ‘Xiari Qixin’ and Camellia azalea is quite close in evolution. These results could not only provide a valuable database for determining the maternal origin of Camellia cultivars, but also contribute to the exploration of the phylogenetic relationship and utilization of germplasm resources for Camellia. Full article

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

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15 pages, 4889 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

ThrRS-Mediated Translation Regulation of the RNA Polymerase III Subunit RPC10 Occurs through an Element with Similarity to Cognate tRNA ASL and Affects tRNA Levels

by Ofri Levi, Monalisha Mallik and Yoav S. Arava

Genes 2023, 14(2), 462; https://doi.org/10.3390/genes14020462 - 10 Feb 2023

Cited by 3 | Viewed by 2454

Abstract

Aminoacyl tRNA synthetases (aaRSs) are a well-studied family of enzymes with a canonical role in charging tRNAs with a specific amino acid. These proteins appear to also have non-canonical roles, including post-transcriptional regulation of mRNA expression. Many aaRSs were found to bind mRNAs [...] Read more.

Aminoacyl tRNA synthetases (aaRSs) are a well-studied family of enzymes with a canonical role in charging tRNAs with a specific amino acid. These proteins appear to also have non-canonical roles, including post-transcriptional regulation of mRNA expression. Many aaRSs were found to bind mRNAs and regulate their translation into proteins. However, the mRNA targets, mechanism of interaction, and regulatory consequences of this binding are not fully resolved. Here, we focused on yeast cytosolic threonine tRNA synthetase (ThrRS) to decipher its impact on mRNA binding. Affinity purification of ThrRS with its associated mRNAs followed by transcriptome analysis revealed a preference for mRNAs encoding RNA polymerase subunits. An mRNA that was significantly bound compared to all others was the mRNA encoding RPC10, a small subunit of RNA polymerase III. Structural modeling suggested that this mRNA includes a stem-loop element that is similar to the anti-codon stem loop (ASL) structure of ThrRS cognate tRNA (tRNA^Thr). We introduced random mutations within this element and found that almost every change from the normal sequence leads to reduced binding by ThrRS. Furthermore, point mutations at six key positions that abolish the predicted ASL-like structure showed a significant decrease in ThrRS binding with a decrease in RPC10 protein levels. Concomitantly, tRNA^Thr levels were reduced in the mutated strain. These data suggest a novel regulatory mechanism in which cellular tRNA levels are regulated through a mimicking element within an RNA polymerase III subunit in a manner that involves the tRNA cognate aaRS. Full article

(This article belongs to the Special Issue Emerging Roles of tRNAs in Health and Disease)

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10 pages, 2570 KiB

Open AccessEditor’s ChoiceTechnical Note

DraculR: A Web-Based Application for In Silico Haemolysis Detection in High-Throughput microRNA Sequencing Data

by Melanie D. Smith, Shalem Y. Leemaqz, Tanja Jankovic-Karasoulos, Dylan McCullough, Dale McAninch, Anya L. Arthurs, James Breen, Claire T. Roberts and Katherine A. Pillman

Genes 2023, 14(2), 448; https://doi.org/10.3390/genes14020448 - 9 Feb 2023

Cited by 2 | Viewed by 2055

Abstract

The search for novel microRNA (miRNA) biomarkers in plasma is hampered by haemolysis, the lysis and subsequent release of red blood cell contents, including miRNAs, into surrounding fluid. The biomarker potential of miRNAs comes in part from their multicompartment origin and the long-lived [...] Read more.

The search for novel microRNA (miRNA) biomarkers in plasma is hampered by haemolysis, the lysis and subsequent release of red blood cell contents, including miRNAs, into surrounding fluid. The biomarker potential of miRNAs comes in part from their multicompartment origin and the long-lived nature of miRNA transcripts in plasma, giving researchers a functional window for tissues that are otherwise difficult or disadvantageous to sample. The inclusion of red-blood-cell-derived miRNA transcripts in downstream analysis introduces a source of error that is difficult to identify posthoc and may lead to spurious results. Where access to a physical specimen is not possible, our tool will provide an in silico approach to haemolysis prediction. We present DraculR, an interactive Shiny/R application that enables a user to upload miRNA expression data from a short-read sequencing of human plasma as a raw read counts table and interactively calculate a metric that indicates the degree of haemolysis contamination. The code, DraculR web tool and its tutorial are freely available as detailed herein. Full article

(This article belongs to the Collection Feature Papers in Bioinformatics)

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11 pages, 3376 KiB

Open AccessEditor’s ChoiceCommunication

Effects of Elexacaftor/Tezacaftor/Ivacaftor on Cardiorespiratory Polygraphy Parameters and Respiratory Muscle Strength in Cystic Fibrosis Patients with Severe Lung Disease

by Alessandro Giallongo, Giuseppe Fabio Parisi, Maria Papale, Sara Manti, Enza Mulé, Donatella Aloisio, Vito Terlizzi, Novella Rotolo and Salvatore Leonardi

Genes 2023, 14(2), 449; https://doi.org/10.3390/genes14020449 - 9 Feb 2023

Cited by 16 | Viewed by 2399

Abstract

Background: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators represent targeted therapies directly acting on the CFTR channel. The triple therapy Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) has been demonstrated to improve lung function and quality of life in cystic fibrosis (CF) patients. However, the effects of ELX/TEZ/IVA [...] Read more.

Background: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators represent targeted therapies directly acting on the CFTR channel. The triple therapy Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) has been demonstrated to improve lung function and quality of life in cystic fibrosis (CF) patients. However, the effects of ELX/TEZ/IVA on sleep-disordered breathing (SDB) and respiratory muscle strength are poorly studied. The aim of this study was to assess the effects of ELX/TEZ/IVA in patients with CF and severe lung disease on cardiorespiratory polygraphy parameters, maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP) measures. Methods: patients with CF aged ≥ 12 who started treatment in a compassionate use program were retrospectively studied through the evaluation of nocturnal cardiorespiratory polygraphy parameters, MIP and MEP; and six-minute walk test (6MWT) at baseline and at months 3, 6, and 12 of treatment. Results: Nine patients (mean age 30.3 ± 6.5 years) with severe CF (mean baseline ppFEV1 34.6 ± 5.1%) were evaluated. A significant improvement in nocturnal oxygenation measured by mean SpO₂ (92.4 vs. 96.4%, p < 0.05), time spent with SpO₂ ≤ 90% (−12.6, −14.6, −15.2 min from baseline at months 3, 6, and 12, respectively, p < 0.05), and respiratory rate (RR) was shown, at month 12 and across the time points compared with baseline, as well as in respiratory muscle strength, although only the change in MEP was significant. Conclusions: We provide further evidence on the efficacy of the CFTR modulators ELX/TEZ/IVA, adding information about their effect on the respiratory muscles’ performance and cardiorespiratory polygraphy parameters in CF patients with severe lung disease. Full article

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

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15 pages, 2204 KiB

Open AccessEditor’s ChoiceArticle

MIF Variant rs755622 Is Associated with Severe Crohn’s Disease and Better Response to Anti-TNF Adalimumab Therapy

by Gregor Jezernik, Mario Gorenjak and Uroš Potočnik

Genes 2023, 14(2), 452; https://doi.org/10.3390/genes14020452 - 9 Feb 2023

Cited by 6 | Viewed by 2563

Abstract

Crohn’s disease (CD), rheumatoid arthritis, psoriatic arthritis and other inflammatory diseases comprise a group of chronic diseases with immune-mediated pathogenesis which share common pathological pathways, as well as treatment strategies including anti-TNF biologic therapy. However, the response rate to anti-TNF therapy among those [...] Read more.

Crohn’s disease (CD), rheumatoid arthritis, psoriatic arthritis and other inflammatory diseases comprise a group of chronic diseases with immune-mediated pathogenesis which share common pathological pathways, as well as treatment strategies including anti-TNF biologic therapy. However, the response rate to anti-TNF therapy among those diseases varies, and approximately one third of patients do not respond. Since pharmacogenetic studies for anti-TNF therapy have been more frequent for other related diseases and are rare in CD, the aim of our study was to further explore markers associated with anti-TNF response in other inflammatory diseases in Slovenian CD patients treated with the anti-TNF drug adalimumab (ADA). We enrolled 102 CD patients on ADA, for which the response was defined after 4, 12, 20 and 30 weeks of treatment, using an IBDQ questionnaire and blood CRP value. We genotyped 41 SNPs significantly associated with response to anti-TNF treatment in other diseases. We found novel pharmacogenetic association between SNP rs755622 in the gene MIF (macrophage migration inhibitory factor) and SNP rs3740691 in the gene ARFGAP2 in CD patients treated with ADA. The strongest and most consistent association with treatment response was found for the variant rs2275913 in gene IL17A (p = 9.73 × 10⁻³). Full article

(This article belongs to the Section Pharmacogenetics)

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8 pages, 268 KiB

Open AccessEditor’s ChoiceCommunication

Impact of pri-let-7a-1 rs10739971 for Gastric Cancer Predisposition in an Amazon Region

by Roberta Borges Andrade, Amanda de Nazaré Cohen-Paes, Diana Feio da Veiga Borges Leal, Karla Beatriz Cardias Cereja Pantoja, Laura Patrícia Albarello Gellen, Darlen Cardoso de Carvalho, Tatiane Piedade de Souza, Marianne Rodrigues Fernandes, Paulo Pimentel de Assumpcão, Rommel Mario Rodríguez Burbano, Sidney Emanuel Batista dos Santos and Ney Pereira Carneiro dos Santos

Genes 2023, 14(2), 453; https://doi.org/10.3390/genes14020453 - 9 Feb 2023

Cited by 1 | Viewed by 1625

Abstract

Gastric cancer (GC) is the fifth most common type of cancer and the fourth leading cause of cancer death. In Brazil, GC has a high incidence and mortality rates, and it is highly variable by region. The Amazon region has significant rising rates [...] Read more.

Gastric cancer (GC) is the fifth most common type of cancer and the fourth leading cause of cancer death. In Brazil, GC has a high incidence and mortality rates, and it is highly variable by region. The Amazon region has significant rising rates among all Brazil regions. Only very few studies have evaluated the association between genetic variants and the risk of gastric cancer in the Brazilian Amazon population. Therefore, this study aimed to investigate associations between single nucleotide polymorphisms of miRNA processing genes and the risk for GC in this population. Potentially functional single nucleotide polymorphisms from miRNA processing genes were genotyped in 159 cases and 193 healthy controls by QuantStudio Real Time PCR. According to our findings, the genotype GG of the variant rs10739971 presents a lower risk to the development of GC in comparison to the remaining genotypes (p = 0.000016; OR = 0.055; 95% CI = 0.015–0.206). This is the first study to report the association of pri-let-7a-1 rs10739971 with GC in the Brazilian Amazon population, which is a highly mixed population with a unique genetic constitution that is different from other populations that are studied in the vast majority of scientific research. Full article

(This article belongs to the Special Issue Molecular Biomarkers of Solid Tumors)

13 pages, 1578 KiB

Open AccessEditor’s ChoiceArticle

The Impact of Variation in the Toll-like Receptor 3 Gene on Epizootic Hemorrhagic Disease in Illinois Wild White-Tailed Deer (Odocoileus virginianus)

by Jacob E. Wessels, Yasuko Ishida, Nelda A. Rivera, Spencer L. Stirewalt, William M. Brown, Jan E. Novakofski, Alfred L. Roca and Nohra E. Mateus-Pinilla

Genes 2023, 14(2), 426; https://doi.org/10.3390/genes14020426 - 8 Feb 2023

Cited by 3 | Viewed by 3584

Abstract

Epizootic hemorrhagic disease (EHD) leads to high mortality in white-tailed deer (Odocoileus virginianus) and is caused by a double-stranded RNA (dsRNA) virus. Toll-like receptor 3 (TLR3) plays a role in host immune detection and response to dsRNA viruses. We, therefore, examined [...] Read more.

Epizootic hemorrhagic disease (EHD) leads to high mortality in white-tailed deer (Odocoileus virginianus) and is caused by a double-stranded RNA (dsRNA) virus. Toll-like receptor 3 (TLR3) plays a role in host immune detection and response to dsRNA viruses. We, therefore, examined the role of genetic variation within the TLR3 gene in EHD among 84 Illinois wild white-tailed deer (26 EHD-positive deer and 58 EHD-negative controls). The entire coding region of the TLR3 gene was sequenced: 2715 base pairs encoding 904 amino acids. We identified 85 haplotypes with 77 single nucleotide polymorphisms (SNPs), of which 45 were synonymous mutations and 32 were non-synonymous. Two non-synonymous SNPs differed significantly in frequency between EHD-positive and EHD-negative deer. In the EHD-positive deer, phenylalanine was relatively less likely to be encoded at codon positions 59 and 116, whereas leucine and serine (respectively) were detected less frequently in EHD-negative deer. Both amino acid substitutions were predicted to impact protein structure or function. Understanding associations between TLR3 polymorphisms and EHD provides insights into the role of host genetics in outbreaks of EHD in deer, which may allow wildlife agencies to better understand the severity of outbreaks. Full article

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

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8 pages, 1112 KiB

Open AccessEditor’s ChoiceCase Report

Hereditary Cancer Syndrome in a Family with Double Mutation in BRIP1 and MUTYH Genes

by Giovanna D’Elia, Gemma Caliendo, Luana Passariello, Luisa Albanese, Jasmine Makker, Anna Maria Molinari and Maria Teresa Vietri

Genes 2023, 14(2), 428; https://doi.org/10.3390/genes14020428 - 8 Feb 2023

Cited by 3 | Viewed by 3249

Abstract

Hereditary cancer syndromes predispose to several types of cancer due to inherited pathogenic variants in susceptibility genes. We describe the case of a 57-year-old woman, diagnosed with breast cancer, and her family. The proband belongs to a family with a suspected tumor syndrome, [...] Read more.

Hereditary cancer syndromes predispose to several types of cancer due to inherited pathogenic variants in susceptibility genes. We describe the case of a 57-year-old woman, diagnosed with breast cancer, and her family. The proband belongs to a family with a suspected tumor syndrome, due to other cancer cases in her family from the paternal and maternal sides. After oncogenetic counseling, she was subjected to mutational analysis with an NGS panel analyzing 27 genes. The genetic analysis showed two monoallelic mutations in low penetrance genes, c.1187G>A (p.G396D) in MUTYH and c.55dup (p.Tyr19Leufs*2) in BRIP1. One of the mutations was inherited from the maternal side and the other from the paternal side, suggesting two different cancer syndrome types in the family. MUTYH mutation was related to the onset of cancers on the paternal side, as confirmed by the occurrence of the same mutation in the proband’s cousin. BRIP1 mutation was found in the proband’s mother, indicating that it was related to the cancer cases observed on the maternal side, including breast cancer and sarcoma. Advances in NGS technologies have allowed the identification of mutations in families with hereditary cancers in genes other than those related to a specific suspected syndrome. A complete oncogenetic counseling, together with molecular tests that enable a simultaneous analysis of multiple genes, is essential for the identification of a correct tumor syndrome and for clinical decision-making in a patient and his/her family. The detection of mutations in multiple susceptibility genes allows the initiation of early risk-reducing measures for identified mutation carriers among family members and to include them in a proper surveillance program for specific syndromes. Moreover, it may enable an adapted treatment for the affected patient, permitting personalized therapeutic options. Full article

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

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32 pages, 810 KiB

Open AccessEditor’s ChoiceReview

Computational Prediction of Protein Intrinsically Disordered Region Related Interactions and Functions

by Bingqing Han, Chongjiao Ren, Wenda Wang, Jiashan Li and Xinqi Gong

Genes 2023, 14(2), 432; https://doi.org/10.3390/genes14020432 - 8 Feb 2023

Cited by 12 | Viewed by 5316

Abstract

Intrinsically Disordered Proteins (IDPs) and Regions (IDRs) exist widely. Although without well-defined structures, they participate in many important biological processes. In addition, they are also widely related to human diseases and have become potential targets in drug discovery. However, there is a big [...] Read more.

Intrinsically Disordered Proteins (IDPs) and Regions (IDRs) exist widely. Although without well-defined structures, they participate in many important biological processes. In addition, they are also widely related to human diseases and have become potential targets in drug discovery. However, there is a big gap between the experimental annotations related to IDPs/IDRs and their actual number. In recent decades, the computational methods related to IDPs/IDRs have been developed vigorously, including predicting IDPs/IDRs, the binding modes of IDPs/IDRs, the binding sites of IDPs/IDRs, and the molecular functions of IDPs/IDRs according to different tasks. In view of the correlation between these predictors, we have reviewed these prediction methods uniformly for the first time, summarized their computational methods and predictive performance, and discussed some problems and perspectives. Full article

(This article belongs to the Special Issue Statistical Methods for Genetic Epidemiology)

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12 pages, 796 KiB

Open AccessEditor’s ChoiceArticle

by Ieva Golubickaite, Rasa Ugenskiene, Agne Bartnykaite, Lina Poskiene, Aurelija Vegiene, Evaldas Padervinskis, Viktoras Rudzianskas and Elona Juozaityte

Genes 2023, 14(2), 434; https://doi.org/10.3390/genes14020434 - 8 Feb 2023

Cited by 1 | Viewed by 2240

Abstract

In 2020, 878,348 newly reported cases and 444,347 deaths related to head and neck cancer were reported. These numbers suggest that there is still a need for molecular biomarkers for the diagnosis and prognosis of the disease. In this study, we aimed to [...] Read more.

In 2020, 878,348 newly reported cases and 444,347 deaths related to head and neck cancer were reported. These numbers suggest that there is still a need for molecular biomarkers for the diagnosis and prognosis of the disease. In this study, we aimed to analyze mitochondria-related mitochondrial transcription factor A (TFAM) and DNA polymerase γ (POLG) single-nucleotide polymorphisms (SNPs) in the head and neck cancer patient group and evaluate associations between SNPs, disease characteristics, and patient outcomes. Genotyping was performed using TaqMan probes with Real-Time polymerase chain reaction. We found associations between TFAM gene SNPs rs11006129 and rs3900887 and patient survival status. We found that patients with the TFAM rs11006129 CC genotype and non-carriers of the T allele had longer survival times than those with the CT genotype or T-allele carriers. Additionally, patients with the TFAM rs3900887 A allele tended to have shorter survival times than non-carriers of the A allele. Our findings suggest that variants in the TFAM gene may play an important role in head and neck cancer patient survival and could be considered and further evaluated as prognostic biomarkers. However, due to the limited sample size (n = 115), further studies in larger and more diverse cohorts are needed to confirm these findings. Full article

(This article belongs to the Special Issue Head and Neck Genetics)

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11 pages, 1397 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

A Cell System-Assisted Strategy for Evaluating the Natural Antioxidant-Induced Double-Stranded DNA Break (DSB) Style

by Yuduki Someya, Sakine Kobayashi, Kazuya Toriumi, Shigeki Takeda, Noritaka Adachi and Aya Kurosawa

Genes 2023, 14(2), 420; https://doi.org/10.3390/genes14020420 - 6 Feb 2023

Cited by 3 | Viewed by 2706

Abstract

Natural antioxidants derived from plants exert various physiological effects, including antitumor effects. However, the molecular mechanisms of each natural antioxidant have not yet been fully elucidated. Identifying the targets of natural antioxidants with antitumor properties in vitro is costly and time-consuming, and the [...] Read more.

Natural antioxidants derived from plants exert various physiological effects, including antitumor effects. However, the molecular mechanisms of each natural antioxidant have not yet been fully elucidated. Identifying the targets of natural antioxidants with antitumor properties in vitro is costly and time-consuming, and the results thus obtained may not reliably reflect in vivo conditions. Therefore, to enhance understanding regarding the antitumor effects of natural antioxidants, we focused on DNA, one of the targets of anticancer drugs, and evaluated whether antioxidants, e.g., sulforaphane, resveratrol, quercetin, kaempferol, and genistein, which exert antitumor effects, induce DNA damage using gene-knockout cell lines derived from human Nalm-6 and HeLa cells pretreated with the DNA-dependent protein kinase inhibitor NU7026. Our results suggested that sulforaphane induces single-strand breaks or DNA strand crosslinks and that quercetin induces double-strand breaks. In contrast, resveratrol showed the ability to exert cytotoxic effects other than DNA damage. Our results also suggested that kaempferol and genistein induce DNA damage via unknown mechanisms. Taken together, the use of this evaluation system facilitates the analysis of the cytotoxic mechanisms of natural antioxidants. Full article

(This article belongs to the Special Issue DNA Damage Induced by Anti-cancer Agents)

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12 pages, 256 KiB

Open AccessEditor’s ChoiceReview

Advances in Ophthalmic Epigenetics and Implications for Epigenetic Therapies: A Review

by Spencer M. Moore and John B. Christoforidis

Genes 2023, 14(2), 417; https://doi.org/10.3390/genes14020417 - 5 Feb 2023

Cited by 4 | Viewed by 3863

Abstract

The epigenome represents a vast molecular apparatus that writes, reads, and erases chemical modifications to the DNA and histone code without changing the DNA base-pair sequence itself. Recent advances in molecular sequencing technology have revealed that epigenetic chromatin marks directly mediate critical events [...] Read more.

The epigenome represents a vast molecular apparatus that writes, reads, and erases chemical modifications to the DNA and histone code without changing the DNA base-pair sequence itself. Recent advances in molecular sequencing technology have revealed that epigenetic chromatin marks directly mediate critical events in retinal development, aging, and degeneration. Epigenetic signaling regulates retinal progenitor (RPC) cell cycle exit during retinal laminar development, giving rise to retinal ganglion cells (RGCs), amacrine cells, horizontal cells, bipolar cells, photoreceptors, and Müller glia. Age-related epigenetic changes such as DNA methylation in the retina and optic nerve are accelerated in pathogenic conditions such as glaucoma and macular degeneration, but reversing these epigenetic marks may represent a novel therapeutic target. Epigenetic writers also integrate environmental signals such as hypoxia, inflammation, and hyperglycemia in complex retinal conditions such as diabetic retinopathy (DR) and choroidal neovascularization (CNV). Histone deacetylase (HDAC) inhibitors protect against apoptosis and photoreceptor degeneration in animal models of retinitis pigmentosa (RP). The epigenome represents an intriguing therapeutic target for age-, genetic-, and neovascular-related retinal diseases, though more work is needed before advancement to clinical trials. Full article

(This article belongs to the Special Issue Ophthalmic Genetics, Epigenetics, and Disease)

6 pages, 238 KiB

Open AccessEditor’s ChoiceCommunication

Effect of Different Anticoagulant Agents on Immune-Related Genes in Leukocytes Isolated from the Whole-Blood of Holstein Cows

by Viviana Floridia, Marta Sfulcini, Enrico D’Alessandro, Luca Cattaneo, Matteo Mezzetti, Luigi Liotta, Erminio Trevisi, Vincenzo Lopreiato and Andrea Minuti

Genes 2023, 14(2), 406; https://doi.org/10.3390/genes14020406 - 4 Feb 2023

Cited by 1 | Viewed by 2609

Abstract

Anticoagulants, such as ethylenediaminetetraacetic acid (EDTA), sodium citrate (Na-citrate), or heparin are normally used in hematological clinical tests to prevent coagulation. Although anticoagulants are fundamental for the correct application of clinical tests, they produce adverse effects in different fields, such as those involving [...] Read more.

Anticoagulants, such as ethylenediaminetetraacetic acid (EDTA), sodium citrate (Na-citrate), or heparin are normally used in hematological clinical tests to prevent coagulation. Although anticoagulants are fundamental for the correct application of clinical tests, they produce adverse effects in different fields, such as those involving specific molecular techniques; for instance, quantitative real time polymerase chain reactions (qPCR) and gene expression evaluation. For this reason, the aim of this study was to evaluate the expression of 14 genes in leukocytes that were isolated from the blood of Holstein cows, and which were collected in Li-heparin, K-EDTA, or Na-citrate tubes; then, they were analyzed using qPCR. Only the SDHA gene showed a significant dependence (p ≤ 0.05) on the anticoagulant that was used with the lowest expression; this was observed in Na-Citrate after being compared with Li-heparin and K-EDTA (p < 0.05). Although a variation in transcript abundance with the three anticoagulants was observed in almost all the investigated genes, the relative abundance levels were not statistically significant. In conclusion, the qPCR results were not influenced by the presence of the anticoagulant; thus, we had the opportunity to choose the test tube that was used in the experiment without interfering effects impacting the gene expression levels caused by the anticoagulant. Full article

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

15 pages, 3864 KiB

Open AccessEditor’s ChoiceArticle

Genome Identification of the Tea Plant (Camellia sinensis) ASMT Gene Family and Its Expression Analysis under Abiotic Stress

by Fangfang Xu, Wenxiang Liu, Hui Wang, Pravej Alam, Wei Zheng and Mohammad Faizan

Genes 2023, 14(2), 409; https://doi.org/10.3390/genes14020409 - 4 Feb 2023

Cited by 9 | Viewed by 3306

Abstract

The tea plant (Camellia sinensis (L.) O. Ktze) is an important cash crop grown worldwide. It is often subjected to environmental stresses that influence the quality and yield of its leaves. Acetylserotonin-O-methyltransferase (ASMT) is a key enzyme in melatonin biosynthesis, and it [...] Read more.

The tea plant (Camellia sinensis (L.) O. Ktze) is an important cash crop grown worldwide. It is often subjected to environmental stresses that influence the quality and yield of its leaves. Acetylserotonin-O-methyltransferase (ASMT) is a key enzyme in melatonin biosynthesis, and it plays a critical role in plant stress responses. In this paper, a total of 20 ASMT genes were identified in tea plants and classified into three subfamilies based on a phylogenetic clustering analysis. The genes were unevenly distributed on seven chromosomes; two pairs of genes showed fragment duplication. A gene sequence analysis showed that the structures of the ASMT genes in the tea plants were highly conserved and that the gene structures and motif distributions slightly differed among the different subfamily members. A transcriptome analysis showed that most CsASMT genes did not respond to drought and cold stresses, and a qRT-PCR analysis showed that CsASMT08, CsASMT09, CsASMT10, and CsASMT20 significantly responded to drought and low-temperature stresses; in particular, CsASMT08 and CsASMT10 were highly expressed under low-temperature stress and negatively regulated in response to drought stress. A combined analysis revealed that CsASMT08 and CsASMT10 were highly expressed and that their expressions differed before and after treatment, which indicates that they are potential regulators of abiotic stress resistance in the tea plant. Our results can facilitate further studies on the functional properties of CsASMT genes in melatonin synthesis and abiotic stress in the tea plant. Full article

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

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14 pages, 2165 KiB

Open AccessEditor’s ChoiceArticle

An Iterative Unsupervised Method for Gene Expression Differentiation

by Olga Georgieva

Genes 2023, 14(2), 412; https://doi.org/10.3390/genes14020412 - 4 Feb 2023

Cited by 1 | Viewed by 1854

Abstract

For several decades, intensive research for understanding gene activity and its role in organism’s lives is the research focus of scientists in different areas. A part of these investigations is the analysis of gene expression data for selecting differentially expressed genes. Methods that [...] Read more.

For several decades, intensive research for understanding gene activity and its role in organism’s lives is the research focus of scientists in different areas. A part of these investigations is the analysis of gene expression data for selecting differentially expressed genes. Methods that identify the interested genes have been proposed on statistical data analysis. The problem is that there is no good agreement among them, as different results are produced by distinct methods. By taking the advantage of the unsupervised data analysis, an iterative clustering procedure that finds differentially expressed genes shows promising results. In the present paper, a comparative study of the clustering methods applied for gene expression analysis is presented to explicate the choice of the clustering algorithm implemented in the method. An investigation of different distance measures is provided to reveal those that increase the efficiency of the method in finding the real data structure. Further, the method is improved by incorporating an additional aggregation measure based on the standard deviation of the expression levels. Its usage increases the gene distinction as a new amount of differentially expressed genes is found. The method is summarized in a detailed procedure. The significance of the method is proved by an analysis of two mice strain data sets. The differentially expressed genes defined by the proposed method are compared with those selected by the well-known statistical methods applied to the same data set. Full article

(This article belongs to the Special Issue Selected Papers from the 9th International Work-Conference on Bioinformatics and Biomedical Engineering (IWBBIO 2022))

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8 pages, 1029 KiB

Open AccessEditor’s ChoiceCommunication

Fusion Gene-Based Classification of Variant Cytogenetic Rearrangements in Acute Myeloid Leukemia

by Mary Gudipati, Melody Butler, Rima Koka, Maria R. Baer and Yi Ning

Genes 2023, 14(2), 396; https://doi.org/10.3390/genes14020396 - 3 Feb 2023

Cited by 1 | Viewed by 2655

Abstract

Acute myeloid leukemia (AML) represents a heterogeneous disease entity that is continuously moving to a more genetically defined classification. The classification of AML with recurrent chromosomal translocations, including those involving core binding factor subunits, plays a critical role in diagnosis, prognosis, treatment stratification, [...] Read more.

Acute myeloid leukemia (AML) represents a heterogeneous disease entity that is continuously moving to a more genetically defined classification. The classification of AML with recurrent chromosomal translocations, including those involving core binding factor subunits, plays a critical role in diagnosis, prognosis, treatment stratification, and residual disease evaluation. Accurate classification of variant cytogenetic rearrangements in AML contributes to effective clinical management. We report here the identification of four variant t(8;V;21) translocations in newly diagnosed AML patients. Two patients showed a t(8;14) and a t(8;10) variation, respectively, with a morphologically normal-appearing chromosome 21 in each initial karyotype. Subsequent fluorescence in situ hybridization (FISH) on metaphase cells revealed cryptic three-way translocations t(8;14;21) and t(8;10;21). Each resulted in RUNX1::RUNX1T1 fusion. The other two patients showed karyotypically visible three-way translocations t(8;16;21) and t(8;20;21), respectively. Each resulted in RUNX1::RUNX1T1 fusion. Our findings demonstrate the importance of recognizing variant forms of t(8;21) translocations and emphasize the value of applying RUNX1::RUNX1T1 FISH for the detection of cryptic and complex rearrangements when abnormalities involving chromosome band 8q22 are observed in patients with AML. Full article

(This article belongs to the Special Issue Advances in Clinical Cytogenetics)

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15 pages, 1815 KiB

Open AccessEditor’s ChoiceArticle

Increased On-Target Rate and Risk of Concatemerization after CRISPR-Enhanced Targeting in ES Cells

by Valérie Erbs, Romain Lorentz, Benjamin Eisenman, Laurence Schaeffer, Laurence Luppi, Loic Lindner, Yann Hérault, Guillaume Pavlovic, Marie Wattenhofer-Donzé and Marie-Christine Birling

Genes 2023, 14(2), 401; https://doi.org/10.3390/genes14020401 - 3 Feb 2023

Cited by 5 | Viewed by 3125

Abstract

The French mouse clinic (Institut Clinique de la Souris; ICS) has produced more than 2000 targeting vectors for ‘à la carte’ mutagenesis in C57BL/6N mice. Although most of the vectors were used successfully for homologous recombination in murine embryonic stem cells (ESCs), a [...] Read more.

The French mouse clinic (Institut Clinique de la Souris; ICS) has produced more than 2000 targeting vectors for ‘à la carte’ mutagenesis in C57BL/6N mice. Although most of the vectors were used successfully for homologous recombination in murine embryonic stem cells (ESCs), a few have failed to target a specific locus after several attempts. We show here that co-electroporation of a CRISPR plasmid with the same targeting construct as the one that failed previously allows the systematic achievement of positive clones. A careful validation of these clones is, however, necessary as a significant number of clones (but not all) show a concatemerization of the targeting plasmid at the locus. A detailed Southern blot analysis permitted characterization of the nature of these events as standard long-range 5′ and 3′ PCRs were not able to distinguish between correct and incorrect alleles. We show that a simple and inexpensive PCR performed prior to ESC amplification allows detection and elimination of those clones with concatemers. Finally, although we only tested murine ESCs, our results highlight the risk of mis-validation of any genetically modified cell line (such as established lines, induced pluripotent stem cells or those used for ex vivo gene therapy) that combines the use of CRISPR/Cas9 and a circular double-stranded donor. We strongly advise the CRISPR community to perform a Southern blot with internal probes when using CRISPR to enhance homologous recombination in any cell type, including fertilized oocytes. Full article

(This article belongs to the Special Issue Transgenic Animal Models for Disease Research)

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13 pages, 1607 KiB

Open AccessEditor’s ChoiceArticle

Delineating the Spectrum of Genetic Variants Associated with Bardet-Biedl Syndrome in Consanguineous Pakistani Pedigrees

by Ali Raza Rao, Aamir Nazir, Samina Imtiaz, Sohail Aziz Paracha, Yar Muhammad Waryah, Ikram Din Ujjan, Ijaz Anwar, Afia Iqbal, Federico A. Santoni, Inayat Shah, Khitab Gul, Hafiz Muhammad Azhar Baig, Ali Muhammad Waryah, Stylianos E. Antonarakis and Muhammad Ansar

Genes 2023, 14(2), 404; https://doi.org/10.3390/genes14020404 - 3 Feb 2023

Cited by 9 | Viewed by 3144

Abstract

This study aimed to find the molecular basis of Bardet-Biedl syndrome (BBS) in Pakistani consanguineous families. A total of 12 affected families were enrolled. Clinical investigations were performed to access the BBS-associated phenotypes. Whole exome sequencing was conducted on one affected individual from [...] Read more.

This study aimed to find the molecular basis of Bardet-Biedl syndrome (BBS) in Pakistani consanguineous families. A total of 12 affected families were enrolled. Clinical investigations were performed to access the BBS-associated phenotypes. Whole exome sequencing was conducted on one affected individual from each family. The computational functional analysis predicted the variants’ pathogenic effects and modeled the mutated proteins. Whole-exome sequencing revealed 9 pathogenic variants in six genes associated with BBS in 12 families. The BBS6/MKS was the most common BBS causative gene identified in five families (5/12, 41.6%), with one novel (c.1226G>A, p.Gly409Glu) and two reported variants. c.774G>A, Thr259LeuTer21 was the most frequent BBS6/MMKS allele in three families 3/5 (60%). Two variants, c.223C>T, p.Arg75Ter and a novel, c. 252delA, p.Lys85STer39 were detected in the BBS9 gene. A novel 8bp deletion c.387_394delAAATAAAA, p. Asn130GlyfsTer3 was found in BBS3 gene. Three known variants were detected in the BBS1, BBS2, and BBS7 genes. Identification of novel likely pathogenic variants in three genes reaffirms the allelic and genetic heterogeneity of BBS in Pakistani patients. The clinical differences among patients carrying the same pathogenic variant may be due to other factors influencing the phenotype, including variants in other modifier genes. Full article

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

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11 pages, 1559 KiB

Open AccessEditor’s ChoiceArticle

Detecting Melanocortin 1 Receptor Gene’s SNPs by CRISPR/enAsCas12a

by Wei Yang, Dagang Tao, Bingrong Xu, Yueting Zheng and Shuhong Zhao

Genes 2023, 14(2), 394; https://doi.org/10.3390/genes14020394 - 2 Feb 2023

Cited by 5 | Viewed by 2328

Abstract

Beyond its powerful genome-editing capabilities, the CRISPR/Cas system has opened up a new era of molecular diagnostics due to its highly specific base recognition and trans-cleavage activity. However, most CRISPR/Cas detection systems are mainly used to detect nucleic acids of bacteria or viruses, [...] Read more.

Beyond its powerful genome-editing capabilities, the CRISPR/Cas system has opened up a new era of molecular diagnostics due to its highly specific base recognition and trans-cleavage activity. However, most CRISPR/Cas detection systems are mainly used to detect nucleic acids of bacteria or viruses, while the application of single nucleotide polymorphism (SNP) detection is limited. The MC1R SNPs were investigated by CRISPR/enAsCas12a and are not limited to the protospacer adjacent motif (PAM) sequence in vitro. Specifically, we optimized the reaction conditions, which proved that the enAsCas12a has a preference for divalent magnesium ion (Mg²⁺) and can effectively distinguish the genes with a single base difference in the presence of Mg²⁺, and the Melanocortin l receptor (MC1R) gene with three kinds of SNP sites (T305C, T363C, and G727A) was quantitatively detected. Since the enAsCas12a is not limited by PAM sequence in vitro, the method shown here can extend this extraordinary CRISPR/enAsCas12a detection system to other SNP targets, thus providing a general SNP detection toolbox. Full article

(This article belongs to the Special Issue CRISPR-Based Nucleic Acid Detection and Genome Editing in Animals)

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21 pages, 1401 KiB

Open AccessEditor’s ChoiceArticle

Assessing Outlier Probabilities in Transcriptomics Data When Evaluating a Classifier

by Magdalena Kircher, Josefin Säurich, Michael Selle and Klaus Jung

Genes 2023, 14(2), 387; https://doi.org/10.3390/genes14020387 - 1 Feb 2023

Viewed by 2963

Abstract

Outliers in the training or test set used to fit and evaluate a classifier on transcriptomics data can considerably change the estimated performance of the model. Hence, an either too weak or a too optimistic accuracy is then reported and the estimated model [...] Read more.

Outliers in the training or test set used to fit and evaluate a classifier on transcriptomics data can considerably change the estimated performance of the model. Hence, an either too weak or a too optimistic accuracy is then reported and the estimated model performance cannot be reproduced on independent data. It is then also doubtful whether a classifier qualifies for clinical usage. We estimate classifier performances in simulated gene expression data with artificial outliers and in two real-world datasets. As a new approach, we use two outlier detection methods within a bootstrap procedure to estimate the outlier probability for each sample and evaluate classifiers before and after outlier removal by means of cross-validation. We found that the removal of outliers changed the classification performance notably. For the most part, removing outliers improved the classification results. Taking into account the fact that there are various, sometimes unclear reasons for a sample to be an outlier, we strongly advocate to always report the performance of a transcriptomics classifier with and without outliers in training and test data. This provides a more diverse picture of a classifier’s performance and prevents reporting models that later turn out to be not applicable for clinical diagnoses. Full article

(This article belongs to the Collection Feature Papers in Bioinformatics)

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10 pages, 2352 KiB

Open AccessEditor’s ChoiceCase Report

De Novo Variant in the KCNJ9 Gene as a Possible Cause of Neonatal Seizures

by Taisiya O. Kochetkova, Dmitry N. Maslennikov, Ekaterina R. Tolmacheva, Jekaterina Shubina, Anna S. Bolshakova, Dzhenneta I. Suvorova, Anna V. Degtyareva, Irina V. Orlovskaya, Maria V. Kuznetsova, Anastasia A. Rachkova, Gennady T. Sukhikh, Denis V. Rebrikov and Dmitriy Yu. Trofimov

Genes 2023, 14(2), 366; https://doi.org/10.3390/genes14020366 - 31 Jan 2023

Cited by 1 | Viewed by 2362

Abstract

Background: The reduction in next-generation sequencing (NGS) costs allows for using this method for newborn screening for monogenic diseases (MDs). In this report, we describe a clinical case of a newborn participating in the EXAMEN project (ClinicalTrials.gov Identifier: NCT05325749). Methods: The child presented [...] Read more.

Background: The reduction in next-generation sequencing (NGS) costs allows for using this method for newborn screening for monogenic diseases (MDs). In this report, we describe a clinical case of a newborn participating in the EXAMEN project (ClinicalTrials.gov Identifier: NCT05325749). Methods: The child presented with convulsive syndrome on the third day of life. Generalized convulsive seizures were accompanied by electroencephalographic patterns corresponding to epileptiform activity. Proband WES expanded to trio sequencing was performed. Results: A differential diagnosis was made between symptomatic (dysmetabolic, structural, infectious) neonatal seizures and benign neonatal seizures. There were no data in favor of the dysmetabolic, structural, or infectious nature of seizures. Molecular karyotyping and whole exome sequencing were not informative. Trio WES revealed a de novo variant in the KCNJ9 gene (1:160087612T > C, p.Phe326Ser, NM_004983), for which, according to the OMIM database, no association with the disease has been described to date. Three-dimensional modeling was used to predict the structure of the KCNJ9 protein using the known structure of its homologs. According to the predictions, Phe326Ser change possibly disrupts the hydrophobic contacts with the valine side chain. Destabilization of the neighboring structures may undermine the formation of GIRK2/GIRK3 tetramers necessary for their proper functioning. Conclusions: We believe that the identified variant may be the cause of the disease in this patient but further studies, including the search for other patients with the KCNJ9 variants, are needed. Full article

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

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20 pages, 13468 KiB

Open AccessEditor’s ChoiceArticle

Making the Genome Huge: The Case of Triatoma delpontei, a Triatominae Species with More than 50% of Its Genome Full of Satellite DNA

by Pablo Mora, Sebastián Pita, Eugenia E. Montiel, José M. Rico-Porras, Teresa Palomeque, Francisco Panzera and Pedro Lorite

Genes 2023, 14(2), 371; https://doi.org/10.3390/genes14020371 - 31 Jan 2023

Cited by 24 | Viewed by 2632

Abstract

The genome of Triatoma delpontei Romaña & Abalos 1947 is the largest within Heteroptera, approximately two to three times greater than other evaluated Heteroptera genomes. Here, the repetitive fraction of the genome was determined and compared with its sister species Triatoma infestans Klug [...] Read more.

The genome of Triatoma delpontei Romaña & Abalos 1947 is the largest within Heteroptera, approximately two to three times greater than other evaluated Heteroptera genomes. Here, the repetitive fraction of the genome was determined and compared with its sister species Triatoma infestans Klug 1834, in order to shed light on the karyotypic and genomic evolution of these species. The T. delpontei repeatome analysis showed that the most abundant component in its genome is satellite DNA, which makes up more than half of the genome. The T. delpontei satellitome includes 160 satellite DNA families, most of them also present in T. infestans. In both species, only a few satellite DNA families are overrepresented on the genome. These families are the building blocks of the C-heterochromatic regions. Two of these satellite DNA families that form the heterochromatin are the same in both species. However, there are satellite DNA families highly amplified in the heterochromatin of one species that in the other species are in low abundance and located in the euchromatin. Therefore, the present results depicted the great impact of the satellite DNA sequences in the evolution of Triatominae genomes. Within this scenario, satellitome determination and analysis led to a hypothesis that explains how satDNA sequences have grown on T. delpontei to reach its huge genome size within true bugs. Full article

(This article belongs to the Special Issue State-of-the-Art in Insect Cytogenetics)

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21 pages, 1707 KiB

Open AccessEditor’s ChoiceReview

Malignancies in Patients with Celiac Disease: Diagnostic Challenges and Molecular Advances

by Mariia Ivanova, Luca Bottiglieri, Elham Sajjadi, Konstantinos Venetis and Nicola Fusco

Genes 2023, 14(2), 376; https://doi.org/10.3390/genes14020376 - 31 Jan 2023

Cited by 12 | Viewed by 4213

Abstract

Celiac disease (CD) is a multiorgan autoimmune disorder of the chronic intestinal disease group characterized by duodenal inflammation in genetically predisposed individuals, precipitated by gluten ingestion. The pathogenesis of celiac disease is now widely studied, overcoming the limits of the purely autoimmune concept [...] Read more.

Celiac disease (CD) is a multiorgan autoimmune disorder of the chronic intestinal disease group characterized by duodenal inflammation in genetically predisposed individuals, precipitated by gluten ingestion. The pathogenesis of celiac disease is now widely studied, overcoming the limits of the purely autoimmune concept and explaining its hereditability. The genomic profiling of this condition has led to the discovery of numerous genes involved in interleukin signaling and immune-related pathways. The spectrum of disease manifestations is not limited to the gastrointestinal tract, and a significant number of studies have considered the possible association between CD and neoplasms. Patients with CD are found to be at increased risk of developing malignancies, with a particular predisposition of certain types of intestinal cancer, lymphomas, and oropharyngeal cancers. This can be partially explained by common cancer hallmarks present in these patients. The study of gut microbiota, microRNAs, and DNA methylation is evolving to find the any possible missing links between CD and cancer incidence in these patients. However, the literature is extremely mixed and, therefore, our understanding of the biological interplay between CD and cancer remains limited, with significant implications in terms of clinical management and screening protocols. In this review article, we seek to provide a comprehensive overview of the genomics, epigenomics, and transcriptomics data on CD and its relation to the most frequent types of neoplasms that may occur in these patients. Full article

(This article belongs to the Special Issue Genetics and Genomics of Gastrointestinal Cancers: From Prevention to Treatment)

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