Genes

12 pages, 1173 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Scan of Wool Production Traits in Akkaraman Sheep

by Yunus Arzik, Mehmet Kizilaslan, Sedat Behrem, Stephen N. White, Lindsay M. W. Piel and Mehmet Ulas Cinar

Genes 2023, 14(3), 713; https://doi.org/10.3390/genes14030713 - 14 Mar 2023

Cited by 22 | Viewed by 4060

Abstract

The objective of this study was to uncover the genetic background of wool quality, a production trait, by estimating genomic heritability and implementing GWAS in Akkaraman sheep. The wool characteristics measured included fibre diameter (FD) and staple length (SL) at the age of [...] Read more.

The objective of this study was to uncover the genetic background of wool quality, a production trait, by estimating genomic heritability and implementing GWAS in Akkaraman sheep. The wool characteristics measured included fibre diameter (FD) and staple length (SL) at the age of 8 months and yearling fibre diameter (YFD), yearling staple length (YSL) and yearling greasy fleece weight (YGFW) at 18 months of age. Animals were genotyped using the Axiom 50 K Ovine Genotyping Array. Maximum likelihood estimations of a linear mixed model (LMM) were used to estimate genomic heritability, where GWAS was conducted following a score test of each trait. Genomic heritability estimates for the traits ranged between 0.22 and 0.63, indicating that phenotypes have a moderate range of heritability. One genome- and six chromosome-wide significant SNPs were associated with the wool traits in Akkaraman lambs. Accordingly, TRIM2, MND1, TLR2, RNF175, CEP290, TMTC3, RERE, SLC45A1, SOX2, MORN1, SKI, FAAP20, PRKCZ, GABRD, CFAP74, CALML6 and TMEM52 genes as well as nine uncharacterized regions (LOC101118971, LOC105609137, LOC105603067, LOC101122892, LOC106991694, LOC106991467, LOC106991455, LOC105616534 and LOC105609719) were defined as plausible candidates. The findings of this study shed light on the genetics of wool quality and yield for the Akkaraman breed and suggests targets for breeders during systematic breeding programmes. Full article

(This article belongs to the Special Issue Genetics and Breeding of Small Ruminants)

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16 pages, 2248 KiB

Open AccessEditor’s ChoiceArticle

An Investigation into Compound Likelihood Ratios for Forensic DNA Mixtures

by Richard Wivell, Hannah Kelly, Jason Kokoszka, Jace Daniels, Laura Dickson, John Buckleton and Jo-Anne Bright

Genes 2023, 14(3), 714; https://doi.org/10.3390/genes14030714 - 14 Mar 2023

Cited by 1 | Viewed by 2960

Abstract

Simple propositions are defined as those with one POI and the remaining contributors unknown under H_p and all unknown contributors under H_a. Conditional propositions are defined as those with one POI, one or more assumed contributors, and the remaining contributors [...] Read more.

Simple propositions are defined as those with one POI and the remaining contributors unknown under H_p and all unknown contributors under H_a. Conditional propositions are defined as those with one POI, one or more assumed contributors, and the remaining contributors (if any) unknown under H_p, and the assumed contributor(s) and N unknown contributors under H_a. In this study, compound propositions are those with multiple POI and the remaining contributors unknown under H_p and all unknown contributors under Ha. We study the performance of these three proposition sets on thirty-two samples (two laboratories × four NOCs × four mixtures) consisting of four mixtures, each with N = 2, N = 3, N = 4, and N = 5 contributors using the probabilistic genotyping software, STRmix™. In this study, it was found that conditional propositions have a much higher ability to differentiate true from false donors than simple propositions. Compound propositions can misstate the weight of evidence given the propositions strongly in either direction. Full article

(This article belongs to the Special Issue Forensic DNA Mixture Interpretation and Probabilistic Genotyping)

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20 pages, 1252 KiB

Open AccessEditor’s ChoiceReview

Telomere Length Changes in Cancer: Insights on Carcinogenesis and Potential for Non-Invasive Diagnostic Strategies

by Zuzana Holesova, Lucia Krasnicanova, Rami Saade, Ondrej Pös, Jaroslav Budis, Juraj Gazdarica, Vanda Repiska and Tomas Szemes

Genes 2023, 14(3), 715; https://doi.org/10.3390/genes14030715 - 14 Mar 2023

Cited by 20 | Viewed by 6989

Abstract

Telomere dynamics play a crucial role in the maintenance of chromosome integrity; changes in telomere length may thus contribute to the development of various diseases including cancer. Understanding the role of telomeric DNA in carcinogenesis and detecting the presence of cell-free telomeric DNA [...] Read more.

Telomere dynamics play a crucial role in the maintenance of chromosome integrity; changes in telomere length may thus contribute to the development of various diseases including cancer. Understanding the role of telomeric DNA in carcinogenesis and detecting the presence of cell-free telomeric DNA (cf-telDNA) in body fluids offer a potential biomarker for novel cancer screening and diagnostic strategies. Liquid biopsy is becoming increasingly popular due to its undeniable benefits over conventional invasive methods. However, the organization and function of cf-telDNA in the extracellular milieu are understudied. This paper provides a review based on 3,398,017 cancer patients, patients with other conditions, and control individuals with the aim to shed more light on the inconsistent nature of telomere lengthening/shortening in oncological contexts. To gain a better understanding of biological factors (e.g., telomerase activation, alternative lengthening of telomeres) affecting telomere homeostasis across different types of cancer, we summarize mechanisms responsible for telomere length maintenance. In conclusion, we compare tissue- and liquid biopsy-based approaches in cancer assessment and provide a brief outlook on the methodology used for telomere length evaluation, highlighting the advances of state-of-the-art approaches in the field. Full article

(This article belongs to the Special Issue DNA Damage and Repair at the Crossroad with Telomeres)

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12 pages, 444 KiB

Open AccessEditor’s ChoiceArticle

Lack of Association of Polymorphism Located Upstream of ABCA1 (rs2472493), in FNDC3B (rs7636836), and Near ANKRD55–MAP3K1 Genes (rs61275591) in Primary Open-Angle Glaucoma Patients of Saudi Origin

by Altaf A. Kondkar, Tahira Sultan, Taif A. Azad, Essam A. Osman, Faisal A. Almobarak, Glenn P. Lobo and Saleh A. Al-Obeidan

Genes 2023, 14(3), 704; https://doi.org/10.3390/genes14030704 - 13 Mar 2023

Cited by 2 | Viewed by 1949

Abstract

Polymorphisms rs2472493 near ABCA1, rs7636836 in FNDC3B, and rs61275591 near the ANKRD55–MAP3K1 genes were previously reported to exhibit genome-wide significance in primary open-angle glaucoma (POAG). Since these polymorphisms have not been investigated in the Arab population of Saudi Arabia, we examined [...] Read more.

Polymorphisms rs2472493 near ABCA1, rs7636836 in FNDC3B, and rs61275591 near the ANKRD55–MAP3K1 genes were previously reported to exhibit genome-wide significance in primary open-angle glaucoma (POAG). Since these polymorphisms have not been investigated in the Arab population of Saudi Arabia, we examined their association with POAG in a Saudi cohort. Genotyping was performed in 152 POAG cases and 246 controls using Taqman real-time assays and their associations with POAG and clinical markers, such as intraocular pressure, cup/disc ratio, and the number of antiglaucoma medications, were tested by statistical methods. There was no association observed between POAG and the minor allele frequencies of rs2472493[G], rs7636836[T], or rs61275591[A]. None of the genetic models such as co-dominant, dominant, recessive, over-dominant, and log-additive demonstrated any genotype link. The Rs2472493 genotype showed a modest association (p = 0.044) with the number of antiglaucoma medications in the POAG group, but no significant genotype effect on post hoc analysis. In addition, a G-T allelic haplotype of rs2472493 (ABCA1) and rs7636836 (FNDC3B) did show an over two-fold increased risk of POAG (odds ratio = 2.18), albeit non-significantly (p = 0.092). Similarly, no other allelic haplotype of the three variants showed any significant association with POAG. Our study did not replicate the genetic association of rs2472493 (ABCA1), rs763683 (FNDC3B), and rs61275591 (ANKRD55–MAP3K1) in POAG and related clinical phenotypes, suggesting that these polymorphisms are not associated with POAG in a Saudi cohort of Arab ethnicity. However, large population-based multicenter studies are needed to validate these results. Full article

(This article belongs to the Special Issue Single-Nucleotide Polymorphisms: Association, Molecular Function, Application, and Progress)

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22 pages, 8657 KiB

Open AccessEditor’s ChoiceArticle

How Physical and Molecular Anthropology Interplay in the Creation of Biological Profiles of Unidentified Migrants

by Elena Pilli, Andrea Palamenghi, Stefania Morelli, Debora Mazzarelli, Danilo De Angelis, Richard L. Jantz and Cristina Cattaneo

Genes 2023, 14(3), 706; https://doi.org/10.3390/genes14030706 - 13 Mar 2023

Cited by 13 | Viewed by 2828

Abstract

The skeletal sex and ancestry of unidentified human crania can be inferred both from physical and from molecular features. This paper depicts and discusses the experiences of physical and molecular anthropologists on a set of commingled crania from the largest Mediterranean shipwreck disaster [...] Read more.

The skeletal sex and ancestry of unidentified human crania can be inferred both from physical and from molecular features. This paper depicts and discusses the experiences of physical and molecular anthropologists on a set of commingled crania from the largest Mediterranean shipwreck disaster on 18 April 2015, in order to facilitate identification of human crania. Twenty-one disarticulated crania that were recovered from the above-mentioned shipwreck were analyzed to estimate skeletal sex and ancestry, following a physical and a molecular pipeline. The physical analyses applied morphological and metric methods that provided posterior probabilities for the crania to be classified into a sex or ancestral group. The molecular analyses were performed on petrous bones via a shotgun sequencing approach that allowed us to determine the sex of each individual and to retrieve the complete mitochondrial genome, Y chromosome single nucleotide polymorphisms, up to 597573 SNPs across the human genome from each individual. The morphometric sex analyses showed that most crania belonged to male individuals, although some estimations remained uncertain or undetermined. Inconsistent results were obtained for ancestry estimation as well, since morphological methods classified the crania mostly as European/White, in contrast to the most numerous African forms determined by craniometric analyses. This quite agreed with molecular analyses that identified only African males. Overall, undetermined and contrasting results were obtained between disciplines, preventing the creation of reliable and sound biological profiles that could provide guidance on the sex and ancestral group of the victims. Therefore, the times may not be mature for a merger of physical and molecular anthropology. However, future investigations of this research avenue would pave the way to the possible development of novel tools, methods, and wider reference databases that could address the limitations of both disciplines. Full article

(This article belongs to the Special Issue Identification of Human Remains for Forensic and Humanitarian Purposes: From Molecular to Physical Methods)

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11 pages, 2716 KiB

Open AccessEditor’s ChoiceArticle

A Biallelic Truncating Variant in the TPR Domain of GEMIN5 Associated with Intellectual Disability and Cerebral Atrophy

by Nazia Ibrahim, Shagufta Naz, Francesca Mattioli, Nicolas Guex, Saima Sharif, Afia Iqbal, Muhammad Ansar and Alexandre Reymond

Genes 2023, 14(3), 707; https://doi.org/10.3390/genes14030707 - 13 Mar 2023

Cited by 7 | Viewed by 2638

Abstract

GEMIN5 is a multifunctional RNA-binding protein required for the assembly of survival motor neurons. Several bi-allelic truncating and missense variants in this gene are reported to cause a neurodevelopmental disorder characterized by cerebellar atrophy, intellectual disability (ID), and motor dysfunction. Whole exome sequencing [...] Read more.

GEMIN5 is a multifunctional RNA-binding protein required for the assembly of survival motor neurons. Several bi-allelic truncating and missense variants in this gene are reported to cause a neurodevelopmental disorder characterized by cerebellar atrophy, intellectual disability (ID), and motor dysfunction. Whole exome sequencing of a Pakistani consanguineous family with three brothers affected by ID, cerebral atrophy, mobility, and speech impairment revealed a novel homozygous 3bp-deletion NM_015465.5:c.3162_3164del that leads to the loss of NM_015465.5 (NP_056280.2):p. (Asp1054_Ala1055delinsGlu) amino acid in one of the α-helixes of the tetratricopeptide repeats of GEMIN5. In silico 3D representations of the GEMIN5 dimerization domain show that this variant likely affects the orientation of the downstream sidechains out of the helix axis, which would affect the packing with neighboring helices. The phenotype of all affected siblings overlaps well with previously reported patients, suggesting that NM_015465.5: c.3162_3164del (NP_056280.2):p. (Asp1054_Ala1055delinsGlu) is a novel GEMIN5 pathogenic variant. Overall, our data expands the molecular and clinical phenotype of the recently described neurodevelopmental disorder with cerebellar atrophy and motor dysfunction (NEDCAM) syndrome. Full article

(This article belongs to the Special Issue Genetic Variants in Human Population and Diseases)

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15 pages, 850 KiB

Open AccessEditor’s ChoiceReview

Folate–Methionine Cycle Disruptions in ASD Patients and Possible Interventions: A Systematic Review

by Melissa Roufael, Tania Bitar, Yonna Sacre, Christian Andres and Walid Hleihel

Genes 2023, 14(3), 709; https://doi.org/10.3390/genes14030709 - 13 Mar 2023

Cited by 13 | Viewed by 16314

Abstract

Autism Spectrum Disorder (ASD) has become a major public health concern due to its rapidly rising incidence over the past few years. Disturbances in folate or methionine metabolism have been identified in many individuals with ASD, suggesting that the folate–methionine cycle may play [...] Read more.

Autism Spectrum Disorder (ASD) has become a major public health concern due to its rapidly rising incidence over the past few years. Disturbances in folate or methionine metabolism have been identified in many individuals with ASD, suggesting that the folate–methionine cycle may play an essential role in the pathogenesis of autism. Thus, changes in metabolite concentrations associated with this cycle could be used as potential biomarkers and therapeutic targets for ASD. The aim of this systematic review is to elucidate the perturbations of this cycle and the possible interventions that may be proposed in this context. Several studies have shown that high levels of homocysteine and low levels of vitamins B12 and folate are associated with ASD. These changes in serum metabolites are influenced by poor diet. In fact, children with ASD tend to eat selectively, which could compromise the quality of their diet and result in nutrient deficiencies. Moreover, these disturbances may also be caused by genetic predispositions such as polymorphisms of the MTHFR gene. Few studies have demonstrated the beneficial effects of the use of nutritional supplements in treating ASD children. Therefore, larger, well-structured studies are recommended to examine the impact of vitamin B12 and folate supplementation on homocysteine levels. Full article

(This article belongs to the Special Issue Psychiatric and Behavioral Genetics)

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18 pages, 6196 KiB

Open AccessEditor’s ChoiceArticle

Codon Usage Analyses Reveal the Evolutionary Patterns among Plastid Genes of Saxifragales at a Larger-Sampling Scale

by De Bi, Shiyun Han, Jun Zhou, Maojin Zhao, Sijia Zhang and Xianzhao Kan

Genes 2023, 14(3), 694; https://doi.org/10.3390/genes14030694 - 11 Mar 2023

Cited by 9 | Viewed by 2391

Abstract

Saxifragales is a 15-family order of early-divergent Eudicots with a rich morphological diversity and an ancient rapid radiation. Codon usage bias (CUB) analyses have emerged as an essential tool for understanding the evolutionary dynamics in genes. Thus far, the codon utilization patterns had [...] Read more.

Saxifragales is a 15-family order of early-divergent Eudicots with a rich morphological diversity and an ancient rapid radiation. Codon usage bias (CUB) analyses have emerged as an essential tool for understanding the evolutionary dynamics in genes. Thus far, the codon utilization patterns had only been reported in four separate genera within Saxifragales. This study provides a comprehensive assessment of the codon manipulation based on 50 plastid genes, covering 11 constituent families at a larger sampling scale. Our results first showed a high preference for AT bases and AT-ending codons. We then used effective number of codons (ENC) to assess a range of codon bias levels in the plastid genes. We also detected high-informative intrafamilial differences of ENC in three families. Subsequently, parity rule 2 (PR2) plot analyses revealed both family-unique and order-shared bias patterns. Most importantly, the ENC plots and neutrality analyses collectively supported the dominant roles of selection in the CUB of Saxifragales plastid genes. Notably, the phylogenetic affinities inferred by both ML and BI methods were consistent with each other, and they all comprised two primary clades and four subclades. These findings significantly enhance our understanding of the evolutionary processes of the Saxifrage order, and could potentially inspire more CUB analyses at higher taxonomic levels. Full article

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

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11 pages, 4833 KiB

Open AccessEditor’s ChoiceCommunication

The Complete Mitochondrial Genome of Homophyllia bowerbanki (Scleractinia, Lobophylliidae): The First Sequence for the Genus Homophyllia

by Peng Tian, Wei Wang, Ziqing Xu, Bingbing Cao, Zhiyu Jia, Fucheng Sun, Jiaguang Xiao and Wentao Niu

Genes 2023, 14(3), 695; https://doi.org/10.3390/genes14030695 - 11 Mar 2023

Cited by 2 | Viewed by 1808

Abstract

Reef-building coral species of the order Scleractinia play an important role in shallow tropical seas by providing an environmental base for the ecosystem. The molecular data of complete mitochondrial genome have become an important source for evaluating phylogenetic and evolutionary studies of Scleractinia. [...] Read more.

Reef-building coral species of the order Scleractinia play an important role in shallow tropical seas by providing an environmental base for the ecosystem. The molecular data of complete mitochondrial genome have become an important source for evaluating phylogenetic and evolutionary studies of Scleractinia. Here, the complete mitogenome of Homophyllia bowerbanki (Milne Edwards and Haime, 1857), collected from Nansha Islands of the South China Sea, was sequenced for the first time through a next-generation sequencing method. H. bowerbanki is the first species of its genus for which the mitogenome was sequenced. This mitogenome was 18,154 bp in size and included two transfer RNA genes (tRNAs), 13 protein-coding genes (PCGs), and two ribosomal RNA genes (rRNAs). It showed a similar gene structure and gene order to the other typical scleractinians. All 17 genes were encoded on the H strand and the total GC content was 33.86% in mitogenome. Phylogenetic analysis (maximum likelihood tree method) showed that H. bowerbanki belonged to the “Robust” clade and clustered together with other two species in the family Lobophylliidae based on 13 PCGs. The mitogenome can provide significant molecular information to clarify the evolutionary and phylogenetic relationships between stony corals and to facilitate their taxonomic classification; it can also support coral species monitoring and conservation efforts. Full article

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

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19 pages, 1526 KiB

Open AccessEditor’s ChoiceReview

The Relevance of Telomerase and Telomere-Associated Proteins in B-Acute Lymphoblastic Leukemia

by Tales Henrique Andrade da Mota, Ricardo Camargo, Estefânia Rodrigues Biojone, Ana Flávia Reis Guimarães, Fabio Pittella-Silva and Diêgo Madureira de Oliveira

Genes 2023, 14(3), 691; https://doi.org/10.3390/genes14030691 - 10 Mar 2023

Cited by 10 | Viewed by 2977

Abstract

Telomeres and telomerase are closely linked to uncontrolled cellular proliferation, immortalization and carcinogenesis. Telomerase has been largely studied in the context of cancer, including leukemias. Deregulation of human telomerase gene hTERT is a well-established step in leukemia development. B-acute lymphoblastic leukemia (B-ALL) recovery [...] Read more.

Telomeres and telomerase are closely linked to uncontrolled cellular proliferation, immortalization and carcinogenesis. Telomerase has been largely studied in the context of cancer, including leukemias. Deregulation of human telomerase gene hTERT is a well-established step in leukemia development. B-acute lymphoblastic leukemia (B-ALL) recovery rates exceed 90% in children; however, the relapse rate is around 20% among treated patients, and 10% of these are still incurable. This review highlights the biological and clinical relevance of telomerase for B-ALL and the implications of its canonical and non-canonical action on signaling pathways in the context of disease and treatment. The physiological role of telomerase in lymphocytes makes the study of its biomarker potential a great challenge. Nevertheless, many works have demonstrated that high telomerase activity or hTERT expression, as well as short telomeres, correlate with poor prognosis in B-ALL. Telomerase and related proteins have been proven to be promising pharmacological targets. Likewise, combined therapy with telomerase inhibitors may turn out to be an alternative strategy for B-ALL. Full article

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

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13 pages, 2723 KiB

Open AccessEditor’s ChoiceArticle

Genetic and Clinical Characterization of Danish Achromatopsia Patients

by Mette Kjøbæk Gundestrup Andersen, Mette Bertelsen, Karen Grønskov, Susanne Kohl and Line Kessel

Genes 2023, 14(3), 690; https://doi.org/10.3390/genes14030690 - 10 Mar 2023

Cited by 7 | Viewed by 3329

Abstract

Achromatopsia is a rare congenital condition with cone photoreceptor dysfunction causing color blindness, reduced vision, nystagmus and photophobia. New treatments are being developed, but the current evidence is still conflicting regarding possible progression over time, and there is no clear genotype-phenotype correlation. This [...] Read more.

Achromatopsia is a rare congenital condition with cone photoreceptor dysfunction causing color blindness, reduced vision, nystagmus and photophobia. New treatments are being developed, but the current evidence is still conflicting regarding possible progression over time, and there is no clear genotype-phenotype correlation. This natural history study aimed to further explore the course of disease and potential clinical differences between various genotypes. The retrospective design allowed for the study of a large cohort with a long follow-up. Patients were identified from the Danish national registries. If not already available, genetic analysis was offered to the patient. Clinical data from 1945–2022 were retrieved from medical records and included best-corrected visual acuity (BCVA), color vision, refractive error, nystagmus, visual fields and fundoscopic findings. We identified variants believed to be disease causing in five of the known achromatopsia genes: CNGA3; CNGB3; GNAT2; PDE6C and PDE6H; and novel variants were identified in CNGB3 and PDE6C. Progressive deterioration of BCVA only attributable to achromatopsia was found in three of 58 patients. Progressive phenotype was seen with variants in CNGB3 and PDE6C. The results indicate that myopia could be more frequently occurring with variants in GNAT2, PDE6C and PDE6H and support the evidence that achromatopsia is a predominantly stationary condition with respect to BCVA. Although a clear genotype-phenotype correlation can still not be concluded, there may be differences in phenotypical characteristics with variants in different genes. Full article

(This article belongs to the Special Issue Genetics in Retinal Diseases)

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19 pages, 703 KiB

Open AccessEditor’s ChoiceArticle

Coexisting Conditions Modifying Phenotypes of Patients with 22q11.2 Deletion Syndrome

by Marta Smyk, Maciej Geremek, Kamila Ziemkiewicz, Tomasz Gambin, Anna Kutkowska-Kaźmierczak, Katarzyna Kowalczyk, Izabela Plaskota, Barbara Wiśniowiecka-Kowalnik, Magdalena Bartnik-Głaska, Magdalena Niemiec, Dominika Grad, Małgorzata Piotrowicz, Dorota Gieruszczak-Białek, Aleksandra Pietrzyk, T. Blaine Crowley, Victoria Giunta, Daniel E. McGinn, Elaine H. Zackai, Oanh Tran, Beverly S. Emanuel, Donna M. McDonald-McGinn and Beata A. Nowakowska Show full author list Hide full author list

Genes 2023, 14(3), 680; https://doi.org/10.3390/genes14030680 - 9 Mar 2023

Cited by 7 | Viewed by 2692

Abstract

22q11.2 deletion syndrome (22q11.2DS) is the most common genomic disorder with an extremely broad phenotypic spectrum. The aim of our study was to investigate how often the additional variants in the genome can affect clinical variation among patients with the recurrent deletion. To [...] Read more.

22q11.2 deletion syndrome (22q11.2DS) is the most common genomic disorder with an extremely broad phenotypic spectrum. The aim of our study was to investigate how often the additional variants in the genome can affect clinical variation among patients with the recurrent deletion. To examine the presence of additional variants affecting the phenotype, we performed microarray in 82 prenatal and 77 postnatal cases and performed exome sequencing in 86 postnatal patients with 22q11.2DS. Within those 159 patients where array was performed, 5 pathogenic and 5 likely pathogenic CNVs were identified outside of the 22q11.2 region. This indicates that in 6.3% cases, additional CNVs most likely contribute to the clinical presentation. Additionally, exome sequencing in 86 patients revealed 3 pathogenic (3.49%) and 5 likely pathogenic (5.81%) SNVs and small CNV. These results show that the extension of diagnostics with genome-wide methods can reveal other clinically relevant changes in patients with 22q11 deletion syndrome. Full article

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

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33 pages, 2450 KiB

Open AccessEditor’s ChoiceReview

Personalized Systemic Therapies in Hereditary Cancer Syndromes

by Luciana Mastrodomenico, Claudia Piombino, Beatrice Riccò, Elena Barbieri, Marta Venturelli, Federico Piacentini, Massimo Dominici, Laura Cortesi and Angela Toss

Genes 2023, 14(3), 684; https://doi.org/10.3390/genes14030684 - 9 Mar 2023

Cited by 12 | Viewed by 4044

Abstract

Hereditary cancer syndromes are inherited disorders caused by germline pathogenic variants (PVs) that lead to an increased risk of developing certain types of cancer, frequently at an earlier age than in the rest of the population. The germline PVs promote cancer development, growth [...] Read more.

Hereditary cancer syndromes are inherited disorders caused by germline pathogenic variants (PVs) that lead to an increased risk of developing certain types of cancer, frequently at an earlier age than in the rest of the population. The germline PVs promote cancer development, growth and survival, and may represent an ideal target for the personalized treatment of hereditary tumors. PARP inhibitors for the treatment of BRCA and PALB2-associated tumors, immune checkpoint inhibitors for tumors associated with the Lynch Syndrome, HIF-2α inhibitor in the VHL-related cancers and, finally, selective RET inhibitors for the treatment of MEN2-associated medullary thyroid cancer are the most successful examples of how a germline PVs can be exploited to develop effective personalized therapies and improve the outcome of these patients. The present review aims to describe and discuss the personalized systemic therapies for inherited cancer syndromes that have been developed and investigated in clinical trials in recent decades. Full article

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

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14 pages, 2634 KiB

Open AccessEditor’s ChoiceArticle

Molecular Heterogeneity of Pediatric AML with Atypical Promyelocytes Accumulation in Children—A Single Center Experience

by Aleksandra Borkovskaia, Sofia Bogacheva, Tatiana Konyukhova, Elina Dadakhanova, Marina Gaskova, Olga Soldatkina, Maria Dubrovina, Alexander Popov, Ekaterina Mikhailova, Evgenia Inushkina, Marat Kazanov, Evgeniy Matveev, Galina Novichkova, Michael Maschan, Alexey Maschan, Yulia Olshanskaya and Elena Zerkalenkova

Genes 2023, 14(3), 675; https://doi.org/10.3390/genes14030675 - 8 Mar 2023

Cited by 3 | Viewed by 3008

Abstract

Acute promyelocytic leukemia (APL) pathogenesis is based on RARA gene translocations, which are of high importance in the diagnosis of and proper therapy selection for APL. However, in some cases acute myeloid leukemia (AML) demonstrates APL-like morphological features such as atypical promyelocytes accumulation. [...] Read more.

Acute promyelocytic leukemia (APL) pathogenesis is based on RARA gene translocations, which are of high importance in the diagnosis of and proper therapy selection for APL. However, in some cases acute myeloid leukemia (AML) demonstrates APL-like morphological features such as atypical promyelocytes accumulation. This type of AML is characterized by the involvement of other RAR family members or completely different genes. In the present study, we used conventional karyotyping, FISH and high-throughput sequencing in a group of 271 de novo AML with atypical promyelocytes accumulation. Of those, 255 cases were shown to carry a typical chromosomal translocation t(15;17)(q24;q21) with PML::RARA chimeric gene formation (94.1%). Other RARA-positive cases exhibited cryptic PML::RARA fusion without t(15;17)(q24;q21) (1.8%, n = 5) and variant t(5;17)(q35;q21) translocation with NPM1::RARA chimeric gene formation (1.5%, n = 4). However, 7 RARA-negative AMLs with atypical promyelocytes accumulation were also discovered. These cases exhibited TBL1XR1::RARB and KMT2A::SEPT6 fusions as well as mutations, e.g., NPM1 insertion and non-recurrent chromosomal aberrations. Our findings demonstrate the genetic diversity of AML with APL-like morphological features, which is of high importance for successful therapy implementation. Full article

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

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15 pages, 2160 KiB

Open AccessEditor’s ChoiceArticle

Novel Variants in the VCP Gene Causing Multisystem Proteinopathy 1

by Rod Carlo Agram Columbres, Yue Chin, Sanjana Pratti, Colin Quinn, Luis F. Gonzalez-Cuyar, Michael Weiss, Fabiola Quintero-Rivera and Virginia Kimonis

Genes 2023, 14(3), 676; https://doi.org/10.3390/genes14030676 - 8 Mar 2023

Cited by 9 | Viewed by 3715

Abstract

Valosin-containing protein (VCP) gene mutations have been associated with a rare autosomal dominant, adult-onset progressive disease known as multisystem proteinopathy 1 (MSP1), or inclusion body myopathy (IBM), Paget’s disease of bone (PDB), frontotemporal dementia (FTD), (IBMPFD), and amyotrophic lateral sclerosis (ALS). [...] Read more.

Valosin-containing protein (VCP) gene mutations have been associated with a rare autosomal dominant, adult-onset progressive disease known as multisystem proteinopathy 1 (MSP1), or inclusion body myopathy (IBM), Paget’s disease of bone (PDB), frontotemporal dementia (FTD), (IBMPFD), and amyotrophic lateral sclerosis (ALS). We report the clinical and genetic analysis findings in five patients, three from the same family, with novel VCP gene variants: NM_007126.5 c.1106T>C (p.I369T), c.478G>A (p.A160T), and c.760A>T (p.I254F), associated with cardinal MSP1 manifestations including myopathy, PDB, and FTD. Our report adds to the spectrum of heterozygous pathogenic variants found in the VCP gene and the high degree of clinical heterogeneity. This case series prompts increased awareness and early consideration of MSP1 in the differential diagnosis of myopathies and/or PDB, dementia, or ALS to improve the diagnosis and early management of clinical symptoms. Full article

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

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17 pages, 7589 KiB

Open AccessEditor’s ChoiceArticle

MicroRNA Target Identification: Revisiting Accessibility and Seed Anchoring

by Nicolas Homberg, Mariana Galvão Ferrarini, Christine Gaspin and Marie-France Sagot

Genes 2023, 14(3), 664; https://doi.org/10.3390/genes14030664 - 7 Mar 2023

Cited by 7 | Viewed by 2686

Abstract

By pairing to messenger RNAs (mRNAs for short), microRNAs (miRNAs) regulate gene expression in animals and plants. Accurately identifying which mRNAs interact with a given miRNA and the precise location of the interaction sites is crucial to reaching a more complete view of [...] Read more.

By pairing to messenger RNAs (mRNAs for short), microRNAs (miRNAs) regulate gene expression in animals and plants. Accurately identifying which mRNAs interact with a given miRNA and the precise location of the interaction sites is crucial to reaching a more complete view of the regulatory network of an organism. Only a few experimental approaches, however, allow the identification of both within a single experiment. Computational predictions of miRNA–mRNA interactions thus remain generally the first step used, despite their drawback of a high rate of false-positive predictions. The major computational approaches available rely on a diversity of features, among which anchoring the miRNA seed and measuring mRNA accessibility are the key ones, with the first being universally used, while the use of the second remains controversial. Revisiting the importance of each is the aim of this paper, which uses Cross-Linking, Ligation, And Sequencing of Hybrids (CLASH) datasets to achieve this goal. Contrary to what might be expected, the results are more ambiguous regarding the use of the seed match as a feature, while accessibility appears to be a feature worth considering, indicating that, at least under some conditions, it may favour anchoring by miRNAs. Full article

(This article belongs to the Special Issue Small RNA Bioinformatics)

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19 pages, 1302 KiB

Open AccessEditor’s ChoiceArticle

Genome Analysis Using Whole-Exome Sequencing of Non-Syndromic Cleft Lip and/or Palate from Malagasy Trios Identifies Variants Associated with Cilium-Related Pathways and Asian Genetic Ancestry

by Zarko Manojlovic, Allyn Auslander, Yuxin Jin, Ryan J. Schmidt, Yili Xu, Sharon Chang, Ruocen Song, Sue A. Ingles, Alana Nunes, KC Vavra, Devin Feigelson, Sylvia Rakotoarison, Melissa DiBona, Kathy Magee, Operation Smile, Anjaramamy Ramamonjisoa and William Magee III

Genes 2023, 14(3), 665; https://doi.org/10.3390/genes14030665 - 7 Mar 2023

Cited by 3 | Viewed by 3445

Abstract

Background: Orofacial clefts (OFCs) are common congenital disabilities that can occur as isolated non-syndromic events or as part of Mendelian syndromes. OFC risk factors vary due to differences in regional environmental exposures, genetic variants, and ethnicities. In recent years, significant progress has been [...] Read more.

Background: Orofacial clefts (OFCs) are common congenital disabilities that can occur as isolated non-syndromic events or as part of Mendelian syndromes. OFC risk factors vary due to differences in regional environmental exposures, genetic variants, and ethnicities. In recent years, significant progress has been made in understanding OFCs, due to advances in sequencing and genotyping technologies. Despite these advances, very little is known about the genetic interplay in the Malagasy population. Methods: Here, we performed high-resolution whole-exome sequencing (WES) on non-syndromic cleft lip with or without palate (nCL/P) trios in the Malagasy population (78 individuals from 26 families (trios)). To integrate the impact of genetic ancestry admixture, we computed both global and local ancestries. Results: Participants demonstrated a high percentage of both African and Asian admixture. We identified damaging variants in primary cilium-mediated pathway genes WNT5B (one family), GPC4 (one family), co-occurrence in MSX1 (five families), WDR11 (one family), and tubulin stabilizer SEPTIN9 (one family). Furthermore, we identified an autosomal homozygous damaging variant in PHGDH (one family) gene that may impact metabiotic activity. Lastly, all variants were predicted to reside on local Asian genetic ancestry admixed alleles. Conclusion: Our results from examining the Malagasy genome provide limited support for the hypothesis that germline variants in primary cilia may be risk factors for nCL/P, and outline the importance of integrating local ancestry components better to understand the multi-ethnic impact on nCL/P. Full article

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

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12 pages, 3750 KiB

Open AccessEditor’s ChoiceCase Report

A Case Report of a Feto-Placental Mosaicism Involving a Segmental Aneuploidy: A Challenge for Genome Wide Screening by Non-Invasive Prenatal Testing of Cell-Free DNA in Maternal Plasma

by Luigia De Falco, Giuseppina Vitiello, Giovanni Savarese, Teresa Suero, Raffaella Ruggiero, Pasquale Savarese, Monica Ianniello, Nadia Petrillo, Mariasole Bruno, Antonietta Legnante, Francesco Fioravanti Passaretti, Carmela Ardisia, Attilio Di Spiezio Sardo and Antonio Fico

Genes 2023, 14(3), 668; https://doi.org/10.3390/genes14030668 - 7 Mar 2023

Cited by 2 | Viewed by 3143

Abstract

Non-invasive prenatal testing (NIPT) using cell-free DNA can detect fetal chromosomal anomalies with high clinical sensitivity and specificity. In approximately 0.1% of clinical cases, the NIPT result and a subsequent diagnostic karyotype are discordant. Here we report a case of a 32-year-old pregnant [...] Read more.

Non-invasive prenatal testing (NIPT) using cell-free DNA can detect fetal chromosomal anomalies with high clinical sensitivity and specificity. In approximately 0.1% of clinical cases, the NIPT result and a subsequent diagnostic karyotype are discordant. Here we report a case of a 32-year-old pregnant patient with a 44.1 Mb duplication on the short arm of chromosome 4 detected by NIPT at 12 weeks’ gestation. Amniocentesis was carried out at 18 weeks’ gestation, followed by conventional and molecular cytogenetic analysis on cells from the amniotic fluid. SNP array analysis found a de novo deletion of 1.2 Mb at chromosome 4, and this deletion was found to be near the critical region of the Wolf-Hirschhorn syndrome. A normal 46,XY karyotype was identified by G-banding analysis. The patient underwent an elective termination and molecular investigations on tissues from the fetus, and the placenta confirmed the presence of type VI true fetal mosaicism. It is important that a patient receives counselling following a high-risk call on NIPT, with appropriate diagnostic analysis advised before any decisions regarding the pregnancy are taken. This case highlights the importance of genetic counselling following a high-risk call on NIPT, especially in light of the increasing capabilities of NIPT detection of sub-chromosomal deletions and duplications. Full article

(This article belongs to the Special Issue Genetics and Genomics of Prenatal Testing)

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12 pages, 1018 KiB

Open AccessEditor’s ChoiceReview

How Genetic Variants in Children with Familial Hypercholesterolemia Not Only Guide Detection, but Also Treatment

by Sibbeliene E. van den Bosch, Willemijn E. Corpeleijn, Barbara A. Hutten and Albert Wiegman

Genes 2023, 14(3), 669; https://doi.org/10.3390/genes14030669 - 7 Mar 2023

Cited by 8 | Viewed by 3913

Abstract

Familial hypercholesterolemia (FH) is a hereditary disorder that causes severely elevated low-density lipoprotein (LDL-C) levels, which leads to an increased risk for premature cardiovascular disease. A variety of genetic variants can cause FH, namely variants in the genes for the LDL receptor ( [...] Read more.

Familial hypercholesterolemia (FH) is a hereditary disorder that causes severely elevated low-density lipoprotein (LDL-C) levels, which leads to an increased risk for premature cardiovascular disease. A variety of genetic variants can cause FH, namely variants in the genes for the LDL receptor (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin/kexin type 9 (PCSK9), and/or LDL-receptor adaptor protein 1 (LDLRAP1). Variants can exist in a heterozygous form (HeFH) or the more severe homozygous form (HoFH). If affected individuals are diagnosed early (through screening), they benefit tremendously from early initiation of lipid-lowering therapy, such as statins, and cardiovascular imaging to detect possible atherosclerosis. Over the last years, due to intensive research on the genetic basis of LDL-C metabolism, novel, promising therapies have been developed to reduce LDL-C levels and subsequently reduce cardiovascular risk. Results from studies on therapies focused on inhibiting PCSK9, a protein responsible for degradation of the LDLR, are impressive. As the effect of PCSK9 inhibitors (PCSK9-i) is dependent of residual LDLR activity, this medication is less potent in patients without functional LDLR (e.g., null/null variant). Novel therapies that are expected to become available in the near future focused on inhibition of another major regulatory protein in lipid metabolism (angiopoietin-like 3 (ANGPTL3)) might dramatically reduce the frequency of apheresis in children with HoFH, independently of their residual LDLR. At present, another independent risk factor for premature cardiovascular disease, elevated levels of lipoprotein(a) (Lp(a)), cannot be effectively treated with medication. Further understanding of the genetic basis of Lp(a) metabolism, however, offers a possibility for the development of novel therapies. Full article

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

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21 pages, 8316 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Identification and Characterization of Ammonium Transporter (AMT) Genes in Rapeseed (Brassica napus L.)

by Jing Dai, Peipei Han, Thomas C. Walk, Ling Yang, Liyu Chen, Yinshui Li, Chiming Gu, Xing Liao and Lu Qin

Genes 2023, 14(3), 658; https://doi.org/10.3390/genes14030658 - 6 Mar 2023

Cited by 11 | Viewed by 2912

Abstract

Ammonium transporters (AMTs) are plasma membrane proteins mediating ammonium uptake and transport. As such, AMTs play vital roles in ammonium acquisition and mobilization, plant growth and development, and stress and pathogen defense responses. Identification of favorable AMT genotypes is a prime target for [...] Read more.

Ammonium transporters (AMTs) are plasma membrane proteins mediating ammonium uptake and transport. As such, AMTs play vital roles in ammonium acquisition and mobilization, plant growth and development, and stress and pathogen defense responses. Identification of favorable AMT genotypes is a prime target for crop improvement. However, to date, systematic identification and expression analysis of AMT gene family members has not yet been reported for rapeseed (Brassica napus L.). In this study, 20 AMT genes were identified in a comprehensive search of the B. napus genome, 14 members of AMT1 and 6 members of AMT2. Tissue expression analyses revealed that the 14 AMT genes were primarily expressed in vegetative organs, suggesting that different BnaAMT genes might function in specific tissues at the different development stages. Meanwhile, qRT-PCR analysis found that several BnaAMTs strongly respond to the exogenous N conditions, implying the functional roles of AMT genes in ammonium absorption in rapeseed. Moreover, the rapeseed AMT genes were found to be differentially regulated by N, P, and K deficiency, indicating that crosstalk might exist in response to different stresses. Additionally, the subcellular localization of several BnaAMT proteins was confirmed in Arabidopsis protoplasts, and their functions were studied in detail by heterologous expression in yeast. In summary, our studies revealed the potential roles of BnaAMT genes in N acquisition or transportation and abiotic stress response and could provide valuable resources for revealing the functionality of AMTs in rapeseed. Full article

(This article belongs to the Special Issue Genomics and Breeding of Oil Crops)

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14 pages, 1804 KiB

Open AccessEditor’s ChoiceArticle

Identification of Two Homozygous Variants in MYBPC3 and SMYD1 Genes Associated with Severe Infantile Cardiomyopathy

by Marta W. Szulik, Miguel Reyes-Múgica, Daniel F. Marker, Ana M. Gomez, Matthew D. Zinn, Leslie K. Walsh, Juan Pablo Ochoa, Sarah Franklin and Lina Ghaloul-Gonzalez

Genes 2023, 14(3), 659; https://doi.org/10.3390/genes14030659 - 6 Mar 2023

Cited by 2 | Viewed by 3594

Abstract

Mutations in cardiac genes are one of the primary causes of infantile cardiomyopathy. In this study, we report the genetic findings of two siblings carrying variations in the MYBPC3 and SMYD1 genes. The first patient is a female proband exhibiting hypertrophic cardiomyopathy (HCM) [...] Read more.

Mutations in cardiac genes are one of the primary causes of infantile cardiomyopathy. In this study, we report the genetic findings of two siblings carrying variations in the MYBPC3 and SMYD1 genes. The first patient is a female proband exhibiting hypertrophic cardiomyopathy (HCM) and biventricular heart failure carrying a truncating homozygous MYBPC3 variant c.1224-52G>A (IVS13-52G>A) and a novel homozygous variant (c.302A>G; p.Asn101Ser) in the SMYD1 gene. The second patient, the proband’s sibling, is a male infant diagnosed with hypertrophic cardiomyopathy and carries the same homozygous MYBPC3 variant. While this specific MYBPC3 variant (c.1224-52G>A, IVS13-52G>A) has been previously reported to be associated with adult-onset hypertrophic cardiomyopathy, this is the first report linking it to infantile cardiomyopathy. In addition, this work describes, for the first time, a novel SMYD1 variant (c.302A>G; p.Asn101Ser) that has never been reported. We performed a histopathological evaluation of tissues collected from both probands and show that these variants lead to myofibrillar disarray, reduced and irregular mitochondrial cristae and cardiac fibrosis. Together, these results provide critical insight into the molecular functionality of these genes in human cardiac physiology. Full article

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

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11 pages, 1299 KiB

Open AccessEditor’s ChoiceArticle

Exome-Wide Association Study of Competitive Performance in Elite Athletes

by Celal Bulgay, Anıl Kasakolu, Hasan Hüseyin Kazan, Raluca Mijaica, Erdal Zorba, Onur Akman, Isık Bayraktar, Rıdvan Ekmekci, Seyrani Koncagul, Korkut Ulucan, Ekaterina A. Semenova, Andrey K. Larin, Nikolay A. Kulemin, Edward V. Generozov, Lorand Balint, Georgian Badicu, Ildus I. Ahmetov and Mehmet Ali Ergun

Genes 2023, 14(3), 660; https://doi.org/10.3390/genes14030660 - 6 Mar 2023

Cited by 18 | Viewed by 4979

Abstract

The aim of the study was to identify genetic variants associated with personal best scores in Turkish track and field athletes and to compare allelic frequencies between sprint/power and endurance athletes and controls using a whole-exome sequencing (WES) approach, followed by replication studies [...] Read more.

The aim of the study was to identify genetic variants associated with personal best scores in Turkish track and field athletes and to compare allelic frequencies between sprint/power and endurance athletes and controls using a whole-exome sequencing (WES) approach, followed by replication studies in independent cohorts. The discovery phase involved 60 elite Turkish athletes (31 sprint/power and 29 endurance) and 20 ethnically matched controls. The replication phase involved 1132 individuals (115 elite Russian sprinters, 373 elite Russian endurance athletes (of which 75 athletes were with VO_2max measurements), 209 controls, 148 Russian and 287 Finnish individuals with muscle fiber composition and cross-sectional area (CSA) data). None of the single nucleotide polymorphisms (SNPs) reached an exome-wide significance level (p < 2.3 × 10⁻⁷) in genotype–phenotype and case–control studies of Turkish athletes. However, of the 53 nominally (p < 0.05) associated SNPs, four functional variants were replicated. The SIRT1 rs41299232 G allele was significantly over-represented in Turkish (p = 0.047) and Russian (p = 0.018) endurance athletes compared to sprint/power athletes and was associated with increased VO_2max (p = 0.037) and a greater proportion of slow-twitch muscle fibers (p = 0.035). The NUP210 rs2280084 A allele was significantly over-represented in Turkish (p = 0.044) and Russian (p = 0.012) endurance athletes compared to sprint/power athletes. The TRPM2 rs1785440 G allele was significantly over-represented in Turkish endurance athletes compared to sprint/power athletes (p = 0.034) and was associated with increased VO_2max (p = 0.008). The AGRN rs4074992 C allele was significantly over-represented in Turkish sprint/power athletes compared to endurance athletes (p = 0.037) and was associated with a greater CSA of fast-twitch muscle fibers (p = 0.024). In conclusion, we present the first WES study of athletes showing that this approach can be used to identify novel genetic markers associated with exercise- and sport-related phenotypes. Full article

(This article belongs to the Special Issue Genetics, Sports and Training)

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17 pages, 11918 KiB

Open AccessEditor’s ChoiceArticle

A Genome-Wide Association Study to Identify Novel Candidate Genes Related to Low-Nitrogen Tolerance in Cucumber (Cucumis sativus L.)

by Bowen Li, Aimin Wei, Xueqiang Tong, Yike Han, Nan Liu, Zhengwu Chen, Hongyu Yang, Huaxiang Wu, Mingjie Lv, Ning Ning Wang and Shengli Du

Genes 2023, 14(3), 662; https://doi.org/10.3390/genes14030662 - 6 Mar 2023

Cited by 2 | Viewed by 2841

Abstract

Cucumber is one of the most important vegetables, and nitrogen is essential for the growth and fruit production of cucumbers. It is crucial to develop cultivars with nitrogen limitation tolerance or high nitrogen efficiency for green and efficient development in cucumber industry. To [...] Read more.

Cucumber is one of the most important vegetables, and nitrogen is essential for the growth and fruit production of cucumbers. It is crucial to develop cultivars with nitrogen limitation tolerance or high nitrogen efficiency for green and efficient development in cucumber industry. To reveal the genetic basis of cucumber response to nitrogen starvation, a genome-wide association study (GWAS) was conducted on a collection of a genetically diverse population of cucumber (Cucumis sativus L.) comprising 88 inbred and DH accessions including the North China type, the Eurasian type, the Japanese and South China type mixed subtype, and the South China type subtype. Phenotypic evaluation of six traits under control (14 mM) and treatment (3.5 mM) N conditions depicted the presence of broad natural variation in the studied population. The GWAS results showed that there were significant differences in the population for nitrogen limitation treatment. Nine significant loci were identified corresponding to six LD blocks, three of which overlapped. Sixteen genes were selected by GO annotation associated with nitrogen. Five low-nitrogen stress tolerance genes were finally identified by gene haplotype analysis: CsaV3_3G003630 (CsNRPD1), CsaV3_3G002970 (CsNRT1.1), CsaV3_4G030260 (CsSnRK2.5), CsaV3_4G026940, and CsaV3_3G011820 (CsNPF5.2). Taken together, the experimental data and identification of candidate genes presented in this study offer valuable insights and serve as a useful reference for the genetic enhancement of nitrogen limitation tolerance in cucumbers. Full article

(This article belongs to the Special Issue Cucumber Genetics and Breeding - a Themed Issue in Memory of Academician Feng Hou (1928 - 2020))

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13 pages, 779 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Associations and Confirmatory Meta-Analyses in Diabetic Retinopathy

by Xinting Yu and Shisong Rong

Genes 2023, 14(3), 653; https://doi.org/10.3390/genes14030653 - 5 Mar 2023

Cited by 13 | Viewed by 6589

Abstract

The present study aimed to summarize and validate the genomic association signals for diabetic retinopathy (DR), proliferative DR, and diabetic macular edema/diabetic maculopathy. A systematic search of the genome-wide association study (GWAS) catalog and PubMed/MELINE databases was conducted to curate a comprehensive list [...] Read more.

The present study aimed to summarize and validate the genomic association signals for diabetic retinopathy (DR), proliferative DR, and diabetic macular edema/diabetic maculopathy. A systematic search of the genome-wide association study (GWAS) catalog and PubMed/MELINE databases was conducted to curate a comprehensive list of significant GWAS discoveries. The top signals were then subjected to meta-analysis using established protocols. The results indicate the need for improved consensus among DR GWASs, highlighting the importance of validation efforts. A subsequent meta-analysis confirmed the association of two SNPs, rs4462262 (ZWINT-MRPS35P3) (odds ratio = 1.38, p = 0.001) and rs7903146 (TCF7L2) (odd ratio = 1.30, p < 0.001), with DR in independent populations, strengthening the evidence of their true association. We also compiled a list of candidate SNPs for further validation. This study highlights the importance of consistent validation and replication efforts in the field of DR genetics. The two identified gene loci warrant further functional investigation to understand their role in DR pathogenesis. Full article

(This article belongs to the Special Issue Feature Papers in Human Genomics and Genetic Diseases)

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13 pages, 1158 KiB

Open AccessEditor’s ChoiceReview

SDHA Germline Mutations in SDH-Deficient GISTs: A Current Update

by Angela Schipani, Margherita Nannini, Annalisa Astolfi and Maria A. Pantaleo

Genes 2023, 14(3), 646; https://doi.org/10.3390/genes14030646 - 4 Mar 2023

Cited by 12 | Viewed by 4561

Abstract

Loss of function of the succinate dehydrogenase complex characterizes 20–40% of all KIT/PDGFRA-negative GIST. Approximately half of SDH-deficient GIST patients lack SDHx mutations and are caused by a hypermethylation of the SDHC promoter, which causes the repression of SDHC transcription and depletion [...] Read more.

Loss of function of the succinate dehydrogenase complex characterizes 20–40% of all KIT/PDGFRA-negative GIST. Approximately half of SDH-deficient GIST patients lack SDHx mutations and are caused by a hypermethylation of the SDHC promoter, which causes the repression of SDHC transcription and depletion of SDHC protein levels through a mechanism described as epimutation. The remaining 50% of SDH-deficient GISTs have mutations in one of the SDH subunits and SDHA mutations are the most common (30%), with consequent loss of SDHA and SDHB protein expression immunohistochemically. SDHB, SDHC, and SDHD mutations in GIST occur in only 20–30% of cases and most of these SDH mutations are germline. More recently, germline mutations in SDHA have also been described in several patients with loss of function of the SDH complex. SDHA-mutant patients usually carry two mutational events at the SDHA locus, either the loss of the wild type allele or a second somatic event in compound heterozygosis. This review provides an overview of all data in the literature regarding SDHA-mutated GIST, especially focusing on the prevalence of germline mutations in SDH-deficient GIST populations who harbor SDHA somatic mutations, and offers a view towards understanding the importance of genetic counselling for SDHA-variant carriers and relatives. Full article

(This article belongs to the Special Issue Genetic Predispositions to Tumors of the Digestive System)

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26 pages, 678 KiB

Open AccessEditor’s ChoiceReview

The Klinefelter Syndrome and Testicular Sperm Retrieval Outcomes

by Rosália Sá, Luís Ferraz, Alberto Barros and Mário Sousa

Genes 2023, 14(3), 647; https://doi.org/10.3390/genes14030647 - 4 Mar 2023

Cited by 21 | Viewed by 11513

Abstract

Klinefelter syndrome (KS), caused by the presence of an extra X chromosome, is the most prevalent chromosomal sexual anomaly, with an estimated incidence of 1:500/1000 per male live birth (karyotype 47,XXY). High stature, tiny testicles, small penis, gynecomastia, feminine body proportions and hair, [...] Read more.

Klinefelter syndrome (KS), caused by the presence of an extra X chromosome, is the most prevalent chromosomal sexual anomaly, with an estimated incidence of 1:500/1000 per male live birth (karyotype 47,XXY). High stature, tiny testicles, small penis, gynecomastia, feminine body proportions and hair, visceral obesity, and testicular failure are all symptoms of KS. Endocrine (osteoporosis, obesity, diabetes), musculoskeletal, cardiovascular, autoimmune disorders, cancer, neurocognitive disabilities, and infertility are also outcomes of KS. Causal theories are discussed in addition to hormonal characteristics and testicular histology. The retrieval of spermatozoa from the testicles for subsequent use in assisted reproduction treatments is discussed in the final sections. Despite testicular atrophy, reproductive treatments allow excellent results, with rates of 40–60% of spermatozoa recovery, 60% of clinical pregnancy, and 50% of newborns. This is followed by a review on the predictive factors for successful sperm retrieval. The risks of passing on the genetic defect to children are also discussed. Although the risk is low (0.63%) when compared to the general population (0.5–1%), patients should be informed about embryo selection through pre-implantation genetic testing (avoids clinical termination of pregnancy). Finally, readers are directed to a number of reviews where they can enhance their understanding of comprehensive diagnosis, clinical care, and fertility preservation. Full article

(This article belongs to the Special Issue Genetic Causes of Human Infertility)

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12 pages, 1017 KiB

Open AccessEditor’s ChoiceArticle

Genomic Diversity and Runs of Homozygosity in Bernese Mountain Dogs

by Anna Letko, Benoît Hédan, Anna Snell, Alexander C. Harris, Vidhya Jagannathan, Göran Andersson, Bodil S. Holst, Elaine A. Ostrander, Pascale Quignon, Catherine André and Tosso Leeb

Genes 2023, 14(3), 650; https://doi.org/10.3390/genes14030650 - 4 Mar 2023

Cited by 10 | Viewed by 5653

Abstract

Bernese mountain dogs are a large dog breed formed in the early 1900s in Switzerland. While originally farm dogs that were used for pulling carts, guarding, and driving cattle, today they are considered multi-purpose companion and family dogs. The breed is predisposed to [...] Read more.

Bernese mountain dogs are a large dog breed formed in the early 1900s in Switzerland. While originally farm dogs that were used for pulling carts, guarding, and driving cattle, today they are considered multi-purpose companion and family dogs. The breed is predisposed to several complex diseases, such as histiocytic sarcoma, degenerative myelopathy, or hip dysplasia. Using whole-genome sequencing (WGS) data, we assessed the genomic architecture of 33 unrelated dogs from four countries: France, Sweden, Switzerland, and the United States. Analysis of runs of homozygosity (ROH) identified 12,643 ROH with an average length of 2.29 Mb and an average inbreeding coefficient of 0.395. Multidimensional scaling analysis of the genetic relatedness revealed limited clustering of European versus USA dogs, suggesting exchanges of breeding stock between continents. Furthermore, only two mtDNA haplotypes were detected in the 33 studied dogs, both of which are widespread throughout multiple dog breeds. WGS-based ROH analyses revealed several fixed or nearly fixed regions harboring discreet morphological trait-associated as well as disease-associated genetic variants. Several genes involved in the regulation of immune cells were found in the ROH shared by all dogs, which is notable in the context of the breed’s strong predisposition to hematopoietic cancers. High levels of inbreeding and relatedness, strongly exaggerated in the last 30 years, have likely led to the high prevalence of specific genetic disorders in this breed. Full article

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

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20 pages, 6212 KiB

Open AccessEditor’s ChoiceArticle

EGFRvIII Promotes the Proneural–Mesenchymal Transition of Glioblastoma Multiforme and Reduces Its Sensitivity to Temozolomide by Regulating the NF-κB/ALDH1A3 Axis

by Zhong-Fang Shi, Guan-Zhang Li, You Zhai, Chang-Qing Pan, Di Wang, Ming-Chen Yu, Chi Liu, Wei Zhang and Xiao-Guang Yu

Genes 2023, 14(3), 651; https://doi.org/10.3390/genes14030651 - 4 Mar 2023

Cited by 9 | Viewed by 3566

Abstract

(1) Background: Glioblastoma multiforme (GBM) is the most common and malignant intracranial tumor in adults. At present, temozolomide (TMZ) is recognized as the preferred chemotherapeutic drug for GBM, but some patients have low sensitivity to TMZ or chemotherapy resistance to TMZ. Our previous [...] Read more.

(1) Background: Glioblastoma multiforme (GBM) is the most common and malignant intracranial tumor in adults. At present, temozolomide (TMZ) is recognized as the preferred chemotherapeutic drug for GBM, but some patients have low sensitivity to TMZ or chemotherapy resistance to TMZ. Our previous study found that GBM patients with EGFRvIII (+) have low sensitivity to TMZ. However, the reasons and possible mechanisms of the chemoradiotherapy resistance in GBM patients with EGFRvIII (+) are not clear. (2) Methods: In this study, tissue samples of patients with GBM, GBM cell lines, glioma stem cell lines, and NSG mice were used to explore the causes and possible mechanisms of low sensitivity to TMZ in patients with EGFRvIII (+)-GBM. (3) Results: The study found that EGFRvIII promoted the proneural–mesenchymal transition of GBM and reduced its sensitivity to TMZ, and EGFRvIII regulated of the expression of ALDH1A3. (4) Conclusions: EGFRvIII activated the NF-κB pathway and further regulated the expression of ALDH1A3 to promote the proneural–mesenchymal transition of GBM and reduce its sensitivity to TMZ, which will provide an experimental basis for the selection of clinical drugs for GBM patients with EGFRvIII (+). Full article

(This article belongs to the Special Issue Computational Biology in Cancer Genomics and Proteomics)

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18 pages, 9545 KiB

Open AccessEditor’s ChoiceArticle

Genomics of Dwarfism in Italian Local Chicken Breeds

by Francesco Perini, Filippo Cendron, Zhou Wu, Natalia Sevane, Zhiqiang Li, Chunhua Huang, Jacqueline Smith, Emiliano Lasagna, Martino Cassandro and Mauro Penasa

Genes 2023, 14(3), 633; https://doi.org/10.3390/genes14030633 - 3 Mar 2023

Cited by 7 | Viewed by 3178

Abstract

The identification of the dwarf phenotype in chicken is based on body weight, height, and shank length, leaving the differentiation between dwarf and small breeds ambiguous. The aims of the present study were to characterize the sequence variations associated with the dwarf phenotype [...] Read more.

The identification of the dwarf phenotype in chicken is based on body weight, height, and shank length, leaving the differentiation between dwarf and small breeds ambiguous. The aims of the present study were to characterize the sequence variations associated with the dwarf phenotype in three Italian chicken breeds and to investigate the genes associated with their phenotype. Five hundred and forty-one chickens from 23 local breeds (from 20 to 24 animals per breed) were sampled. All animals were genotyped with the 600 K chicken SNP array. Three breeds were described as “dwarf”, namely, Mericanel della Brianza (MERI), Mugellese (MUG), and Pepoi (PPP). We compared MERI, MUG, and PPP with the four heaviest breeds in the dataset by performing genome-wide association studies. Results showed significant SNPs associated with dwarfism in the MERI and MUG breeds, which shared a candidate genomic region on chromosome 1. Due to this similarity, MERI and MUG were analyzed together as a meta-population, observing significant SNPs in the LEMD3 and HMGA2 genes, which were previously reported as being responsible for dwarfism in different species. In conclusion, MERI and MUG breeds seem to share a genetic basis of dwarfism, which differentiates them from the small PPP breed. Full article

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

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18 pages, 2814 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Association Study for Grain Protein, Thousand Kernel Weight, and Normalized Difference Vegetation Index in Bread Wheat (Triticum aestivum L.)

by Gopalareddy Krishnappa, Hanif Khan, Hari Krishna, Narayana Bhat Devate, Satish Kumar, Chandra Nath Mishra, Om Parkash, Sachin Kumar, Monu Kumar, Harohalli Masthigowda Mamrutha, Gyanendra Pratap Singh and Gyanendra Singh

Genes 2023, 14(3), 637; https://doi.org/10.3390/genes14030637 - 3 Mar 2023

Cited by 13 | Viewed by 3448

Abstract

Genomic regions governing grain protein content (GPC), 1000 kernel weight (TKW), and normalized difference vegetation index (NDVI) were studied in a set of 280 bread wheat genotypes. The genome-wide association (GWAS) panel was genotyped using a 35K Axiom array and phenotyped in three [...] Read more.

Genomic regions governing grain protein content (GPC), 1000 kernel weight (TKW), and normalized difference vegetation index (NDVI) were studied in a set of 280 bread wheat genotypes. The genome-wide association (GWAS) panel was genotyped using a 35K Axiom array and phenotyped in three environments. A total of 26 marker-trait associations (MTAs) were detected on 18 chromosomes covering the A, B, and D subgenomes of bread wheat. The GPC showed the maximum MTAs (16), followed by NDVI (6), and TKW (4). A maximum of 10 MTAs was located on the B subgenome, whereas, 8 MTAs each were mapped on the A and D subgenomes. In silico analysis suggest that the SNPs were located on important putative candidate genes such as NAC domain superfamily, zinc finger RING-H2-type, aspartic peptidase domain, folylpolyglutamate synthase, serine/threonine-protein kinase LRK10, pentatricopeptide repeat, protein kinase-like domain superfamily, cytochrome P450, and expansin. These candidate genes were found to have different roles including regulation of stress tolerance, nutrient remobilization, protein accumulation, nitrogen utilization, photosynthesis, grain filling, mitochondrial function, and kernel development. The effects of newly identified MTAs will be validated in different genetic backgrounds for further utilization in marker-aided breeding. Full article

(This article belongs to the Special Issue Wheat Genomics, Genetics and Breeding)

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12 pages, 1482 KiB

Open AccessEditor’s ChoiceArticle

Novel Clustering Methods Identified Three Caries Status-Related Clusters Based on Oral Microbiome in Thai Mother–Child Dyads

by Samantha Manning, Jin Xiao, Yihong Li, Prakaimuk Saraithong, Bruce J. Paster, George Chen, Yan Wu and Tong Tong Wu

Genes 2023, 14(3), 641; https://doi.org/10.3390/genes14030641 - 3 Mar 2023

Cited by 2 | Viewed by 2318

Abstract

Early childhood caries (ECC) is a disease that globally affects pre-school children. It is important to identify both protective and risk factors associated with this disease. This paper examined a set of saliva samples of Thai mother–child dyads and aimed to analyze how [...] Read more.

Early childhood caries (ECC) is a disease that globally affects pre-school children. It is important to identify both protective and risk factors associated with this disease. This paper examined a set of saliva samples of Thai mother–child dyads and aimed to analyze how the maternal factors and oral microbiome of the dyads influence the development of ECC. However, heterogeneous latent subpopulations may exist that have different characteristics in terms of caries development. Therefore, we introduce a novel method to cluster the correlated outcomes of dependent observations while selecting influential independent variables to unearth latent groupings within this dataset and reveal their association in each group. This paper describes the discovery of three heterogeneous clusters in the dataset, each with its own unique mother–child outcome trend, as well as identifying several microbial factors that contribute to ECC. Significantly, the three identified clusters represent three typical clinical conditions in which mother–child dyads have typical (cluster 1), high–low (cluster 2), and low–high caries experiences (cluster 3) compared to the overall trend of mother–child caries status. Intriguingly, the variables identified as the driving attributes of each cluster, including specific taxa, have the potential to be used in the future as caries preventive measures. Full article

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

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12 pages, 2204 KiB

Open AccessEditor’s ChoiceArticle

Causal Association between Iritis or Uveitis and Glaucoma: A Two-Sample Mendelian Randomisation Study

by Je Hyun Seo and Young Lee

Genes 2023, 14(3), 642; https://doi.org/10.3390/genes14030642 - 3 Mar 2023

Cited by 7 | Viewed by 3501

Abstract

Recent studies have suggested an association between iritis or uveitis and glaucoma. This study investigated the causal relationship between glaucoma and iritis and uveitis as exposures in a multi-ethnic population. Single-nucleotide polymorphisms associated with exposures to iritis and uveitis from the genome-wide association [...] Read more.

Recent studies have suggested an association between iritis or uveitis and glaucoma. This study investigated the causal relationship between glaucoma and iritis and uveitis as exposures in a multi-ethnic population. Single-nucleotide polymorphisms associated with exposures to iritis and uveitis from the genome-wide association study (GWAS) data of Biobank Japan (BBJ) and the meta-analysis data from BBJ and UK Biobank (UKB) were used as instrumental variables (IVs). The GWAS dataset for glaucoma was extracted from the meta-analysis data (n = 240,302) of Genetic Epidemiology Research in Adult Health and Aging and UKB. The casual estimates were assessed with a two-sample Mendelian randomisation (MR) test using the inverse-variance-weighted (IVW) method, weighted median method, MR–Egger method, and MR-Pleiotropy Residual Sum and Outlier test. The IVW method revealed a significant causal association between iritis and glaucoma using IVs (p < 5.0 ×

10^{- 8}

) from the East Asian population (n = 2) (odds ratio [OR] = 1.01, p = 0.017), a significant association between iritis exposures (p < 5.0 ×

10^{- 8}

) in the multi-ethnic population (n = 11) (OR = 1.04, p = 0.001), and a significant causal association between uveitis exposures (n = 10 with p < 5.0 ×

10^{- 8}

) and glaucoma in the multi-ethnic population (OR = 1.04, p = 0.001). Iritis and uveitis had causal effects on glaucoma risk based on IVs from the multi-ethnic population. These findings imply that the current classifications of uveitic glaucoma and open-angle glaucoma overlap, indicating the need for further investigating these complex relationships. Full article

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

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26 pages, 4147 KiB

Open AccessEditor’s ChoiceArticle

Molecular Phylogenetic Relationships and Unveiling Novel Genetic Diversity among Slow and Pygmy Lorises, including Resurrection of Xanthonycticebus intermedius

by Mary E. Blair, Giang T. H. Cao, Elora H. López-Nandam, Daniel A. Veronese-Paniagua, Mark G. Birchette, Marina Kenyon, Badrul M. Md-Zain, Rachel A. Munds, K. Anne-Isola Nekaris, Vincent Nijman, Christian Roos, Hoàng M. Thach, Eleanor J. Sterling and Minh D. Le

Genes 2023, 14(3), 643; https://doi.org/10.3390/genes14030643 - 3 Mar 2023

Cited by 14 | Viewed by 6998

Abstract

Genetic analysis of historical museum collections presents an opportunity to clarify the evolutionary history of understudied primate groups, improve taxonomic inferences, and inform conservation efforts. Among the most understudied primate groups, slow and pygmy lorises (genera Nycticebus and Xanthonycticebus) are nocturnal strepsirrhines [...] Read more.

Genetic analysis of historical museum collections presents an opportunity to clarify the evolutionary history of understudied primate groups, improve taxonomic inferences, and inform conservation efforts. Among the most understudied primate groups, slow and pygmy lorises (genera Nycticebus and Xanthonycticebus) are nocturnal strepsirrhines found in South and Southeast Asia. Previous molecular studies have supported five species, but studies using morphological data suggest the existence of at least nine species. We sequenced four mitochondrial loci, CO1, cytb, d-loop, and ND4, for a total of 3324 aligned characters per sample from 41 historical museum specimens for the most comprehensive geographic coverage to date for these genera. We then combined these sequences with a larger dataset composed of samples collected in Vietnam as well as previously published sequences (total sample size N = 62). We inferred phylogenetic relationships using Bayesian inference and maximum likelihood methods based on data from each locus and on concatenated sequences. We also inferred divergence dates for the most recent common ancestors of major lineages using a BEAST analysis. Consistent with previous studies, we found support for Xanthonycticebus pygmaeus as a basal taxon to the others in the group. We also confirmed the separation between lineages of X. pygmaeus from northern Vietnam/Laos/China and southern Vietnam/Cambodia and included a taxonomic revision recognizing a second taxon of pygmy loris, X. intermedius. Our results found support for multiple reciprocally monophyletic taxa within Borneo and possibly Java. The study will help inform conservation management of these trade-targeted animals as part of a genetic reference database for determining the taxonomic unit and provenance of slow and pygmy lorises confiscated from illegal wildlife trade activities. Full article

(This article belongs to the Special Issue Primate Phylogeny and Genetics)

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12 pages, 2004 KiB

Open AccessEditor’s ChoiceReview

Genetic Diversity in the mtDNA of Physarum polycephalum

by Freya Hammar and Dennis L. Miller

Genes 2023, 14(3), 628; https://doi.org/10.3390/genes14030628 - 2 Mar 2023

Viewed by 3043

Abstract

The mtDNA of the myxomycete Physarum polycephalum can contain as many as 81 genes. These genes can be grouped in three different categories. The first category includes 46 genes that are classically found on the mtDNA of many organisms. However, 43 of these genes [...] Read more.

The mtDNA of the myxomycete Physarum polycephalum can contain as many as 81 genes. These genes can be grouped in three different categories. The first category includes 46 genes that are classically found on the mtDNA of many organisms. However, 43 of these genes are cryptogenes that require a unique type of RNA editing (MICOTREM). A second category of gene is putative protein-coding genes represented by 26 significant open reading frames. However, these genes do not appear to be transcribed during the growth of the plasmodium and are currently unassigned since they do not have any apparent similarity to other classical mitochondrial protein-coding genes. The third category of gene is found in the mtDNA of some strains of P. polycephalum. These genes derive from a linear mitochondrial plasmid with nine significant, but unassigned, open reading frames which can integrate into the mitochondrial DNA by recombination. Here, we review the mechanism and evolution of the RNA editing necessary for cryptogene expression, discuss possible origins for the 26 unassigned open reading frames based on tentative identification of their protein product, and discuss the implications to mtDNA structure and replication of the integration of the linear mitochondrial plasmid. Full article

(This article belongs to the Special Issue Advanced Research on Mitochondrial Genome)

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14 pages, 1266 KiB

Open AccessEditor’s ChoiceArticle

Reproductive and Agronomic Characterization of Novel Apomictic Hybrids of Paspalum (Poaceae)

by Elsa Andrea Brugnoli, Alex Leonel Zilli, Florencia Marcón, Enzo Caballero, Eric Javier Martínez and Carlos Alberto Acuña

Genes 2023, 14(3), 631; https://doi.org/10.3390/genes14030631 - 2 Mar 2023

Cited by 1 | Viewed by 1768

Abstract

The tetraploid germplasm of Paspalum contains a large diversity that can be used to generate better forages. The objective was to evaluate a group of Paspalum notatum and Paspalum simplex apomictic hybrids for a set of agronomic traits and apomixis expressivity. Forage yield, cold [...] Read more.

The tetraploid germplasm of Paspalum contains a large diversity that can be used to generate better forages. The objective was to evaluate a group of Paspalum notatum and Paspalum simplex apomictic hybrids for a set of agronomic traits and apomixis expressivity. Forage yield, cold tolerance, winter regrowth, and seed yield were evaluated. The expressivity of apomixis was evaluated in P. simplex hybrids by flow cytometry. Progeny testing with molecular markers was used to determine the genotypic variability in the progeny. Differences within P. notatum and P. simplex hybrids were observed for all traits, and some of them were superior in comparison with the controls. The accumulated forage yield during three years was 988 g m⁻² in the P. notatum hybrids, whereas, in P. simplex, the average forage yield per harvest (40 days of regrowth) was 180 g m⁻². In P. simplex, the apomixis expressivity varied between 0 and 100%, and 65% of the hybrids showed high apomixis expressivity (superior to 70%). The genotypic mean homogeneity in the progeny was 76% and 85% in P. notatum and P. simplex, respectively. The generation of hybrids with high apomixis expressivity that combine good agronomic performance and homogeneity in the offspring is possible in tetraploid P. notatum and P. simplex. Full article

(This article belongs to the Special Issue Genetic Diversity, Conservation and Utilization of Plant Genetic Resources)

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13 pages, 2123 KiB

Open AccessEditor’s ChoiceArticle

Microsatellite Genome-Wide Database Development for the Commercial Blackhead Seabream (Acanthopagrus schlegelii)

by Xinhui Luo, Lichun Zhang and Songlin Chen

Genes 2023, 14(3), 620; https://doi.org/10.3390/genes14030620 - 1 Mar 2023

Cited by 3 | Viewed by 2696

Abstract

Simple sequence repeats (SSRs), the markers with the highest polymorphism and co-dominance degrees, offer a crucial genetic research resource. Limited SSR markers in blackhead seabream have been reported. The availability of the blackhead seabream genome assembly provided the opportunity to carry out genome-wide [...] Read more.

Simple sequence repeats (SSRs), the markers with the highest polymorphism and co-dominance degrees, offer a crucial genetic research resource. Limited SSR markers in blackhead seabream have been reported. The availability of the blackhead seabream genome assembly provided the opportunity to carry out genome-wide identification for all microsatellite markers, and bioinformatic analyses open the way for developing a microsatellite genome-wide database in blackhead seabream. In this study, a total of 412,381 SSRs were identified in the 688.08 Mb genome by Krait software. Whole-genome sequences (10×) of 42 samples were aligned against the reference genome and genotyped using the HipSTR tools by comparing and counting repeat number variation across the SSR loci. A total of 156,086 SSRs with a 2–4 bp repeat were genotyped by HipSTR tools, which accounted for 55.78% of the 2–4 bp SSRs in the reference genome. High accuracy of genotyping was observed by comparing HipSTR tools and PCR amplification. A set of 109,131 loci with a number of alleles ≥ 3 and with a number of genotyped individuals ≥ 6 were reserved to constitute the polymorphic SSR database. Fifty-one polymorphic SSR loci were identified through PCR amplification. This strategy to develop polymorphic SSR markers not only obtained a large set of polymorphic SSRs but also eliminated the need for laborious experimental screening. SSR markers developed in this study may facilitate blackhead seabream research, which lays a certain foundation for further gene tagging and genetic linkage analysis, such as marker-assisted selection, genetic mapping, as well as comparative genomic analysis. Full article

(This article belongs to the Special Issue Genetics and Genomics in Aquatic Animals)

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14 pages, 4533 KiB

Open AccessEditor’s ChoiceArticle

Integration Analysis of circRNA–miRNA–mRNA and Identification of Critical Networks in Valgus-Varus Deformity (Gallus gallus)

by Jianzeng Li, Yanchao Ma, Chunxia Cai, Lujie Zhang, Xinxin Liu, Ruirui Jiang, Donghua Li, Zhuanjian Li, Xiangtao Kang, Yadong Tian and Ruili Han

Genes 2023, 14(3), 622; https://doi.org/10.3390/genes14030622 - 1 Mar 2023

Cited by 2 | Viewed by 2062

Abstract

Valgus-valgus deformity (VVD) is a common leg deformity in broilers with inward or outward deviation of the tibiotarsus and tarsometatarsus. The competing endogenous RNA (ceRNA) network plays an essential role in the study of leg disease. However, its role in the etiology and [...] Read more.

Valgus-valgus deformity (VVD) is a common leg deformity in broilers with inward or outward deviation of the tibiotarsus and tarsometatarsus. The competing endogenous RNA (ceRNA) network plays an essential role in the study of leg disease. However, its role in the etiology and pathogenesis of VVD remains unclear. Here, based on case (VVD) and control (normal) group design, we performed analyses of differentially expressed circRNAs (DEcircRNAs), differentially expressed miRNAs (DEmiRNAs) and differentially expressed mRNAs (DEmRNAs). Transcriptome data derived 86 DEcircRNAs, 13 DEmiRNAs and 410 DEmRNAs. Functional analysis showed that DEmRNAs were significantly enriched in cell cycle, apoptosis, ECM-receptor interaction, FoxO signaling pathway and protein processing synthesis. DEcirc/miRNA-associated DEmRNAs were associated with skeletal and muscle growth and development pathways, including mTOR, Wnt, and VEGF signaling pathways. Subsequently, a circRNA–miRNA–mRNA regulatory network was constructed based on the ceRNA hypothesis, including 8 circRNAs, 6 miRNAs, and 31 mRNAs, which were significantly enriched in the skeletal developmental pathway. Finally, two key mRNAs (CDC20 and CTNNB1) and their regulatory axes were screened by the PPI network and cytohubba. The expression levels of CDC20 and CTNNB1 in cartilage and seven other tissues were also quantified by qPCR. In conclusion, we analyzed the functions of DEmRNA, DEcircRNA and DEmiRNA and constructed the hub ceRNA regulatory axis, and obtained two hub genes, CDC20 and CTNNB1. The study more deeply explored the etiology and pathogenesis of VVD and lays the foundation for further study of the role of the ceRNA network on skeletal development. Full article

(This article belongs to the Special Issue Poultry Breeding: Genetics and Genomics)

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11 pages, 1380 KiB

Open AccessEditor’s ChoiceArticle

The Complete Mitochondrial Genome of Dendrogale murina (Tupaiidae) and Phylogeny of Scandentia

by Tatyana Petrova, Olga Bondareva, Semyon Bodrov, Alexei Abramov and Natalia Abramson

Genes 2023, 14(3), 624; https://doi.org/10.3390/genes14030624 - 1 Mar 2023

Cited by 2 | Viewed by 2670

Abstract

In this paper, we report the complete mitochondrial genome of the northern smooth-tailed treeshrew Dendrogale murina, which was sequenced for the first time using the Illumina next-generation sequencing (NGS) technology. The total length of the mitochondrial genome is 16,844–16,850 bp and encodes [...] Read more.

In this paper, we report the complete mitochondrial genome of the northern smooth-tailed treeshrew Dendrogale murina, which was sequenced for the first time using the Illumina next-generation sequencing (NGS) technology. The total length of the mitochondrial genome is 16,844–16,850 bp and encodes 37 genes, including two ribosomal RNAs (rRNAs) 12S and 16S, 22 transfer RNAs (tRNAs), 13 protein-coding genes (PCGs), and a D-loop in the characteristic arrangement of family Tupaiidae (Mammalia: Scandentia). The overall base composition of the complete mitochondrial DNA is A (33.5%), C (25.5%), G (13.9%), and T (27.1%). Phylogenetic analysis of Scandentia mitochondrial genomes showed a classic pattern, which was revealed previously while using individual phylogenetic markers. The result of the current study is consistent with one based on the latest morphological studies, with the basal position of Ptilocercus and Dendrogale sister to the rest of the Tupaiidae genera. The divergence time of the Dendrogale genus is estimated as Eocene–Oligocene, with the mean value of 35.8 MYA, and the Ptilocercus genus probably separated at about 46.3 MYA. We observe an increase in the age of all nodes within the Scandentia, except for a decrease in the age of separation of Ptilocercus. This result can be explained both by the addition of new mitochondrial genome data in the analysis and the usage of new calibration points from recently published data. Full article

(This article belongs to the Special Issue Phylogenomics and Molecular Evolution)

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13 pages, 1813 KiB

Open AccessEditor’s ChoiceArticle

Identification and Pyramiding Major QTL Loci for Simultaneously Enhancing Aflatoxin Resistance and Yield Components in Peanut

by Gaorui Jin, Nian Liu, Bolun Yu, Yifei Jiang, Huaiyong Luo, Li Huang, Xiaojing Zhou, Liying Yan, Yanping Kang, Dongxin Huai, Yinbing Ding, Yuning Chen, Xin Wang, Huifang Jiang, Yong Lei, Jinxiong Shen and Boshou Liao

Genes 2023, 14(3), 625; https://doi.org/10.3390/genes14030625 - 1 Mar 2023

Cited by 4 | Viewed by 2278

Abstract

Peanut is susceptible to Aspergillus flavus infection, and the consequent aflatoxin contamination has been recognized as an important risk factor affecting food safety and industry development. Planting peanut varieties with resistance to aflatoxin contamination is regarded as an ideal approach to decrease the [...] Read more.

Peanut is susceptible to Aspergillus flavus infection, and the consequent aflatoxin contamination has been recognized as an important risk factor affecting food safety and industry development. Planting peanut varieties with resistance to aflatoxin contamination is regarded as an ideal approach to decrease the risk in food safety, but most of the available resistant varieties have not been extensively used in production because of their low yield potential mostly due to possessing small pods and seeds. Hence, it is highly necessary to integrate resistance to aflatoxin and large seed weight. In this study, an RIL population derived from a cross between Zhonghua 16 with high yield and J 11 with resistance to infection of A. flavus and aflatoxin production, was used to identify quantitative trait locus (QTL) for aflatoxin production (AP) resistance and hundred-seed weight (HSW). From combined analysis using a high-density genetic linkage map constructed, 11 QTLs for AP resistance with 4.61–11.42% phenotypic variation explanation (PVE) and six QTLs for HSW with 3.20–28.48% PVE were identified, including three major QTLs for AP resistance (qAFTA05.1, qAFTB05.2 and qAFTB06.3) and three for HSW (qHSWA05, qHSWA08 and qHSWB06). In addition, qAFTA05.1, qAFTB06.3, qHSWA05, qHSWA08 and qHSWB06 were detected in multiple environments. The aflatoxin contents under artificial inoculation were decreased by 34.77–47.67% in those segregated lines harboring qAFTA05.1, qAFTB05.2 and qAFTB06.3, while the HSWs were increased by 47.56–49.46 g in other lines harboring qHSWA05, qHSWA08 and qHSWB06. Conditional QTL mapping indicated that HSW and percent seed infection index (PSII) had no significant influence on aflatoxin content. Interestingly, the QT 1059 simultaneously harboring alleles of aflatoxin content including qAFTA05.1 and qAFTB05.2, alleles of PSII including qPSIIB03.1, qPSIIB03.2, and qPSIIB10 and alleles of HSW including qHSWA05, qHSWB06, qHSWA08 had better resistance to A. flavus infection and to toxin production and higher yield potential compared with the two parents of the RIL. The above identified major loci for AP resistance and HWS would be helpful for marker-assisted selection in peanut breeding. Full article

(This article belongs to the Special Issue Peanut Genetics and Omics)

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15 pages, 2643 KiB

Open AccessEditor’s ChoiceArticle

Deep Learning-Based Feature Extraction with MRI Data in Neuroimaging Genetics for Alzheimer’s Disease

by Dipnil Chakraborty, Zhong Zhuang, Haoran Xue, Mark B. Fiecas, Xiatong Shen and Wei Pan

Genes 2023, 14(3), 626; https://doi.org/10.3390/genes14030626 - 1 Mar 2023

Cited by 8 | Viewed by 5352

Abstract

The prognosis and treatment of patients suffering from Alzheimer’s disease (AD) have been among the most important and challenging problems over the last few decades. To better understand the mechanism of AD, it is of great interest to identify genetic variants associated with [...] Read more.

The prognosis and treatment of patients suffering from Alzheimer’s disease (AD) have been among the most important and challenging problems over the last few decades. To better understand the mechanism of AD, it is of great interest to identify genetic variants associated with brain atrophy. Commonly, in these analyses, neuroimaging features are extracted based on one of many possible brain atlases with FreeSurf and other popular software; this, however, may cause the loss of important information due to our incomplete knowledge about brain function embedded in these suboptimal atlases. To address the issue, we propose convolutional neural network (CNN) models applied to three-dimensional MRI data for the whole brain or multiple, divided brain regions to perform completely data-driven and automatic feature extraction. These image-derived features are then used as endophenotypes in genome-wide association studies (GWASs) to identify associated genetic variants. When we applied this method to ADNI data, we identified several associated SNPs that have been previously shown to be related to several neurodegenerative/mental disorders, such as AD, depression, and schizophrenia. Full article

(This article belongs to the Special Issue Molecular Biomarkers in Alzheimer’s Disease)

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11 pages, 1045 KiB

Open AccessEditor’s ChoiceReview

The Developmental Origins of Cancer: A Review of the Genes Expressed in Embryonic Cells with Implications for Tumorigenesis

by Savitha Balachandran and Aru Narendran

Genes 2023, 14(3), 604; https://doi.org/10.3390/genes14030604 - 28 Feb 2023

Cited by 18 | Viewed by 4196

Abstract

Tumorigenesis, which involves the uncontrolled proliferation and differentiation of cells, has been observed to imitate a variety of pathways vital to embryonic development, motivating cancer researchers to explore the genetic origins of these pathways. The pluripotency gene regulatory network is an established collection [...] Read more.

Tumorigenesis, which involves the uncontrolled proliferation and differentiation of cells, has been observed to imitate a variety of pathways vital to embryonic development, motivating cancer researchers to explore the genetic origins of these pathways. The pluripotency gene regulatory network is an established collection of genes that induces stemness in embryonic cells. Dysregulation in the expression genes of the pluripotency gene networks including OCT4, SOX2, NANOG and REX1 have been implicated in tumor development, and have been observed to result in poorer patient outcomes. The p53 pathway is a highly important regulatory process in a multitude of cell types, including embryonic, and the tumor suppressor gene TP53 is widely regarded as being one of the most important genes involved in tumorigenesis. Dysregulations in TP53 expression, along with altered expression of developmentally originating p53 regulators such as MDM2 and MDM4 have been implicated in various cancers, leading to poorer prognosis. Epithelial–mesenchymal transition (EMT), the process allowing epithelial cells to undergo biochemical changes to mesenchymal phenotypes, also plays a vital role in the fate of both embryonic and neoplastic cells. Genes that regulate EMT such as Twist1, SOX9 and REX1 have been associated with an increased occurrence of EMT in cancer cells, leading to enhanced cell stemness, proliferation and metastasis. The class of RNA that does not encode for proteins, known as non-coding RNA, has been implicated in a variety of cellular processes and emerging research has shown that its dysregulation can lead to uncontrolled cell proliferation and differentiation. Genes that have been shown to play a role in this dysregulation include PIWIL1, LIN28A and LIN28B, and have been associated with poorer patient outcomes and more aggressive cancer subtypes. The identification of these developmentally regulated genes in tumorigenesis has proved to play an advantageous role in cancer diagnosis and prognosis, and has provided researchers with a multitude of new target mechanisms for novel chemotherapeutic research. Full article

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

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15 pages, 3911 KiB

Open AccessEditor’s ChoiceArticle

Biogeography and Genetic Diversity of Terrestrial Mites in the Ross Sea Region, Antarctica

by Gemma E. Collins, Monica R. Young, Peter Convey, Steven L. Chown, S. Craig Cary, Byron J. Adams, Diana H. Wall and Ian D. Hogg

Genes 2023, 14(3), 606; https://doi.org/10.3390/genes14030606 - 28 Feb 2023

Cited by 7 | Viewed by 4361

Abstract

Free-living terrestrial mites (Acari) have persisted through numerous glacial cycles in Antarctica. Very little is known, however, of their genetic diversity and distribution, particularly within the Ross Sea region. To redress this gap, we sampled mites throughout the Ross Sea region, East Antarctica, [...] Read more.

Free-living terrestrial mites (Acari) have persisted through numerous glacial cycles in Antarctica. Very little is known, however, of their genetic diversity and distribution, particularly within the Ross Sea region. To redress this gap, we sampled mites throughout the Ross Sea region, East Antarctica, including Victoria Land and the Queen Maud Mountains (QMM), covering a latitudinal range of 72–85 °S, as well as Lauft Island near Mt. Siple (73 °S) in West Antarctica and Macquarie Island (54^oS) in the sub-Antarctic. We assessed genetic diversity using mitochondrial cytochrome c oxidase subunit I gene sequences (COI-5P DNA barcode region), and also morphologically identified voucher specimens. We obtained 130 sequences representing four genera: Nanorchestes (n = 30 sequences), Stereotydeus (n = 46), Coccorhagidia (n = 18) and Eupodes (n = 36). Tree-based analyses (maximum likelihood) revealed 13 genetic clusters, representing as many as 23 putative species indicated by barcode index numbers (BINs) from the Barcode of Life Datasystems (BOLD) database. We found evidence for geographically-isolated cryptic species, e.g., within Stereotydeus belli and S. punctatus, as well as unique genetic groups occurring in sympatry (e.g., Nanorchestes spp. in QMM). Collectively, these data confirm high genetic divergence as a consequence of geographic isolation over evolutionary timescales. From a conservation perspective, additional targeted sampling of understudied areas in the Ross Sea region should be prioritised, as further diversity is likely to be found in these short-range endemic mites. Full article

(This article belongs to the Special Issue Polar Genomics)

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11 pages, 1795 KiB

Open AccessEditor’s ChoiceArticle

SCP4ssd: A Serverless Platform for Nucleotide Sequence Synthesis Difficulty Prediction Using an AutoML Model

by Jianqi Zhang, Shuai Ren, Zhenkui Shi, Ruoyu Wang, Haoran Li, Huijuan Tian, Miao Feng, Xiaoping Liao and Hongwu Ma

Genes 2023, 14(3), 605; https://doi.org/10.3390/genes14030605 - 28 Feb 2023

Viewed by 2192

Abstract

DNA synthesis is widely used in synthetic biology to construct and assemble sequences ranging from short RBS to ultra-long synthetic genomes. Many sequence features, such as the GC content and repeat sequences, are known to affect the synthesis difficulty and subsequently the synthesis [...] Read more.

DNA synthesis is widely used in synthetic biology to construct and assemble sequences ranging from short RBS to ultra-long synthetic genomes. Many sequence features, such as the GC content and repeat sequences, are known to affect the synthesis difficulty and subsequently the synthesis cost. In addition, there are latent sequence features, especially local characteristics of the sequence, which might affect the DNA synthesis process as well. Reliable prediction of the synthesis difficulty for a given sequence is important for reducing the cost, but this remains a challenge. In this study, we propose a new automated machine learning (AutoML) approach to predict the DNA synthesis difficulty, which achieves an F1 score of 0.930 and outperforms the current state-of-the-art model. We found local sequence features that were neglected in previous methods, which might also affect the difficulty of DNA synthesis. Moreover, experimental validation based on ten genes of Escherichia coli strain MG1655 shows that our model can achieve an 80% accuracy, which is also better than the state of art. Moreover, we developed the cloud platform SCP4SSD using an entirely cloud-based serverless architecture for the convenience of the end users. Full article

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

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18 pages, 4333 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Nanopore-Based Direct RNA Sequencing of the Trypanosoma brucei Transcriptome Identifies Novel lncRNAs

by Elisabeth Kruse and H. Ulrich Göringer

Genes 2023, 14(3), 610; https://doi.org/10.3390/genes14030610 - 28 Feb 2023

Cited by 7 | Viewed by 3669

Abstract

Trypanosomatids are single-cell eukaryotic parasites. Unlike higher eukaryotes, they control gene expression post-transcriptionally and not at the level of transcription initiation. This involves all known cellular RNA circuits, from mRNA processing to mRNA decay, to translation, in addition to a large panel of [...] Read more.

Trypanosomatids are single-cell eukaryotic parasites. Unlike higher eukaryotes, they control gene expression post-transcriptionally and not at the level of transcription initiation. This involves all known cellular RNA circuits, from mRNA processing to mRNA decay, to translation, in addition to a large panel of RNA-interacting proteins that modulate mRNA abundance. However, other forms of gene regulation, for example by lncRNAs, cannot be excluded. LncRNAs are poorly studied in trypanosomatids, with only a single lncRNA characterized to date. Furthermore, it is not clear whether the complete inventory of trypanosomatid lncRNAs is known, because of the inherent cDNA-recoding and DNA-amplification limitations of short-read RNA sequencing. Here, we overcome these limitations by using long-read direct RNA sequencing (DRS) on nanopore arrays. We analyze the native RNA pool of the two main lifecycle stages of the African trypanosome Trypanosoma brucei, with a special emphasis on the inventory of lncRNAs. We identify 207 previously unknown lncRNAs, 32 of which are stage-specifically expressed. We also present insights into the complexity of the T. brucei transcriptome, including alternative transcriptional start and stop sites and potential transcript isoforms, to provide a bias-free understanding of the intricate RNA landscape in T. brucei. Full article

(This article belongs to the Special Issue Genetics and Proteogenomics of Kinetoplastids)

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14 pages, 7200 KiB

Open AccessEditor’s ChoiceArticle

Identification and Characterization of Phytocyanin Family Genes in Cotton Genomes

by Muhammad Bilal Tufail, Muhammad Yasir, Dongyun Zuo, Hailiang Cheng, Mushtaque Ali, Abdul Hafeez, Mahtab Soomro and Guoli Song

Genes 2023, 14(3), 611; https://doi.org/10.3390/genes14030611 - 28 Feb 2023

Cited by 8 | Viewed by 2372

Abstract

Phytocyanins (PCs) are a class of plant-specific blue copper proteins that have been demonstrated to play a role in electron transport and plant development. Through analysis of the copper ligand residues, spectroscopic properties, and domain architecture of the protein, PCs have been grouped [...] Read more.

Phytocyanins (PCs) are a class of plant-specific blue copper proteins that have been demonstrated to play a role in electron transport and plant development. Through analysis of the copper ligand residues, spectroscopic properties, and domain architecture of the protein, PCs have been grouped into four subfamilies: uclacyanins (UCs), stellacyanins (SCs), plantacyanins (PLCs), and early nodulin-like proteins (ENODLs). The present study aimed to identify and characterise the PCs present in three distinct cotton species (Gossypium hirsutum, Gossyium arboreum, and Gossypium raimondii) through the identification of 98, 63, and 69 genes respectively. We grouped PCs into four clades by using bioinformatics analysis and sequence alignment, which exhibit variations in gene structure and motif distribution. PCs are distributed across all chromosomes in each of the three species, with varying numbers of exons per gene and multiple conserved motifs, and with a minimum of 1 and maximum of 11 exons found on one gene. Transcriptomic data and qRT-PCR analysis revealed that two highly differentiated PC genes were expressed at the fibre initiation stage, while three highly differentiated PCs were expressed at the fibre elongation stage. These findings serve as a foundation for further investigations aimed at understanding the contribution of this gene family in cotton fibre production. Full article

(This article belongs to the Special Issue Genome-Wide Identifications: Recent Trends in Genomic Studies)

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35 pages, 567 KiB

Open AccessEditor’s ChoiceReview

Transcriptomic Studies on Intracranial Aneurysms

by Rafal Morga and Joanna Pera

Genes 2023, 14(3), 613; https://doi.org/10.3390/genes14030613 - 28 Feb 2023

Cited by 3 | Viewed by 2647

Abstract

Intracranial aneurysm (IA) is a relatively common vascular malformation of an intracranial artery. In most cases, its presence is asymptomatic, but IA rupture causing subarachnoid hemorrhage is a life-threating condition with very high mortality and disability rates. Despite intensive studies, molecular mechanisms underlying [...] Read more.

Intracranial aneurysm (IA) is a relatively common vascular malformation of an intracranial artery. In most cases, its presence is asymptomatic, but IA rupture causing subarachnoid hemorrhage is a life-threating condition with very high mortality and disability rates. Despite intensive studies, molecular mechanisms underlying the pathophysiology of IA formation, growth, and rupture remain poorly understood. There are no specific biomarkers of IA presence or rupture. Analysis of expression of mRNA and other RNA types offers a deeper insight into IA pathobiology. Here, we present results of published human studies on IA-focused transcriptomics. Full article

(This article belongs to the Special Issue Genomics of Stroke)

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18 pages, 1711 KiB

Open AccessEditor’s ChoiceReview

TERRA and Telomere Maintenance in the Yeast Saccharomyces cerevisiae

by Bechara Zeinoun, Maria Teresa Teixeira and Aurélia Barascu

Genes 2023, 14(3), 618; https://doi.org/10.3390/genes14030618 - 28 Feb 2023

Cited by 12 | Viewed by 5167

Abstract

Telomeres are structures made of DNA, proteins and RNA found at the ends of eukaryotic linear chromosomes. These dynamic nucleoprotein structures protect chromosomal tips from end-to-end fusions, degradation, activation of damage checkpoints and erroneous DNA repair events. Telomeres were thought to be transcriptionally [...] Read more.

Telomeres are structures made of DNA, proteins and RNA found at the ends of eukaryotic linear chromosomes. These dynamic nucleoprotein structures protect chromosomal tips from end-to-end fusions, degradation, activation of damage checkpoints and erroneous DNA repair events. Telomeres were thought to be transcriptionally silent regions because of their constitutive heterochromatin signature until telomeric long non-coding RNAs (LncRNAs) were discovered. One of them, TERRA (TElomeric Repeat-containing RNA), starts in the subtelomeric regions towards the chromosome ends from different telomeres and has been extensively studied in many evolutionarily distant eukaryotes. Changes in TERRA’s expression can lead to telomeric dysfunction, interfere with the replicative machinery and impact telomere length. TERRA also co-localizes in vivo with telomerase, and can form RNA:DNA hybrid structures called R-loops, which have been implicated in the onset of senescence and the alternative lengthening of telomere (ALT) pathway. Yet, the molecular mechanisms involving TERRA, as well as its function, remain elusive. Here, we review the current knowledge of TERRA transcription, structure, expression, regulation and its multiple telomeric and extra-telomeric functions in the budding yeast Saccharomyces cerevisiae. Full article

(This article belongs to the Special Issue DNA Damage and Repair at the Crossroad with Telomeres)

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22 pages, 2896 KiB

Open AccessEditor’s ChoiceArticle

Chromosome-Length Assembly of the Baikal Seal (Pusa sibirica) Genome Reveals a Historically Large Population Prior to Isolation in Lake Baikal

by Aliya Yakupova, Andrey Tomarovsky, Azamat Totikov, Violetta Beklemisheva, Maria Logacheva, Polina L. Perelman, Aleksey Komissarov, Pavel Dobrynin, Ksenia Krasheninnikova, Gaik Tamazian, Natalia A. Serdyukova, Mike Rayko, Tatiana Bulyonkova, Nikolay Cherkasov, Vladimir Pylev, Vladimir Peterfeld, Aleksey Penin, Elena Balanovska, Alla Lapidus, DNA Zoo Consortium, Stephen J. OBrien, Alexander Graphodatsky, Klaus-Peter Koepfli and Sergei Kliver Show full author list Hide full author list

Genes 2023, 14(3), 619; https://doi.org/10.3390/genes14030619 - 28 Feb 2023

Cited by 9 | Viewed by 5962

Abstract

Pusa sibirica, the Baikal seal, is the only extant, exclusively freshwater, pinniped species. The pending issue is, how and when they reached their current habitat—the rift lake Baikal, more than three thousand kilometers away from the Arctic Ocean. To explore the demographic [...] Read more.

Pusa sibirica, the Baikal seal, is the only extant, exclusively freshwater, pinniped species. The pending issue is, how and when they reached their current habitat—the rift lake Baikal, more than three thousand kilometers away from the Arctic Ocean. To explore the demographic history and genetic diversity of this species, we generated a de novo chromosome-length assembly, and compared it with three closely related marine pinniped species. Multiple whole genome alignment of the four species compared with their karyotypes showed high conservation of chromosomal features, except for three large inversions on chromosome VI. We found the mean heterozygosity of the studied Baikal seal individuals was relatively low (0.61 SNPs/kbp), but comparable to other analyzed pinniped samples. Demographic reconstruction of seals revealed differing trajectories, yet remarkable variations in Ne occurred during approximately the same time periods. The Baikal seal showed a significantly more severe decline relative to other species. This could be due to the difference in environmental conditions encountered by the earlier populations of Baikal seals, as ice sheets changed during glacial–interglacial cycles. We connect this period to the time of migration to Lake Baikal, which occurred ~3–0.3 Mya, after which the population stabilized, indicating balanced habitat conditions. Full article

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

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10 pages, 2163 KiB

Open AccessEditor’s ChoiceCommunication

PARK2 Microdeletion or Duplications Have Been Implicated in Different Neurological Disorders Including Early Onset Parkinson Disease

by Ausaf Ahmad, Dingani Nkosi and Mohammed A. Iqbal

Genes 2023, 14(3), 600; https://doi.org/10.3390/genes14030600 - 27 Feb 2023

Cited by 7 | Viewed by 3101

Abstract

The PARK2 gene is located on 6q26, encodes ubiquitin-E3- ligase, and is a transcriptional repressor of p53. It contains 12 exons. PARK2 copy number variants has been reported in various types of neurodevelopmental disorders, namely schizophrenia, Parkinson’s disease (PD), autism spectrum disorder (ASD), [...] Read more.

The PARK2 gene is located on 6q26, encodes ubiquitin-E3- ligase, and is a transcriptional repressor of p53. It contains 12 exons. PARK2 copy number variants has been reported in various types of neurodevelopmental disorders, namely schizophrenia, Parkinson’s disease (PD), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD). In this retrospective study, nine cases (five with microdeletion and four with microduplication) are reported with 6q26 deletion disrupting the PARK2 gene. Microdeletion sizes ranged between 215 Kb and 356 Kb, and duplication between 279 Kb and 726 Kb. These were present within the exons 7–10. Family follow up with FISH probes revealed paternal inheritance in two cases, maternal in two cases, and de novo origin in one case. Our results support previous studies showing that patients with PARK2 CNVs involving exons 5–12 might be more deleterious and cause a unique syndrome. Comprehensive analysis of additional case studies is needed to have a full characterization of this neurological disorder syndrome. Full article

(This article belongs to the Section Cytogenomics)

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35 pages, 9131 KiB

Open AccessEditor’s ChoiceArticle

Elucidation of the Landscape of Alternatively Spliced Genes and Features in the Dorsal Striatum of Aggressive/Aggression-Deprived Mice in the Model of Chronic Social Conflicts

by Vladimir Babenko, Olga Redina, Dmitry Smagin, Irina Kovalenko, Anna Galyamina and Natalia Kudryavtseva

Genes 2023, 14(3), 599; https://doi.org/10.3390/genes14030599 - 27 Feb 2023

Cited by 2 | Viewed by 2544

Abstract

Both aggressive and aggression-deprived (AD) individuals represent pathological cases extensively studied in psychiatry and substance abuse disciplines. We employed the animal model of chronic social conflicts curated in our laboratory for over 30 years. In the study, we pursued the task of evaluation [...] Read more.

Both aggressive and aggression-deprived (AD) individuals represent pathological cases extensively studied in psychiatry and substance abuse disciplines. We employed the animal model of chronic social conflicts curated in our laboratory for over 30 years. In the study, we pursued the task of evaluation of the key events in the dorsal striatum transcriptomes of aggression-experienced mice and AD species, as compared with the controls, using RNA-seq profiling. We evaluated the alternative splicing-mediated transcriptome dynamics based on the RNA-seq data. We confined our attention to the exon skipping (ES) events as the major AS type for animals. We report the concurrent posttranscriptional and posttranslational regulation of the ES events observed in the phosphorylation cycles (in phosphoproteins and their targets) in the neuron-specific genes of the striatum. Strikingly, we found that major neurospecific splicing factors (Nova1, Ptbp1, 2, Mbnl1, 2, and Sam68) related to the alternative splicing regulation of cAMP genes (Darpp-32, Grin1, Ptpn5, Ppp3ca, Pde10a, Prkaca, Psd95, and Adora1) are upregulated specifically in aggressive individuals as compared with the controls and specifically AD animals, assuming intense switching between isoforms in the cAMP-mediated (de)phosphorylation signaling cascade. We found that the coding alternative splicing events were mostly attributed to synaptic plasticity and neural development-related proteins, while the nonsense-mediated decay-associated splicing events are mostly attributed to the mRNA processing of genes, including the spliceosome and splicing factors. In addition, considering the gene families, the transporter (Slc) gene family manifested most of the ES events. We found out that the major molecular systems employing AS for their plasticity are the ‘spliceosome’, ‘chromatin rearrangement complex’, ‘synapse’, and ‘neural development/axonogenesis’ GO categories. Finally, we state that approximately 35% of the exon skipping variants in gene coding regions manifest the noncoding variants subject to nonsense-mediated decay, employed as a homeostasis-mediated expression regulation layer and often associated with the corresponding gene expression alteration. Full article

(This article belongs to the Special Issue Recent Advances of Brain Transcriptomics)

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