Genes

13 pages, 1991 KiB

Open AccessArticle

Poking COVID-19: Insights on Genomic Constraints among Immune-Related Genes between Qatari and Italian Populations

by Hamdi Mbarek, Massimiliano Cocca, Yasser Al-Sarraj, Chadi Saad, Massimo Mezzavilla, Wadha AlMuftah, Dario Cocciadiferro, Antonio Novelli, Isabella Quinti, Azza AlTawashi, Salvino Salvaggio, Asma AlThani, Giuseppe Novelli and Said I. Ismail

Genes 2021, 12(11), 1842; https://doi.org/10.3390/genes12111842 - 22 Nov 2021

Cited by 1 | Viewed by 2541

Abstract

Host genomic information, specifically genomic variations, may characterize susceptibility to disease and identify people with a higher risk of harm, leading to better targeting of care and vaccination. Italy was the epicentre for the spread of COVID-19 in Europe, the first country to [...] Read more.

Host genomic information, specifically genomic variations, may characterize susceptibility to disease and identify people with a higher risk of harm, leading to better targeting of care and vaccination. Italy was the epicentre for the spread of COVID-19 in Europe, the first country to go into a national lockdown and has one of the highest COVID-19 associated mortality rates. Qatar, on the other hand has a very low mortality rate. In this study, we compared whole-genome sequencing data of 14398 adults and Qatari-national to 925 Italian individuals. We also included in the comparison whole-exome sequence data from 189 Italian laboratory-confirmed COVID-19 cases. We focused our study on a curated list of 3619 candidate genes involved in innate immunity and host-pathogen interaction. Two population-gene metric scores, the Delta Singleton-Cohort variant score (DSC) and Sum Singleton-Cohort variant score (SSC), were applied to estimate the presence of selective constraints in the Qatari population and in the Italian cohorts. Results based on DSC and SSC metrics demonstrated a different selective pressure on three genes (MUC5AC, ABCA7, FLNA) between Qatari and Italian populations. This study highlighted the genetic differences between Qatari and Italian populations and identified a subset of genes involved in innate immunity and host-pathogen interaction. Full article

(This article belongs to the Special Issue COVID-19 and Molecular Genetics)

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17 pages, 3951 KiB

Open AccessArticle

Target-Site Mutations and Expression of ALS Gene Copies Vary According to Echinochloa Species

by Silvia Panozzo, Elisa Mascanzoni, Laura Scarabel, Andrea Milani, Giliardi Dalazen, Aldo J. Merotto, Patrick J. Tranel and Maurizio Sattin

Genes 2021, 12(11), 1841; https://doi.org/10.3390/genes12111841 - 22 Nov 2021

Cited by 16 | Viewed by 1974

Abstract

The sustainability of rice cropping systems is jeopardized by the large number and variety of populations of polyploid Echinochloa spp. resistant to ALS inhibitors. Better knowledge of the Echinochloa species present in Italian rice fields and the study of ALS genes involved in [...] Read more.

The sustainability of rice cropping systems is jeopardized by the large number and variety of populations of polyploid Echinochloa spp. resistant to ALS inhibitors. Better knowledge of the Echinochloa species present in Italian rice fields and the study of ALS genes involved in target-site resistance could significantly contribute to a better understanding of resistance evolution and management. Using a CAPS-rbcL molecular marker, two species, E. crus-galli (L.) P. Beauv. and E. oryzicola (Vasinger) Vasing., were identified as the most common species in rice in Italy. Mutations involved in ALS inhibitor resistance in the different species were identified and associated with the ALS homoeologs. The relative expression of the ALS gene copies was evaluated. Molecular characterization led to the identification of three ALS genes in E. crus-galli and two in E. oryzicola. The two species also carried different point mutations conferring resistance: Ala122Asn in E. crus-galli and Trp574Leu in E. oryzicola. Mutations were carried in the same gene copy (ALS1), which was significantly more expressed than the other copies (ALS2 and ALS3) in both species. These results explain the high resistance level of these populations and why mutations in the other ALS copies are not involved in herbicide resistance. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Herbicide Resistance in Weeds)

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19 pages, 1594 KiB

Open AccessReview

Gene Therapeutic Approaches for the Treatment of Mitochondrial Dysfunction in Parkinson’s Disease

by Jannik Prasuhn and Norbert Brüggemann

Genes 2021, 12(11), 1840; https://doi.org/10.3390/genes12111840 - 22 Nov 2021

Cited by 13 | Viewed by 3448

Abstract

Background: Mitochondrial dysfunction has been identified as a pathophysiological hallmark of disease onset and progression in patients with Parkinsonian disorders. Besides the overall emergence of gene therapies in treating these patients, this highly relevant molecular concept has not yet been defined as a [...] Read more.

Background: Mitochondrial dysfunction has been identified as a pathophysiological hallmark of disease onset and progression in patients with Parkinsonian disorders. Besides the overall emergence of gene therapies in treating these patients, this highly relevant molecular concept has not yet been defined as a target for gene therapeutic approaches. Methods: This narrative review will discuss the experimental evidence suggesting mitochondrial dysfunction as a viable treatment target in patients with monogenic and idiopathic Parkinson’s disease. In addition, we will focus on general treatment strategies and crucial challenges which need to be overcome. Results: Our current understanding of mitochondrial biology in parkinsonian disorders opens up the avenue for viable treatment strategies in Parkinsonian disorders. Insights can be obtained from primary mitochondrial diseases. However, substantial knowledge gaps and unique challenges of mitochondria-targeted gene therapies need to be addressed to provide innovative treatments in the future. Conclusions: Mitochondria-targeted gene therapies are a potential strategy to improve an important primary disease mechanism in Parkinsonian disorders. However, further studies are needed to address the unique design challenges for mitochondria-targeted gene therapies. Full article

(This article belongs to the Special Issue Parkinson's Disease: Genetics and Pathogenesis)

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27 pages, 323 KiB

Open AccessArticle

Characteristics Associated with Tumor Development in Individuals Diagnosed with Beckwith–Wiedemann Spectrum: Novel Tumor-(epi)Genotype-Phenotype Associations in the BWSp Population

by Kelly A. Duffy, Kelly D. Getz, Evan R. Hathaway, Mallory E. Byrne, Suzanne P. MacFarland and Jennifer M. Kalish

Genes 2021, 12(11), 1839; https://doi.org/10.3390/genes12111839 - 21 Nov 2021

Cited by 8 | Viewed by 2137

Abstract

Beckwith–Wiedemann Spectrum (BWSp) is the most common epigenetic childhood cancer predisposition disorder. BWSp is caused by (epi)genetic changes affecting the BWS critical region on chromosome 11p15. Clinically, BWSp represents complex molecular and phenotypic heterogeneity resulting in a range of presentations from Classic BWS [...] Read more.

Beckwith–Wiedemann Spectrum (BWSp) is the most common epigenetic childhood cancer predisposition disorder. BWSp is caused by (epi)genetic changes affecting the BWS critical region on chromosome 11p15. Clinically, BWSp represents complex molecular and phenotypic heterogeneity resulting in a range of presentations from Classic BWS to milder features. The previously reported tumor risk based on Classic BWS cohorts is 8–10% and routine tumor screening has been recommended. This work investigated the tumor risk and correlation with phenotype within a cohort of patients from Classic BWS to BWSp using a mixed-methods approach to explore phenotype and epigenotype profiles associated with tumor development through statistical analyses with post-hoc retrospective case series review. We demonstrated that tumor risk across BWSp differs from Classic BWS and that certain phenotypic features are associated with specific epigenetic causes; nephromegaly and/or hyperinsulinism appear associated with cancer in some patients. We also demonstrated that prenatal and perinatal factors that are not currently part of the BWSp classification may factor into tumor risk. Additionally, blood testing results are not necessarily synonymous with tissue testing results. Together, it appears that the current understanding from Classic BWS of (epi)genetics and phenotype correlations with tumors is not represented in the BWSp. Further study is needed in this complex population. Full article

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

15 pages, 4608 KiB

Open AccessArticle

Impact of a Novel W2027L Mutation and Non-Target Site Resistance on Acetyl-CoA Carboxylase-Inhibiting Herbicides in a French Lolium multiflorum Population

by Shiv Shankhar Kaundun, Joe Downes, Lucy Victoria Jackson, Sarah-Jane Hutchings and Eddie Mcindoe

Genes 2021, 12(11), 1838; https://doi.org/10.3390/genes12111838 - 21 Nov 2021

Cited by 5 | Viewed by 2228

Abstract

Herbicides that inhibit acetyl-CoA carboxylase (ACCase) are among the few remaining options for the post-emergence control of Lolium species in small grain cereal crops. Here, we determined the mechanism of resistance to ACCase herbicides in a Lolium multiflorum population (HGR) from France. A [...] Read more.

Herbicides that inhibit acetyl-CoA carboxylase (ACCase) are among the few remaining options for the post-emergence control of Lolium species in small grain cereal crops. Here, we determined the mechanism of resistance to ACCase herbicides in a Lolium multiflorum population (HGR) from France. A combined biological and molecular approach detected a novel W2027L ACCase mutation that affects aryloxyphenoxypropionate (FOP) but not cyclohexanedione (DIM) or phenylpyraxoline (DEN) subclasses of ACCase herbicides. Both the wild-type tryptophan and mutant leucine 2027-ACCase alleles could be positively detected in a single DNA-based-derived polymorphic amplified cleaved sequence (dPACS) assay that contained the targeted PCR product and a cocktail of two discriminating restriction enzymes. Additionally, we identified three well-characterised I1781L, I2041T, and D2078G ACCase target site resistance mutations as well as non-target site resistance in HGR. The non-target site component endowed high levels of resistance to FOP herbicides whilst partially impacting on the efficacy of pinoxaden and cycloxydim. This study adequately assessed the contribution of the W2027L mutation and non-target site mechanism in conferring resistance to ACCase herbicides in HGR. It also highlights the versatility and robustness of the dPACS method to simultaneously identify different resistance-causing alleles at a single ACCase codon. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Herbicide Resistance in Weeds)

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20 pages, 480 KiB

Open AccessReview

The Genetics of Inherited Cholestatic Disorders in Neonates and Infants: Evolving Challenges

by Rebecca Jeyaraj, Kirsten McKay Bounford, Nicola Ruth, Carla Lloyd, Fiona MacDonald, Christian J. Hendriksz, Ulrich Baumann, Paul Gissen and Deirdre Kelly

Genes 2021, 12(11), 1837; https://doi.org/10.3390/genes12111837 - 21 Nov 2021

Cited by 9 | Viewed by 2768

Abstract

Many inherited conditions cause cholestasis in the neonate or infant. Next-generation sequencing methods can facilitate a prompt diagnosis in some of these cases; application of these methods in patients with liver diseases of unknown cause has also uncovered novel gene-disease associations and improved [...] Read more.

Many inherited conditions cause cholestasis in the neonate or infant. Next-generation sequencing methods can facilitate a prompt diagnosis in some of these cases; application of these methods in patients with liver diseases of unknown cause has also uncovered novel gene-disease associations and improved our understanding of physiological bile secretion and flow. By helping to define the molecular basis of certain cholestatic disorders, these methods have also identified new targets for therapy as well patient subgroups more likely to benefit from specific therapies. At the same time, sequencing methods have presented new diagnostic challenges, such as the interpretation of single heterozygous genetic variants. This article discusses those challenges in the context of neonatal and infantile cholestasis, focusing on difficulties in predicting variant pathogenicity, the possibility of other causal variants not identified by the genetic screen used, and phenotypic variability among patients with variants in the same genes. A prospective, observational study performed between 2010–2013, which sequenced six important genes (ATP8B1, ABCB11, ABCB4, NPC1, NPC2 and SLC25A13) in an international cohort of 222 patients with infantile liver disease, is given as an example of potential benefits and challenges that clinicians could face having received a complex genetic result. Further studies including large cohorts of patients with paediatric liver disease are needed to clarify the spectrum of phenotypes associated with, as well as appropriate clinical response to, single heterozygous variants in cholestasis-associated genes. Full article

(This article belongs to the Special Issue Genetics and Genomics of Inherited Metabolic Diseases)

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8 pages, 874 KiB

Open AccessCase Report

Marfan Syndrome Caused by Disruption of the FBN1 Gene due to A Reciprocal Chromosome Translocation

by Anna Clara Schnause, Katalin Komlosi, Barbara Herr, Jürgen Neesen, Paul Dremsek, Thomas Schwarz, Andreas Tzschach, Sabine Jägle, Ekkehart Lausch, Judith Fischer and Birgitta Gläser

Genes 2021, 12(11), 1836; https://doi.org/10.3390/genes12111836 - 21 Nov 2021

Cited by 10 | Viewed by 3690

Abstract

Marfan syndrome (MFS) is a hereditary connective tissue disease caused by heterozygous mutations in the fibrillin-1 gene (FBN1) located on chromosome 15q21.1. A complex chromosomal rearrangement leading to MFS has only been reported in one case so far. We report on [...] Read more.

Marfan syndrome (MFS) is a hereditary connective tissue disease caused by heterozygous mutations in the fibrillin-1 gene (FBN1) located on chromosome 15q21.1. A complex chromosomal rearrangement leading to MFS has only been reported in one case so far. We report on a mother and daughter with marfanoid habitus and no pathogenic variant in the FBN1 gene after next generation sequencing (NGS) analysis, both showing a cytogenetically reciprocal balanced translocation between chromosomes 2 and 15. By means of fluorescence in situ hybridization of Bacterial artificial chromosome (BAC) clones from the breakpoint area on chromosome 15 the breakpoint was narrowed down to a region of approximately 110 kb in FBN1. With the help of optical genome mapping (OGM), the translocation breakpoints were further refined on chromosomes 2 and 15. Sequencing of the regions affected by the translocation identified the breakpoint of chromosome 2 as well as the breakpoint of chromosome 15 in the FBN1 gene leading to its disruption. To our knowledge, this is the first report of patients with typical clinical features of MFS showing a cytogenetically reciprocal translocation involving the FBN1 gene. Our case highlights the importance of structural genome variants as an underlying cause of monogenic diseases and the useful clinical application of OGM in the elucidation of structural variants. Full article

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

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15 pages, 313 KiB

Open AccessReview

The Role of Genetic Pathways in the Development of Chemoradiation Resistance in Nasopharyngeal Carcinoma (NPC) Patients

by Norhafiza Mat Lazim, Che Ismail Che Lah, Wan Khairunnisa Wan Juhari, Sarina Sulong, Bin Alwi Zilfalil and Baharudin Abdullah

Genes 2021, 12(11), 1835; https://doi.org/10.3390/genes12111835 - 21 Nov 2021

Cited by 5 | Viewed by 2517

Abstract

Management of nasopharyngeal carcinoma (NPC) remains elusive despite new developments and advancement that has been made in the current management approaches. A patient’s survival and prognosis remain dismal especially for a late-stage disease. This is highly attribute to the chemoradiation resistance. Arrays of [...] Read more.

Management of nasopharyngeal carcinoma (NPC) remains elusive despite new developments and advancement that has been made in the current management approaches. A patient’s survival and prognosis remain dismal especially for a late-stage disease. This is highly attribute to the chemoradiation resistance. Arrays of genes and molecular mechanisms underlie the development of chemoradiation resistance in NPC. Imperatively, unravelling the true pathogenesis of chemoradiation resistance is crucial as these significant proteins and genes can be modulated to produce an effective therapeutic target. It is pivotal to identify the chemoradiation resistance at the very beginning in order to combat the chemoradiation resistance efficiently. Intense research in the genetic ecosphere is critical, as the discovery and development of novel therapeutic targets can be used for screening, diagnosis, and treating the chemoradiation resistance aggressively. This will escalate the management trajectory of NPC patients. This article highlights the significance of genetic and molecular factors that play critical roles in the chemoradiation resistance and how these factors may be modified for next-generation targeted therapy products. Full article

(This article belongs to the Special Issue Deciphering Epigenetic Signature in Human Health and Disease)

14 pages, 1412 KiB

Open AccessArticle

DRD4 Exon 3 Gene Polymorphisms in Patients Diagnosed with Polysubstance Use Disorder and Co-Occurrence of a Depressive Episode

by Krzysztof Chmielowiec, Jolanta Chmielowiec, Jolanta Masiak, Małgorzata Czekaj, Piotr Krawczyk, Ewelina Soroka, Małgorzata Śmiarowska, Wojciech Musiał, Tomasz Pawłowski and Anna Grzywacz

Genes 2021, 12(11), 1834; https://doi.org/10.3390/genes12111834 - 20 Nov 2021

Cited by 2 | Viewed by 2142

Abstract

Background: There has been a noticeable and systematic growth of the use of psychoactive substances over the past few decades. Dual diagnosis is a clinical term referring to the occurrence of psychoactive substance use disorder comorbid with another psychiatric disorder in the same [...] Read more.

Background: There has been a noticeable and systematic growth of the use of psychoactive substances over the past few decades. Dual diagnosis is a clinical term referring to the occurrence of psychoactive substance use disorder comorbid with another psychiatric disorder in the same person. The most common type of dual diagnosis is the co-occurrence of alcohol use disorder and mood disorders in the form of a depressive episode. Co-occurrent substance use disorders are frequently influenced by genetic factors. In selecting our area of research, we focused on dopamine and the DRD4 (Dopamine Receptor D4) gene polymorphism as well as associations with personality features. The aim of the study: The aim of the study was to compare DRD4 exon 3 (DRD4 Ex3) gene polymorphisms in patients diagnosed with polysubstance use disorder and co-occurrence of a depressive episode to DRD4 exon 3 gene polymorphisms in patients diagnosed with polysubstance use disorder and without co-occurrence of a depressive episode and a group of healthy volunteers. The study also aimed at establishing associations between personality features and DRD4 exon 3 gene polymorphisms of male patients diagnosed with polysubstance use disorder with co-occurrence of a depressive episode which may present a specific endophenotype of this group of patients. Methods: The study group comprised 602 male volunteers: patients diagnosed with polysubstance use disorder comorbid with a depressive episode (PUD MDD) (n = 95; mean age = 28.29, standard deviation (SD) = 7.40), patients diagnosed with polysubstance use disorder (PUD) (n = 206; mean age = 28.13, SD = 5.97), and controls (n = 301; mean age = 22.13, SD = 4.57). The patients and control subjects were diagnosed by a psychiatrist using the Mini International Neuropsychiatric Interview (MINI), the NEO Five-Factor Personality Inventory (NEO-FFI), and the State-Trait Anxiety Inventory (STAI) questionnaires. An analysis of the DRD4 exon 3 polymorphism was performed. Results: The patients diagnosed with PUD MDD compared to the control group of healthy volunteers showed significantly higher scores on both the STAI status and features scale and the NEO-FFI Neuroticism and Openness Scale, as well as lower scores on the Extraversion, Agreeableness, and Conscientiousness NEO-FFI scales. In the DRD4 exon 3 gene polymorphism, the s allele was more frequent in the PUD MDD compared to the l allele, which was less frequent. The results of the 2 × 3 factor analysis of variance (ANOVA) in patients and controls and the variant DRD4 exon 3 interaction were found on the Extraversion Scale and the Conscientiousness Scale of the NEO-FFI. Conclusions: The associations show that psychological factors combined with genetic data create a new area of research on addiction, including the problem of dual diagnosis. However, we want to be careful and draw no definite conclusions at this stage of our research. Full article

(This article belongs to the Special Issue Feature Papers: Molecular Genetics and Genomics)

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29 pages, 1031 KiB

Open AccessReview

Dyrk1a from Gene Function in Development and Physiology to Dosage Correction across Life Span in Down Syndrome

by Helin Atas-Ozcan, Véronique Brault, Arnaud Duchon and Yann Herault

Genes 2021, 12(11), 1833; https://doi.org/10.3390/genes12111833 - 20 Nov 2021

Cited by 22 | Viewed by 4206

Abstract

Down syndrome is the main cause of intellectual disabilities with a large set of comorbidities from developmental origins but also that appeared across life span. Investigation of the genetic overdosage found in Down syndrome, due to the trisomy of human chromosome 21, has [...] Read more.

Down syndrome is the main cause of intellectual disabilities with a large set of comorbidities from developmental origins but also that appeared across life span. Investigation of the genetic overdosage found in Down syndrome, due to the trisomy of human chromosome 21, has pointed to one main driver gene, the Dual-specificity tyrosine-regulated kinase 1A (Dyrk1a). Dyrk1a is a murine homolog of the drosophila minibrain gene. It has been found to be involved in many biological processes during development and in adulthood. Further analysis showed its haploinsufficiency in mental retardation disease 7 and its involvement in Alzheimer’s disease. DYRK1A plays a role in major developmental steps of brain development, controlling the proliferation of neural progenitors, the migration of neurons, their dendritogenesis and the function of the synapse. Several strategies targeting the overdosage of DYRK1A in DS with specific kinase inhibitors have showed promising evidence that DS cognitive conditions can be alleviated. Nevertheless, providing conditions for proper temporal treatment and to tackle the neurodevelopmental and the neurodegenerative aspects of DS across life span is still an open question. Full article

(This article belongs to the Special Issue Models and Advances in Genetics of Down Syndrome)

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8 pages, 1422 KiB

Open AccessOpinion

Measuring Exercise-Induced Secreted Protein Acidic and Rich in Cysteine Expression as a Molecular Tool to Optimize Personalized Medicine

by Abdelaziz Ghanemi, Mayumi Yoshioka and Jonny St-Amand

Genes 2021, 12(11), 1832; https://doi.org/10.3390/genes12111832 - 20 Nov 2021

Cited by 11 | Viewed by 1834

Abstract

The numerous exercise benefits for health as well as applications for diseases has lead to exercise being prescribed in many pathological conditions. Secreted protein acidic and rich in cysteine (SPARC) gene expression is stimulated by exercise and SPARC has been suggested as a [...] Read more.

The numerous exercise benefits for health as well as applications for diseases has lead to exercise being prescribed in many pathological conditions. Secreted protein acidic and rich in cysteine (SPARC) gene expression is stimulated by exercise and SPARC has been suggested as a molecular mediator of exercise. Therefore, we suggest using this property for personalized medicine. This can be achieved by prescribing the exercise with a pattern (duration, intensity, etc.) that corresponds to the optimum SPARC/Sparc expression. We expect this approach to optimize the exercise therapy in both the preventive and curative contexts. In the research field, measuring exercise -dependent expression of Sparc would represent a molecular tool to further optimize the selection of exercise animal models as well. Full article

(This article belongs to the Special Issue Public Health Genetics and Genomics)

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12 pages, 6002 KiB

Open AccessArticle

Identification, Analysis, and Confirmation of Seed Storability-Related Loci in Dongxiang Wild Rice (Oryza rufipogon Griff.)

by Minmin Zhao, Biaolin Hu, Yuanwei Fan, Gumu Ding, Wanling Yang, Yong Chen, Yanhong Chen, Jiankun Xie and Fantao Zhang

Genes 2021, 12(11), 1831; https://doi.org/10.3390/genes12111831 - 19 Nov 2021

Cited by 5 | Viewed by 1993

Abstract

Dongxiang wild rice (Oryza rufipogon Griff.) (DXWR) has strong seed storability and identifying its elite gene resources may facilitate genetic improvements in rice seed storability. In this study, we developed two backcross inbred lines (BILs) populations, with DXWR as a common donor [...] Read more.

Dongxiang wild rice (Oryza rufipogon Griff.) (DXWR) has strong seed storability and identifying its elite gene resources may facilitate genetic improvements in rice seed storability. In this study, we developed two backcross inbred lines (BILs) populations, with DXWR as a common donor parent and two rice varieties (F6 and R974) as recipient parents. Bulked segregant analysis via whole genome sequencing (BSA-seq) was used to identify seed storability-related loci in the DXWR and F6 population. Two main genomic regions containing 18,550,000–20,870,000 bp on chromosome 4 and 7,860,000–9,780,000 bp on chromosome 9 were identified as candidate loci of DXWR seed storability; these overlapped partially with seed storability-related quantitative trait loci (QTLs) discovered in previous studies, suggesting that these loci may provide important regions for isolating the responsible genes. In total, 448 annotated genes were predicted within the identified regions, of which 274 and 82 had nonsynonymous and frameshift mutations, respectively. We detected extensive metabolic activities and cellular processes during seed storability and confirmed the effects of the seed storability-related candidate loci using four BILs from DXWR and R974. These results may facilitate the cloning of DXWR seed storability-related genes, thereby elucidating rice seed storability and its improvement potential. Full article

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

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28 pages, 2323 KiB

Open AccessEditor’s ChoiceArticle

Genomewide Association Analyses of Lactation Persistency and Milk Production Traits in Holstein Cattle Based on Imputed Whole-Genome Sequence Data

by Victor B. Pedrosa, Flavio S. Schenkel, Shi-Yi Chen, Hinayah R. Oliveira, Theresa M. Casey, Melkaye G. Melka and Luiz F. Brito

Genes 2021, 12(11), 1830; https://doi.org/10.3390/genes12111830 - 19 Nov 2021

Cited by 36 | Viewed by 4135

Abstract

Lactation persistency and milk production are among the most economically important traits in the dairy industry. In this study, we explored the association of over 6.1 million imputed whole-genome sequence variants with lactation persistency (LP), milk yield (MILK), fat yield (FAT), fat percentage [...] Read more.

Lactation persistency and milk production are among the most economically important traits in the dairy industry. In this study, we explored the association of over 6.1 million imputed whole-genome sequence variants with lactation persistency (LP), milk yield (MILK), fat yield (FAT), fat percentage (FAT%), protein yield (PROT), and protein percentage (PROT%) in North American Holstein cattle. We identified 49, 3991, 2607, 4459, 805, and 5519 SNPs significantly associated with LP, MILK, FAT, FAT%, PROT, and PROT%, respectively. Various known associations were confirmed while several novel candidate genes were also revealed, including ARHGAP35, NPAS1, TMEM160, ZC3H4, SAE1, ZMIZ1, PPIF, LDB2, ABI3, SERPINB6, and SERPINB9 for LP; NIM1K, ZNF131, GABRG1, GABRA2, DCHS1, and SPIDR for MILK; NR6A1, OLFML2A, EXT2, POLD1, GOT1, and ETV6 for FAT; DPP6, LRRC26, and the KCN gene family for FAT%; CDC14A, RTCA, HSTN, and ODAM for PROT; and HERC3, HERC5, LALBA, CCL28, and NEURL1 for PROT%. Most of these genes are involved in relevant gene ontology (GO) terms such as fatty acid homeostasis, transporter regulator activity, response to progesterone and estradiol, response to steroid hormones, and lactation. The significant genomic regions found contribute to a better understanding of the molecular mechanisms related to LP and milk production in North American Holstein cattle. Full article

(This article belongs to the Special Issue Genome-Wide Association Analysis of Cattle)

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16 pages, 2873 KiB

Open AccessArticle

CircNFIC Balances Inflammation and Apoptosis by Sponging miR-30e-3p and Regulating DENND1B Expression

by Yangfeng Chen, Zhijun Wang, Xiaolan Chen, Xi Peng and Qinghua Nie

Genes 2021, 12(11), 1829; https://doi.org/10.3390/genes12111829 - 19 Nov 2021

Cited by 7 | Viewed by 1988

Abstract

Disordered inflammation and apoptosis are closely related to diseases, and inflammation can also promote cell apoptosis, where growing evidence has shown that circular RNAs (circRNAs) play important roles. Lipopolysaccharide (LPS) is the main component of the cytoderm of gram-negative bacterium, which can cause [...] Read more.

Disordered inflammation and apoptosis are closely related to diseases, and inflammation can also promote cell apoptosis, where growing evidence has shown that circular RNAs (circRNAs) play important roles. Lipopolysaccharide (LPS) is the main component of the cytoderm of gram-negative bacterium, which can cause inflammatory responses in macrophages. We constructed an inflammatory model by exposing chicken macrophage cell lines (also known as HD11) to LPS for in vitro experiments. In this study, we validated a novel circRNA—circNFIC—which was dramatically up-regulated in tissues infected by coccidia and cells exposed to LPS. Besides, circNFIC could significantly promote the expression levels of pro-inflammation factors, including (IL-1β, TNFα, and IFNγ) and pro-apoptosis maker genes (caspase 3 and caspase 8) in HD11 exposed to LPS or not. In terms of mechanism, circNFIC exerted notable effects on DENND1B to regulate cell inflammation and apoptosis by sponging miR-30e-3p. The molecular functions played by miR-30e-3p and DENND1B have been explored, respectively. In addition, the effects of circNFIC knockdown suppressing the expression of pro-inflammatory and pro-apoptosis functions could be reversed by a miR-30e-3p inhibitor. On the whole, circNFIC promoted cell inflammation and apoptosis via the miR-30e-3p/DENND1B axis. Full article

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

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6 pages, 990 KiB

Open AccessCase Report

An Atypical Case of Congenital Erythropoietic Porphyria

by Bénédicte Sudrié-Arnaud, Marine Legendre, Sarah Snanoudj, Fanny Pelluard, Soumeya Bekri and Abdellah Tebani

Genes 2021, 12(11), 1828; https://doi.org/10.3390/genes12111828 - 19 Nov 2021

Cited by 2 | Viewed by 2473

Abstract

Congenital erythropoietic porphyria (CEP, OMIM #606938) is a severe autosomal recessive inborn error of heme biosynthesis. This rare panethnic disease is due to a deficiency of uroporphyrinogen III synthase (or cosynthase). Subsequently, its substrate, the hydroxymethylbilane is subsequently converted into uroporphyrinogen I in [...] Read more.

Congenital erythropoietic porphyria (CEP, OMIM #606938) is a severe autosomal recessive inborn error of heme biosynthesis. This rare panethnic disease is due to a deficiency of uroporphyrinogen III synthase (or cosynthase). Subsequently, its substrate, the hydroxymethylbilane is subsequently converted into uroporphyrinogen I in a non-enzymatic manner. Of note, uroporphyrinogen I cannot be metabolized into heme and its accumulation in red blood cells results in intramedullary and intravascular hemolysis. The related clinical symptoms occur most frequently during antenatal or neonatal periods but may also appear in late adulthood. The main antenatal clinical presentation is a non-immune hydrops fetalis. We report here two cases of antenatal CEP deficiency and a review of the reported cases in the literature. Full article

(This article belongs to the Special Issue Genetics and Genomics of Inherited Metabolic Diseases)

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15 pages, 14979 KiB

Open AccessReview

Genetic Variability of the Functional Domains of Chromodomains Helicase DNA-Binding (CHD) Proteins

by Ana R. Cardoso, Mónica Lopes-Marques, Manuela Oliveira, António Amorim, Maria J. Prata and Luísa Azevedo

Genes 2021, 12(11), 1827; https://doi.org/10.3390/genes12111827 - 19 Nov 2021

Cited by 7 | Viewed by 2565

Abstract

In the past few years, there has been an increasing neuroscientific interest in understanding the function of mammalian chromodomains helicase DNA-binding (CHD) proteins due to their association with severe developmental syndromes. Mammalian CHDs include nine members (CHD1 to CHD9), grouped into subfamilies according [...] Read more.

In the past few years, there has been an increasing neuroscientific interest in understanding the function of mammalian chromodomains helicase DNA-binding (CHD) proteins due to their association with severe developmental syndromes. Mammalian CHDs include nine members (CHD1 to CHD9), grouped into subfamilies according to the presence of specific functional domains, generally highly conserved in evolutionary terms. Mutations affecting these domains hold great potential to disrupt protein function, leading to meaningful pathogenic scenarios, such as embryonic defects incompatible with life. Here, we analysed the evolution of CHD proteins by performing a comparative study of the functional domains of CHD proteins between orthologous and paralogous protein sequences. Our findings show that the highest degree of inter-species conservation was observed at Group II (CHD3, CHD4, and CHD5) and that most of the pathological variations documented in humans involve amino acid residues that are conserved not only between species but also between paralogs. The parallel analysis of both orthologous and paralogous proteins, in cases where gene duplications have occurred, provided extra information showing patterns of flexibility as well as interchangeability between amino acid positions. This added complexity needs to be considered when the impact of novel mutations is assessed in terms of evolutionary conservation. Full article

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

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17 pages, 2774 KiB

Open AccessArticle

Selective Sweeps and Polygenic Adaptation Drive Local Adaptation along Moisture and Temperature Gradients in Natural Populations of Coast Redwood and Giant Sequoia

by Amanda R. De La Torre, Manoj K. Sekhwal and David B. Neale

Genes 2021, 12(11), 1826; https://doi.org/10.3390/genes12111826 - 19 Nov 2021

Cited by 4 | Viewed by 2919

Abstract

Dissecting the genomic basis of local adaptation is a major goal in evolutionary biology and conservation science. Rapid changes in the climate pose significant challenges to the survival of natural populations, and the genomic basis of long-generation plant species is still poorly understood. [...] Read more.

Dissecting the genomic basis of local adaptation is a major goal in evolutionary biology and conservation science. Rapid changes in the climate pose significant challenges to the survival of natural populations, and the genomic basis of long-generation plant species is still poorly understood. Here, we investigated genome-wide climate adaptation in giant sequoia and coast redwood, two iconic and ecologically important tree species. We used a combination of univariate and multivariate genotype–environment association methods and a selective sweep analysis using non-overlapping sliding windows. We identified genomic regions of potential adaptive importance, showing strong associations to moisture variables and mean annual temperature. Our results found a complex architecture of climate adaptation in the species, with genomic regions showing signatures of selective sweeps, polygenic adaptation, or a combination of both, suggesting recent or ongoing climate adaptation along moisture and temperature gradients in giant sequoia and coast redwood. The results of this study provide a first step toward identifying genomic regions of adaptive significance in the species and will provide information to guide management and conservation strategies that seek to maximize adaptive potential in the face of climate change. Full article

(This article belongs to the Section Population and Evolutionary Genetics and Genomics)

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11 pages, 448 KiB

Open AccessReview

Genetic and Genomic Epidemiology of Stroke in People of African Ancestry

by Savvina Prapiadou, Stacie L. Demel and Hyacinth I. Hyacinth

Genes 2021, 12(11), 1825; https://doi.org/10.3390/genes12111825 - 19 Nov 2021

Cited by 7 | Viewed by 2144

Abstract

Stroke is one of the leading causes of disability and death worldwide and places a significant burden on healthcare systems. There are significant racial/ethnic differences in the incidence, subtype, and prognosis of stroke, between people of European and African ancestry, of which only [...] Read more.

Stroke is one of the leading causes of disability and death worldwide and places a significant burden on healthcare systems. There are significant racial/ethnic differences in the incidence, subtype, and prognosis of stroke, between people of European and African ancestry, of which only about 50% can be explained by traditional stroke risk facts. However, only a small number of genetic studies include individuals of African descent, leaving many gaps in our understanding of stroke genetics among this population. This review article highlights the need for and significance of including African-ancestry individuals in stroke genetic studies and points to the efforts that have been made towards this direction. Additionally, we discuss the caveats, opportunities, and next steps in African stroke genetics—a field still in its infancy but with great potential for expanding our understanding of stroke biology and for developing new therapeutic strategies. Full article

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

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13 pages, 2044 KiB

Open AccessArticle

The Genetic Landscape of Inherited Retinal Diseases in a Mexican Cohort: Genes, Mutations and Phenotypes

by Cristina Villanueva-Mendoza, Miquel Tuson, David Apam-Garduño, Marta de Castro-Miró, Raul Tonda, Jean Remi Trotta, Gemma Marfany, Rebeca Valero, Vianney Cortés-González and Roser Gonzàlez-Duarte

Genes 2021, 12(11), 1824; https://doi.org/10.3390/genes12111824 - 19 Nov 2021

Cited by 14 | Viewed by 3559

Abstract

In this work, we aimed to provide the genetic diagnosis of a large cohort of patients affected with inherited retinal dystrophies (IRDs) from Mexico. Our data add valuable information to the genetic portrait in rare ocular diseases of Mesoamerican populations, which are mostly [...] Read more.

In this work, we aimed to provide the genetic diagnosis of a large cohort of patients affected with inherited retinal dystrophies (IRDs) from Mexico. Our data add valuable information to the genetic portrait in rare ocular diseases of Mesoamerican populations, which are mostly under-represented in genetic studies. A cohort of 144 unrelated probands with a clinical diagnosis of IRD were analyzed by next-generation sequencing using target gene panels (overall including 346 genes and 65 intronic sequences). Four unsolved cases were analyzed by whole-exome sequencing (WES). The pathogenicity of new variants was assessed by in silico prediction algorithms and classified following the American College of Medical Genetics and Genomics (ACMG) guidelines. Pathogenic or likely pathogenic variants were identified in 105 probands, with a final diagnostic yield of 72.9%; 17 cases (11.8%) were partially solved. Eighteen patients were clinically reclassified after a genetic diagnostic test (17.1%). In our Mexican cohort, mutations in 48 genes were found, with ABCA4, CRB1, RPGR and USH2A as the major contributors. Notably, over 50 new putatively pathogenic variants were identified. Our data highlight cases with relevant clinical and genetic features due to mutations in the RAB28 and CWC27 genes, enrich the novel mutation repertoire and expand the IRD landscape of the Mexican population. Full article

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

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10 pages, 1774 KiB

Open AccessArticle

LAMA2 Nonsense Variant in an Italian Greyhound with Congenital Muscular Dystrophy

by Matthias Christen, Victoria Indzhova, Ling T. Guo, Vidhya Jagannathan, Tosso Leeb, G. Diane Shelton and Josep Brocal

Genes 2021, 12(11), 1823; https://doi.org/10.3390/genes12111823 - 19 Nov 2021

Cited by 2 | Viewed by 2304

Abstract

A 4-month-old, male Italian Greyhound with clinical signs of a neuromuscular disease was investigated. The affected dog presented with an abnormal short-strided gait, generalized muscle atrophy, and poor growth since 2-months of age. Serum biochemistry revealed a marked elevation in creatine kinase activity. [...] Read more.

A 4-month-old, male Italian Greyhound with clinical signs of a neuromuscular disease was investigated. The affected dog presented with an abnormal short-strided gait, generalized muscle atrophy, and poor growth since 2-months of age. Serum biochemistry revealed a marked elevation in creatine kinase activity. Electrodiagnostic testing supported a myopathy. Histopathology of muscle biopsies confirmed a dystrophic phenotype with excessive variability in myofiber size, degenerating fibers, and endomysial fibrosis. A heritable form of congenital muscular dystrophy (CMD) was suspected, and a genetic analysis initiated. We sequenced the genome of the affected dog and compared the data to that of 795 control genomes. This search revealed a private homozygous nonsense variant in LAMA2, XM_022419950.1:c.3285G>A, predicted to truncate 65% of the open reading frame of the wild type laminin α2 protein, XP_022275658.1:p.(Trp1095*). Immunofluorescent staining performed on muscle cryosections from the affected dog confirmed the complete absence of laminin α2 in skeletal muscle. LAMA2 loss of function variants were shown to cause severe laminin α2-related CMD in humans, mouse models, and in one previously described dog. Our data together with current knowledge on other species suggest the LAMA2 nonsense variant as cause for the CMD phenotype in the investigated dog. Full article

(This article belongs to the Special Issue Canine Genetics 2)

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49 pages, 4894 KiB

Open AccessReview

Sex Chromosomes and Master Sex-Determining Genes in Turtles and Other Reptiles

by Dominique Thépot

Genes 2021, 12(11), 1822; https://doi.org/10.3390/genes12111822 - 19 Nov 2021

Cited by 11 | Viewed by 25819

Abstract

Among tetrapods, the well differentiated heteromorphic sex chromosomes of birds and mammals have been highly investigated and their master sex-determining (MSD) gene, Dmrt1 and SRY, respectively, have been identified. The homomorphic sex chromosomes of reptiles have been the least studied, but the [...] Read more.

Among tetrapods, the well differentiated heteromorphic sex chromosomes of birds and mammals have been highly investigated and their master sex-determining (MSD) gene, Dmrt1 and SRY, respectively, have been identified. The homomorphic sex chromosomes of reptiles have been the least studied, but the gap with birds and mammals has begun to fill. This review describes our current knowledge of reptilian sex chromosomes at the cytogenetic and molecular level. Most of it arose recently from various studies comparing male to female gene content. This includes restriction site-associated DNA sequencing (RAD-Seq) experiments in several male and female samples, RNA sequencing and identification of Z- or X-linked genes by male/female comparative transcriptome coverage, and male/female transcriptomic or transcriptome/genome substraction approaches allowing the identification of Y- or W-linked transcripts. A few putative master sex-determining (MSD) genes have been proposed, but none has been demonstrated yet. Lastly, future directions in the field of reptilian sex chromosomes and their MSD gene studies are considered. Full article

(This article belongs to the Special Issue Sex Chromosome Evolution and Meiosis)

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10 pages, 1595 KiB

Open AccessArticle

Hemoglobin A₂ and Heterogeneous Diagnostic Relevance Observed in Eight New Variants of the Delta Globin Gene

by Noraesah Mahmud, Massimo Maffei, Massimo Mogni, Gian Luca Forni, Valeria Maria Pinto, Giuseppina Barberio, Silvana Ungari, Antonella Maffè, Cristina Curcio, Francesco Zanolli, Raffaella Paventa, Mariarosa Carta, Alberta Caleffi, Mariella Mercadanti, Sauro Maoggi, Giovanni Ivaldi and Domenico Coviello

Genes 2021, 12(11), 1821; https://doi.org/10.3390/genes12111821 - 19 Nov 2021

Cited by 1 | Viewed by 1777

Abstract

Background: Hemoglobin A (Hb A) (α₂β₂) in the normal adult subject constitutes 96–98% of hemoglobin, and Hb F is normally less than 1%, while for hemoglobin A₂ (Hb A₂) (α₂δ₂), the normal [...] Read more.

Background: Hemoglobin A (Hb A) (α₂β₂) in the normal adult subject constitutes 96–98% of hemoglobin, and Hb F is normally less than 1%, while for hemoglobin A₂ (Hb A₂) (α₂δ₂), the normal reference values are between 2.0 and 3.3%. It is important to evaluate the presence of possible delta gene mutations in a population at high risk for globin gene defects in order to correctly diagnose the β-thalassemia carrier. Methods: The most used methods for the quantification of Hb A₂ are based on automated high performance liquid chromatography (HPLC) or capillary electrophoresis (CE). In particular Hb analyses were performed by HPLC on three dedicated devices. DNA analyses were performed according to local standard protocols. Results: Here, we described eight new δ-globin gene variants discovered and characterized in some laboratories in Northern Italy in recent years. These new variants were added to the many already known Hb A₂ variants that were found with an estimated frequency of about 1–2% during the screening tests in our laboratories. Conclusions: The knowledge recognition of the delta variant on Hb analysis and accurate molecular characterization is crucial to provide an accurate definitive thalassemia diagnosis, particularly in young subjects who would like to ask for a prenatal diagnosis or preimplantation genetic diagnosis. Full article

(This article belongs to the Special Issue Genetic Tests)

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23 pages, 1361 KiB

Open AccessArticle

Spectrum of Genetic Diseases in Tunisia: Current Situation and Main Milestones Achieved

by Nessrine Mezzi, Olfa Messaoud, Rahma Mkaouar, Nadia Zitouna, Safa Romdhane, Ghaith Abdessalem, Cherine Charfeddine, Faouzi Maazoul, Ines Ouerteni, Yosr Hamdi, Anissa Zaouak, Ridha Mrad, Sonia Abdelhak and Lilia Romdhane

Genes 2021, 12(11), 1820; https://doi.org/10.3390/genes12111820 - 19 Nov 2021

Cited by 3 | Viewed by 2358

Abstract

Genetic diseases in Tunisia are a real public health problem given their chronicity and the lack of knowledge concerning their prevalence and etiology, and the high rates of consanguinity. Hence, we performed systematic reviews of the literature in order to provide a more [...] Read more.

Genetic diseases in Tunisia are a real public health problem given their chronicity and the lack of knowledge concerning their prevalence and etiology, and the high rates of consanguinity. Hence, we performed systematic reviews of the literature in order to provide a more recent spectrum of these disorders and to expose the challenges that still exist to tackle these kinds of diseases. A manual textual data mining was conducted using MeSH and PubMed databases. Collected data were classified according to the CIM-10 classification and the transmission mode. The spectrum of these diseases is estimated to be 589 entities. This suggests remarkable progress through the development of biomedical health research activities and building capacities. Sixty percent of the reported disorders are autosomal recessive, which could be explained by the high prevalence of endogamous mating. Congenital malformations (29.54%) are the major disease group, followed by metabolic diseases (22%). Sixty percent of the genetic diseases have a known molecular etiology. We also reported additional cases of comorbidity that seem to be a common phenomenon in our population. We also noticed that epidemiological data are scarce. Newborn and carrier screening was only limited to pilot projects for a few genetic diseases. Collected data are being integrated into a database under construction that will be a valuable decision-making tool. This study provides the current situation of genetic diseases in Tunisia and highlights their particularities. Early detection of the disease is important to initiate critical intervention and to reduce morbidity and mortality. Full article

(This article belongs to the Special Issue Genetic Tests)

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11 pages, 1023 KiB

Open AccessFeature PaperArticle

Pattern of New Gene Origination in a Special Fish Lineage, the Flatfishes

by Haorong Li, Chunyan Chen, Zhongkai Wang, Kun Wang, Yongxin Li and Wen Wang

Genes 2021, 12(11), 1819; https://doi.org/10.3390/genes12111819 - 19 Nov 2021

Cited by 3 | Viewed by 1911

Abstract

Origination of new genes are of inherent interest of evolutionary geneticists for decades, but few studies have addressed the general pattern in a fish lineage. Using our recent released whole genome data of flatfishes, which evolved one of the most specialized body plans [...] Read more.

Origination of new genes are of inherent interest of evolutionary geneticists for decades, but few studies have addressed the general pattern in a fish lineage. Using our recent released whole genome data of flatfishes, which evolved one of the most specialized body plans in vertebrates, we identified 1541 (6.9% of the starry flounder genes) flatfish-lineage-specific genes. The origination pattern of these flatfish new genes is largely similar to those observed in other vertebrates, as shown by the proportion of DNA-mediated duplication (1317; 85.5%), RNA-mediated duplication (retrogenes; 96; 6.2%), and de novo–origination (128; 8.3%). The emergence rate of species-specific genes is 32.1 per Mya and the whole average level rate for the flatfish-lineage-specific genes is 20.9 per Mya. A large proportion (31.4%) of these new genes have been subjected to selection, in contrast to the 4.0% in primates, while the old genes remain quite similar (66.4% vs. 65.0%). In addition, most of these new genes (70.8%) are found to be expressed, indicating their functionality. This study not only presents one example of systematic new gene identification in a teleost taxon based on comprehensive phylogenomic data, but also shows that new genes may play roles in body planning. Full article

(This article belongs to the Special Issue How Do New Genes Originate and Evolve?)

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19 pages, 905 KiB

Open AccessArticle

Gene Expression Profiles Suggest a Better Cold Acclimation of Polyploids in the Alpine Species Ranunculus kuepferi (Ranunculaceae)

by Eleni Syngelaki, Claudia Paetzold and Elvira Hörandl

Genes 2021, 12(11), 1818; https://doi.org/10.3390/genes12111818 - 18 Nov 2021

Cited by 10 | Viewed by 1982

Abstract

Alpine habitats are shaped by harsh abiotic conditions and cold climates. Temperature stress can affect phenotypic plasticity, reproduction, and epigenetic profiles, which may affect acclimation and adaptation. Distribution patterns suggest that polyploidy seems to be advantageous under cold conditions. Nevertheless, whether temperature stress [...] Read more.

Alpine habitats are shaped by harsh abiotic conditions and cold climates. Temperature stress can affect phenotypic plasticity, reproduction, and epigenetic profiles, which may affect acclimation and adaptation. Distribution patterns suggest that polyploidy seems to be advantageous under cold conditions. Nevertheless, whether temperature stress can induce gene expression changes in different cytotypes, and how the response is initialized through gene set pathways and epigenetic control remain vague for non-model plants. The perennial alpine plant Ranunculus kuepferi was used to investigate the effect of cold stress on gene expression profiles. Diploid and autotetraploid individuals were exposed to cold and warm conditions in climate growth chambers and analyzed via transcriptome sequencing and qRT-PCR. Overall, cold stress changed gene expression profiles of both cytotypes and induced cold acclimation. Diploids changed more gene set pathways than tetraploids, and suppressed pathways involved in ion/cation homeostasis. Tetraploids mostly activated gene set pathways related to cell wall and plasma membrane. An epigenetic background for gene regulation in response to temperature conditions is indicated. Results suggest that perennial alpine plants can respond to temperature extremes via altered gene expression. Tetraploids are better acclimated to cold conditions, enabling them to colonize colder climatic areas in the Alps. Full article

(This article belongs to the Special Issue Genetic Diversity of Plant Tolerance to Environmental Restraints)

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16 pages, 37818 KiB

Open AccessArticle

Genetic and Phenotypic Landscape of PRPH2-Associated Retinal Dystrophy in Japan

by Akio Oishi, Kaoru Fujinami, Go Mawatari, Nobuhisa Naoi, Yasuhiro Ikeda, Shinji Ueno, Kazuki Kuniyoshi, Takaaki Hayashi, Hiroyuki Kondo, Atsushi Mizota, Kei Shinoda, Sentaro Kusuhara, Makoto Nakamura, Takeshi Iwata, Akitaka Tsujikawa and Kazushige Tsunoda

Genes 2021, 12(11), 1817; https://doi.org/10.3390/genes12111817 - 18 Nov 2021

Cited by 8 | Viewed by 3085

Abstract

Peripherin-2 (PRPH2) is one of the causative genes of inherited retinal dystrophy. While the gene is relatively common in Caucasians, reports from Asian ethnicities are limited. In the present study, we report 40 Japanese patients from 30 families with PRPH2-associated [...] Read more.

Peripherin-2 (PRPH2) is one of the causative genes of inherited retinal dystrophy. While the gene is relatively common in Caucasians, reports from Asian ethnicities are limited. In the present study, we report 40 Japanese patients from 30 families with PRPH2-associated retinal dystrophy. We identified 17 distinct pathogenic or likely pathogenic variants using next-generation sequencing. Variants p.R142W and p.V200E were relatively common in the cohort. The age of onset was generally in the 40’s; however, some patients had earlier onset (age: 5 years). Visual acuity of the patients ranged from hand motion to 1.5 (Snellen equivalent 20/13). The patients showed variable phenotypes such as retinitis pigmentosa, cone-rod dystrophy, and macular dystrophy. Additionally, intrafamilial phenotypic variability was observed. Choroidal neovascularization was observed in three eyes of two patients with retinitis pigmentosa. The results demonstrate the genotypic and phenotypic variations of the disease in the Asian cohort. Full article

(This article belongs to the Special Issue Ophthalmic Genetics)

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9 pages, 43090 KiB

Open AccessArticle

Clinical and Genetic Study of X-Linked Juvenile Retinoschisis in the Czech Population

by Bohdan Kousal, Lucia Hlavata, Hana Vlaskova, Lenka Dvorakova, Michaela Brichova, Zora Dubska, Hana Langrova, Andrea L. Vincent, Lubica Dudakova and Petra Liskova

Genes 2021, 12(11), 1816; https://doi.org/10.3390/genes12111816 - 18 Nov 2021

Cited by 4 | Viewed by 2079

Abstract

The aim of this study was to identify RS1 pathogenic variants in Czech patients with X-linked retinoschisis (XLRS) and to describe the associated phenotypes, including natural history, in some cases. Twenty-one affected males from 17 families were included. The coding region of RS1 [...] Read more.

The aim of this study was to identify RS1 pathogenic variants in Czech patients with X-linked retinoschisis (XLRS) and to describe the associated phenotypes, including natural history, in some cases. Twenty-one affected males from 17 families were included. The coding region of RS1 was directly sequenced and segregation of the identified mutations was performed in available family members. In total, 12 disease-causing variants within RS1 were identified; of these c.20del, c.275G>A, c.[375_379del; 386A>T], c.539C>A and c.575_576insT were novel, all predicted to be null alleles. The c.539C>A mutation occurred de novo. Three patients (aged 8, 11 and 19 years) were misdiagnosed as having intermediate uveitis and treated with systemic steroids. Repeat spectral domain optical coherence tomography examinations in four eyes documented the transition from cystoid macular lesions to macular atrophy in the fourth decade of life. Four individuals were treated with topical dorzolamide and in two of them, complete resolution of the cystic macular lesions bilaterally was achieved, while one patient was noncompliant. Rebound phenomenon after discontinuation of dorzolamide for 7 days was documented in one case. Misdiagnosis of XLRS for uveitis is not uncommon; therefore, identification of disease-causing variants is of considerable benefit to the affected individuals. Full article

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

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19 pages, 2017 KiB

Open AccessFeature PaperArticle

New Genes in the Drosophila Y Chromosome: Lessons from D. willistoni

by João Ricchio, Fabiana Uno and A. Bernardo Carvalho

Genes 2021, 12(11), 1815; https://doi.org/10.3390/genes12111815 - 18 Nov 2021

Cited by 2 | Viewed by 2343

Abstract

Y chromosomes play important roles in sex determination and male fertility. In several groups (e.g., mammals) there is strong evidence that they evolved through gene loss from a common X-Y ancestor, but in Drosophila the acquisition of new genes plays a major role. [...] Read more.

Y chromosomes play important roles in sex determination and male fertility. In several groups (e.g., mammals) there is strong evidence that they evolved through gene loss from a common X-Y ancestor, but in Drosophila the acquisition of new genes plays a major role. This conclusion came mostly from studies in two species. Here we report the identification of the 22 Y-linked genes in D. willistoni. They all fit the previously observed pattern of autosomal or X-linked testis-specific genes that duplicated to the Y. The ratio of gene gains to gene losses is ~25 in D. willistoni, confirming the prominent role of gene gains in the evolution of Drosophila Y chromosomes. We also found four large segmental duplications (ranging from 62 kb to 303 kb) from autosomal regions to the Y, containing ~58 genes. All but four of these duplicated genes became pseudogenes in the Y or disappeared. In the GK20609 gene the Y-linked copy remained functional, whereas its original autosomal copy degenerated, demonstrating how autosomal genes are transferred to the Y chromosome. Since the segmental duplication that carried GK20609 contained six other testis-specific genes, it seems that chance plays a significant role in the acquisition of new genes by the Drosophila Y chromosome. Full article

(This article belongs to the Special Issue How Do New Genes Originate and Evolve?)

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15 pages, 4587 KiB

Open AccessTechnical Note

Zoo: Selecting Transcriptomic and Methylomic Biomarkers by Ensembling Animal-Inspired Swarm Intelligence Feature Selection Algorithms

by Yuanyuan Han, Lan Huang and Fengfeng Zhou

Genes 2021, 12(11), 1814; https://doi.org/10.3390/genes12111814 - 18 Nov 2021

Cited by 3 | Viewed by 1829

Abstract

Biological omics data such as transcriptomes and methylomes have the inherent “large p small n” paradigm, i.e., the number of features is much larger than that of the samples. A feature selection (FS) algorithm selects a subset of the transcriptomic or methylomic biomarkers [...] Read more.

Biological omics data such as transcriptomes and methylomes have the inherent “large p small n” paradigm, i.e., the number of features is much larger than that of the samples. A feature selection (FS) algorithm selects a subset of the transcriptomic or methylomic biomarkers in order to build a better prediction model. The hidden patterns in the FS solution space make it challenging to achieve a feature subset with satisfying prediction performances. Swarm intelligence (SI) algorithms mimic the target searching behaviors of various animals and have demonstrated promising capabilities in selecting features with good machine learning performances. Our study revealed that different SI-based feature selection algorithms contributed complementary searching capabilities in the FS solution space, and their collaboration generated a better feature subset than the individual SI feature selection algorithms. Nine SI-based feature selection algorithms were integrated to vote for the selected features, which were further refined by the dynamic recursive feature elimination framework. In most cases, the proposed Zoo algorithm outperformed the existing feature selection algorithms on transcriptomics and methylomics datasets. Full article

(This article belongs to the Section Bioinformatics)

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19 pages, 4152 KiB

Open AccessArticle

Circulatory Endothelin 1-Regulating RNAs Panel: Promising Biomarkers for Non-Invasive NAFLD/NASH Diagnosis and Stratification: Clinical and Molecular Pilot Study

by Reda Albadawy, Sara H. A. Agwa, Eman Khairy, Maha Saad, Naglaa El Touchy, Mohamed Othman, Mohamed El Kassas and Marwa Matboli

Genes 2021, 12(11), 1813; https://doi.org/10.3390/genes12111813 - 18 Nov 2021

Cited by 5 | Viewed by 2380

Abstract

Nonalcoholic fatty liver disease (NAFLD) is one of the major seeds of liver cirrhosis and hepatocellular carcinoma. There is no convenient reliable non-invasive early diagnostic tool available for NAFLD/NASH diagnosis and stratification. Recently, the role of cytosolic sensor, stimulator of interferon genes (STING) [...] Read more.

Nonalcoholic fatty liver disease (NAFLD) is one of the major seeds of liver cirrhosis and hepatocellular carcinoma. There is no convenient reliable non-invasive early diagnostic tool available for NAFLD/NASH diagnosis and stratification. Recently, the role of cytosolic sensor, stimulator of interferon genes (STING) signaling pathway in pathogenesis of nonalcoholic steatohepatitis (NASH) has been evidenced in research. We have selected EDN1/TNF/MAPK3/EP300/hsa-miR-6888-5p/lncRNA RABGAP1L-DT-206 RNA panel from bioinformatics microarrays databases related to STING pathway and NAFLD/NASH pathogenesis. We have used reverse-transcriptase real-time polymerase chain reaction to assess the expression of the serum RNAs panel in NAFLD/NASH without suspicion of advanced fibrosis, NAFLD/with NASH patients with suspicion of advanced fibrosis and controls. Additionally, we have assessed the diagnostic performance of the Ribonucleic acid (RNA) panel. We have detected upregulation of the EDN1 regulating RNAs panel expression in NAFLD/NASH cases compared to healthy controls. We concluded that this circulatory RNA panel could enable us to discriminate NAFLD/NASH cases from controls, and also NAFLD/NASH cases (F1, F2) from advanced fibrosis stages (F3, F4). Full article

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

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