Genes

12 pages, 1295 KiB

Open AccessEditor’s ChoiceArticle

Improving Hereditary Hemorrhagic Telangiectasia Molecular Diagnosis: A Referral Center Experience

by Cinthia Aguilera, Ariadna Padró-Miquel, Anna Esteve-Garcia, Pau Cerdà, Raquel Torres-Iglesias, Núria Llecha and Antoni Riera-Mestre

Genes 2023, 14(3), 772; https://doi.org/10.3390/genes14030772 - 22 Mar 2023

Cited by 1 | Viewed by 2502

Abstract

Background: Hereditary hemorrhagic telangiectasia (HHT) is a rare vascular disease inherited in an autosomal dominant manner. Disease-causing variants in endoglin (ENG) and activin A receptor type II-like 1 (ACVRL1) genes are detected in more than 90% of the patients [...] Read more.

Background: Hereditary hemorrhagic telangiectasia (HHT) is a rare vascular disease inherited in an autosomal dominant manner. Disease-causing variants in endoglin (ENG) and activin A receptor type II-like 1 (ACVRL1) genes are detected in more than 90% of the patients undergoing molecular testing. The identification of variants of unknown significance is often seen as a challenge in clinical practice that makes family screening and genetic counseling difficult. Here, we show that the implementation of cDNA analysis to assess the effect of splice site variants on mRNA splicing is a powerful tool. Methods: Gene panel sequencing of genes associated with HHT and other arteriovenous malformation-related syndromes was performed. To evaluate the effect of the splice site variants, cDNA analysis of ENG and ACVRL1 genes was carried out. Results: three novel splice site variants were identified in ENG (c.68-2A > T and c.1311+4_1311+8del) and ACVLR1 (c.526-6C > G) genes correspondingly in three individuals with HHT that met ≥ 3 Curaçao criteria. All three variants led to an aberrant splicing inducing exon skipping (ENG:c.68-2A > T and ACVRL1:c.526-6C > G) or intron retention (ENG:c.1311+4_1311+8del) allowing the confirmation of the predicted effect on splicing and the reclassification from unknown significance to pathogenic/likely pathogenic of two of them. Conclusions: RNA analysis should be performed to assess and/or confirm the impact of variants on splicing. The molecular diagnosis of HHT patients is crucial to allow family screening and accurate genetic counseling. A multidisciplinary approach including clinicians and geneticists is crucial when dealing with patients with rare diseases. Full article

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

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12 pages, 2610 KiB

Open AccessEditor’s ChoiceArticle

The Expression Patterns of Exogenous Plant miRNAs in Chickens

by Hao Li, Pu Zhang, Diyan Li, Binlong Chen, Jing Li and Tao Wang

Genes 2023, 14(3), 760; https://doi.org/10.3390/genes14030760 - 21 Mar 2023

Cited by 1 | Viewed by 2369

Abstract

(1) Background: MicroRNAs (miRNAs) are involved in a variety of biological processes, such as cell proliferation, cell differentiation, and organ development. Recent studies have shown that plant miRNAs may enter the diet and play physiological and/or pathophysiological roles in human health and disease; [...] Read more.

(1) Background: MicroRNAs (miRNAs) are involved in a variety of biological processes, such as cell proliferation, cell differentiation, and organ development. Recent studies have shown that plant miRNAs may enter the diet and play physiological and/or pathophysiological roles in human health and disease; however, little is known about plant miRNAs in chickens. (2) Methods: Here, we analyzed miRNA sequencing data, with the use of five Chinese native chicken breeds and six different tissues (heart, liver, spleen, lung, kidney, and leg muscle), and used Illumina sequencing to detect the expression of plant miRNAs in the pectoralis muscles at fourteen developmental stages of Tibetan chickens. (3) Results: The results showed that plant miRNAs are detectable in multiple tissues and organs in different chicken breeds. Surprisingly, we found that plant miRNAs, such as tae-miR2018, were detectable in free-range Tibetan chicken embryos at different stages. The results of gavage feeding experiments also showed that synthetic tae-miR2018 was detectable in caged Tibetan chickens after ingestion. The analysis of tae-miR2018 showed that its target genes were related to skeletal muscle organ development, regulation of mesodermal cell fate specification, growth factor activity, negative regulation of the cell cycle, and regulation of growth, indicating that exogenous miRNA may regulate the development of chicken embryos. Further cell cultures and exogenous miRNA uptake assay experiments showed that synthetic wheat miR2018 can be absorbed by chicken myoblasts. (4) Conclusions: Our study found that chickens can absorb and deposit plant miRNAs in various tissues and organs. The plant miRNAs detected in embryos may be involved in the development of chicken embryos. Full article

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

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2 pages, 178 KiB

Open AccessEditor’s ChoiceCorrection

Correction: Noguchi et al. PCR-Based Screening of Spinal Muscular Atrophy for Newborn Infants in Hyogo Prefecture, Japan. Genes 2022, 13, 2110

by Yoriko Noguchi, Ryosuke Bo, Hisahide Nishio, Hisayuki Matsumoto, Keiji Matsui, Yoshihiko Yano, Masami Sugawara, Go Ueda, Yogik Onky Silvana Wijaya, Emma Tabe Eko Niba, Masakazu Shinohara, Yoshihiro Bouike, Atsuko Takeuchi, Kentaro Okamoto, Toshio Saito, Hideki Shimomura, Tomoko Lee, Yasuhiro Takeshima, Kazumoto Iijima, Kandai Nozu and Hiroyuki Awano Show full author list Hide full author list

Genes 2023, 14(3), 759; https://doi.org/10.3390/genes14030759 - 21 Mar 2023

Cited by 1 | Viewed by 1638

Abstract

The authors wish to make the following correction to this paper [...] Full article

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

12 pages, 875 KiB

Open AccessEditor’s ChoiceArticle

Association of Single Nucleotide Polymorphism in the DGAT1 Gene with the Fatty Acid Composition of Cows Milked Once and Twice a Day

by Inthujaa Sanjayaranj, Alastair K. H. MacGibbon, Stephen E. Holroyd, Patrick W. M. Janssen, Hugh T. Blair and Nicolas Lopez-Villalobos

Genes 2023, 14(3), 767; https://doi.org/10.3390/genes14030767 - 21 Mar 2023

Cited by 2 | Viewed by 2271

Abstract

A single nucleotide polymorphism (SNP) rs109421300 of the diacylglycerol acyltransferase 1 (DGAT1) on bovine chromosome 14 is associated with fat yield, fat percentage, and protein percentage. This study aimed to investigate the effect of SNP rs109421300 on production traits and the [...] Read more.

A single nucleotide polymorphism (SNP) rs109421300 of the diacylglycerol acyltransferase 1 (DGAT1) on bovine chromosome 14 is associated with fat yield, fat percentage, and protein percentage. This study aimed to investigate the effect of SNP rs109421300 on production traits and the fatty acid composition of milk from cows milked once a day (OAD) and twice a day (TAD) under New Zealand grazing conditions. Between September 2020 and March 2021, 232 cows from a OAD herd and 182 cows from a TAD herd were genotyped. The CC genotype of SNP rs109421300 was associated with significantly (p < 0.05) higher fat yield, fat percentage, and protein percentage, and lower milk and protein yields in both milking frequencies. The CC genotype was also associated with significantly (p < 0.05) higher proportions of C16:0 and C18:0, higher predicted solid fat content at 10 °C (SFC₁₀), and lower proportions of C4:0 and C18:1 cis-9 in both milking frequencies. The association of SNP with fatty acids was similar in both milking frequencies, with differences in magnitudes. The SFC₁₀ of cows milked OAD was lower than cows milked TAD for all three SNP genotypes suggesting the suitability of OAD milk for producing easily spreadable butter. These results demonstrate that selecting cows with the CC genotype is beneficial for New Zealand dairy farmers with the current payment system, however, this would likely result in less spreadable butter. Full article

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

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22 pages, 6636 KiB

Open AccessEditor’s ChoiceArticle

Transcriptome and Metabolome Profiling Provide Insights into Flavonoid Synthesis in Acanthus ilicifolius Linn

by Zhihua Wu, Zhen Wang, Yaojian Xie, Guo Liu, Xiuhua Shang and Ni Zhan

Genes 2023, 14(3), 752; https://doi.org/10.3390/genes14030752 - 20 Mar 2023

Cited by 6 | Viewed by 2842

Abstract

Acanthus ilicifolius is an important medicinal plant in mangrove forests, which is rich in secondary metabolites with various biological activities. In this study, we used transcriptomic analysis to obtain differentially expressed genes in the flavonoid metabolic pathway and metabolomic methods to detect changes [...] Read more.

Acanthus ilicifolius is an important medicinal plant in mangrove forests, which is rich in secondary metabolites with various biological activities. In this study, we used transcriptomic analysis to obtain differentially expressed genes in the flavonoid metabolic pathway and metabolomic methods to detect changes in the types and content in the flavonoid metabolic synthesis pathway. The results showed that DEGs were identified in the mature roots vs. leaves comparison (9001 up-regulated and 8910 down-regulated), mature roots vs. stems comparison (5861 up-regulated and 7374 down-regulated), and mature stems vs. leaves comparison (10,837 up-regulated and 11,903 down-regulated). Furthermore, two AiCHS genes and four AiCHI genes were up-regulated in the mature roots vs. stems of mature A. ilicifolius, and were down-regulated in mature stems vs. leaves, which were highly expressed in the A. ilicifolius stems. A total of 215 differential metabolites were found in the roots vs. leaves of mature A. ilicifolius, 173 differential metabolites in the roots vs. stems, and 228 differential metabolites in the stems vs. leaves. The metabolomic results showed that some flavonoids in A. ilicifolius stems were higher than in the roots. A total of 18 flavonoid differential metabolites were detected in the roots, stems, and leaves of mature A. ilicifolius. In mature leaves, quercetin-3-O-glucoside-7-O-rhamnoside, gossypitrin, isoquercitrin, quercetin 3,7-bis-O-β-D-glucoside, and isorhamnetin 3-O-β-(2″-O-acetyl-β-D-glucuronide) were found in a high content, while in mature roots, di-O-methylquercetin and isorhamnetin were the major compounds. The combined analysis of the metabolome and transcriptome revealed that DEGs and differential metabolites were related to flavonoid biosynthesis. This study provides a theoretical basis for analyzing the molecular mechanism of flavonoid synthesis in A. ilicifolius and provides a reference for further research and exploitation of its medicinal value. Full article

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

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11 pages, 704 KiB

Open AccessEditor’s ChoiceArticle

Therapeutic Targeting of P53: A Comparative Analysis of APR-246 and COTI-2 in Human Tumor Primary Culture 3-D Explants

by Adam J. Nagourney, Joshua B. Gipoor, Steven S. Evans, Paulo D’Amora, Max S. Duesberg, Paula J. Bernard, Federico Francisco and Robert A. Nagourney

Genes 2023, 14(3), 747; https://doi.org/10.3390/genes14030747 - 19 Mar 2023

Cited by 5 | Viewed by 3879

Abstract

Background: TP53 is the most commonly mutated gene in human cancer with loss of function mutations largely concentrated in “hotspots” affecting DNA binding. APR-246 and COTI-2 are small molecules under investigation in P53 mutated cancers. APR binds to P53 cysteine residues, altering [...] Read more.

Background: TP53 is the most commonly mutated gene in human cancer with loss of function mutations largely concentrated in “hotspots” affecting DNA binding. APR-246 and COTI-2 are small molecules under investigation in P53 mutated cancers. APR binds to P53 cysteine residues, altering conformation, while COTI-2 showed activity in P53 mutant tumors by a computational platform. We compared APR-246 and COTI-2 activity in human tumor explants from 247 surgical specimens. Methods: Ex vivo analyses of programmed cell death measured drug-induced cell death by delayed-loss-of-membrane integrity and ATP content. The LC50s were compared by Z-Score. Synergy was conducted by the method of Chou and Talalay, and correlations were performed by Pearson moment. Results: APR-246 and COTI-2 activity favored hematologic neoplasms, but solid tumor activity varied by diagnosis. COTI-2 and APR-246 activity did not correlate (R = 0.1028) (NS). COTI-2 activity correlated with nitrogen mustard, cisplatin and gemcitabine, doxorubicin and selumetinib, with a trend for APR-246 with doxorubicin. For ovarian cancer, COTI-2 showed synergy with cisplatin at 25%. Conclusions: COTI-2 and APR-246 activity differ by diagnosis. A lack of correlation supports distinct modes of action. Cisplatin synergy is consistent with P53’s role in DNA damage. Different mechanisms of action may underlie disease specificity and offer better disease targeting. Full article

(This article belongs to the Topic Advances in Genetics and Precision Medicine in Human Diseases)

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4 pages, 198 KiB

Open AccessEditor’s ChoiceEditorial

Special Issue “Parkinson’s Disease: Genetics and Pathogenesis”

by Suzanne Lesage and Joanne Trinh

Genes 2023, 14(3), 737; https://doi.org/10.3390/genes14030737 - 17 Mar 2023

Cited by 2 | Viewed by 2208

Abstract

Parkinson’s disease (PD) is a common and incurable neurodegenerative disease, affecting 1% of the population over the age of 65 [...] Full article

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

9 pages, 676 KiB

Open AccessEditor’s ChoiceBrief Report

Comparing Gene Panels for Non-Retinal Indications: A Systematic Review

by Rebecca Procopio, Jose S. Pulido, Kammi B. Gunton, Zeba A. Syed, Daniel Lee, Mark L. Moster, Robert Sergott, Julie A. Neidich and Margaret M. Reynolds

Genes 2023, 14(3), 738; https://doi.org/10.3390/genes14030738 - 17 Mar 2023

Viewed by 1997

Abstract

Importance: The options for genetic testing continue to grow for ocular conditions, including optic atrophy, anterior segment dysgenesis, cataracts, corneal dystrophy, nystagmus, and glaucoma. Gene panels can vary in content and coverage, as we and others have evaluated in inherited retinal disease (IRD). [...] Read more.

Importance: The options for genetic testing continue to grow for ocular conditions, including optic atrophy, anterior segment dysgenesis, cataracts, corneal dystrophy, nystagmus, and glaucoma. Gene panels can vary in content and coverage, as we and others have evaluated in inherited retinal disease (IRD). Objective: To describe gene panel testing options for inherited eye disease phenotypes and their differences. This review is important for making diagnostic decisions. Evidence review: A licensed, certified genetic counselor (RP) used Concert Genetics and the search terms optic atrophy, corneal dystrophy, cataract, glaucoma, anterior segment dysgenesis, microphthalmia/anophthalmia, and nystagmus to identify available testing options performed by CLIA-certified commercial genetic testing laboratories. Other co-authors were surveyed with respect to genetic panels used for the indications of interest. Ophthalmic panels were then compared using Concert Genetics in addition to their own websites. Findings: Panels from each clinical category were included and summarized. This comparison highlighted the differences and similarities between panels so that clinicians can make informed decisions. Conclusions: Access to genetic testing is increasing. The diagnostic yield of genetic testing is increasing. Each panel is different, so phenotyping or characterizing clinical characteristics that may help predict a specific genotype, as well as pre-test hypotheses regarding a genotype, should shape the choice of panels. Full article

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

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2 pages, 571 KiB

Open AccessEditor’s ChoiceCorrection

Correction: Leske, B.A.; Biddulph, T.B. Estimating Effects of Radiation Frost on Wheat Using a Field-Based Frost Control Treatment to Stop Freezing Damage. Genes 2022, 13, 578

by Brenton A. Leske and Thomas Ben Biddulph

Genes 2023, 14(3), 728; https://doi.org/10.3390/genes14030728 - 16 Mar 2023

Cited by 1 | Viewed by 1093

Abstract

In the original publication [...] Full article

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

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12 pages, 4097 KiB

Open AccessEditor’s ChoiceArticle

Internal Transcribed Spacer and 16S Amplicon Sequencing Identifies Microbial Species Associated with Asbestos in New Zealand

by Erin Doyle, Dan Blanchon, Sarah Wells, Peter de Lange, Pete Lockhart, Nick Waipara, Michael Manefield, Shannon Wallis and Terri-Ann Berry

Genes 2023, 14(3), 729; https://doi.org/10.3390/genes14030729 - 16 Mar 2023

Cited by 3 | Viewed by 2768

Abstract

Inhalation of asbestos fibres can cause lung inflammation and the later development of asbestosis, lung cancer, and mesothelioma, and the use of asbestos is banned in many countries. In most countries, large amounts of asbestos exists within building stock, buried in landfills, and [...] Read more.

Inhalation of asbestos fibres can cause lung inflammation and the later development of asbestosis, lung cancer, and mesothelioma, and the use of asbestos is banned in many countries. In most countries, large amounts of asbestos exists within building stock, buried in landfills, and in contaminated soil. Mechanical, thermal, and chemical treatment options do exist, but these are expensive, and they are not effective for contaminated soil, where only small numbers of asbestos fibres may be present in a large volume of soil. Research has been underway for the last 20 years into the potential use of microbial action to remove iron and other metal cations from the surface of asbestos fibres to reduce their toxicity. To access sufficient iron for metabolism, many bacteria and fungi produce organic acids, or iron-chelating siderophores, and in a growing number of experiments these have been found to degrade asbestos fibres in vitro. This paper uses the internal transcribed spacer (ITS) and 16S amplicon sequencing to investigate the fungal and bacterial diversity found on naturally-occurring asbestos minerals, asbestos-containing building materials, and asbestos-contaminated soils with a view to later selectively culturing promising species, screening them for siderophore production, and testing them with asbestos fibres in vitro. After filtering, 895 ITS and 1265 16S amplicon sequencing variants (ASVs) were detected across the 38 samples, corresponding to a range of fungal, bacteria, cyanobacterial, and lichenized fungal species. Samples from Auckland (North Island, New Zealand) asbestos cement, Auckland asbestos-contaminated soils, and raw asbestos rocks from Kahurangi National Park (South Island, New Zealand) were comprised of very different microbial communities. Five of the fungal species detected in this study are known to produce siderophores. Full article

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

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10 pages, 640 KiB

Open AccessEditor’s ChoiceArticle

SCN9A rs6746030 Polymorphism and Pain Perception in Combat Athletes and Non-Athletes

by Katarzyna Leźnicka, Maciej Pawlak, Marek Sawczuk, Agata Gasiorowska and Agata Leońska-Duniec

Genes 2023, 14(3), 733; https://doi.org/10.3390/genes14030733 - 16 Mar 2023

Cited by 5 | Viewed by 2659

Abstract

One of the genes associated with pain perception is SCN9A, which encodes an α-subunit of the voltage gated sodium channel, NaV1.7, a crucial player in peripheral pain sensation. It has been suggested that a common missense polymorphism within SCN9A (rs6746030; G>A; R1150W) [...] Read more.

One of the genes associated with pain perception is SCN9A, which encodes an α-subunit of the voltage gated sodium channel, NaV1.7, a crucial player in peripheral pain sensation. It has been suggested that a common missense polymorphism within SCN9A (rs6746030; G>A; R1150W) may affect nociception in the general population, but its effects of pain perception in athletes remain unknown. Therefore, the aim of the study was to investigate the association between a polymorphism within SCN9A (rs6746030) and pain perception (pain threshold and pain tolerance) in the group of combat athletes (n = 214) and students (n = 92) who did not participate in sports at a professional level. Genotyping was carried out using TaqMan Real-Time PCR method. No significant differences were found between the SCN9A genotype distributions with respect to the pain threshold. However, the probability of having a high pain threshold was higher in the combat sports group than in the control group. The probability of having a decreased pain tolerance was higher in the carriers of the GA and AA genotype than in the homozygotes of the GG genotype. Moreover, the possibility of having a high pain threshold was higher in the combat athlete group than in the control group. The results of our study suggest that the SCN9A rs6746030 polymorphism may affect pain perception. However, the additional effect of the experimental group may suggest that pain tolerance is significantly modulated by other factors, such as the systematic exposure of the athletes’ bodies to short-term high-intensity stimuli during training sessions. Full article

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

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20 pages, 14568 KiB

Open AccessEditor’s ChoiceArticle

FERMT1 Is a Prognostic Marker Involved in Immune Infiltration of Pancreatic Adenocarcinoma Correlating with m⁶A Modification and Necroptosis

by Qian Wu, Jin Li, Pei Wang, Qihang Peng, Zhongcui Kang, Yiting Deng, Jiayi Li, Dehong Yan, Feng Ge and Ying Chen

Genes 2023, 14(3), 734; https://doi.org/10.3390/genes14030734 - 16 Mar 2023

Cited by 5 | Viewed by 2650

Abstract

As an important member of the kindlin family, fermitin family member 1 (FERMT1) can interact with integrin and its aberrant expression involves multiple tumors. However, there are few systematic studies on FERMT1 in pancreatic carcinoma (PAAD). We used several public databases to analyze [...] Read more.

As an important member of the kindlin family, fermitin family member 1 (FERMT1) can interact with integrin and its aberrant expression involves multiple tumors. However, there are few systematic studies on FERMT1 in pancreatic carcinoma (PAAD). We used several public databases to analyze the expression level and clinicopathological characteristics of FERMT1 in PAAD. Meanwhile, the correlation between FERMT1 expression and diagnostic and prognostic value, methylation, potential biological function, immune infiltration, and sensitivity to chemotherapy drugs in PAAD patients were investigated. FERMT1 was significantly up-regulated in PAAD and correlated with T stage, and histologic grade. High FERMT1 expression was closely connected with poor prognosis and can be used to diagnose PAAD. Moreover, the methylation of six CpG sites of FERMT1 was linked to prognosis, and FERMT1 expression was significantly related to N6-methyladenosine (m⁶A) modification. Functional enrichment analysis revealed that FERMT1 co-expression genes participated in diverse biological functions including necroptosis. In addition, the expression of FERMT1 was associated with immune cell infiltration and the expression of immune checkpoint molecules. Finally, FERMT1 overexpression may be sensitive to chemotherapy drugs such as Palbociclib, AM-5992 and TAE-226. FERMT1 can serve as a diagnostic and prognostic marker of PAAD, which is connected with immune cell infiltration and the modulation of m⁶A and necroptosis. Full article

(This article belongs to the Section Bioinformatics)

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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 2926

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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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 1939

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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15 pages, 4754 KiB

Open AccessEditor’s ChoiceArticle

Molecular Epidemiology and Diversity of SARS-CoV-2 in Ethiopia, 2020–2022

by Abay Sisay, Derek Tshiabuila, Stephanie van Wyk, Abraham Tesfaye, Gerald Mboowa, Samuel O. Oyola, Sofonias Kifle Tesema, Cheryl Baxter, Darren Martin, Richard Lessells, Houriiyah Tegally, Monika Moir, Jennifer Giandhari, Sureshnee Pillay, Lavanya Singh, Yajna Ramphal, Arisha Maharaj, Yusasha Pillay, Akhil Maharaj, Yeshnee Naidoo, Upasana Ramphal, Lucious Chabuka, Eduan Wilkinson, Tulio de Oliveira, Adey Feleke Desta and James E. San Show full author list Hide full author list

Genes 2023, 14(3), 705; https://doi.org/10.3390/genes14030705 - 13 Mar 2023

Cited by 11 | Viewed by 4737

Abstract

Ethiopia is the second most populous country in Africa and the sixth most affected by COVID-19 on the continent. Despite having experienced five infection waves, >499,000 cases, and ~7500 COVID-19-related deaths as of January 2023, there is still no detailed genomic epidemiological report [...] Read more.

Ethiopia is the second most populous country in Africa and the sixth most affected by COVID-19 on the continent. Despite having experienced five infection waves, >499,000 cases, and ~7500 COVID-19-related deaths as of January 2023, there is still no detailed genomic epidemiological report on the introduction and spread of SARS-CoV-2 in Ethiopia. In this study, we reconstructed and elucidated the COVID-19 epidemic dynamics. Specifically, we investigated the introduction, local transmission, ongoing evolution, and spread of SARS-CoV-2 during the first four infection waves using 353 high-quality near-whole genomes sampled in Ethiopia. Our results show that whereas viral introductions seeded the first wave, subsequent waves were seeded by local transmission. The B.1.480 lineage emerged in the first wave and notably remained in circulation even after the emergence of the Alpha variant. The B.1.480 was outcompeted by the Delta variant. Notably, Ethiopia’s lack of local sequencing capacity was further limited by sporadic, uneven, and insufficient sampling that limited the incorporation of genomic epidemiology in the epidemic public health response in Ethiopia. These results highlight Ethiopia’s role in SARS-CoV-2 dissemination and the urgent need for balanced, near-real-time genomic sequencing. Full article

(This article belongs to the Special Issue Emerging and Reemerging Viral Pathogens)

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17 pages, 1257 KiB

Open AccessEditor’s ChoiceArticle

Doxorubicin and Cisplatin Modulate miR-21, miR-106, miR-126, miR-155 and miR-199 Levels in MCF7, MDA-MB-231 and SK-BR-3 Cells That Makes Them Potential Elements of the DNA-Damaging Drug Treatment Response Monitoring in Breast Cancer Cells—A Preliminary Study

by Anna Mizielska, Iga Dziechciowska, Radosław Szczepański, Małgorzata Cisek, Małgorzata Dąbrowska, Jan Ślężak, Izabela Kosmalska, Marta Rymarczyk, Klaudia Wilkowska, Barbara Jacczak, Ewa Totoń, Natalia Lisiak, Przemysław Kopczyński and Błażej Rubiś

Genes 2023, 14(3), 702; https://doi.org/10.3390/genes14030702 - 12 Mar 2023

Cited by 10 | Viewed by 4209

Abstract

One of the most innovative medical trends is personalized therapy, based on simple and reproducible methods that detect unique features of cancer cells. One of the good prognostic and diagnostic markers may be the miRNA family. Our work aimed to evaluate changes in [...] Read more.

One of the most innovative medical trends is personalized therapy, based on simple and reproducible methods that detect unique features of cancer cells. One of the good prognostic and diagnostic markers may be the miRNA family. Our work aimed to evaluate changes in selected miRNA levels in various breast cancer cell lines (MCF7, MDA-MB-231, SK-BR-3) treated with doxorubicin or cisplatin. The selection was based on literature data regarding the most commonly altered miRNAs in breast cancer (21-3p, 21-5p, 106a-5p, 126-3p, 126-5p, 155-3p, 155-5p, 199b-3p, 199b-5p, 335-3p, 335-5p). qPCR assessment revealed significant differences in the basal levels of some miRNAs in respective cell lines, with the most striking difference in miR-106a-5p, miR-335-5p and miR-335-3p—all of them were lowest in MCF7, while miR-153p was not detected in SK-BR-3. Additionally, different alterations of selected miRNAs were observed depending on the cell line and the drug. However, regardless of these variables, 21-3p/-5p, 106a, 126-3p, 155-3p and 199b-3p miRNAs were shown to respond either to doxorubicin or to cisplatin treatment. These miRNAs seem to be good candidates for markers of breast cancer cell response to doxorubicin or cisplatin. Especially since some earlier reports suggested their role in affecting pathways and expression of genes associated with the DNA-damage response. However, it must be emphasized that the preliminary study shows effects that may be highly related to the applied drug itself and its concentration. Thus, further examination, including human samples, is required. Full article

(This article belongs to the Special Issue The Ins and Outs of miRNAs as Biomarkers)

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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 1795

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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22 pages, 692 KiB

Open AccessEditor’s ChoiceReview

Treatment-Resistant Schizophrenia, Clozapine Resistance, Genetic Associations, and Implications for Precision Psychiatry: A Scoping Review

by Jiangbo Ying, Qian Hui Chew, Roger S. McIntyre and Kang Sim

Genes 2023, 14(3), 689; https://doi.org/10.3390/genes14030689 - 10 Mar 2023

Cited by 10 | Viewed by 6203

Abstract

Treatment-resistant schizophrenia (TRS) is often associated with severe burden of disease, poor quality of life and functional impairment. Clozapine is the gold standard for the treatment of TRS, although it is also known to cause significant side effects in some patients. In view [...] Read more.

Treatment-resistant schizophrenia (TRS) is often associated with severe burden of disease, poor quality of life and functional impairment. Clozapine is the gold standard for the treatment of TRS, although it is also known to cause significant side effects in some patients. In view of the burgeoning interest in the role of genetic factors in precision psychiatry, we conducted a scoping review to narratively summarize the current genetic factors associated with TRS, clozapine resistance and side effects to clozapine treatment. We searched PubMed from inception to December 2022 and included 104 relevant studies in this review. Extant evidence comprised associations between TRS and clozapine resistance with genetic factors related to mainly dopaminergic and serotoninergic neurotransmitter systems, specifically, TRS and rs4680, rs4818 within COMT, and rs1799978 within DRD2; clozapine resistance and DRD3 polymorphisms, CYP1A2 polymorphisms; weight gain with LEP and SNAP-25 genes; and agranulocytosis risk with HLA-related polymorphisms. Future studies, including replication in larger multi-site samples, are still needed to elucidate putative risk genes and the interactions between different genes and their correlations with relevant clinical factors such as psychopathology, psychosocial functioning, cognition and progressive changes with treatment over time in TRS and clozapine resistance. Full article

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

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21 pages, 758 KiB

Open AccessEditor’s ChoiceReview

The Autism Spectrum: Behavioral, Psychiatric and Genetic Associations

by Ann Genovese and Merlin G. Butler

Genes 2023, 14(3), 677; https://doi.org/10.3390/genes14030677 - 9 Mar 2023

Cited by 96 | Viewed by 28975

Abstract

Autism spectrum disorder (ASD) consists of a group of heterogeneous genetic neurobehavioral disorders associated with developmental impairments in social communication skills and stereotypic, rigid or repetitive behaviors. We review common behavioral, psychiatric and genetic associations related to ASD. Autism affects about 2% of [...] Read more.

Autism spectrum disorder (ASD) consists of a group of heterogeneous genetic neurobehavioral disorders associated with developmental impairments in social communication skills and stereotypic, rigid or repetitive behaviors. We review common behavioral, psychiatric and genetic associations related to ASD. Autism affects about 2% of children with 4:1 male-to-female ratio and a heritability estimate between 70 and 90%. The etiology of ASD involves a complex interplay between inheritance and environmental factors influenced by epigenetics. Over 800 genes and dozens of genetic syndromes are associated with ASD. Novel gene–protein interactions with pathway and molecular function analyses have identified at least three functional pathways including chromatin modeling, Wnt, Notch and other signaling pathways and metabolic disturbances involving neuronal growth and dendritic spine profiles. An estimated 50% of individuals with ASD are diagnosed with chromosome deletions or duplications (e.g., 15q11.2, BP1-BP2, 16p11.2 and 15q13.3), identified syndromes (e.g., Williams, Phelan-McDermid and Shprintzen velocardiofacial) or single gene disorders. Behavioral and psychiatric conditions in autism impacted by genetics influence clinical evaluations, counseling, diagnoses, therapeutic interventions and treatment approaches. Pharmacogenetics testing is now possible to help guide the selection of psychotropic medications to treat challenging behaviors or co-occurring psychiatric conditions commonly seen in ASD. In this review of the autism spectrum disorder, behavioral, psychiatric and genetic observations and associations relevant to the evaluation and treatment of individuals with ASD are discussed. Full article

(This article belongs to the Special Issue Genes, Phenotypes and Molecular Mechanisms for Personalized Medicine in Autism)

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15 pages, 2589 KiB

Open AccessEditor’s ChoiceReview

The Role of PRMT5 in Immuno-Oncology

by Yoshinori Abe, Takumi Sano and Nobuyuki Tanaka

Genes 2023, 14(3), 678; https://doi.org/10.3390/genes14030678 - 9 Mar 2023

Cited by 19 | Viewed by 6426

Abstract

Immune checkpoint inhibitor (ICI) therapy has caused a paradigm shift in cancer therapeutic strategy. However, this therapy only benefits a subset of patients. The difference in responses to ICIs is believed to be dependent on cancer type and its tumor microenvironment (TME). The [...] Read more.

Immune checkpoint inhibitor (ICI) therapy has caused a paradigm shift in cancer therapeutic strategy. However, this therapy only benefits a subset of patients. The difference in responses to ICIs is believed to be dependent on cancer type and its tumor microenvironment (TME). The TME is favorable for cancer progression and metastasis and can also help cancer cells to evade immune attacks. To improve the response to ICIs, it is crucial to understand the mechanism of how the TME is maintained. Protein arginine methyltransferase 5 (PRMT5) di-methylates arginine residues in its substrates and has essential roles in the epigenetic regulation of gene expression, signal transduction, and the fidelity of mRNA splicing. Through these functions, PRMT5 can support cancer cell immune evasion. PRMT5 is necessary for regulatory T cell (Treg) functions and promotes cancer stemness and the epithelial–mesenchymal transition. Specific factors in the TME can help recruit Tregs, tumor-associated macrophages, and myeloid-derived suppressor cells into tumors. In addition, PRMT5 suppresses antigen presentation and the production of interferon and chemokines, which are necessary to recruit T cells into tumors. Overall, PRMT5 supports an immunosuppressive TME. Therefore, PRMT5 inhibition would help recover the immune cycle and enable the immune system-mediated elimination of cancer cells. Full article

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

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15 pages, 1846 KiB

Open AccessEditor’s ChoiceArticle

Optical Genome Mapping Reveals and Characterizes Recurrent Aberrations and New Fusion Genes in Adult ALL

by Lisa-Marie Vieler, Verena Nilius-Eliliwi, Roland Schroers, Deepak Ben Vangala, Huu Phuc Nguyen and Wanda Maria Gerding

Genes 2023, 14(3), 686; https://doi.org/10.3390/genes14030686 - 9 Mar 2023

Cited by 13 | Viewed by 3462

Abstract

(1) Background: In acute lymphoblastic leukemia (ALL) the genetic characterization remains challenging. Due to the genetic heterogeneity of mutations in adult patients, only a small proportion of aberrations can be analyzed with standard routine diagnostics. Optical genome mapping (OGM) has recently opened up [...] Read more.

(1) Background: In acute lymphoblastic leukemia (ALL) the genetic characterization remains challenging. Due to the genetic heterogeneity of mutations in adult patients, only a small proportion of aberrations can be analyzed with standard routine diagnostics. Optical genome mapping (OGM) has recently opened up new possibilities for the characterization of structural variants on a genome-wide level, thus enabling simultaneous analysis for a broad spectrum of genetic aberrations. (2) Methods: 11 adult ALL patients were examined using OGM. (3) Results: Genetic results obtained by karyotyping and FISH were confirmed by OGM for all patients. Karyotype was redefined, and additional genetic information was obtained in 82% (9/11) of samples by OGM, previously not diagnosed by standard of care. Besides gross-structural chromosome rearrangements, e.g., ring chromosome 9 and putative isodicentric chromosome 8q, deletions in CDKN2A/2B were detected in 7/11 patients, defining an approx. 20 kb minimum region of overlap, including an alternative exon 1 of the CDKN2A gene. The results further confirm recurrent ALL aberrations (e.g., PAX5, ETV6, VPREB1, IKZF1). (4) Conclusions: Genome-wide OGM analysis enables a broad genetic characterization in adult ALL patients in one single workup compared to standard clinical testing, facilitating a detailed genetic diagnosis, risk-stratification, and target-directed treatment strategies. Full article

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

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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 2978

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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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 3409

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 3085

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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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 3567

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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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 2817

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, 6830 KiB

Open AccessEditor’s ChoiceArticle

Identification of Selection Signatures and Loci Associated with Important Economic Traits in Yunan Black and Huainan Pigs

by Yachun Han, Tao Tan, Zixin Li, Zheng Ma, Ganqiu Lan, Jing Liang, Kui Li and Lijing Bai

Genes 2023, 14(3), 655; https://doi.org/10.3390/genes14030655 - 5 Mar 2023

Cited by 5 | Viewed by 2441

Abstract

Henan Province is located in central China and rich in domestic pig populations; Huainan (HN) pigs are one of three Henan indigenous breeds with great performance, including early maturation, strong disease resistance and high meat quality. Yunan (YN) black pigs are a typical, [...] Read more.

Henan Province is located in central China and rich in domestic pig populations; Huainan (HN) pigs are one of three Henan indigenous breeds with great performance, including early maturation, strong disease resistance and high meat quality. Yunan (YN) black pigs are a typical, newly cultivated breed, synthesized between HN pigs and American Duroc, and are subjected to selection for important traits, such as fast growth and excellent meat quality. However, the genomic differences, selection signatures and loci associated with important economic traits in YN black pigs and HN pigs are still not well understood. In this study, based on high-density SNP chip analysis of 159 samples covering commercial DLY (Duroc × Landrace × Large White) pigs, HN pigs and YN black pigs, we performed a comprehensive analysis of phylogenetic relationships and genetic diversity among the three breeds. Furthermore, we used composite likelihood ratio tests (CLR) and F-statistics (Fst) to identify specific signatures of selection associated with important economic traits and potential candidate genes. We found 147 selected regions (top 1%) harboring 90 genes based on genetic differentiation (Fst) in the YN-DLY group. In the HN-DLY group, 169 selected regions harbored 58 genes. In the YN-HN group, 179 selected regions harbored 77 genes. In addition, the QTLs database with the most overlapping regions was associated with triglyceride level, number of mummified pigs, hemoglobin and loin muscle depth for YN black pigs, litter size and intramuscular fat content for HN pigs, and humerus length, linolenic acid content and feed conversion ratio mainly in DLY pigs. Of note, overlapping 14 tissue-specific promoters’ annotation with the top Fst 1% selective regions systematically demonstrated the muscle-specific and hypothalamus-specific regulatory elements in YN black pigs. Taken together, these results contribute to an accurate knowledge of crossbreeding, thus benefitting the evaluation of production performance and improving the genome-assisted breeding of other important indigenous pig in the future. Full article

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

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23 pages, 3887 KiB

Open AccessEditor’s ChoiceArticle

CNN_FunBar: Advanced Learning Technique for Fungi ITS Region Classification

by Ritwika Das, Anil Rai and Dwijesh Chandra Mishra

Genes 2023, 14(3), 634; https://doi.org/10.3390/genes14030634 - 3 Mar 2023

Cited by 6 | Viewed by 4710

Abstract

Fungal species identification from metagenomic data is a highly challenging task. Internal Transcribed Spacer (ITS) region is a potential DNA marker for fungi taxonomy prediction. Computational approaches, especially deep learning algorithms, are highly efficient for better pattern recognition and classification of large datasets [...] Read more.

Fungal species identification from metagenomic data is a highly challenging task. Internal Transcribed Spacer (ITS) region is a potential DNA marker for fungi taxonomy prediction. Computational approaches, especially deep learning algorithms, are highly efficient for better pattern recognition and classification of large datasets compared to in silico techniques such as BLAST and machine learning methods. Here in this study, we present CNN_FunBar, a convolutional neural network-based approach for the classification of fungi ITS sequences from UNITE+INSDC reference datasets. Effects of convolution kernel size, filter numbers, k-mer size, degree of diversity and category-wise frequency of ITS sequences on classification performances of CNN models have been assessed at all taxonomic levels (species, genus, family, order, class and phylum). It is observed that CNN models can produce >93% average accuracy for classifying ITS sequences from balanced datasets with 500 sequences per category and 6-mer frequency features at all levels. The comparative study has revealed that CNN_FunBar can outperform machine learning-based algorithms (SVM, KNN, Naïve-Bayes and Random Forest) as well as existing fungal taxonomy prediction software (funbarRF, Mothur, RDP Classifier and SINTAX). The present study will be helpful for fungal taxonomy classification using large metagenomic datasets. Full article

(This article belongs to the Special Issue Omics and Bioinformatics)

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14 pages, 833 KiB

Open AccessEditor’s ChoiceArticle

Body Fluid Identification in Samples Collected after Intimate and Social Contact: A Comparison of Two mRNA Profiling Methods and the Additional Information Gained by cSNP Genotypes

by Helen Johannessen, Erin Hanson, Peter Gill, Cordula Haas, Erik Francisco Bergseth, Jack Ballantyne and Ane Elida Fonneløp

Genes 2023, 14(3), 636; https://doi.org/10.3390/genes14030636 - 3 Mar 2023

Cited by 7 | Viewed by 3906

Abstract

The ability to associate a contributor with a specific body fluid in a crime stain can aid casework investigation. The detection of body fluids combined with DNA analyses may supply essential information, but as the two tests are independent, they may not be [...] Read more.

The ability to associate a contributor with a specific body fluid in a crime stain can aid casework investigation. The detection of body fluids combined with DNA analyses may supply essential information, but as the two tests are independent, they may not be associated. Recently, the analysis of coding region SNPs (cSNPs) within the RNA transcript has been proven to be a promising method to face this challenge. In this study, we performed targeted RNA sequencing of 158 samples (boxershorts, fingernail swabs and penile swabs) collected from 12 couples at different time points post-intimate contact and after non-intimate contact, using the Ion S5™ System and BFID-cSNP-6F assay. The aim of the study was to compare the performance of the MPS and CE methods in the detection of mRNA markers, and to associate body fluids with contributors by their cSNP genotypes. The results of the study show a lower success rate in the detection of vaginal mucosa by the MPS compared to the CE method. However, the additional information obtained with the cSNP genotypes could successfully associate body fluids with contributors in most cases. Full article

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

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13 pages, 297 KiB

Open AccessEditor’s ChoiceArticle

“What We Know and What We Do Not Know about Evolutionary Genetic Adaptation to High Altitude Hypoxia in Andean Aymaras”

by Ricardo Amaru, Jihyun Song, N. Scott Reading, Victor R. Gordeuk and Josef T. Prchal

Genes 2023, 14(3), 640; https://doi.org/10.3390/genes14030640 - 3 Mar 2023

Cited by 7 | Viewed by 3450

Abstract

Three well-studied populations living at high altitudes are Tibetans, Andeans (Aymaras and Quechuas), and Ethiopians. Unlike Tibetans and Ethiopians who have similar hemoglobin (Hb) levels as individuals living at sea level, Aymara Hb levels increase when living at higher altitudes. Our previous whole [...] Read more.

Three well-studied populations living at high altitudes are Tibetans, Andeans (Aymaras and Quechuas), and Ethiopians. Unlike Tibetans and Ethiopians who have similar hemoglobin (Hb) levels as individuals living at sea level, Aymara Hb levels increase when living at higher altitudes. Our previous whole genome study of Aymara people revealed several selected genes that are involved in cardiovascular functions, but their relationship with Hb levels was not elucidated. Here, we studied the frequencies of known evolutionary-selected variants in Tibetan and Aymara populations and their correlation with high Hb levels in Aymara. We genotyped 177 Aymaras at three different altitudes: 400 m (Santa Cruz), 4000 m (La Paz), and 5000 m (Chorolque), and correlated the results with the elevation of residence. Some of the Tibetan-selected variants also exist in Aymaras, but at a lower prevalence. Two of 10 Tibetan selected variants of EPAS1 were found (rs13005507 and rs142764723) and these variants did not correlate with Hb levels. Allele frequencies of 5 Aymara selected SNPs (heterozygous and homozygous) at 4000 m (rs11578671_BRINP3, rs34913965_NOS2, rs12448902_SH2B1, rs10744822_TBX5, and rs487105_PYGM) were higher compared to Europeans. The allelic frequencies of rs11578671_BRINP3, rs34913965_NOS2, and rs10744822_SH2B1 were significantly higher for Aymaras living at 5000 m than those at 400 m elevation. Variant rs11578671, close to the BRINP3 coding region, correlated with Hb levels in females. Variant rs34913965 (NOS2) correlated with leukocyte counts. Variants rs12448902 (SH2B1) and rs34913965 (NOS2) associated with higher platelet levels. The correlation of these SNPs with blood cell counts demonstrates that the selected genetic variants in Aymara influence hematopoiesis and cardiovascular effects. Full article

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

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 2289

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, 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 3007

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 1754

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 2672

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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18 pages, 2025 KiB

Open AccessEditor’s ChoiceArticle

Winners and Losers of Atlantification: The Degree of Ocean Warming Affects the Structure of Arctic Microbial Communities

by Antonia Ahme, Anabel Von Jackowski, Rebecca A. McPherson, Klara K. E. Wolf, Mario Hoppmann, Stefan Neuhaus and Uwe John

Genes 2023, 14(3), 623; https://doi.org/10.3390/genes14030623 - 1 Mar 2023

Cited by 13 | Viewed by 3549

Abstract

Arctic microbial communities (i.e., protists and bacteria) are increasingly subjected to an intrusion of new species via Atlantification and an uncertain degree of ocean warming. As species differ in adaptive traits, these oceanic conditions may lead to compositional changes with functional implications for [...] Read more.

Arctic microbial communities (i.e., protists and bacteria) are increasingly subjected to an intrusion of new species via Atlantification and an uncertain degree of ocean warming. As species differ in adaptive traits, these oceanic conditions may lead to compositional changes with functional implications for the ecosystem. In June 2021, we incubated water from the western Fram Strait at three temperatures (2 °C, 6 °C, and 9 °C), mimicking the current and potential future properties of the Arctic Ocean. Our results show that increasing the temperature to 6 °C only minorly affects the community, while an increase to 9 °C significantly lowers the diversity and shifts the composition. A higher relative abundance of large hetero- and mixotrophic protists was observed at 2 °C and 6 °C compared to a higher abundance of intermediate-sized temperate diatoms at 9 °C. The compositional differences at 9 °C led to a higher chlorophyll a:POC ratio, but the C:N ratio remained similar. Our results contradict the common assumption that smaller organisms and heterotrophs are favored under warming and strongly indicate a thermal limit between 6 °C and 9 °C for many Arctic species. Consequently, the magnitude of temperature increase is a crucial factor for microbial community reorganization and the ensuing ecological consequences in the future Arctic Ocean. Full article

(This article belongs to the Special Issue Polar Genomics)

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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 2046

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 1 | Viewed by 2654

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 2258

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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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 2166

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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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 2609

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, 937 KiB

Open AccessEditor’s ChoiceReview

Fate Decisions of Chicken Primordial Germ Cells (PGCs): Development, Integrity, Sex Determination, and Self-Renewal Mechanisms

by Kennosuke Ichikawa and Hiroyuki Horiuchi

Genes 2023, 14(3), 612; https://doi.org/10.3390/genes14030612 - 28 Feb 2023

Cited by 11 | Viewed by 5188

Abstract

Primordial germ cells (PGCs) are precursor cells of sperm and eggs. The fate decisions of chicken PGCs in terms of their development, integrity, and sex determination have unique features, thereby providing insights into evolutionary developmental biology. Additionally, fate decisions in the context of [...] Read more.

Primordial germ cells (PGCs) are precursor cells of sperm and eggs. The fate decisions of chicken PGCs in terms of their development, integrity, and sex determination have unique features, thereby providing insights into evolutionary developmental biology. Additionally, fate decisions in the context of a self-renewal mechanism have been applied to establish culture protocols for chicken PGCs, enabling the production of genome-edited chickens and the conservation of genetic resources. Thus, studies on the fate decisions of chicken PGCs have significantly contributed to both academic and industrial development. Furthermore, studies on fate decisions have rapidly advanced owing to the recent development of essential research technologies, such as genome editing and RNA sequencing. Here, we reviewed the status of fate decisions of chicken PGCs and provided insight into other important research issues that require attention. Full article

(This article belongs to the Special Issue Avian Genomics and Transgenesis)

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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 5909

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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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 2515

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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24 pages, 7083 KiB

Open AccessEditor’s ChoiceArticle

Improving Agrobacterium tumefaciens−Mediated Genetic Transformation for Gene Function Studies and Mutagenesis in Cucumber (Cucumis sativus L.)

by Hanqiang Liu, Jianyu Zhao, Feifan Chen, Zhiming Wu, Junyi Tan, Nhien Hao Nguyen, Zhihui Cheng and Yiqun Weng

Genes 2023, 14(3), 601; https://doi.org/10.3390/genes14030601 - 27 Feb 2023

Cited by 12 | Viewed by 5297

Abstract

In the post−genomics era, Agrobacterium tumefaciens−mediated genetic transformation is becoming an increasingly indispensable tool for characterization of gene functions and crop improvement in cucumber (Cucumis sativus L.). However, cucumber transformation efficiency is still low. In this study, we evaluated the effects [...] Read more.

In the post−genomics era, Agrobacterium tumefaciens−mediated genetic transformation is becoming an increasingly indispensable tool for characterization of gene functions and crop improvement in cucumber (Cucumis sativus L.). However, cucumber transformation efficiency is still low. In this study, we evaluated the effects of several key factors affecting the shoot−regeneration rate and overall transformation efficiency in cucumber including genotypes, the age and sources of explants, Agrobacterium strains, infection/co−cultivation conditions, and selective agents. We showed that in general, North China cucumbers exhibited higher shoot−regeneration rate than US pickling or slicing cucumbers. The subapical ground meristematic regions from cotyledons or the hypocotyl had a similar shoot−regeneration efficiency that was also affected by the age of the explants. Transformation with the Agrobacterium strain AGL1 yielded a higher frequency of positive transformants than with GV3101. The antibiotic kanamycin was effective in selection against non−transformants or chimeras. Optimization of various factors was exemplified with the development of transgenic plants overexpressing the LittleLeaf (LL) gene or RNAi of the APRR2 gene in three cucumber lines. The streamlined protocol was also tested in transgenic studies in three additional genes. The overall transformation efficiency defined by the number of verified transgenic plants out of the number of seeds across multiple experiments was 0.2–1.7%. Screening among T₁ OE transgenic plants identified novel, inheritable mutants for leaf or fruit color or size/shape, suggesting T−DNA insertion as a potential source of mutagenesis. The Agrobacterium−mediated transformation protocol from this study could be used as the baseline for further improvements in cucumber transformation. 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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15 pages, 790 KiB

Open AccessEditor’s ChoiceReview

Nanoplastics Toxicity Specific to Liver in Inducing Metabolic Dysfunction—A Comprehensive Review

by Shoumi Haldar, Nounenuo Yhome, Yuvashree Muralidaran, Senthilkumar Rajagopal and Prabhakar Mishra

Genes 2023, 14(3), 590; https://doi.org/10.3390/genes14030590 - 26 Feb 2023

Cited by 32 | Viewed by 5459

Abstract

Plastic pollution in the world is widespread and growing. The environment is swamped with nanoplastics (<100 nm), and the health consequences of these less visible pollutants are unknown. Furthermore, there is evidence that microplastics can release nanoplastics by digestive disintegration, implying that macroplastic [...] Read more.

Plastic pollution in the world is widespread and growing. The environment is swamped with nanoplastics (<100 nm), and the health consequences of these less visible pollutants are unknown. Furthermore, there is evidence that microplastics can release nanoplastics by digestive disintegration, implying that macroplastic exposure can cause direct and indirect disease via nanoplastics. The existence and impact of nanoplastics in numerous tissues from invertebrates to larger vertebrates that consume significant amounts of plastics were investigated, and histopathological techniques were utilized to determine physiological reactions and inflammation from the plastics. Nanoplastics enters an organism through the respiratory and gastro-intestinal tract where they accumulate into the liver through blood circulation via absorption, or epidermal infiltration. It is stated that macroplastics can cause damage directly at the site of exposure, whereas nanoplastics can influence the liver, causing subsequent damage to other organs. Multi-organ dysfunction is brought on by liver changes, and nanoplastics can readily enter the gut-liver axis and disturb the gut microflora. By exploring the literature and summarizing the research that has been published to date, this review article reveals the deleterious effect and mechanisms of nanoplastics on the pathophysiological functions of the hepatic system. Full article

(This article belongs to the Special Issue Liver Disease: Genetic Research and Clinical Diagnosis)

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11 pages, 398 KiB

Open AccessEditor’s ChoiceArticle

Cell Type Annotation Model Selection: General-Purpose vs. Pattern-Aware Feature Gene Selection in Single-Cell RNA-Seq Data

by Akram Vasighizaker, Yash Trivedi and Luis Rueda

Genes 2023, 14(3), 596; https://doi.org/10.3390/genes14030596 - 26 Feb 2023

Cited by 1 | Viewed by 2697

Abstract

With the advances in high-throughput sequencing technology, an increasing amount of research in revealing heterogeneity among cells has been widely performed. Differences between individual cells’ functionality are determined based on the differences in the gene expression profiles. Although the observations indicate a great [...] Read more.

With the advances in high-throughput sequencing technology, an increasing amount of research in revealing heterogeneity among cells has been widely performed. Differences between individual cells’ functionality are determined based on the differences in the gene expression profiles. Although the observations indicate a great performance of clustering methods, manual annotation of the clusters of cells is a challenge yet to be addressed more scalable and faster. On the other hand, due to the lack of enough labelled datasets, just a few supervised techniques have been used in cell type identification, and they obtained more robust results compared to clustering methods. A recent study showed that a complementary step of feature selection helped support vector machine (SVM) to outperform other classifiers in different scenarios. In this article, we compare and evaluate the performance of two state-of-the-art supervised methods, XGBoost and SVM, with information gain as a feature selection method. The results of the experiments on three standard scRNA-seq datasets indicate that XGBoost automatically annotates cell types in a simpler and more scalable framework. Additionally, it sheds light on the potential use of boosting tree approaches combined with deep neural networks to capture underlying information of single-cell RNA-Seq data more effectively. It can be used to identify marker genes and other applications in biological studies. Full article

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

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24 pages, 2372 KiB

Open AccessEditor’s ChoiceReview

Epigenetic Regulation of β-Globin Genes and the Potential to Treat Hemoglobinopathies through Epigenome Editing

by Letizia Fontana, Zoe Alahouzou, Annarita Miccio and Panagiotis Antoniou

Genes 2023, 14(3), 577; https://doi.org/10.3390/genes14030577 - 25 Feb 2023

Cited by 12 | Viewed by 8124

Abstract

Beta-like globin gene expression is developmentally regulated during life by transcription factors, chromatin looping and epigenome modifications of the β-globin locus. Epigenome modifications, such as histone methylation/demethylation and acetylation/deacetylation and DNA methylation, are associated with up- or down-regulation of gene expression. The understanding [...] Read more.

Beta-like globin gene expression is developmentally regulated during life by transcription factors, chromatin looping and epigenome modifications of the β-globin locus. Epigenome modifications, such as histone methylation/demethylation and acetylation/deacetylation and DNA methylation, are associated with up- or down-regulation of gene expression. The understanding of these mechanisms and their outcome in gene expression has paved the way to the development of new therapeutic strategies for treating various diseases, such as β-hemoglobinopathies. Histone deacetylase and DNA methyl-transferase inhibitors are currently being tested in clinical trials for hemoglobinopathies patients. However, these approaches are often uncertain, non-specific and their global effect poses serious safety concerns. Epigenome editing is a recently developed and promising tool that consists of a DNA recognition domain (zinc finger, transcription activator-like effector or dead clustered regularly interspaced short palindromic repeats Cas9) fused to the catalytic domain of a chromatin-modifying enzyme. It offers a more specific targeting of disease-related genes (e.g., the ability to reactivate the fetal γ-globin genes and improve the hemoglobinopathy phenotype) and it facilitates the development of scarless gene therapy approaches. Here, we summarize the mechanisms of epigenome regulation of the β-globin locus, and we discuss the application of epigenome editing for the treatment of hemoglobinopathies. Full article

(This article belongs to the Special Issue Gene Editing for Therapy and Reverse Genetics of Blood Diseases)

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13 pages, 3318 KiB

Open AccessEditor’s ChoiceArticle

Estimates of Genomic Heritability and the Marker-Derived Gene for Re(Production) Traits in Xinggao Sheep

by Zaixia Liu, Shaoyin Fu, Xiaolong He, Xuewen Liu, Caixia Shi, Lingli Dai, Biao Wang, Yuan Chai, Yongbin Liu and Wenguang Zhang

Genes 2023, 14(3), 579; https://doi.org/10.3390/genes14030579 - 25 Feb 2023

Cited by 3 | Viewed by 2593

Abstract

Xinggao sheep are a breed of Chinese domestic sheep that are adapted to the extremely cold climatic features of the Hinggan League in China. The economically vital reproductive trait of ewes (litter size, LS) and productive traits of lambs (birth weight, BWT; weaning [...] Read more.

Xinggao sheep are a breed of Chinese domestic sheep that are adapted to the extremely cold climatic features of the Hinggan League in China. The economically vital reproductive trait of ewes (litter size, LS) and productive traits of lambs (birth weight, BWT; weaning weight, WWT; and average daily gain, ADG) are expressed in females and later in life after most of the selection decisions have been made. This study estimated the genetic parameters for four traits to explore the genetic mechanisms underlying the variation, and we performed genome-wide association study (GWAS) tests on a small sample size to identify novel marker trait associations (MTAs) associated with prolificacy and growth. We detected two suggestive significant single-nucleotide polymorphisms (SNPs) associated with LS and eight significant SNPs for BWT, WWT, and ADG. These candidate loci and genes also provide valuable information for further fine-mapping of QTLs and improvement of reproductive and productive traits in sheep. Full article

(This article belongs to the Special Issue Genetics and Breeding of Sheep and Goats)

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18 pages, 4052 KiB

Open AccessEditor’s ChoiceArticle

Whole-Genome Sequencing Data Reveal New Loci Affecting Milk Production in German Black Pied Cattle (DSN)

by Paula Korkuć, Guilherme B. Neumann, Deike Hesse, Danny Arends, Monika Reißmann, Siham Rahmatalla, Katharina May, Manuel J. Wolf, Sven König and Gudrun A. Brockmann

Genes 2023, 14(3), 581; https://doi.org/10.3390/genes14030581 - 25 Feb 2023

Cited by 11 | Viewed by 2493

Abstract

German Black Pied (DSN) is considered an ancestral population of the Holstein breed. The goal of the current study was to fine-map genomic loci for milk production traits and to provide sequence variants for selection. We studied genome-wide associations for milk-production traits in [...] Read more.

German Black Pied (DSN) is considered an ancestral population of the Holstein breed. The goal of the current study was to fine-map genomic loci for milk production traits and to provide sequence variants for selection. We studied genome-wide associations for milk-production traits in 2160 DSN cows. Using 11.7 million variants from whole-genome sequencing of 304 representative DSN cattle, we identified 1980 associated variants (−log₁₀(p) ≥ 7.1) in 13 genomic loci on 9 chromosomes. The highest significance was found for the MGST1 region affecting milk fat content (−log₁₀(p) = 11.93, MAF = 0.23, substitution effect of the minor allele (ß_MA) = −0.151%). Different from Holstein, DGAT1 was fixed (0.97) for the alanine protein variant for high milk and protein yield. A key gene affecting protein content was CSN1S1 (−log₁₀(p) = 8.47, MAF = 049, ß_MA = −0.055%) and the GNG2 region (−log₁₀(p) = 10.48, MAF = 0.34, ß_MA = 0.054%). Additionally, we suggest the importance of FGF12 for protein and fat yield, HTR3C for milk yield, TLE4 for milk and protein yield, and TNKS for milk and fat yield. Selection for favored alleles can improve milk yield and composition. With respect to maintaining the dual-purpose type of DSN, unfavored linkage to genes affecting muscularity has to be investigated carefully, before the milk-associated variants can be applied for selection in the small population. Full article

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

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15 pages, 878 KiB

Open AccessEditor’s ChoiceArticle

CoNet: Efficient Network Regression for Survival Analysis in Transcriptome-Wide Association Studies—With Applications to Studies of Breast Cancer

by Jiayi Han, Liye Zhang, Ran Yan, Tao Ju, Xiuyuan Jin, Shukang Wang, Zhongshang Yuan and Jiadong Ji

Genes 2023, 14(3), 586; https://doi.org/10.3390/genes14030586 - 25 Feb 2023

Viewed by 2089

Abstract

Transcriptome-wide association studies (TWASs) aim to detect associations between genetically predicted gene expression and complex diseases or traits through integrating genome-wide association studies (GWASs) and expression quantitative trait loci (eQTL) mapping studies. Most current TWAS methods analyze one gene at a time, ignoring [...] Read more.

Transcriptome-wide association studies (TWASs) aim to detect associations between genetically predicted gene expression and complex diseases or traits through integrating genome-wide association studies (GWASs) and expression quantitative trait loci (eQTL) mapping studies. Most current TWAS methods analyze one gene at a time, ignoring the correlations between multiple genes. Few of the existing TWAS methods focus on survival outcomes. Here, we propose a novel method, namely a COx proportional hazards model for NEtwork regression in TWAS (CoNet), that is applicable for identifying the association between one given network and the survival time. CoNet considers the general relationship among the predicted gene expression as edges of the network and quantifies it through pointwise mutual information (PMI), which is under a two-stage TWAS. Extensive simulation studies illustrate that CoNet can not only achieve type I error calibration control in testing both the node effect and edge effect, but it can also gain more power compared with currently available methods. In addition, it demonstrates superior performance in real data application, namely utilizing the breast cancer survival data of UK Biobank. CoNet effectively accounts for network structure and can simultaneously identify the potential effecting nodes and edges that are related to survival outcomes in TWAS. Full article

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

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