Genes

11 pages, 281 KiB

Open AccessArticle

An Assessment of MT1A (rs11076161), MT2A (rs28366003) and MT1L (rs10636) Gene Polymorphisms and MT2 Concentration in Women with Endometrial Pathologies

by Kaja Michalczyk, Patrycja Kapczuk, Grzegorz Witczak, Piotr Tousty, Mateusz Bosiacki, Mateusz Kurzawski, Dariusz Chlubek and Aneta Cymbaluk-Płoska

Genes 2023, 14(3), 773; https://doi.org/10.3390/genes14030773 - 22 Mar 2023

Viewed by 1440

Abstract

Several studies have indicated a relationship between metallothionein (MT) polymorphisms and the development of different pathologies, including neoplastic diseases. However, no studies thus far have been conducted on the influence of MT polymorphisms and the development of endometrial lesions, including endometrial cancer. This [...] Read more.

Several studies have indicated a relationship between metallothionein (MT) polymorphisms and the development of different pathologies, including neoplastic diseases. However, no studies thus far have been conducted on the influence of MT polymorphisms and the development of endometrial lesions, including endometrial cancer. This study included 140 patients with normal endometrial tissue, endometrial polyps, uterine myomas and endometrial cancer. The tissue MT2 concentration was determined using the ELISA method. MT1A, MT2A and MT1L polymorphisms were analyzed using TaqMan real-time PCR genotyping assays. We found no statistical difference between the tissue MT2 concentration in patients with EC vs. benign endometrium (p = 0.579). However, tissue MT2 concentration was significantly different between uterine fibromas and normal endometrial tissue samples (p = 0.019). Menopause status did not influence the tissue MT2 concentration (p = 0.282). There were no significant associations between the prevalence of MT1A, MT2A and MT1L polymorphisms and MT2 concentration. The age, menopausal status, and diabetes status of patients were identified as EC risk factors. Full article

(This article belongs to the Special Issue Gene Regulation in Cancers)

12 pages, 1295 KiB

Open AccessArticle

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 1508

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)

► Show Figures

Figure 1

16 pages, 332 KiB

Open AccessReview

Unraveling Psychiatric Disorders through Neural Single-Cell Transcriptomics Approaches

by Samar N. Chehimi, Richard C. Crist and Benjamin C. Reiner

Genes 2023, 14(3), 771; https://doi.org/10.3390/genes14030771 - 22 Mar 2023

Cited by 1 | Viewed by 3148

Abstract

The development of single-cell and single-nucleus transcriptome technologies is enabling the unraveling of the molecular and cellular heterogeneity of psychiatric disorders. The complexity of the brain and the relationships between different brain regions can be better understood through the classification of individual cell [...] Read more.

The development of single-cell and single-nucleus transcriptome technologies is enabling the unraveling of the molecular and cellular heterogeneity of psychiatric disorders. The complexity of the brain and the relationships between different brain regions can be better understood through the classification of individual cell populations based on their molecular markers and transcriptomic features. Analysis of these unique cell types can explain their involvement in the pathology of psychiatric disorders. Recent studies in both human and animal models have emphasized the importance of transcriptome analysis of neuronal cells in psychiatric disorders but also revealed critical roles for non-neuronal cells, such as oligodendrocytes and microglia. In this review, we update current findings on the brain transcriptome and explore molecular studies addressing transcriptomic alterations identified in human and animal models in depression and stress, neurodegenerative disorders (Parkinson’s and Alzheimer’s disease), schizophrenia, opioid use disorder, and alcohol and psychostimulant abuse. We also comment on potential future directions in single-cell and single-nucleus studies. Full article

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

13 pages, 6805 KiB

Open AccessArticle

Genome-Wide Identification and Expression Analysis of TPS Gene Family in Liriodendron chinense

by Zijian Cao, Qianxi Ma, Yuhao Weng, Jisen Shi, Jinhui Chen and Zhaodong Hao

Genes 2023, 14(3), 770; https://doi.org/10.3390/genes14030770 - 22 Mar 2023

Cited by 2 | Viewed by 2700

Abstract

Terpenoids play a key role in plant growth and development, supporting resistance regulation and terpene synthase (TPS), which is the last link in the synthesis process of terpenoids. Liriodendron chinense, commonly called the Chinese tulip tree, is a rare and endangered tree species [...] Read more.

Terpenoids play a key role in plant growth and development, supporting resistance regulation and terpene synthase (TPS), which is the last link in the synthesis process of terpenoids. Liriodendron chinense, commonly called the Chinese tulip tree, is a rare and endangered tree species of the family Magnoliaceae. However, the genome-wide identification of the TPS gene family and its transcriptional responses to development and abiotic stress are still unclear. In the present study, we identified a total of 58 TPS genes throughout the L. chinense genome. A phylogenetic tree analysis showed that they were clustered into five subfamilies and unevenly distributed across six chromosomes. A cis-acting element analysis indicated that LcTPSs were assumed to be highly responsive to stress hormones, such as methyl jasmonate (MeJA) and abscisic acid (ABA). Consistent with this, transcriptome data showed that most LcTPS genes responded to abiotic stress, such as cold, drought, and hot stress, at the transcriptional level. Further analysis showed that LcTPS genes were expressed in a tissue-dependent manner, especially in buds, leaves, and bark. Quantitative reverse transcription PCR (qRT-PCR) analysis confirmed that LcTPS expression was significantly higher in mature leaves compared to young leaves. These results provide a reference for understanding the function and role of the TPS family, laying a foundation for further study of the regulation of TPS in terpenoid biosynthesis in L. chinense. Full article

(This article belongs to the Special Issue Abiotic Stress in Land Plants: Molecular Genetics and Genomics)

► Show Figures

Figure 1

6 pages, 933 KiB

Open AccessOpinion

Systemic Retinoids for Generalized Verrucosis Due to Congenital Immunodeficiency: Case Reports and Review of the Literature

by Hideyuki Kosumi, Ken Natsuga, Teruki Yanagi and Hideyuki Ujiie

Genes 2023, 14(3), 769; https://doi.org/10.3390/genes14030769 - 22 Mar 2023

Viewed by 1632

Abstract

Generalized verrucosis (GV) is a group of immunodeficiency disorders accompanied by widespread human papillomavirus infection. We revisit two cases of GV due to congenital interleukin-7 deficiency successfully treated with systemic retinoids. We also present a review of the literature on the use of [...] Read more.

Generalized verrucosis (GV) is a group of immunodeficiency disorders accompanied by widespread human papillomavirus infection. We revisit two cases of GV due to congenital interleukin-7 deficiency successfully treated with systemic retinoids. We also present a review of the literature on the use of systemic retinoids to treat GV. Our review suggests that systemic retinoids are a safe and effective option for managing recalcitrant wart lesions in cases of GV. Full article

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

► Show Figures

Figure 1

17 pages, 4604 KiB

Open AccessArticle

Two Complete Mitochondrial Genomes of Leptobrachium (Anura: Megophryidae: Leptobrachiinae): Characteristics, Population Divergences, and Phylogenetic Implications

by Qiang Zhou, Hong-Mei Xiang, Ming-Yao Zhang, Ying Liu, Zhi-Rong Gu, Xiang-Ying Lan, Jin-Xiu Wang and Wan-Sheng Jiang

Genes 2023, 14(3), 768; https://doi.org/10.3390/genes14030768 - 21 Mar 2023

Viewed by 1369

Abstract

The mustache toads Leptobrachium boringii and Leptobrachium liui are two attractive species in Megophryidae, in which adult males have mustache-like keratinized nuptial spines on their upper lip. However, both are under threat due to multiple factors, of which scientific studies are still very limited. [...] Read more.

The mustache toads Leptobrachium boringii and Leptobrachium liui are two attractive species in Megophryidae, in which adult males have mustache-like keratinized nuptial spines on their upper lip. However, both are under threat due to multiple factors, of which scientific studies are still very limited. In this study, two new complete mitochondrial genomes of L. boringii and L. liui were sequenced, assembled, and annotated based on next-generation sequencing. The mitogenome lengths of L. boringii and L. liui were found to be 17,100 and 17,501 bp, respectively, with both containing 13 protein coding genes, 23 tRNAs, 2 rRNAs, and 1 non-coding control region. Nucleotide diversity analyses indicate that atp8, atp6, and nad2 showed higher nucleotide diversity than cox1, cox3, and cytb. The intraspecific genetic distances among three different populations of L. boringii exceed 4%, and those between two populations of L. liui reach 7%. Phylogenetic relationships support their division into two subfamilies of Megophryidae (Leptobrachiinae and Megophryinae) as well as two species groups within Leptobrachium, corresponding to the number of keratinized nuptial spines (10–48 in the L. boringii species group vs. 2–6 in the L. liui species group). The two new mitogenomes reported in this study provide valuable data for future molecular evolutionary and conservation studies of the genus Leptobrachium and other Megophryidae toads. Full article

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

► Show Figures

Figure 1

12 pages, 875 KiB

Open AccessArticle

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 1 | Viewed by 1364

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)

► Show Figures

Figure 1

16 pages, 3695 KiB

Open AccessArticle

Floral Development Stage-Specific Transcriptomic Analysis Reveals the Formation Mechanism of Different Shapes of Ray Florets in Chrysanthemum

by Ya Pu, Minling Liao, Junzhuo Li, Yuankai Tian, Zhongman Wang, Xiang Song and Silan Dai

Genes 2023, 14(3), 766; https://doi.org/10.3390/genes14030766 - 21 Mar 2023

Cited by 2 | Viewed by 1497

Abstract

The formation mechanism of different ray floret shapes of chrysanthemum (Chrysanthemum × morifolium) remains elusive due to its complex genetic background. C. vestitum, with the basic ray floret shapes of the flat, spoon, and tubular types, is considered a model [...] Read more.

The formation mechanism of different ray floret shapes of chrysanthemum (Chrysanthemum × morifolium) remains elusive due to its complex genetic background. C. vestitum, with the basic ray floret shapes of the flat, spoon, and tubular types, is considered a model material for studying ray floret morphogenesis. In this study, the flat and tubular type lines of C. vestitum at specific stages were used to investigate the key genes that regulate morphological differences in ray florets. We found that the expression levels of genes related to auxin synthesis, transport, and response were generally higher in the tubular type than in the flat type. CvARF3 was highly expressed in the flat type, while CvARF5 and CvARF6 were highly expressed in the tubular type. Additionally, the transcription levels of Class B and E genes closely related to petal development, including CvPI, CvAP3, Cvdefh21, CvSEP3, and CvCDM77, were expressed at higher levels in the tubular type than the flat type. Based on the results, it is proposed that auxin plays a key role in the development of ray florets, and auxin-related genes, especially CvARFs, may be key genes to control the morphological difference of ray florets. Simultaneously, MADS-box genes are involved in the co-regulation of ray floret morphogenesis. The results provide novel insights into the molecular mechanism of different petal type formation and lay a theoretical foundation for the directional breeding of petal type in chrysanthemums. Full article

(This article belongs to the Special Issue Genetic Studies of Ornamental Horticulture and Floriculture)

► Show Figures

Figure 1

13 pages, 6041 KiB

Open AccessCommunication

Genetic Characterization and Insular Habitat Enveloping of Endangered Leaf-Nosed Bat, Hipposideros nicobarulae (Mammalia: Chiroptera) in India: Phylogenetic Inference and Conservation Implication

by Shantanu Kundu, Manokaran Kamalakannan, Tanoy Mukherjee, Dhriti Banerjee and Hyun-Woo Kim

Genes 2023, 14(3), 765; https://doi.org/10.3390/genes14030765 - 21 Mar 2023

Viewed by 1631

Abstract

The Nicobar leaf-nosed Bat (Hipposideros nicobarulae) was described in the early 20th century; however, its systematic classification has been debated for over 100 years. This endangered and endemic species has achieved species status through morphological data in the last 10 years. [...] Read more.

The Nicobar leaf-nosed Bat (Hipposideros nicobarulae) was described in the early 20th century; however, its systematic classification has been debated for over 100 years. This endangered and endemic species has achieved species status through morphological data in the last 10 years. However, the genetic information and phylogenetic relationships of H. nicobarulae remain neglected. The generated mitochondrial cytochrome b gene (mtCytb) sequences (438 bp) of H. nicobarulae contains 53.42–53.65% AT composition and 1.82% variable sites. The studied species, H. nicobarulae maintains an 8.1% to 22.6% genetic distance from other Hipposideros species. The genetic divergence estimated in this study is congruent with the concept of gene speciation in bats. The Bayesian and Maximum-Likelihood phylogenies clearly discriminated all Hipposideros species and showed a sister relationship between H. nicobarulae and H. cf. antricola. Current mtCytb-based investigations of H. nicobarulae have confirmed the species status at the molecular level. Further, the MaxEnt-based species distribution modelling illustrates the most suitable habitat of H. nicobarulae (294 km²), of which the majority (171 km²) is located on Great Nicobar Island. The present study suggests rigorous sampling across the range, taxonomic coverage, the generation of multiple molecular markers (mitochondrial and nuclear), as well as more ecological information, which will help in understanding population genetic structure, habitat suitability, and the implementation of appropriate conservation action plans for H. nicobarulae and other Hipposideros species. Full article

(This article belongs to the Special Issue Evolution, Molecular Ecology, Phylogeography, and Phylogenetics of Mammals)

► Show Figures

Figure 1

12 pages, 2847 KiB

Open AccessArticle

Next-Generation Sequencing (NGS) Analysis Illustrates the Phenotypic Variability of Collagen Type IV Nephropathies

by Miriam Zacchia, Giovanna Capolongo, Francesca Del Vecchio Blanco, Floriana Secondulfo, Neha Gupta, Giancarlo Blasio, Rosa Maria Pollastro, Angela Cervesato, Giulio Piluso, Giuseppe Gigliotti, Annalaura Torella, Vincenzo Nigro, Alessandra F. Perna, Giovambattista Capasso and Francesco Trepiccione

Genes 2023, 14(3), 764; https://doi.org/10.3390/genes14030764 - 21 Mar 2023

Viewed by 1492

Abstract

Mutations in COL4A3-A5 cause a spectrum of glomerular disorders, including thin basement membrane nephropathy (TBMN) and Alport syndrome (AS). The wide application of next-generation sequencing (NGS) in the last few years has revealed that mutations in these genes are not limited to these [...] Read more.

Mutations in COL4A3-A5 cause a spectrum of glomerular disorders, including thin basement membrane nephropathy (TBMN) and Alport syndrome (AS). The wide application of next-generation sequencing (NGS) in the last few years has revealed that mutations in these genes are not limited to these clinical entities. In this study, 176 individuals with a clinical diagnosis of inherited kidney disorders underwent an NGS-based analysis to address the underlying cause; those who changed or perfected the clinical diagnosis after molecular analysis were selected. In 5 out of 83 individuals reaching a molecular diagnosis, the genetic result was unexpected: three individuals showed mutations in collagen type IV genes. These patients showed the following clinical pictures: (1) familial focal segmental glomerulosclerosis; (2) end-stage renal disease (ESRD) diagnosed incidentally in a 49-year-old man, with diffuse cortical calcifications on renal imaging; and (3) dysmorphic and asymmetric kidneys with multiple cysts and signs of tubule–interstitial defects. Genetic analysis revealed rare heterozygote/compound heterozygote COL4A4-A5 variants. Our study highlights the key role of NGS in the diagnosis of inherited renal disorders and shows the phenotype variability in patients carrying mutations in collagen type IV genes. Full article

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

► Show Figures

Figure 1

16 pages, 3790 KiB

Open AccessArticle

Expression of INPP5D Isoforms in Human Brain: Impact of Alzheimer’s Disease Neuropathology and Genetics

by Diana J. Zajac, James Simpson, Eric Zhang, Ishita Parikh and Steven Estus

Genes 2023, 14(3), 763; https://doi.org/10.3390/genes14030763 - 21 Mar 2023

Cited by 7 | Viewed by 1957

Abstract

The single nucleotide polymorphisms rs35349669 and rs10933431 within Inositol Polyphosphate-5-Phosphatase D (INPP5D) are strongly associated with Alzheimer’s Disease risk. To better understand INPP5D expression in the brain, we investigated INPP5D isoform expression as a function of rs35349669 and rs10933431, as well [...] Read more.

The single nucleotide polymorphisms rs35349669 and rs10933431 within Inositol Polyphosphate-5-Phosphatase D (INPP5D) are strongly associated with Alzheimer’s Disease risk. To better understand INPP5D expression in the brain, we investigated INPP5D isoform expression as a function of rs35349669 and rs10933431, as well as Alzheimer’s disease neuropathology, by qPCR and isoform-specific primers. In addition, INPP5D allelic expression imbalance was evaluated relative to rs1141328 within exon 1. Expression of INPP5D isoforms associated with transcription start sites in exon 1 and intron 14 was increased in individuals with high Alzheimer’s disease neuropathology. In addition, a novel variant with 47bp lacking from exon 12 increased expression in Alzheimer’s Disease brains, accounting for 13% of total INPP5D expression, and was found to undergo nonsense-mediated decay. Although inter-individual variation obscured a possible polymorphism effect on INPP5D isoform expression as measured by qPCR, rs35349669 was associated with rs1141328 allelic expression imbalance, suggesting that rs35349669 is significantly associated with full-length INPP5D isoform expression. In summary, expression of INPP5D isoforms with start sites in exon 1 and intron 14 are increased in brains with high Alzheimer’s Disease neuropathology, a novel isoform lacking the phosphatase domain was significantly increased with the disease, and the polymorphism rs35349669 correlates with allele-specific full-length INPP5D expression. Full article

(This article belongs to the Special Issue Genetics: Insights into Alzheimer’s Disease)

► Show Figures

Figure 1

7 pages, 664 KiB

Open AccessOpinion

Genetic Risk Scores and Missing Heritability in Ovarian Cancer

by Yasaman Fatapour and James P. Brody

Genes 2023, 14(3), 762; https://doi.org/10.3390/genes14030762 - 21 Mar 2023

Cited by 1 | Viewed by 1581

Abstract

Ovarian cancers are curable by surgical resection when discovered early. Unfortunately, most ovarian cancers are diagnosed in the later stages. One strategy to identify early ovarian tumors is to screen women who have the highest risk. This opinion article summarizes the accuracy of [...] Read more.

Ovarian cancers are curable by surgical resection when discovered early. Unfortunately, most ovarian cancers are diagnosed in the later stages. One strategy to identify early ovarian tumors is to screen women who have the highest risk. This opinion article summarizes the accuracy of different methods used to assess the risk of developing ovarian cancer, including family history, BRCA genetic tests, and polygenic risk scores. The accuracy of these is compared to the maximum theoretical accuracy, revealing a substantial gap. We suggest that this gap, or missing heritability, could be caused by epistatic interactions between genes. An alternative approach to computing genetic risk scores, using chromosomal-scale length variation should incorporate epistatic interactions. Future research in this area should focus on this and other alternative methods of characterizing genomes. Full article

(This article belongs to the Special Issue Advances in Genetics and Genomics of Ovarian Cancer)

► Show Figures

Figure 1

13 pages, 1677 KiB

Open AccessArticle

Development of Improved DNA Collection and Extraction Methods for Handled Documents

by Ashley G. Morgan and Mechthild Prinz

Genes 2023, 14(3), 761; https://doi.org/10.3390/genes14030761 - 21 Mar 2023

Cited by 1 | Viewed by 1680

Abstract

Handwritten documents may contain probative DNA, but most crime laboratories do not process this evidence. DNA recovery should not impair other evidence processing such as latent prints or indented writing. In this study, single fingermarks on paper were sampled with flocked swabs, cutting, [...] Read more.

Handwritten documents may contain probative DNA, but most crime laboratories do not process this evidence. DNA recovery should not impair other evidence processing such as latent prints or indented writing. In this study, single fingermarks on paper were sampled with flocked swabs, cutting, and dry vacuuming. In addition, two extraction methods were compared for the sample type. DNA yields were low across all methods; however, this work confirms the ability to recover DNA from paper and the usefulness of the vacuum sampling method combined with the Chelex-Tween method. Stability of touch DNA deposits were compared over an 11-month period to better understand degradation that may occur over time. No significant difference in DNA recovery was observed, suggesting DNA deposits on paper are stable over an 11-month span. Full article

(This article belongs to the Special Issue Improved Methods in Forensic DNA Analysis)

► Show Figures

Figure 1

12 pages, 2610 KiB

Open AccessArticle

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 2 | Viewed by 1466

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)

► Show Figures

Figure 1

2 pages, 178 KiB

Open AccessCorrection

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

Viewed by 1037

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)

14 pages, 6370 KiB

Open AccessReview

A Population Genetic Perspective on Subsistence Systems in the Sahel/Savannah Belt of Africa and the Historical Role of Pastoralism

by Viktor Černý, Edita Priehodová and Cesar Fortes-Lima

Genes 2023, 14(3), 758; https://doi.org/10.3390/genes14030758 - 20 Mar 2023

Cited by 2 | Viewed by 2612

Abstract

This review focuses on the Sahel/Savannah belt, a large region of Africa where two alternative subsistence systems (pastoralism and agriculture), nowadays, interact. It is a long-standing question whether the pastoralists became isolated here from other populations after cattle began to spread into Africa [...] Read more.

This review focuses on the Sahel/Savannah belt, a large region of Africa where two alternative subsistence systems (pastoralism and agriculture), nowadays, interact. It is a long-standing question whether the pastoralists became isolated here from other populations after cattle began to spread into Africa (~8 thousand years ago, kya) or, rather, began to merge with other populations, such as agropastoralists, after the domestication of sorghum and pearl millet (~5 kya) and with the subsequent spread of agriculture. If we look at lactase persistence, a trait closely associated with pastoral lifestyle, we see that its variants in current pastoralists distinguish them from their farmer neighbours. Most other (mostly neutral) genetic polymorphisms do not, however, indicate such clear differentiation between these groups; they suggest a common origin and/or an extensive gene flow. Genetic affinity and ecological symbiosis between the two subsistence systems can help us better understand the population history of this African region. In this review, we show that genomic datasets of modern Sahel/Savannah belt populations properly collected in local populations can complement the still insufficient archaeological research of this region, especially when dealing with the prehistory of mobile populations with perishable material culture and therefore precarious archaeological visibility. Full article

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

► Show Figures

Figure 1

13 pages, 2013 KiB

Open AccessReview

Current Approaches to and the Application of Intracytoplasmic Sperm Injection (ICSI) for Avian Genome Editing

by Shusei Mizushima, Tomohiro Sasanami, Tamao Ono and Asato Kuroiwa

Genes 2023, 14(3), 757; https://doi.org/10.3390/genes14030757 - 20 Mar 2023

Cited by 1 | Viewed by 1928

Abstract

Poultry are one of the most valuable resources for human society. They are also recognized as a powerful experimental animal for basic research on embryogenesis. Demands for the supply of low-allergen eggs and bioreactors have increased with the development of programmable genome editing [...] Read more.

Poultry are one of the most valuable resources for human society. They are also recognized as a powerful experimental animal for basic research on embryogenesis. Demands for the supply of low-allergen eggs and bioreactors have increased with the development of programmable genome editing technology. The CRISPR/Cas9 system has recently been used to produce transgenic animals and various animals in the agricultural industry and has also been successfully adopted for the modification of chicken and quail genomes. In this review, we describe the successful establishment of genome-edited lines combined with germline chimera production systems mediated by primordial germ cells and by viral infection in poultry. The avian intracytoplasmic sperm injection (ICSI) system that we previously established and recent advances in ICSI for genome editing are also summarized. Full article

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

► Show Figures

Graphical abstract

22 pages, 732 KiB

Open AccessReview

Current Status and Prospects of the Single-Cell Sequencing Technologies for Revealing the Pathogenesis of Pregnancy-Associated Disorders

by Dmitry D. Naydenov, Elena S. Vashukova, Yury A. Barbitoff, Yulia A. Nasykhova and Andrey S. Glotov

Genes 2023, 14(3), 756; https://doi.org/10.3390/genes14030756 - 20 Mar 2023

Cited by 2 | Viewed by 2381

Abstract

Single-cell RNA sequencing (scRNA-seq) is a method that focuses on the analysis of gene expression profile in individual cells. This method has been successfully applied to answer the challenging questions of the pathogenesis of multifactorial diseases and open up new possibilities in the [...] Read more.

Single-cell RNA sequencing (scRNA-seq) is a method that focuses on the analysis of gene expression profile in individual cells. This method has been successfully applied to answer the challenging questions of the pathogenesis of multifactorial diseases and open up new possibilities in the prognosis and prevention of reproductive diseases. In this article, we have reviewed the application of scRNA-seq to the analysis of the various cell types and their gene expression changes in normal pregnancy and pregnancy complications. The main principle, advantages, and limitations of single-cell technologies and data analysis methods are described. We discuss the possibilities of using the scRNA-seq method for solving the fundamental and applied tasks related to various pregnancy-associated disorders. Finally, we provide an overview of the scRNA-seq findings for the common pregnancy-associated conditions, such as hyperglycemia in pregnancy, recurrent pregnancy loss, preterm labor, polycystic ovary syndrome, and pre-eclampsia. Full article

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

► Show Figures

Figure 1

18 pages, 2069 KiB

Open AccessArticle

Moderation of Structural DNA Properties by Coupled Dinucleotide Contents in Eukaryotes

by Aaron Sievers, Liane Sauer, Marc Bisch, Jan Sprengel, Michael Hausmann and Georg Hildenbrand

Genes 2023, 14(3), 755; https://doi.org/10.3390/genes14030755 - 20 Mar 2023

Cited by 1 | Viewed by 1220

Abstract

Dinucleotides are known as determinants for various structural and physiochemical properties of DNA and for binding affinities of proteins to DNA. These properties (e.g., stiffness) and bound proteins (e.g., transcription factors) are known to influence important biological functions, such as transcription regulation and [...] Read more.

Dinucleotides are known as determinants for various structural and physiochemical properties of DNA and for binding affinities of proteins to DNA. These properties (e.g., stiffness) and bound proteins (e.g., transcription factors) are known to influence important biological functions, such as transcription regulation and 3D chromatin organization. Accordingly, the question arises of how the considerable variations in dinucleotide contents of eukaryotic chromosomes could still provide consistent DNA properties resulting in similar functions and 3D conformations. In this work, we investigate the hypothesis that coupled dinucleotide contents influence DNA properties in opposite directions to moderate each other’s influences. Analyzing all 2478 chromosomes of 155 eukaryotic species, considering bias from coding sequences and enhancers, we found sets of correlated and anti-correlated dinucleotide contents. Using computational models, we estimated changes of DNA properties resulting from this coupling. We found that especially pure A/T dinucleotides (AA, TT, AT, TA), known to influence histone positioning and AC/GT contents, are relevant moderators and that, e.g., the Roll property, which is known to influence histone affinity of DNA, is preferably moderated. We conclude that dinucleotide contents might indirectly influence transcription and chromatin 3D conformation, via regulation of histone occupancy and/or other mechanisms. Full article

(This article belongs to the Section Bioinformatics)

► Show Figures

Figure 1

16 pages, 1602 KiB

Open AccessArticle

Differential Effects of ABCG5/G8 Gene Region Variants on Lipid Profile, Blood Pressure Status, and Gallstone Disease History in Taiwan

by Ming-Sheng Teng, Kuan-Hung Yeh, Lung-An Hsu, Hsin-Hua Chou, Leay-Kiaw Er, Semon Wu and Yu-Lin Ko

Genes 2023, 14(3), 754; https://doi.org/10.3390/genes14030754 - 20 Mar 2023

Cited by 1 | Viewed by 1940

Abstract

ABCG5 and ABCG8 are two key adenosine triphosphate-binding cassette (ABC) proteins that regulate whole-body sterol trafficking. This study aimed to elucidate the association between ABCG5/G8 gene region variants and lipid profile, cardiometabolic traits, and gallstone disease history in Taiwan. A total of 1494 [...] Read more.

ABCG5 and ABCG8 are two key adenosine triphosphate-binding cassette (ABC) proteins that regulate whole-body sterol trafficking. This study aimed to elucidate the association between ABCG5/G8 gene region variants and lipid profile, cardiometabolic traits, and gallstone disease history in Taiwan. A total of 1494 Taiwan Biobank participants with whole-genome sequencing data and 117,679 participants with Axiom Genome-Wide CHB Array data were enrolled for analysis. Using genotype–phenotype and stepwise linear regression analyses, we found independent associations of four Asian-specific ABCG5 variants, rs119480069, rs199984328, rs560839317, and rs748096191, with total, low-density lipoprotein (LDL), and non-high-density lipoprotein (HDL) cholesterol levels (all p ≤ 0.0002). Four other variants, which were in nearly complete linkage disequilibrium, exhibited genome-wide significant associations with gallstone disease history, and the ABCG8 rs11887534 variant showed a trend of superiority for gallstone disease history in a nested logistic regression model (p = 0.074). Through regional association analysis of various other cardiometabolic traits, two variants of the PLEKHH2, approximately 50 kb from the ABCG5/G8 region, exhibited significant associations with blood pressure status (p < 10⁻⁶). In conclusion, differential effects of ABCG5/G8 region variants were noted for lipid profile, blood pressure status, and gallstone disease history in Taiwan. These results indicate the crucial role of individualized assessment of ABCG5/G8 variants for different cardiometabolic phenotypes. Full article

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

► Show Figures

Graphical abstract

14 pages, 4340 KiB

Open AccessArticle

Comprehensive Analysis of Calcium Sensor Families, CBL and CIPK, in Aeluropus littoralis and Their Expression Profile in Response to Salinity

by Mozhdeh Arab, Hamid Najafi Zarrini, Ghorbanali Nematzadeh, Parviz Heidari, Seyyed Hamidreza Hashemipetroudi and Markus Kuhlmann

Genes 2023, 14(3), 753; https://doi.org/10.3390/genes14030753 - 20 Mar 2023

Cited by 8 | Viewed by 1312

Abstract

Plants have acquired sets of highly regulated and complex signaling pathways to respond to unfavorable environmental conditions during evolution. Calcium signaling, as a vital mechanism, enables plants to respond to external stimuli, including abiotic and biotic stresses, and coordinate the basic processes of [...] Read more.

Plants have acquired sets of highly regulated and complex signaling pathways to respond to unfavorable environmental conditions during evolution. Calcium signaling, as a vital mechanism, enables plants to respond to external stimuli, including abiotic and biotic stresses, and coordinate the basic processes of growth and development. In the present study, two calcium sensor families, CBL and CIPK, were investigated in a halophyte plant, Aeluropus littoralis, with a comprehensive analysis. Here, six AlCBL genes, and twenty AlCIPK genes were studied. The analysis of the gene structure and conserved motifs, as well as physicochemical properties, showed that these genes are highly conserved during evolution. The expression levels of AlCBL genes and AlCIPK genes were evaluated under salt stress in leaf and root tissue. Based on the real-time RT-PCR results, the AlCIPK gene family had a higher variation in mRNA abundance than the AlCBL gene family. AlCIPK genes were found to have a higher abundance in leaves than in roots. The results suggest that the correlation between AlCBL genes and AlCIPK is tissue-specific, and different correlations can be expected in leaves and roots. Based on these correlations, AlCIPK3.1–AlCBL4.1 and AlCIPK1.2–AlCBL4.4 can be co-expressed in the root tissue, while AlCBL10 has the potential to be co-expressed with AlCIPK5, AlCIPK26, and AlCIPK12.3 in the leaf tissue. Our findings reveal valuable information on the structure and function of calcium sensor families in A. littoralis, a halophyte plant, that can be used in future research on the biological function of CBLs and CIPKs on salt stress resistance. Full article

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

► Show Figures

Figure 1

22 pages, 6636 KiB

Open AccessArticle

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 1 | Viewed by 1459

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)

► Show Figures

Figure 1

12 pages, 9485 KiB

Open AccessArticle

Evaluating the Effects of Cryopreservation on the Viability and Gene Expression of Porcine-Ear-Skin Fibroblasts

by Jiacheng Cao, Yingyu Xie, Jing Wang, Yongjie Huang, Xiaohan Zhang, Tianfang Xiao and Shaoming Fang

Genes 2023, 14(3), 751; https://doi.org/10.3390/genes14030751 - 20 Mar 2023

Viewed by 1766

Abstract

Owing to the inherent heterogeneity and plasticity of fibroblasts, they are considered as the conventional biological resources for basic and clinical medical research. Thus, it is essential to generate knowledge about the establishment of fibroblast cultures and the effects of cryopreservation processes on [...] Read more.

Owing to the inherent heterogeneity and plasticity of fibroblasts, they are considered as the conventional biological resources for basic and clinical medical research. Thus, it is essential to generate knowledge about the establishment of fibroblast cultures and the effects of cryopreservation processes on their biological characteristics. Since the pig (Sus scrofa) possesses numerous genetic, physiological, and anatomical similarities with humans, porcine fibroblasts are naturally regarded as useful analogues of human fibroblasts. Nonetheless, less attention has been given to the alterations in viability and gene expression of cryopreserved porcine fibroblasts. In this study, we aimed to obtain fibroblasts from porcine ear skin and evaluate the effects of cryopreservation on the cell survival, proliferation, and gene expression profiles of the fibroblasts by trypan-blue-staining assay, Cell Counting kit-8 (CCK-8) assay, and RNA-sequencing analysis, respectively. Our results suggested that morphologically stable fibroblast cultures can be constructed from pig-ear skin. The post-thaw survival rate of the cryopreserved fibroblasts at 0 h and 24 h was over 90%. The proliferative activity of the cryopreserved fibroblasts was similar to that of the non-cryopreserved fibroblasts after 7 days of in vitro culture, which suggested that cryopreservation did not influence the viability. The RNA-sequencing analysis indicated that this should be attributed to the 867 differentially expressed genes (DGEs) identified, which are involved in molecular process related to cell recovery and survival after cryo-stimulation. In addition, eight important DEGs BMP2, GDF15, EREG, AREG, HBEGF, LIF, IL-6, and HOX-7 could potentially be applied to improve the efficiency of fibroblast cryopreservation, but comprehensive and systematic studies on understanding the underlying mechanisms responsible for their modulatory roles are urgently needed. Full article

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

► Show Figures

Figure 1

18 pages, 2255 KiB

Open AccessArticle

Network-Based and Machine-Learning Approaches Identify Diagnostic and Prognostic Models for EMT-Type Gastric Tumors

by Mehdi Sadeghi, Mohammad Reza Karimi, Amir Hossein Karimi, Nafiseh Ghorbanpour Farshbaf, Abolfazl Barzegar and Ulf Schmitz

Genes 2023, 14(3), 750; https://doi.org/10.3390/genes14030750 - 19 Mar 2023

Viewed by 1674

Abstract

The microsatellite stable/epithelial-mesenchymal transition (MSS/EMT) subtype of gastric cancer represents a highly aggressive class of tumors associated with low rates of survival and considerably high probabilities of recurrence. In the era of precision medicine, the accurate and prompt diagnosis of tumors of this [...] Read more.

The microsatellite stable/epithelial-mesenchymal transition (MSS/EMT) subtype of gastric cancer represents a highly aggressive class of tumors associated with low rates of survival and considerably high probabilities of recurrence. In the era of precision medicine, the accurate and prompt diagnosis of tumors of this subtype is of vital importance. In this study, we used Weighted Gene Co-expression Network Analysis (WGCNA) to identify a differentially expressed co-expression module of mRNAs in EMT-type gastric tumors. Using network analysis and linear discriminant analysis, we identified mRNA motifs and microRNA-based models with strong prognostic and diagnostic relevance: three models comprised of (i) the microRNAs miR-199a-5p and miR-141-3p, (ii) EVC/EVC2/GLI3, and (iii) PDE2A/GUCY1A1/GUCY1B1 gene expression profiles distinguish EMT-type tumors from other gastric tumors with high accuracy (Area Under the Receiver Operating Characteristic Curve (AUC) = 0.995, AUC = 0.9742, and AUC = 0.9717; respectively). Additionally, the DMD/ITGA1/CAV1 motif was identified as the top motif with consistent relevance to prognosis (hazard ratio > 3). Molecular functions of the members of the identified models highlight the central roles of MAPK, Hh, and cGMP/cAMP signaling in the pathology of the EMT subtype of gastric cancer and underscore their potential utility in precision therapeutic approaches. Full article

(This article belongs to the Special Issue Transcriptomics and Bioinformatics in Precision Medicine)

► Show Figures

Figure 1

13 pages, 3051 KiB

Open AccessArticle

Proteome and Ubiquitylome Analyses of Maize Endoplasmic Reticulum under Heat Stress

by Chunyan Gao, Xiaohui Peng, Luoying Zhang, Qi Zhao, Liguo Ma, Qi Yu, Xuechun Lian, Lei Gao, Langyu Xiong and Shengben Li

Genes 2023, 14(3), 749; https://doi.org/10.3390/genes14030749 - 19 Mar 2023

Cited by 2 | Viewed by 1592

Abstract

High temperatures severely affect plant growth and pose a threat to global crop production. Heat causes the accumulation of misfolded proteins in the endoplasmic reticulum(ER), as well as triggering the heat-shock response (HSR) in the cytosol and the unfolded protein response (UPR) in [...] Read more.

High temperatures severely affect plant growth and pose a threat to global crop production. Heat causes the accumulation of misfolded proteins in the endoplasmic reticulum(ER), as well as triggering the heat-shock response (HSR) in the cytosol and the unfolded protein response (UPR) in the ER. Excessive misfolded proteins undergo further degradation through ER-associated degradation (ERAD). Although much research on the plant heat stress response has been conducted, the regulation of ER-localized proteins has not been well-studied thus far. We isolated the microsome fraction from heat-treated and untreated maize seedlings and performed proteome and ubiquitylome analyses. Of the 8306 total proteins detected in the proteomics analysis, 1675 proteins were significantly up-regulated and 708 proteins were significantly down-regulated. Global ubiquitination analysis revealed 1780 proteins with at least one ubiquitination site. Motif analysis revealed that alanine and glycine are the preferred amino acids upstream and downstream of ubiquitinated lysine sites. ERAD components were found to be hyper-ubiquitinated after heat treatment, implying the feedback regulation of ERAD activity through protein degradation. Full article

(This article belongs to the Special Issue Maize Molecular Genetics and Functional Genomics)

► Show Figures

Figure 1

11 pages, 1254 KiB

Open AccessReview

Homozygous TNNI3 Mutations and Severe Early Onset Dilated Cardiomyopathy: Patient Report and Review of the Literature

by Ugo Sorrentino, Ilaria Gabbiato, Chiara Canciani, Davide Calosci, Chiara Rigon, Daniela Zuccarello and Matteo Cassina

Genes 2023, 14(3), 748; https://doi.org/10.3390/genes14030748 - 19 Mar 2023

Cited by 2 | Viewed by 1766

Abstract

The TNNI3 gene encodes for the cardiac isoform of troponin I, a pivotal component of the sarcomeric structure of the myocardium. While heterozygous TNNI3 missense mutations have long been associated with autosomal dominant hypertrophic and restrictive cardiomyopathies, the role of TNNI3 null mutations [...] Read more.

The TNNI3 gene encodes for the cardiac isoform of troponin I, a pivotal component of the sarcomeric structure of the myocardium. While heterozygous TNNI3 missense mutations have long been associated with autosomal dominant hypertrophic and restrictive cardiomyopathies, the role of TNNI3 null mutations has been more debated due to the paucity and weak characterization of reported cases and the low penetrance of heterozygous genotypes. In recent years, however, an increasing amount of evidence has validated the hypothesis that biallelic TNNI3 null mutations cause a severe form of neonatal dilated cardiomyopathy. Here, we expand the case series reporting two unrelated patients afflicted with early onset dilated cardiomyopathy, due to homozygosity for the p.Arg98* TNNI3 variant, which had thus far been documented only in heterozygous patients and apparently healthy carriers, and the recurrent p.Arg69Alafs*8 variant, respectively. A review of previously reported biallelic TNNI3 loss-of-function variants and their associated cardiac phenotypes was also performed. Full article

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

► Show Figures

Figure 1

11 pages, 704 KiB

Open AccessArticle

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

Viewed by 1767

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)

► Show Figures

Figure 1

25 pages, 9121 KiB

Open AccessArticle

Terrain Ruggedness and Canopy Height Predict Short-Range Dispersal in the Critically Endangered Black-and-White Ruffed Lemur

by Amanda N. Mancini, Aparna Chandrashekar, Jean Pierre Lahitsara, Daisy Gold Ogbeta, Jeanne Arline Rajaonarivelo, Ndimbintsoa Rojoarinjaka Ranaivorazo, Joseane Rasoazanakolona, Mayar Safwat, Justin Solo, Jean Guy Razafindraibe, Georges Razafindrakoto and Andrea L. Baden

Genes 2023, 14(3), 746; https://doi.org/10.3390/genes14030746 - 18 Mar 2023

Viewed by 2525

Abstract

Dispersal is a fundamental aspect of primates’ lives and influences both population and community structuring, as well as species evolution. Primates disperse within an environmental context, where both local and intervening environmental factors affect all phases of dispersal. To date, research has primarily [...] Read more.

Dispersal is a fundamental aspect of primates’ lives and influences both population and community structuring, as well as species evolution. Primates disperse within an environmental context, where both local and intervening environmental factors affect all phases of dispersal. To date, research has primarily focused on how the intervening landscape influences primate dispersal, with few assessing the effects of local habitat characteristics. Here, we use a landscape genetics approach to examine between- and within-site environmental drivers of short-range black-and-white ruffed lemur (Varecia variegata) dispersal in the Ranomafana region of southeastern Madagascar. We identified the most influential drivers of short-range ruffed lemur dispersal as being between-site terrain ruggedness and canopy height, more so than any within-site habitat characteristic evaluated. Our results suggest that ruffed lemurs disperse through the least rugged terrain that enables them to remain within their preferred tall-canopied forest habitat. Furthermore, we noted a scale-dependent environmental effect when comparing our results to earlier landscape characteristics identified as driving long-range ruffed lemur dispersal. We found that forest structure drives short-range dispersal events, whereas forest presence facilitates long-range dispersal and multigenerational gene flow. Together, our findings highlight the importance of retaining high-quality forests and forest continuity to facilitate dispersal and maintain functional connectivity in ruffed lemurs. Full article

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

► Show Figures

Graphical abstract

16 pages, 2174 KiB

Open AccessArticle

Integration of Stemness Gene Signatures Reveals Core Functional Modules of Stem Cells and Potential Novel Stemness Genes

by Tânia Barata, Isabel Duarte and Matthias E. Futschik

Genes 2023, 14(3), 745; https://doi.org/10.3390/genes14030745 - 18 Mar 2023

Cited by 3 | Viewed by 1693

Abstract

Stem cells encompass a variety of different cell types which converge on the dual capacity to self-renew and differentiate into one or more lineages. These characteristic features are key for the involvement of stem cells in crucial biological processes such as development and [...] Read more.

Stem cells encompass a variety of different cell types which converge on the dual capacity to self-renew and differentiate into one or more lineages. These characteristic features are key for the involvement of stem cells in crucial biological processes such as development and ageing. To decipher their underlying genetic substrate, it is important to identify so-called stemness genes that are common to different stem cell types and are consistently identified across different studies. In this meta-analysis, 21 individual stemness signatures for humans and another 21 for mice, obtained from a variety of stem cell types and experimental techniques, were compared. Although we observed biological and experimental variability, a highly significant overlap between gene signatures was identified. This enabled us to define integrated stemness signatures (ISSs) comprised of genes frequently occurring among individual stemness signatures. Such integrated signatures help to exclude false positives that can compromise individual studies and can provide a more robust basis for investigation. To gain further insights into the relevance of ISSs, their genes were functionally annotated and connected within a molecular interaction network. Most importantly, the present analysis points to the potential roles of several less well-studied genes in stemness and thus provides promising candidates for further experimental validation. Full article

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

► Show Figures

Figure 1

16 pages, 5298 KiB

Open AccessArticle

A Missense Mutation c.1132G > A in Fumarate Hydratase (FH) Leads to Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) Syndrome and Insights into Clinical Management in Uterine Leiomyomata

by Yue Shi, Yan Xu, Chao Wang, Yiqing Chen, Xiaojun Ren, Yu Kang and Chao Wang

Genes 2023, 14(3), 744; https://doi.org/10.3390/genes14030744 - 18 Mar 2023

Cited by 1 | Viewed by 1927

Abstract

Background: HLRCC syndrome is a hereditary cancer predisposition syndrome caused by heterozygous germline pathogenic variant of the fumarate hydratase (FH) gene and characterized by cutaneous leiomyomas (CL), uterine leiomyomas (UL), and renal cell carcinoma (RCC). Loss of function variant of FH gene inactivates [...] Read more.

Background: HLRCC syndrome is a hereditary cancer predisposition syndrome caused by heterozygous germline pathogenic variant of the fumarate hydratase (FH) gene and characterized by cutaneous leiomyomas (CL), uterine leiomyomas (UL), and renal cell carcinoma (RCC). Loss of function variant of FH gene inactivates the Kreb’s cycle enzyme activity and predisposes individuals with such variant to the development of HLRCC. Methods: Next-generation sequencing (NGS) and Sanger confirmation were given to family members accessible. Following that, a functional study in vitro was performed to further confirm the pathogenicity of the variant. FH-Wild type (FH-WT) and FH-mutant (FH-MUT) (E378K) plasmid were constructed and transfected into 293T and uterine leiomyoma cell lines, respectively. Proliferation assessment was executed to show how this mutation affects the growth of uterine leiomyoma. qPCR and Western blotting were performed to investigate the change of transcription and translation of FH with mutation (E378K), and FH enzyme assay activity were tested in 293T cells with mutation and wild-type plasmids. Results: Here, we presented two families with the same missense variant (c.1132G > A) that has not been reported as a germline mutation in hereditary uterine leiomyomas before and classified as VUS in gene databases. Our in vitro experiments supported the pathogenicity of this missense variant, especially in uterine leiomyomata. Conclusions: According to the American College of Medical Genetics (ACMG) guideline, the E378K variant was classified as likely pathogenic (with evidence PS4_support, PS3_support, PM2_support, PP1, PP3 and PP4 evidence). Further insights into clinical management in uterine leiomyomata were discussed and should be practiced in gynecological clinical settings. Full article

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

► Show Figures

Figure 1

Journal Menu

Journal Browser

Genes, Volume 14, Issue 3 (March 2023) – 240 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI