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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 22818

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Prof. Dr. Mikhail I. Churnosov

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Department of Medical Biological Disciplines, Belgorod State University, 85 Pobedy Street, 308015 Belgorod, Russia
Interests: genes; human diseases; associations; biomarkers; bioinformatic analysis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The study of the causes and mechanisms of human disease development, despite the numerous works carried out in this field, continues to be the focus of attention of various scientific research teams. The essential role of genetic factors in the formation of the vast majority of human diseases is beyond doubt. At the same time, despite the substantial accumulated factual material on this theme, there is no complete and definitive understanding of the pathogenetics of most human diseases at the moment. Often, the data obtained are not confirmed in subsequent studies, and in some cases, they are contradictory. It is necessary to continue further genetic-epidemiological studies in order to establish genetic factors that determine the susceptibility to various human diseases in different ethnic and territorial groups. Obtaining new data on the contribution of genetic factors to the formation of human diseases and the role of gene–gene and gene–environment interactions affecting the risk of developing diseases will significantly advance our understanding of the pathogenetics of diseases. Ultimately, this will create prerequisites for the use of candidate genes as effective biomarkers in practical medicine.

This Special Issue will compile new data on the role of genetic factors in the formation of different human diseases to better understand the genetic and molecular mechanisms of human disorder development.

Dr. Mikhail I. Churnosov
Guest Editor

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Published Papers (14 papers)

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Editorial

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7 pages, 191 KiB

Open AccessEditorial

Special Issue: “Genes and Human Diseases”

by Mikhail Churnosov

Int. J. Mol. Sci. 2024, 25(8), 4455; https://doi.org/10.3390/ijms25084455 - 18 Apr 2024

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Abstract

Studying mechanisms of development and the causes of various human diseases continues to be the focus of attention of various researchers [...] Full article

(This article belongs to the Special Issue Genes and Human Diseases)

Research

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15 pages, 2679 KiB

Open AccessArticle

Trisomies Reorganize Human 3D Genome

by Irina V. Zhegalova, Petr A. Vasiluev, Ilya M. Flyamer, Anastasia S. Shtompel, Eugene Glazyrina, Nadezda Shilova, Marina Minzhenkova, Zhanna Markova, Natalia V. Petrova, Erdem B. Dashinimaev, Sergey V. Razin and Sergey V. Ulianov

Int. J. Mol. Sci. 2023, 24(22), 16044; https://doi.org/10.3390/ijms242216044 - 07 Nov 2023

Viewed by 1647

Abstract

Trisomy is the presence of one extra copy of an entire chromosome or its part in a cell nucleus. In humans, autosomal trisomies are associated with severe developmental abnormalities leading to embryonic lethality, miscarriage or pronounced deviations of various organs and systems at birth. Trisomies are characterized by alterations in gene expression level, not exclusively on the trisomic chromosome, but throughout the genome. Here, we applied the high-throughput chromosome conformation capture technique (Hi-C) to study chromatin 3D structure in human chorion cells carrying either additional chromosome 13 (Patau syndrome) or chromosome 16 and in cultured fibroblasts with extra chromosome 18 (Edwards syndrome). The presence of extra chromosomes results in systematic changes of contact frequencies between small and large chromosomes. Analyzing the behavior of individual chromosomes, we found that a limited number of chromosomes change their contact patterns stochastically in trisomic cells and that it could be associated with lamina-associated domains (LAD) and gene content. For trisomy 13 and 18, but not for trisomy 16, the proportion of compacted loci on a chromosome is correlated with LAD content. We also found that regions of the genome that become more compact in trisomic cells are enriched in housekeeping genes, indicating a possible decrease in chromatin accessibility and transcription level of these genes. These results provide a framework for understanding the mechanisms of pan-genome transcription dysregulation in trisomies in the context of chromatin spatial organization. Full article

(This article belongs to the Special Issue Genes and Human Diseases)

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11 pages, 4419 KiB

Open AccessArticle

Genomic Evolution and Transcriptional Changes in the Evolution of Prostate Cancer into Neuroendocrine and Ductal Carcinoma Types

by Srinivasa R. Rao, Andrew Protheroe, Lucia Cerundolo, David Maldonado-Perez, Lisa Browning, Alastair D. Lamb, Richard J. Bryant, Ian G. Mills, Dan J. Woodcock, Freddie C. Hamdy, Ian P. M. Tomlinson and Clare Verrill

Int. J. Mol. Sci. 2023, 24(16), 12722; https://doi.org/10.3390/ijms241612722 - 12 Aug 2023

Cited by 1 | Viewed by 1066

Abstract

Prostate cancer is typically of acinar adenocarcinoma type but can occasionally present as neuroendocrine and/or ductal type carcinoma. These are associated with clinically aggressive disease, and the former often arises on a background of androgen deprivation therapy, although it can also arise de novo. Two prostate cancer cases were sequenced by exome capture from archival tissue. Case 1 was de novo small cell neuroendocrine carcinoma and ductal adenocarcinoma with three longitudinal samples over 5 years. Case 2 was a single time point after the development of treatment-related neuroendocrine prostate carcinoma. Case 1 showed whole genome doubling in all samples and focal amplification of AR in all samples except the first time point. Phylogenetic analysis revealed a common ancestry for ductal and small cell carcinoma. Case 2 showed 13q loss (involving RB1) in both adenocarcinoma and small cell carcinoma regions, and 3p gain, 4p loss, and 17p loss (involving TP53) in the latter. By using highly curated samples, we demonstrate for the first time that small-cell neuroendocrine and ductal prostatic carcinoma can have a common ancestry. We highlight whole genome doubling in a patient with prostate cancer relapse, reinforcing its poor prognostic nature. Full article

(This article belongs to the Special Issue Genes and Human Diseases)

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14 pages, 672 KiB

Open AccessArticle

Whole-Exome and Transcriptome Sequencing Expands the Genotype of Majewski Osteodysplastic Primordial Dwarfism Type II

by Flaviana Marzano, Matteo Chiara, Arianna Consiglio, Gabriele D’Amato, Mattia Gentile, Valentina Mirabelli, Maria Piane, Camilla Savio, Marco Fabiani, Domenica D’Elia, Elisabetta Sbisà, Gioacchino Scarano, Fortunato Lonardo, Apollonia Tullo, Graziano Pesole and Maria Felicia Faienza

Int. J. Mol. Sci. 2023, 24(15), 12291; https://doi.org/10.3390/ijms241512291 - 31 Jul 2023

Cited by 1 | Viewed by 876

Abstract

Microcephalic Osteodysplastic Primordial Dwarfism type II (MOPDII) represents the most common form of primordial dwarfism. MOPD clinical features include severe prenatal and postnatal growth retardation, postnatal severe microcephaly, hypotonia, and an increased risk for cerebrovascular disease and insulin resistance. Autosomal recessive biallelic loss-of-function genomic variants in the centrosomal pericentrin (PCNT) gene on chromosome 21q22 cause MOPDII. Over the past decade, exome sequencing (ES) and massive RNA sequencing have been effectively employed for both the discovery of novel disease genes and to expand the genotypes of well-known diseases. In this paper we report the results both the RNA sequencing and ES of three patients affected by MOPDII with the aim of exploring whether differentially expressed genes and previously uncharacterized gene variants, in addition to PCNT pathogenic variants, could be associated with the complex phenotype of this disease. We discovered a downregulation of key factors involved in growth, such as IGF1R, IGF2R, and RAF1, in all three investigated patients. Moreover, ES identified a shortlist of genes associated with deleterious, rare variants in MOPDII patients. Our results suggest that Next Generation Sequencing (NGS) technologies can be successfully applied for the molecular characterization of the complex genotypic background of MOPDII. Full article

(This article belongs to the Special Issue Genes and Human Diseases)

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30 pages, 7555 KiB

Open AccessArticle

Differentially Expressed Genes Regulating Glutathione Metabolism, Protein-Folding, and Unfolded Protein Response in Pancreatic β-Cells in Type 2 Diabetes Mellitus

by Elena Klyosova, Iuliia Azarova, Stepan Buikin and Alexey Polonikov

Int. J. Mol. Sci. 2023, 24(15), 12059; https://doi.org/10.3390/ijms241512059 - 27 Jul 2023

Cited by 2 | Viewed by 1403

Abstract

Impaired redox homeostasis in the endoplasmic reticulum (ER) may contribute to proinsulin misfolding and thus to activate the unfolded protein response (UPR) and apoptotic pathways, culminating in pancreatic β-cell loss and type 2 diabetes (T2D). The present study was designed to identify differentially expressed genes (DEGs) encoding enzymes for glutathione metabolism and their impact on the expression levels of genes regulating protein folding and UPR in β-cells of T2D patients. The GEO transcriptome datasets of β-cells of diabetics and non-diabetics, GSE20966 and GSE81608, were analyzed for 142 genes of interest using limma and GREIN software, respectively. Diabetic β-cells showed dataset-specific patterns of DEGs (FDR ≤ 0.05) implicated in the regulation of glutathione metabolism (ANPEP, PGD, IDH2, and CTH), protein-folding (HSP90AB1, HSP90AA1, HSPA1B, HSPA8, BAG3, NDC1, NUP160, RLN1, and RPS19BP1), and unfolded protein response (CREB3L4, ERP27, and BID). The GCLC gene, encoding the catalytic subunit of glutamate–cysteine ligase, the first rate-limiting enzyme of glutathione biosynthesis, was moderately down-regulated in diabetic β-cells from both datasets (p ≤ 0.05). Regression analysis established that genes involved in the de novo synthesis of glutathione, GCLC, GCLM, and GSS affect the expression levels of genes encoding molecular chaperones and those involved in the UPR pathway. This study showed for the first time that diabetic β-cells exhibit alterations in the expression of genes regulating glutathione metabolism, protein-folding, and UPR and provided evidence for the molecular crosstalk between impaired redox homeostasis and abnormal protein folding, underlying ER stress in type 2 diabetes. Full article

(This article belongs to the Special Issue Genes and Human Diseases)

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14 pages, 983 KiB

Open AccessArticle

Apoptosis Genes as a Key to Identification of Inverse Comorbidity of Huntington’s Disease and Cancer

by Elena Yu. Bragina, Densema E. Gomboeva, Olga V. Saik, Vladimir A. Ivanisenko, Maxim B. Freidin, Maria S. Nazarenko and Valery P. Puzyrev

Int. J. Mol. Sci. 2023, 24(11), 9385; https://doi.org/10.3390/ijms24119385 - 27 May 2023

Cited by 1 | Viewed by 2132

Abstract

Cancer and neurodegenerative disorders present overwhelming challenges for healthcare worldwide. Epidemiological studies showed a decrease in cancer rates in patients with neurodegenerative disorders, including the Huntington disease (HD). Apoptosis is one of the most important processes for both cancer and neurodegeneration. We suggest that genes closely connected with apoptosis and associated with HD may affect carcinogenesis. We applied reconstruction and analysis of gene networks associated with HD and apoptosis and identified potentially important genes for inverse comorbidity of cancer and HD. The top 10 high-priority candidate genes included APOE, PSEN1, INS, IL6, SQSTM1, SP1, HTT, LEP, HSPA4, and BDNF. Functional analysis of these genes was carried out using gene ontology and KEGG pathways. By exploring genome-wide association study results, we identified genes associated with neurodegenerative and oncological disorders, as well as their endophenotypes and risk factors. We used publicly available datasets of HD and breast and prostate cancers to analyze the expression of the identified genes. Functional modules of these genes were characterized according to disease-specific tissues. This integrative approach revealed that these genes predominantly exert similar functions in different tissues. Apoptosis along with lipid metabolism dysregulation and cell homeostasis maintenance in the response to environmental stimulus and drugs are likely key processes in inverse comorbidity of cancer in patients with HD. Overall, the identified genes represent the promising targets for studying molecular relations of cancer and HD. Full article

(This article belongs to the Special Issue Genes and Human Diseases)

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13 pages, 1686 KiB

Open AccessArticle

Simultaneous Copy Number Alteration and Single-Nucleotide Variation Analysis in Matched Aqueous Humor and Tumor Samples in Children with Retinoblastoma

by Michael J. Schmidt, Rishvanth K. Prabakar, Sarah Pike, Venkata Yellapantula, Chen-Ching Peng, Peter Kuhn, James Hicks, Liya Xu and Jesse L. Berry

Int. J. Mol. Sci. 2023, 24(10), 8606; https://doi.org/10.3390/ijms24108606 - 11 May 2023

Cited by 5 | Viewed by 1789

Abstract

Retinoblastoma (RB) is a childhood cancer that forms in the developing retina of young children; this tumor cannot be biopsied due to the risk of provoking extraocular tumor spread, which dramatically alters the treatment and survival of the patient. Recently, aqueous humor (AH), the clear fluid in the anterior chamber of the eye, has been developed as an organ-specific liquid biopsy for investigation of in vivo tumor-derived information found in the cell-free DNA (cfDNA) of the biofluid. However, identifying somatic genomic alterations, including both somatic copy number alterations (SCNAs) and single nucleotide variations (SNVs) of the RB1 gene, typically requires either: (1) two distinct experimental protocols—low-pass whole genome sequencing for SCNAs and targeted sequencing for SNVs—or (2) expensive deep whole genome or exome sequencing. To save time and cost, we applied a one-step targeted sequencing method to identify both SCNAs and RB1 SNVs in children with RB. High concordance (median = 96.2%) was observed in comparing SCNA calls derived from targeted sequencing to the traditional low-pass whole genome sequencing method. We further applied this method to investigate the degree of concordance of genomic alterations between paired tumor and AH samples from 11 RB eyes. We found 11/11 AH samples (100%) had SCNAs, and 10 of them (90.1%) with recurrent RB-SCNAs, while only nine out of 11 tumor samples (81.8%) had positive RB-SCNA signatures in both low-pass and targeted methods. Eight out of the nine (88.9%) detected SNVs were shared between AH and tumor samples. Ultimately, 11/11 cases have somatic alterations identified, including nine RB1 SNVs and 10 recurrent RB-SCNAs with four focal RB1 deletions and one MYCN gain. The results presented show the feasibility of utilizing one sequencing approach to obtain SCNA and targeted SNV data to capture a broad genomic scope of RB disease, which may ultimately expedite clinical intervention and be less expensive than other methods. Full article

(This article belongs to the Special Issue Genes and Human Diseases)

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13 pages, 1340 KiB

Open AccessArticle

Pathogenic Variants of SLC22A12 (URAT1) and SLC2A9 (GLUT9) in Spanish Patients with Renal Hypouricemia: Founder Effect of SLC2A9 Variant c.374C>T; p.(T125M)

by Ana Perdomo-Ramirez, Elizabeth Cordoba-Lanus, Carmen Jane Trujillo-Frias, Carolina Gonzalez-Navasa, Elena Ramos-Trujillo, Maria Isabel Luis-Yanes, Victor Garcia-Nieto and Felix Claverie-Martin

Int. J. Mol. Sci. 2023, 24(9), 8455; https://doi.org/10.3390/ijms24098455 - 08 May 2023

Cited by 1 | Viewed by 1684

Abstract

Renal hypouricemia (RHUC) is a rare inherited disorder characterized by impaired urate reabsorption in the proximal tubule resulting in low urate serum levels and increased urate excretion. Some patients may present severe complications such as exercise-induced acute renal failure and nephrolithiasis. RHUC is caused by inactivating mutations in the SLC22A12 (RHUC type 1) or SLC2A9 (RHUC type 2) genes, which encode urate transporters URAT1 and GLUT9, respectively. In this study, our goal was to identify mutations associated with twenty-one new cases with RHUC through direct sequencing of SLC22A12 and SLC2A9 coding exons. Additionally, we carried out an SNPs-haplotype analysis to determine whether the rare SLC2A9 variant c.374C>T; p.(T125M), which is recurrent in Spanish families with RHUC type 2, had a common-linked haplotype. Six intragenic informative SNPs were analyzed using PCR amplification from genomic DNA and direct sequencing. Our results showed that ten patients carried the SLC22A12 mutation c.1400C>T; p.(T467M), ten presented the SLC2A9 mutation c.374C>T, and one carried a new SLC2A9 heterozygous mutation, c.593G>A; p.(R198H). Patients carrying the SLC2A9 mutation c.374C>T share a common-linked haplotype, confirming that it emerged due to a founder effect. Full article

(This article belongs to the Special Issue Genes and Human Diseases)

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20 pages, 3584 KiB

Open AccessArticle

Risk Effects of rs1799945 Polymorphism of the HFE Gene and Intergenic Interactions of GWAS-Significant Loci for Arterial Hypertension in the Caucasian Population of Central Russia

by Tatiana Ivanova, Maria Churnosova, Maria Abramova, Irina Ponomarenko, Evgeny Reshetnikov, Inna Aristova, Inna Sorokina and Mikhail Churnosov

Int. J. Mol. Sci. 2023, 24(9), 8309; https://doi.org/10.3390/ijms24098309 - 05 May 2023

Cited by 6 | Viewed by 1648

Abstract

The aim of this case-control replicative study was to investigate the link between GWAS-impact for arterial hypertension (AH) and/or blood pressure (BP) gene polymorphisms and AH risk in Russian subjects (Caucasian population of Central Russia). AH (n = 939) and control (n = 466) cohorts were examined for ten GWAS AH/BP risk loci. The genotypes/alleles of these SNP and their combinations (SNP–SNP interactions) were tested for their association with the AH development using a logistic regression statistical procedure. The genotype GG of the SNP rs1799945 (C/G) HFE was strongly linked with an increased AH risk (ORrecGG = 2.53; 95%CIrecGG1.03–6.23; ppermGG = 0.045). The seven SNPs such as rs1173771 (G/A) AC026703.1, rs1799945 (C/G) HFE, rs805303 (G/A) BAG6, rs932764 (A/G) PLCE1, rs4387287 (C/A) OBFC1, rs7302981 (G/A) CERS5, rs167479 (T/G) RGL3, out of ten regarded loci, were related with AH within eight SNP–SNP interaction models (<0.001 ≤ pperm-interaction ≤ 0.047). Three polymorphisms such as rs8068318 (T/C) TBX2, rs633185 (C/G) ARHGAP42, and rs2681472 (A/G) ATP2B1 were not linked with AH. The pairwise rs805303 (G/A) BAG6–rs7302981 (G/A) CERS5 combination was a priority in determining the susceptibility to AH (included in six out of eight SNP–SNP interaction models [75%] and described 0.82% AH entropy). AH-associated variants are conjecturally functional for 101 genes involved in processes related to the immune system (major histocompatibility complex protein, processing/presentation of antigens, immune system process regulation, etc.). In conclusion, the rs1799945 polymorphism of the HFE gene and intergenic interactions of BAG6, CERS5, AC026703.1, HFE, PLCE1, OBFC1, RGL3 have been linked with AH risky in the Caucasian population of Central Russia. Full article

(This article belongs to the Special Issue Genes and Human Diseases)

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17 pages, 5760 KiB

Open AccessArticle

MicroRNA Expression Signatures in Clear Cell Renal Cell Carcinoma: High-Throughput Searching for Key miRNA Markers in Patients from the Volga-Ural Region of Eurasian Continent

by Irina Gilyazova, Elizaveta Ivanova, Adel Izmailov, Ildar Sharifgaliev, Alexandra Karunas, Elena Pudova, Anastasiya Kobelyatskaya, Gulshat Gilyazova, Angelina Izmailova, Valentin Pavlov and Elza Khusnutdinova

Int. J. Mol. Sci. 2023, 24(8), 6909; https://doi.org/10.3390/ijms24086909 - 07 Apr 2023

Cited by 2 | Viewed by 1606

Abstract

Clear cell renal cell carcinoma (ccRCC) is characterized by high molecular genetic heterogeneity, metastatic activity and unfavorable prognosis. MicroRNAs (miRNA) are 22-nucleotide noncoding RNAs that are aberrantly expressed in cancer cells and have gained serious consideration as non-invasive cancer biomarkers. We investigated possible differential miRNA signatures that may differentiate high-grade ccRCC from primary disease stages. High-throughput miRNAs expression profiling, using TaqMan OpenArray Human MicroRNA panel, was performed in a group of 21 ccRCC patients. The obtained data was validated in 47 ccRCC patients. We identified nine dysregulated miRNAs (miRNA-210, -642, -18a, -483-5p, -455-3p, -487b, -582-3p, -199b and -200c) in tumor ccRCC tissue compared to normal renal parenchyma. Our results show that the combination of miRNA-210, miRNA-483-5p, miRNA-455 and miRNA-200c is able to distinguish low and high TNM ccRCC stages. Additionally, miRNA-18a, -210, -483-5p and -642 showed statistically significant differences between the low stage tumor ccRCC tissue and normal renal tissue. Contrariwise, the high stages of the tumor process were accompanied by alteration in the expression levels of miRNA-200c, -455-3p and -582-3p. Although the biological roles of these miRNAs in ccRCC are not totally clear, our findings need additional investigations into their involvement in the pathogenesis of ccRCC. Prospective studies with large study cohorts of ccRCC patients are important to further establish the clinical validity of our miRNA markers to predict ccRCC. Full article

(This article belongs to the Special Issue Genes and Human Diseases)

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18 pages, 4652 KiB

Open AccessArticle

Antibiotic Resistance Genes in Aerosols: Baseline from Kuwait

by Nazima Habibi, Saif Uddin, Montaha Behbehani, Mohamed Kishk, Nasreem Abdul Razzack, Farhana Zakir and Anisha Shajan

Int. J. Mol. Sci. 2023, 24(7), 6756; https://doi.org/10.3390/ijms24076756 - 04 Apr 2023

Cited by 3 | Viewed by 1867

Abstract

Antimicrobial resistance (AMR) is one of the biggest threats to human health worldwide. The World Health Organization (WHO, Geneva, Switzerland) has launched the “One-Health” approach, which encourages assessment of antibiotic-resistant genes (ARGs) within environments shared by human-animals-plants-microbes to constrain and alleviate the development of AMR. Aerosols as a medium to disseminate ARGs, have received minimal attention. In the present study, we investigated the distribution and abundance of ARGs in indoor and outdoor aerosols collected from an urban location in Kuwait and the interior of three hospitals. The high throughput quantitative polymerase chain reaction (HT-qPCR) approach was used for this purpose. The results demonstrate the presence of aminoglycoside, beta-lactam, fluoroquinolone, tetracycline, macrolide-lincosamide-streptogramin B (MLSB), multidrug-resistant (MDR) and vancomycin-resistant genes in the aerosols. The most dominant drug class was beta-lactam and the genes were IMP-2-group (0.85), Per-2 group (0.65), OXA-54 (0.57), QnrS (0.50) and OXA-55 (0.55) in the urban non-clinical settings. The indoor aerosols possessed a richer diversity (Observed, Chao1, Shannon’s and Pielou’s evenness) of ARGs compared to the outdoors. Seasonal variations (autumn vs. winter) in relative abundances and types of ARGs were also recorded (R² of 0.132 at p < 0.08). The presence of ARGs was found in both the inhalable (2.1 µm, 1.1 µm, 0.7 µm and < 0.3 µm) and respirable (>9.0 µm, 5.8 µm, 4.7 µm and 3.3 µm) size fractions within hospital aerosols. All the ARGs are of pathogenic bacterial origin and are hosted by pathogenic forms. The findings present baseline data and underpin the need for detailed investigations looking at aerosol as a vehicle for ARG dissemination among human and non-human terrestrial biota. Full article

(This article belongs to the Special Issue Genes and Human Diseases)

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Review

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19 pages, 1973 KiB

Open AccessReview

Research Advances in the Role of the Tropomyosin Family in Cancer

by Yucheng Meng, Ke Huang, Mingxuan Shi, Yifei Huo, Liang Han, Bin Liu and Yi Li

Int. J. Mol. Sci. 2023, 24(17), 13295; https://doi.org/10.3390/ijms241713295 - 27 Aug 2023

Cited by 1 | Viewed by 1393

Abstract

Cancer is one of the most difficult diseases for human beings to overcome. Its development is closely related to a variety of factors, and its specific mechanisms have been a hot research topic in the field of scientific research. The tropomyosin family (Tpm) is a group of proteins closely related to the cytoskeleton and actin, and recent studies have shown that they play an important role in various cancers, participating in a variety of biological activities, including cell proliferation, invasion, and migration, and have been used as biomarkers for various cancers. The purpose of this review is to explore the research progress of the Tpm family in tumorigenesis development, focusing on the molecular pathways associated with them and their relevant activities involved in tumors. PubMed and Web of Science databases were searched for relevant studies on the role of Tpms in tumorigenesis and development and the activities of Tpms involved in tumors. Data from the literature suggest that the Tpm family is involved in tumor cell proliferation and growth, tumor cell invasion and migration, tumor angiogenesis, tumor cell apoptosis, and immune infiltration of the tumor microenvironment, among other correlations. It can be used as a potential biomarker for early diagnosis, follow-up, and therapeutic response of some tumors. The Tpm family is involved in cancer in a close relationship with miRNAs and LncRNAs. Tpms are involved in tumor tissue invasion and migration as a key link. On this basis, TPM is frequently used as a biomarker for various cancers. However, the specific molecular mechanism of its involvement in cancer progression has not been explained clearly, which remains an important direction for future research. Full article

(This article belongs to the Special Issue Genes and Human Diseases)

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24 pages, 3837 KiB

Open AccessReview

CLEC16A—An Emerging Master Regulator of Autoimmunity and Neurodegeneration

by Rahul Pandey, Marina Bakay and Hakon Hakonarson

Int. J. Mol. Sci. 2023, 24(9), 8224; https://doi.org/10.3390/ijms24098224 - 04 May 2023

Cited by 4 | Viewed by 2420

Abstract

CLEC16A is emerging as an important genetic risk factor for several autoimmune disorders and for Parkinson disease (PD), opening new avenues for translational research and therapeutic development. While the exact role of CLEC16A in health and disease is still being elucidated, the gene plays a critical role in the regulation of autophagy, mitophagy, endocytosis, intracellular trafficking, immune function, and in biological processes such as insulin secretion and others that are important to cellular homeostasis. As shown in both human and animal modeling studies, CLEC16A hypofunction predisposes to both autoinflammatory phenotype and neurodegeneration. While the two are clearly related, further functional studies are needed to fully understand the mechanisms involved for optimized therapeutic interventions. Based on recent data, mitophagy-inducing drugs may be warranted, and such therapy should be tested in clinical trials as these drugs would tackle the underlying pathogenic mechanism (s) and could treat or prevent symptoms of autoimmunity and neurodegeneration in individuals with CLEC16A risk variants. Accordingly, interventions directed at reversing the dysregulated mitophagy and the consequences of loss of function of CLEC16A without activating other detrimental cellular pathways could present an effective therapy. This review presents the emerging role of CLEC16A in health and disease and provides an update on the disease processes that are attributed to variants located in the CLEC16A gene, which are responsible for autoimmune disorders and neurodegeneration with emphasis on how this information is being translated into practical and effective applications in the clinic. Full article

(This article belongs to the Special Issue Genes and Human Diseases)

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8 pages, 3128 KiB

Open AccessCase Report

Case Report: A Novel Homozygous Variant of the SERPINF1 Gene in Rare Osteogenesis Imperfecta Type VI

by Irina Zh. Zhalsanova, Anna Evgenievna Postrigan, Nail Raushanovich Valiakhmetov, Nikita Aleksandrovich Kolesnikov, Daria Ivanovna Zhigalina, Aleksei Andreevich Zarubin, Valeria Viktorovna Petrova, Larisa Ivanovna Minaycheva, Gulnara Narimanovna Seitova, Nikolay Alekseevich Skryabin and Vadim Anatolevich Stepanov

Int. J. Mol. Sci. 2023, 24(7), 6672; https://doi.org/10.3390/ijms24076672 - 03 Apr 2023

Viewed by 1483

Abstract

Osteogenesis imperfecta (OI) is a group of connective tissue disorders with different types of inheritance. OI is characterized by bone fragility and deformities, frequent fractures, low bone-mineral density, and impaired bone micro-architectonics. We described here a case of a one-year-old Tuvan patient with multiple fractures. The disease manifestation occurred first at 12 weeks of age as a shoulder joint bruise, and during the year, the patient sustained 27 fractures. Genetic testing revealed a novel homozygous mutation, c.259_260insCGGCC (p.T87fs), in the SERPINF1 gene. This insertion leads to an open-reading frameshift, and the mutation is not represented in the databases. Mutations in SERPINF1 lead to type VI OI, the clinical picture of which is similar to the disease phenotype manifestation of the patient. Thus, the patient’s diagnosis was established by finding a novel pathogenic variant in the SERPINF1 gene. Full article

(This article belongs to the Special Issue Genes and Human Diseases)

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