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American Journal of Reproductive... Dec 2020Insufficient response to oxidative stress in placenta is proposed as a contributing factor for preeclampsia (PE) development. Glutathione S-transferases (GST) have... (Meta-Analysis)
Meta-Analysis Review
Insufficient response to oxidative stress in placenta is proposed as a contributing factor for preeclampsia (PE) development. Glutathione S-transferases (GST) have significant role in detoxification processes. Conflicting results were published by several research groups regarding GST T1 and GST M1 deletion polymorphism as risk factors for PE. The aim of the present meta-analysis was to get a better understanding of the impact of these polymorphisms in preeclampsia development. To identify relevant case-control studies, the author team searched Clarivate Analytics Web of Science, Scopus, PubMed, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, major subject journals, and gray literature. Pooled odds ratios and 95% confidence intervals for GST M1 and GST T1 deletion polymorphism and preeclampsia were derived from random effects models. This meta-analysis included 10 eligible studies. The pooled analyses showed no association between GST M1/GST T1 deletion polymorphisms and susceptibility to PE. Even though high heterogeneity was founded among results for GST M1 and double null genotypes, Egger's and Begg's tests (0.17 and 0.18, respectively) revealed no statistical evidence of publication bias among included studies. The present updated systematic review and meta-analysis found no association between GST M1 and GST T1 deletion polymorphism and PE risk.
Topics: Female; Genetic Predisposition to Disease; Genotype; Glutathione Transferase; Humans; Polymorphism, Genetic; Pre-Eclampsia; Pregnancy; Risk; Sequence Deletion
PubMed: 32658338
DOI: 10.1111/aji.13303 -
No Shinkei Geka. Neurological Surgery Jan 2022Several important revisions were made regarding the classification of brain tumors in the newest version(5th edition)of the WHO classification of tumours of the central...
Several important revisions were made regarding the classification of brain tumors in the newest version(5th edition)of the WHO classification of tumours of the central nervous system published in 2021. Now, most so-called "lower-grade glioma(s)" fall into the category of IDH-mutant diffuse glioma, represented by astrocytoma and oligodendroglioma. For the diagnosis of these IDH-mutant gliomas, the determination of genetic alterations in /, , chromosome 1p/19q, , promoter, and / is important. Generally, in addition to the mutation, astrocytomas have mutation and mutation, whereas oligodendrogliomas have 1p/19q codeletion and promoter mutation. For tumor grading in the new WHO classification, astrocytomas harboring / homozygous deletion can be categorized as WHO grade 4 astrocytomas, even though they do not have microvascular proliferation or necrosis. For these IDH-mutant tumors, molecular targeted therapy for IDH mutation has been under development. Several enzymatic inhibitors of IDH1/2 have been tested in clinical trials and were suggested to have some clinical effectiveness. Currently, large-scale trials are ongoing. Besides these inhibitors, other strategies for targeting IDH mutations, such as immunotherapy and therapy targeting aberrant metabolic pathways resulting from IDH mutation are also examined. These novel therapies will be beneficial to patients.
Topics: Brain Neoplasms; Glioma; Homozygote; Humans; Isocitrate Dehydrogenase; Mutation; Precision Medicine; Sequence Deletion
PubMed: 35169082
DOI: 10.11477/mf.1436204527 -
Genes Apr 2021To date only five patients with 8p23.2-pter microdeletions manifesting a mild-to-moderate cognitive impairment and/or developmental delay, dysmorphisms and...
To date only five patients with 8p23.2-pter microdeletions manifesting a mild-to-moderate cognitive impairment and/or developmental delay, dysmorphisms and neurobehavioral issues were reported. The smallest microdeletion described by Wu in 2010 suggested a critical region (CR) of 2.1 Mb including several genes, out of which , , , and are the main candidates. Here we present seven additional patients with 8p23.2-pter microdeletions, ranging from 71.79 kb to 4.55 Mb. The review of five previously reported and nine Decipher patients confirmed the association of the CR with a variable clinical phenotype characterized by intellectual disability/developmental delay, including language and speech delay and/or motor impairment, behavioral anomalies, autism spectrum disorder, dysmorphisms, microcephaly, fingers/toes anomalies and epilepsy. Genotype analysis allowed to narrow down the 8p23.3 candidate region which includes only , and genes, accounting for the main signs of the broad clinical phenotype associated to 8p23.2-pter microdeletions. This region is more restricted compared to the previously proposed CR. Overall, our data favor the hypothesis that is the actual strongest candidate for neurodevelopmental/behavioral phenotypes. Additional patients will be necessary to validate the pathogenic role of and better define how the two contiguous genes, and , might contribute to the clinical phenotype.
Topics: Adolescent; Adult; Autism Spectrum Disorder; Child; Child, Preschool; Chromosome Deletion; Chromosomes, Human, Pair 8; Cognitive Dysfunction; Developmental Disabilities; Female; Humans; Infant; Intellectual Disability; Male; Microcephaly; Phenotype; Sequence Deletion
PubMed: 33925474
DOI: 10.3390/genes12050652 -
Journal of Human Genetics Jan 2020During the past decade, the search for pathogenic mutations in rare human genetic diseases has involved huge efforts to sequence coding regions, or the entire genome,... (Review)
Review
During the past decade, the search for pathogenic mutations in rare human genetic diseases has involved huge efforts to sequence coding regions, or the entire genome, using massively parallel short-read sequencers. However, the approximate current diagnostic rate is <50% using these approaches, and there remain many rare genetic diseases with unknown cause. There may be many reasons for this, but one plausible explanation is that the responsible mutations are in regions of the genome that are difficult to sequence using conventional technologies (e.g., tandem-repeat expansion or complex chromosomal structural aberrations). Despite the drawbacks of high cost and a shortage of standard analytical methods, several studies have analyzed pathogenic changes in the genome using long-read sequencers. The results of these studies provide hope that further application of long-read sequencers to identify the causative mutations in unsolved genetic diseases may expand our understanding of the human genome and diseases. Such approaches may also be applied to molecular diagnosis and therapeutic strategies for patients with genetic diseases in the future.
Topics: Chromosome Aberrations; DNA Transposable Elements; Genome, Human; High-Throughput Nucleotide Sequencing; Humans; Rare Diseases; Sequence Analysis, DNA; Sequence Deletion; Sequence Inversion; Tandem Repeat Sequences
PubMed: 31558760
DOI: 10.1038/s10038-019-0671-8 -
STAR Protocols Dec 2020Since its first application for site-directed mutagenesis, the CRISPR-Cas9 system has revolutionized genome engineering. Here, we present a validated workflow for the...
Since its first application for site-directed mutagenesis, the CRISPR-Cas9 system has revolutionized genome engineering. Here, we present a validated workflow for the generation of targeted genomic deletions in zebrafish, including the design, cloning, and synthesis of single-guide RNAs and Cas9 mRNA, followed by microinjection in zebrafish embryos and subsequent genotype screening for the establishment of a mutant line. The versatility and efficiency of this pipeline makes the generation of zebrafish models a widely used approach in functional genetics. For complete details on the use and execution of this protocol, please refer to Amorim et al. (2020).
Topics: Animals; CRISPR-Cas Systems; Gene Editing; Genetic Engineering; Genome; Genomics; Microinjections; Mutagenesis, Site-Directed; RNA, Guide, CRISPR-Cas Systems; Sequence Deletion; Zebrafish
PubMed: 33377102
DOI: 10.1016/j.xpro.2020.100208 -
Genes, Chromosomes & Cancer Nov 2019Pediatric poorly differentiated chordoma is a subtype of chordoma with a much more aggressive clinical course and has been characterized by loss of SMARCB1. This study...
Pediatric poorly differentiated chordoma is a subtype of chordoma with a much more aggressive clinical course and has been characterized by loss of SMARCB1. This study characterizes the molecular features of these tumors in comparison to conventional chordoma. A search of records between 1990 and 2017 at Massachusetts General Hospital identified two patients with sufficient excess tissue for molecular analysis and a third patient diagnosed with a highly cellular conventional chordoma. The three tumors were sent for array comparative genomic hybridization for genome-wide copy number variants; multiplex PCR for single-nucleotide variants; and RNA-sequencing for fusions. Poorly differentiated chordoma showed chromosome 22q loss, including SMARCB1, with no identifiable mutations on multiplex PCR. The cellular conventional chordoma showed a complex pattern of chromosomal gains and losses involving 12 chromosomes, and an RB1 mutation at low allelic frequency. RNA-Seq identified no disease-defining gene fusion events. Poorly differentiated chordoma appears to represent a distinct type of tumor that is genetically unrelated to conventional chordoma. Recognition of this subtype is important because these malignancies should be treated aggressively with multimodality therapy, and possibly targeted therapy.
Topics: Chordoma; Chromosome Deletion; Comparative Genomic Hybridization; DNA Copy Number Variations; Gene Deletion; Humans; Multiplex Polymerase Chain Reaction; Mutation; Polymorphism, Single Nucleotide; Retinoblastoma Binding Proteins; SMARCB1 Protein; Sequence Analysis, RNA; Ubiquitin-Protein Ligases
PubMed: 31135077
DOI: 10.1002/gcc.22782 -
Infection, Genetics and Evolution :... Jul 2020COVID-19 is a viral respiratory illness caused by a new coronavirus called SARS-CoV-2. The World Health Organization declared the SARS-CoV-2 outbreak a global public...
COVID-19 is a viral respiratory illness caused by a new coronavirus called SARS-CoV-2. The World Health Organization declared the SARS-CoV-2 outbreak a global public health emergency. We performed genetic analyses of eighty-six complete or near-complete genomes of SARS-CoV-2 and revealed many mutations and deletions on coding and non-coding regions. These observations provided evidence of the genetic diversity and rapid evolution of this novel coronavirus.
Topics: Betacoronavirus; Evolution, Molecular; Genetic Variation; Genome, Viral; Mutation; SARS-CoV-2; Sequence Deletion
PubMed: 32092483
DOI: 10.1016/j.meegid.2020.104260 -
ACS Synthetic Biology Oct 2021A large number of fuselloviruses have been found in acidic hot springs around the globe. They share a set of highly conserved genes (core genes) and possess a varying...
A large number of fuselloviruses have been found in acidic hot springs around the globe. They share a set of highly conserved genes (core genes) and possess a varying number of less-conserved genes (non-core genes). However, the functions of most of these genes are unknown. Recent studies show that as many as half of these genes tolerate mutation. In this study, we conducted a genetic analysis on spindle-shaped virus 22 (SSV22), an alphafusellovirus with fewer open reading frames (ORFs) than most of the isolated fuselloviruses. Both deletion and frame-shift mutations were introduced into nearly all of the 26 ORFs of the viral genome. A total of 17 ORFs were indispensable, and two additional ORFs were required for the optimal infectivity of the virus. Deletion of either VP2 or VP3, the two structural proteins, did not affect the morphology or infectivity of the virus. An infectious SSV22 derivative carrying a minimal genome of 20 ORFs was obtained. The SSV22 capsid was capable of accommodating a genome as large as ∼18 kb, or ∼7 kb larger than that of the wild-type virus. The viral capsid varied in both the length and width, but not in shape, with the size of the genome. Our results will facilitate the analysis of crucial protein-protein interactions between SSV22 and the host during viral infection and help explore the use of SSV22 as a vector for DNA delivery in potential applications.
Topics: Frameshift Mutation; Fuselloviridae; Genes, Viral; Open Reading Frames; Sequence Deletion; Synthetic Biology; Viral Genome Packaging; Viral Structural Proteins; Virulence
PubMed: 34543007
DOI: 10.1021/acssynbio.1c00232 -
Medicine Jul 2019Researchers have evaluated the associations between mitochondrial DNA (mtDNA) 4977 bp deletion and presbycusis. This study aimed to assess the differences of mtDNA... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Researchers have evaluated the associations between mitochondrial DNA (mtDNA) 4977 bp deletion and presbycusis. This study aimed to assess the differences of mtDNA 4977 bp deletion between presbycusis patients and controls by conducting a meta-analysis of published studies.
METHODS
Databases, including PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Data were searched to collect case-control studies on the correlation between mitochondrial DNA 4977 bp deletion and presbycusis. The research findings of related articles were collected according to the inclusion criteria. Pooled odds ratios (ORs) and corresponding confidence intervals (CIs) were calculated. Meanwhile, subgroup analysis was performed to examine the source of heterogeneity. Revman 5.3 and Stata 12.0 software were used for data synthesis.
RESULTS
Eight English and Chinese studies were included in the meta-analysis, the results of which showed that mitochondrial DNA 4977 bp deletion could increase the risk of presbycusis (OR = 8.16, 95% CI: 3.51-18.99), and the difference was statistically significant (P <. 01). Analysis of the polled OR showed the incidence of mtDNA 4977 bp deletion was 8.50 times higher in Asians with presbycusis than in the control group. And the OR in the studies of occidentals was 7.24. Sample source analysis was also performed with the sample source divided by temporal bone source and other sources (hair and blood). The OR was 4.18 and 22.36 for the temporal bone and other sources, respectively.
CONCLUSION
Mitochondrial DNA 4977 bp deletion could increase the risk of presbycusis.
Topics: Case-Control Studies; DNA, Mitochondrial; Humans; Presbycusis; Sequence Deletion
PubMed: 31277167
DOI: 10.1097/MD.0000000000016302 -
Analytical Methods : Advancing Methods... Nov 2022A 4-way strand exchange competitive DNA testing system based on Holliday junction has an advantage in realizing high sensitivity and specificity simultaneously. However,...
A 4-way strand exchange competitive DNA testing system based on Holliday junction has an advantage in realizing high sensitivity and specificity simultaneously. However, the kinetics is limited without enzyme assisting. Herein, we constructed a method that combined a 4-way strand migration system and exonuclease III (Exo III). For the properties of Exo III that has high catalytic effects and no specific recognition site, a DNA probe assisted by Exo III is easy to design and synthesize. We applied the system to detect different lengths of deletion mutation, and the results showed that the time to differentiate wild-type DNA and mutant-type DNA was so short within 5-20 min. Besides, the discrimination factor (DF) was as high as 1177.88 for EGFR-15-nt deletion, and the mutation detection limit was as low as 0.02% for PBRM1-8-nt deletion. Without adding any other specific label, the Exo III-amplified 4-way strand migration system is a simple, sensitive, selective, and cost-effective method that suggests a potential possibility for the diagnosis of cancers.
Topics: Biosensing Techniques; Exodeoxyribonucleases; DNA; Sequence Deletion
PubMed: 36263761
DOI: 10.1039/d2ay01421a