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Pediatric Cardiology Jan 2020Congenital heart defects (CHD) are the most common congenital problems in neonates. The basis for CHD is multifactorial, involving genetic and environmental components.... (Review)
Review
Congenital heart defects (CHD) are the most common congenital problems in neonates. The basis for CHD is multifactorial, involving genetic and environmental components. The elucidation of genetic components remains difficult because it is a genetically heterogeneous disease. Currently, the major identified genetic causes include chromosomal abnormalities, large subchromosomal deletions/duplications, and point mutations. However, much more remains to be unraveled. An important insight from the research on the genetics of CHD is that any change at the genetic level that alters the dosage of genes required in any process during heart development results in a developmental defect. The use of conventional gene identification (linkage analysis and direct targeted sequencing) methods followed by the rapid advancements in high-throughput technologies (copy number variant platforms, SNP arrays, and next-generation sequencing) has identified an extensive list of genetic causes. However, the most common presentation of CHD is in the form of sporadic cases. Therefore, it is important to identify their underlying genetic cause. In this review, we revisit the causal genetic factors of CHD and discuss the clinical implications of research in the field.
Topics: DNA Copy Number Variations; Heart Defects, Congenital; High-Throughput Nucleotide Sequencing; Humans; Infant, Newborn; Point Mutation
PubMed: 31872283
DOI: 10.1007/s00246-019-02271-4 -
Zhejiang Da Xue Xue Bao. Yi Xue Ban =... Apr 2021To establish a rabbit model of proprotein convertase subtilisin/kexin type9 () point mutation with CRISPR/Cas9 gene editing technique. According to the PubMed gene...
To establish a rabbit model of proprotein convertase subtilisin/kexin type9 () point mutation with CRISPR/Cas9 gene editing technique. According to the PubMed gene protein data, the PCSK9 protein functional regions of human and rabbit were analyzed by Blast. The 386S (Ser) amino acid functional region of human gene was homologous to the 485S of rabbit gene. Three small guide RNAs and one single-stranded donor oligonucleotide were designed according to the 485S base substitution position and sequence analysis of rabbit gene. The synthetic small guide RNAs, Cas9 mRNA and single-stranded donor oligonucleotide were co-injected into the cytoplasm of rabbit fertilized eggs and the embryos were transferred into the pregnant rabbits. PCR, TA cloning and off-target analysis were performed on the F0 rabbits to identify whether the PCSK9 mutation was successful. Fifteen F0 rabbits were obtained. The sequencing results showed that one of them was PCSK9 point mutation homozygote and two of them were PCSK9 point mutation heterozygotes, and the mutation could be stably inherited. The rabbit model of PCSK9 point mutation was successfully constructed by CRISPR/Cas9 technique, which provides an animal model for exploring the molecular mechanism of impaired PCSK9 function and developing reliable and effective diagnosis and treatment measures.
Topics: Animals; CRISPR-Cas Systems; Humans; Point Mutation; Proprotein Convertase 9; Rabbits
PubMed: 34137224
DOI: 10.3724/zdxbyxb-2021-0133 -
International Journal of Molecular... Aug 2023The m.3243A>G mutation in the tRNA Leu(UUR) gene (MT-TL1) is one of the most common pathogenic point mutations in human mtDNA. Patient symptoms vary widely and the... (Review)
Review
The m.3243A>G mutation in the tRNA Leu(UUR) gene (MT-TL1) is one of the most common pathogenic point mutations in human mtDNA. Patient symptoms vary widely and the severity of the disease ranges from asymptomatic to lethal. The reason for the high heterogeneity of m.3243A>G-associated disease is still unknown, and the treatment options are limited, with only supportive interventions available. Furthermore, the heteroplasmic nature of the m.3243A>G mutation and lack of specific animal models of mtDNA mutations have challenged the study of m.3243A>G, and, besides patient data, only cell models have been available for studies. The most commonly used cell models are patient derived, such as fibroblasts and induced pluripotent stem cell (iPSC)-derived models, and cybrid models where the mutant DNA is transferred to an acceptor cell. Studies on cell models have revealed cell-type-specific effects of the m.3243A>G mutation and that the tolerance for this mutation varies between cell types and between patients. In this review, we summarize the literature on the effects of m.3243A>G in cell models.
Topics: Animals; Humans; Mutation; Mitochondria; Point Mutation; In Situ Hybridization; DNA, Mitochondrial
PubMed: 37686280
DOI: 10.3390/ijms241713478 -
Advances in Genetics 2020
Topics: Animals; Biological Evolution; Earth, Planet; Humans; Origin of Life; Point Mutation
PubMed: 33081929
DOI: 10.1016/S0065-2660(20)30036-5 -
International Journal of Molecular... Dec 2022Genetic aberrations, including chromosomal rearrangements, loss or amplification of DNA, and point mutations, are major elements of cancer development [...].
Genetic aberrations, including chromosomal rearrangements, loss or amplification of DNA, and point mutations, are major elements of cancer development [...].
Topics: Humans; Epigenesis, Genetic; Chromosome Aberrations; Neoplasms; Point Mutation; DNA
PubMed: 36555088
DOI: 10.3390/ijms232415446 -
Biosensors & Bioelectronics Mar 2024Gene point mutations play a significant role in the development of cancer. Therefore, developing a sensitive, specific, and universally applicable method for detecting...
Gene point mutations play a significant role in the development of cancer. Therefore, developing a sensitive, specific, and universally applicable method for detecting gene point mutation is crucial for clinical diagnosis, prognosis, and cancer treatment. Recently, gene point mutation detection methods based on CRISPR/Cas12a detection have emerged. However, existing methods generally lack universality and specificity. In this study, we have developed a CRISPR/Cas12a-based method that combines improved allele-specific polymerase chain reaction and single base extension to translate the point mutation information in the target dsDNA into length information in ssDNA activators to overcome the limitations associated with PAM sequences in the CRISPR/Cas12a system. Our method achieved a detection limit of 0.002% for clinically significant EGFR T790M mutation. The CRISPR/Cas12a system we constructed demonstrates high sensitivity, specificity, and universality in detecting gene point mutations, making it a promising tool for clinical cancer screening.
Topics: Humans; Point Mutation; Mutation; CRISPR-Cas Systems; ErbB Receptors; Lung Neoplasms; Protein Kinase Inhibitors; Biosensing Techniques
PubMed: 38142668
DOI: 10.1016/j.bios.2023.115936 -
Journal of the American Nutrition... Jul 2022Single-point mutation diseases in which substitution of one nucleotide with another in a gene occurs include familial Alzheimer's disease (fAD), familial Parkinson's... (Review)
Review
Single-point mutation diseases in which substitution of one nucleotide with another in a gene occurs include familial Alzheimer's disease (fAD), familial Parkinson's disease (fPD), and familial Creutzfeldt-Jacob disease (fCJD) as well as Huntington's disease (HD), sickle cell anemia, and hemophilia. Inevitability of occurrence of these diseases is certain. However, the time of appearance of symptoms could be influenced by the diet, environment, and possibly other genetic factors. There are no effective approaches to delay the onset or progression of symptoms of these diseases. The fact that increased oxidative stress and inflammation significantly contribute to the initiation and progression of these point mutation diseases shows that antioxidants could be useful. The major objectives are (a) to present evidence that increased oxidative stress and chronic inflammation are associated with selected single-point mutation diseases, such as fAD, fPD, and fCJD, HD, sickle cell anemia, and hemophilia; (b) to describe limited studies on the role of individual antioxidants in experimental models of some of these diseases; and (c) to discuss a rationale for utilizing a comprehensive mixture of micronutrients, which may delay the development and progression of symptoms of above diseases by simultaneously reducing oxidative and inflammatory damages.Key teaching pointsSelected single-point mutation diseases and their pattern of inheritanceCharacteristics of each selected single-point mutation diseaseEvidence for increased oxidative stress and inflammation in each diseasePotential reasons for failure of single antioxidants in human studiesRationale for using a comprehensive mixture of micronutrients in delaying the onset and progression of single-point mutation diseases.
Topics: Anemia, Sickle Cell; Antioxidants; Hemophilia A; Humans; Huntington Disease; Inflammation; Micronutrients; Point Mutation; Trace Elements
PubMed: 34227926
DOI: 10.1080/07315724.2021.1910592 -
NEJM Evidence Oct 2023Hairy cell leukemia (HCL) is an uncommon B-cell neoplasm uniquely characterized by a high prevalence of the mutation, which leads to constitutive activation of the...
Hairy cell leukemia (HCL) is an uncommon B-cell neoplasm uniquely characterized by a high prevalence of the mutation, which leads to constitutive activation of the mitogen-activated protein kinase (MAPK) pathway. In fact, the point mutation is identified in nearly all cases of HCL; however, it is absent in HCL variant (vHCL) and rare in other B-cell neoplasms. Notably, in contrast to melanoma or other BRAF mutant solid tumors, HCL exhibits very few other mutations, potentially explaining the high response rates observed in patients treated with mutant BRAF-targeted agents, such as vemurafenib.
Topics: Humans; Leukemia, Hairy Cell; Proto-Oncogene Proteins B-raf; Vemurafenib; Antineoplastic Agents; Point Mutation
PubMed: 38320184
DOI: 10.1056/EVIDe2300173 -
World Journal of Microbiology &... Jul 2020The fermentation of industrial bacteria encounters a serious problem in continuous culture, i.e. the production traits lose. However, current research on the mechanism... (Review)
Review
The fermentation of industrial bacteria encounters a serious problem in continuous culture, i.e. the production traits lose. However, current research on the mechanism of strain degeneration is not clear enough, and there are few methods to effectively control the degeneration. Under growth restriction, the mutation rate of fermentation strains increases. Many cellular processes and poor fermentation conditions can trigger the transposition of transposable elements, SOS response, and RpoS-controlled adaptive mutations, causing genetic instability. Genetic instability which resulted from point mutations and genomic rearrangements can be responsible for strain degeneration. This mini-review summarizes the degeneration phenomena and mechanisms in common industrial bacteria and highlights three mechanisms of strain degeneration, including the transposition of transposable elements, SOS response, and adaptive mutations. According to different mutation mechanisms, many promising strategies have been proposed to increase the stability and the yield of industrial strains, for example, developing platform strains free of insertion sequence to enhance the stability of recombinant plasmid, using SOS inhibitors to block the SOS response, and improving environmental tolerance capacity and fermentation conditions to reduce adaptive mutations.
Topics: DNA Transposable Elements; Fermentation; Genomic Instability; Industrial Microbiology; Mutation; Phenotype; Point Mutation; Recombination, Genetic
PubMed: 32681370
DOI: 10.1007/s11274-020-02901-7 -
Pest Management Science Nov 2023Fusarium pseudograminearum is one of the dominant pathogens of Fusarium crown rot (FCR) worldwide. Unfortunately, no fungicides have yet been registered for the control...
BACKGROUND
Fusarium pseudograminearum is one of the dominant pathogens of Fusarium crown rot (FCR) worldwide. Unfortunately, no fungicides have yet been registered for the control of FCR in wheat in China. Pydiflumetofen, a new-generation succinate dehydrogenase inhibitor, exhibits excellent inhibitory activity to Fusarium spp. A resistance risk assessment of F. pseudograminearum to pydiflumetofen and the resistance mechanism involved have not yet been investigated.
RESULTS
The median effective concentration (EC ) value of 103 F. pseudograminearum isolates to pydiflumetofen was 0.0162 μg mL , and the sensitivity exhibited a unimodal distribution. Four resistant mutants were generated by fungicide adaption, which possessed similar or impaired fitness compared to corresponding parental isolates based on the results of mycelial growth, conidiation, conidium germination rate, and virulence determination. Pydiflumetofen showed strong positive cross-resistance with cyclobutrifluram and fluopyram but no cross-resistance with carbendazim, phenamacril, tebuconazole, fludioxonil, or pyraclostrobin. Sequence alignment revealed that pydiflumetofen-resistant F. pseudograminearum mutants had two single-point mutations of A83V or R86K in FpSdhC . Molecular docking further confirmed that point mutation of A83V or R86K in FpSdhC could confer resistance of F. pseudograminearum to pydiflumetofen.
CONCLUSION
Fusarium pseudograminearum shows an overall moderate risk of developing resistance to pydiflumetofen, and point mutation FpSdhC or FpSdhC could confer pydiflumetofen resistance in F. pseudograminearum. This study provided vital data for monitoring the emergence of resistance and developing resistance management strategies for pydiflumetofen. © 2023 Society of Chemical Industry.
Topics: Point Mutation; Fusarium; Molecular Docking Simulation; Plant Diseases; Fungicides, Industrial
PubMed: 37326415
DOI: 10.1002/ps.7616