27 results about "Missense mutation" patented technology

The present invention generally relates to tRNA-based effector molecules for use in inserting missense mutations into the open reading frame (ORF) of a gene, e.g., for the treatment of repetitive sequence amplification diseases.

This invention discloses a method for directed evolution of antibiotic-resistant Escherichia coli strains based on cytidine deaminase, belonging to the field of microbial directed evolution and genetic engineering technology. This method uses E. coli as the host, introducing a recombinant plasmid expressing an optimized double-stranded cytidine deaminase mutant. Utilizing the low toxicity and high mutagenicity of this mutant, continuous passage evolution is carried out under gradient concentrations of aminoglycoside antibiotics (kanamycin and streptomycin). Combined with whole-genome sequencing, molecular docking, and reverse genetics verification, the A145T missense mutation in the wcaE gene is identified as the core functional site. This invention overcomes the shortcomings of traditional spontaneous and chemical mutagenesis, which suffer from low efficiency and significant strain damage. The mutation type is controllable, the evolutionary cycle is short, and the obtained engineered strains can tolerate up to 300 mg / L kanamycin while exhibiting streptomycin cross-resistance, and the genetic stability of the tolerance trait is strong. This method is simple, highly reproducible, and suitable for industrial breeding of stress-resistant E. coli, and can be widely applied in antibiotic fermentation, industrial microbial culture, and other scenarios.

The invention relates to the technical field of agricultural breeding, and discloses a molecular marker related to egg shell color and application of the molecular marker, the SNP molecular marker corresponds to the 18378867 site from the 5'terminal on a chicken reference genome GRCg6a 6 # chromosome published in an Ensembl gene browser database, and the base of the site is C / T and is missense mutation on an ABCG2 gene. The SNP molecular marker is related to the egg shell color, is a new molecular marker, can accelerate the breeding progress of the character by detecting the genotype of the locus of a chicken individual to be determined and performing early selection on the chicken with the dominant genotype, and has great application value and economic benefit.

To provide new plants exhibiting improved resistance to nematodes, seeds and parts of the plants, methods of making and using such seeds and plants, and new SmD1 alleles that result in modified SmD1 proteins associated with such improved resistance to nematodes.SOLUTION: Provided are plants comprising SmD1 alleles encoding SmD1 proteins having at least 90% amino acid sequence identity to a particular sequence, wherein the SmD1 proteins comprise missense mutations resulting in modified SmD1 proteins that confer enhanced nematode resistance.SELECTED DRAWING: None

In general, the current disclosure relates to the tRNAs that encode for one amino acid but are covalently linked to a different amino acid. The tRNAs can correct missense mutations by providing a different amino acid during protein synthesis. Such tRNAs can be used to correct disease-causing missense mutations.

The invention provides a novel human distal bile duct cancer cell line with TP53 missense mutation and application, the novel human distal bile duct cancer cell line CBC3T-3 is established, the cell line is preserved in the China Center for Type Culture Collection (the preservation number is CCTCC NO: C202555), the uniqueness and stability of the cell line are proved through STR typing and karyotype analysis, and the TP53 missense mutation novel human distal bile duct cancer cell line has the advantages that the TP53 missense mutation novel human distal bile duct cancer cell line CBC3T-3 can be used for preparing the TP53 missense mutation novel human distal bile duct cancer cell line CBC3T-3; and a plurality of driver gene mutations including TP53 missense mutation are carried. The CBC3T-3 has strong proliferation, invasion and migration capabilities, has high tumor formation rate in immunodeficient mice, is resistant to cis-platinum and sensitive to paclitaxel and gemcitabine, and provides an experimental basis for selection of clinical chemotherapy regimens. According to the model, the TP53 missense mutation type distal bile duct cancer in-vitro model is successfully established, and a key experimental platform is provided for deeply researching the drug resistance mechanism of the TP53 missense mutation type distal bile duct cancer and developing an individualized treatment strategy aiming at the subtype of the TP53 missense mutation type distal bile duct cancer.

The disclosure provides methods for treating estrogen receptor positive (ER+) cancer in a patient who has progressed on an aromatase inhibitor. Of particular interest are ER+ cancers that do not harbor a gain of function missense mutation within the ligand binding domain (LBD) of the Estrogen Receptor 1 (ESR1) gene. The provided methods involve the administration of an effective amount of lasofoxifene, a pharmaceutically acceptable salt, prodrug or functional derivative thereof.

The application relates to the technical field of agricultural breeding, and discloses a molecular marker related to eggshell color and application thereof. The SNP molecular marker corresponds to a site of 18378867 from a 5' end on a chromosome 6 of a chicken reference genome GRCg6a published in an Ensembl genome browser database, the base of the site is C / T, and the site is a missense mutation on an ABCG2 gene. The SNP molecular marker related to the eggshell color is a new molecular marker. By detecting the genotype of the site of a chicken individual to be determined, early selection is carried out on the chicken with an advantageous genotype, the breeding progress of the trait can be accelerated, and the application has great application value and economic benefits.

A gene signature for evaluating likely sensitivity of a cancer cell to treatment with inhibitors of Werner syndrome RecQ helicase (WRN) is provided. For cancer cells that have microsatellite instability (MSI) and / or mismatch repair deficiency (dMMR), sensitivity to treatment with a WRN inhibitor is likely if the cancer cell has a loss of function mutation in at least two of KMT2D, ARID1A or RAD50, or if the cancer cell has a loss of function mutation in ARID1A only, without loss of function mutations in KMT2D and RAD50. Cancer cells that are MSI and / or dMMR in which both ARID1A and at least one of KMT2D and RAD50 are wild type or have only missense mutations are unlikely to be sensitive to treatment with WRN inhibitors.

The invention provides an anti-tumor drug cell screening model establishment method based on a TBR1 site-directed mutant and application, and belongs to the technical field of biological medicine. By analyzing data of patients with medullary blastoma (MB) in children hospital of Nanjing Medical University and clinical patients with MB in EGA database, it is found that the proportion of Group 4 subtype MB is the highest, and TBR1 mutation specifically exists in Group 4 subtype MB; a mutation spectrum of TBR1 in Group 4 subtype MB clinical patient data is analyzed, a result shows that mutation is missense mutation, mutation sites are all concentrated in a T-box structural domain of TBR1, and a TBR1-G275 site is high-frequency mutation; the method comprises the following steps: designing a site 275 of a pegRNA targeted TBR1 T-box region by using a CRISPR-Cas9-based PE (Polyethylene) technology, carrying out site-directed mutagenesis on TBR1 in a Group 4 subtype D283 cell line on a genome level, and successfully constructing the Group 4 subtype MB cell model with TBR1-G275C mutation by using a method of drug screening, monoclonal culture and final sequencing verification.

The application provides a method and system for predicting the influence of missense mutations on clinical drug efficacy based on deep learning, comprising the following steps: S1, obtaining and preprocessing drug and mutant protein sequence data sets; S2, normalizing drug input data; S3, normalizing mutant protein sequence input data; S4, building a deep learning model according to the normalized data, and outputting a prediction classification. The application can predict the influence of mutations on clinical drug efficacy only using the structure attributes of drugs and mutant protein sequences. Since the application uses a relatively small feature dimension, it supports high-throughput mutation drug efficacy prediction with low computational overhead. The application can use a deep learning method to predict the influence of mutations on clinical drug use with high precision while maintaining interpretability, and the input features do not include clinical drug information and crystal structure determination experimental information.

Provided are RNAi involving siRNA, shRNA or antisense oligonucleotide (ASO) that reduce the expression of toxic KIF1A alleles, thereby reducing the production of mutant KIF1A, for use in the treatment of KAND. Also provided are RNA targeting oligonucleotides that reduce the expression of toxic KIF1A alleles herein incorporate sequences that target common benign single nucleotide polymorphisms (SNPs) that are cis present with one or more pathogenic KIF1A mutations.

The application belongs to the technical field of gene diagnosis, and discloses a new pathogenic gene CYLC1 of sperm head deformity and a mutation detection reagent thereof; the new pathogenic gene CYLC1 of sperm head deformity is used as a candidate gene diagnosis object of sperm head deformity, and four homozygous missense mutations thereof are c.1157A>C / p.N386T, c.1377G>T / p.K459N, c.1402T>G / p.S468A and c.1834T>A / p.C612S. The application can use the detection reagent to perform simple, fast and accurate gene diagnosis on sperm head deformity patients, and is also helpful for understanding pathogenesis, genetic counseling, prenatal diagnosis and gene therapy. The application can also use the established Cylc1 gene knockout mouse model to reveal the role and mechanism of Calicin-1 protein on sperm acrosome anchoring and head development of mammals.

The invention discloses application of a reagent for detecting SCN2B and / or SCN4B gene mutation in preparation of a hereditary arrhythmia detection product. According to the present invention, through the dual detection system combining whole exon sequencing with Sanger sequencing verification, the accurate capture of the pathogenic mutation such as SCN2B-R28Q / Y69H / P210L and SCN4B-T211M is achieved, and the problem that only SCN5A is determined as the main pathogenic gene in the clinical diagnosis of J wave syndrome (JWS) at present, and the gene detection of about 70-80% of patients is negative is solved. Wherein the three missense mutations of the SCN2B and the SCN4B-T211M variation are reported in the JWS for the first time, and the SCN4B is clear as the JWS pathogenic gene for the first time, so that the pathogenic gene spectrum of the JWS is obviously expanded. A detection product developed on the basis of the method can realize early accurate diagnosis, provide personalized risk assessment (such as sudden death early warning induced by fever) for patients, guide genetic screening of family members and remarkably improve clinical diagnosis and treatment efficiency.

The invention belongs to the technical field of bioinformatics, and discloses a common value evaluation method and device for tumor neoantigens, equipment and a storage medium, missense mutation analysis is performed by acquiring mutation data of a pan cancer sample, a plurality of missense mutation sites are obtained and compared with a human genome to obtain candidate mutation sites, and the candidate mutation sites are used for evaluating the common value of the tumor neoantigens. Extracting the newborn peptide fragment corresponding to each candidate mutation site, inputting the newborn peptide fragment into the prediction model, predicting the binding score of the newborn peptide fragment and the human leukocyte antigen, and calculating the common value score of each newborn peptide fragment according to the number of the newborn peptide fragments generated at the candidate mutation sites and the corresponding binding score of the newborn peptide fragment and the human leukocyte antigen; according to the method, the new peptide fragments are sorted according to the descending order of the scores, and the new antigen sequence is screened out from the sorting result, so that the new antigen value can be effectively evaluated based on the number of the new peptide fragments generated by the site and the binding scores of the corresponding new peptide fragments and the human leukocyte antigen, and the new antigen with higher adaptability is screened out.

The application discloses application of a reagent for detecting SCN2B and / or SCN4B gene mutation in preparation of a genetic arrhythmia detection product. Through a double detection system of whole exon sequencing combined with Sanger sequencing verification, the application realizes accurate capture of pathogenic mutations such as SCN2B-R28Q / Y69H / P210L and SCN4B-T211M, and solves the difficulty that only SCN5A is confirmed as a main pathogenic gene in the current clinical diagnosis of J wave syndrome (JWS), and about 70%-80% of patients have gene detection negative. The three missense mutations of SCN2B and the SCN4B-T211M variation are reported for the first time in JWS, and SCN4B is confirmed as a pathogenic gene of JWS for the first time, which significantly expands the pathogenic gene spectrum of JWS. The detection product developed based on this can realize early accurate diagnosis, provide personalized risk assessment (such as early warning of sudden death induced by fever) for patients, and guide genetic screening of family members, and significantly improves the clinical diagnosis and treatment efficiency.

The application discloses an SCN5A mutant gene, wherein a base G at a genomic position chr3:38607917 is mutated into a base A, or a base G at a genomic position chr3:38620923 is mutated into a base T, with reference to a gene sequence GRCh37. The hybrid missense mutation of the base G at the genomic position chr3:38607917 into the base A and / or the hybrid missense mutation of the base G at the genomic position chr3:38620923 into the base T can distinguish a supraventricular syndrome patient from normal people, and can also be used as a biomarker for assisting clinical diagnosis of the supraventricular syndrome. The primers and the kit provided by the application provide a new drug target for human beings to conquer the supraventricular syndrome, and promote the research and development of innovative drugs.

The present invention relates to a therapeutic oligonucleotide for use in treating a disease in a subject that is associated with or caused by a missense, nonsense or in-frame indel mutation in a gene of the genome of the subject, wherein the therapeutic oligonucleotide is capable of specifically hybridizing to the 5'-splice site, the 3'-splice site or an exonic splicing enhancer (ESE) of an out-of- frame exon in the gene with the missense, nonsense or in-frame indel mutation, thereby causing skipping of the out-of-frame exon.

The invention discloses a molecular marker related to efficient utilization of slash phosphorus and application of the molecular marker, and belongs to the technical field of molecular biology. The molecular marker is two missense mutation SNP (Single Nucleotide Polymorphism) sites: SNP-1 (620th site, C-G) and SNP-2 (1897th site, AG-GC) located in a slash pine PeSTOP1 gene coding region. Specific genotypes (a GG type of SNP-1 and a GC / GC type of SNP-2) are obviously related to high phosphorus utilization efficiency and a high-low-phosphorus-resistance comprehensive evaluation value. The invention further provides a primer pair and a kit for detecting the marker and an application method of the primer pair and the kit in auxiliary screening of the slash pine with efficient phosphorus utilization. Through the molecular marker, rapid and accurate genotype identification can be realized in the seedling stage, the defects of long period and low efficiency of traditional phenotype screening are overcome, and a core tool is provided for efficient utilization and genetic improvement of slash pine phosphorus and molecular marker assisted breeding.

This invention discloses a Mycoplasma caprineis subspecies Mccp NM strain and its applications. Whole-genome alignment of this strain revealed 422 missense mutations, 132 frameshift mutations, and several key insertion / deletion variations compared to the existing vaccine strain C87001. In virulence studies, at a concentration of 1×10⁻⁶... 9 In healthy, susceptible goats, intratracheal injection at a CCU / mL dose resulted in all experimental goats exhibiting typical symptoms of caprine contagious pleuropneumonia. Autopsy revealed pleural effusion and liver-like lesions in the lungs. The inactivated vaccine prepared using this strain demonstrated good safety in goats. Challenge protection tests showed that the vaccine of this invention provided 100% protection against homologous challenge with the NM strain and 80% protection against the heterologous C87002 strain, while commercially available vaccines offered only 40% protection against the NM strain. This invention overcomes the deficiency of existing vaccines in providing insufficient protection against clinical variants, offering an effective technical reserve and candidate vaccine for addressing immunization failure caused by Mccp antigen mutations.

The application provides a molecular marker and breeding method for Lueyang black-bone hen eggshell color breeding, and particularly relates to the field of molecular breeding. The application finds that a missense mutation (C21R) in an ABCG2 gene is related to Lueyang black-bone hen brown eggshell color variation, and therefore can be used for molecular assisted breeding of Lueyang black-bone hen brown eggshell color. C21R is a missense mutation occurring at the 21st cysteine of the ABCG2 protein, caused by SNP g.17548092T>C. The breeding method is to detect the C21R site genotype of a to-be-tested individual by PCR amplification and Sanger sequencing. According to the detection result, CC type individuals are selected and reserved for breeding, which can assist in breeding a new black-bone hen strain producing deep brown eggshells; and TT type individuals are selected and reserved for breeding, which can assist in breeding a new black-bone hen strain producing light brown eggshells. The application solves the problem that the existing Lueyang black-bone hen has different egg colors due to gene mutation, and can greatly shorten the breeding time of a new black-bone hen strain producing a specific brown eggshell color and reduce the breeding cost.

The purpose of the present invention is to provide a means for selecting subject-derived neoantigens. The above problem is solved by providing a method for selecting a subject-derived neoantigen, said method comprising: a step of acquiring sequence data of a normal cell and a cancer cell derived from a subject, a step of identifying a gene having a genetic mutation specific to the cancer cell, and a step of identifying a peptide based on a wild-type gene corresponding to the gene having the genetic mutation specific to the cancer cell from a major histocompatibility complex (MHC)-presented peptide database, wherein the genetic mutation is a missense mutation, and the peptide based on the wild-type gene corresponding to the gene having the genetic mutation has a wild-type amino acid corresponding to the position of an amino acid mutation due to the genetic mutation.

Methods of treating a patient diagnosed with or suspected of having Fabry disease and methods of enhancing α - GalA in a patient diagnosed with or suspected of having Fabry disease are provided.SOLUTION: Certain methods comprise administering to the patient a therapeutically effective dose of a pharmacological chaperone for α -GalA, wherein the patient has a missense mutation in the nucleic acid sequence encoding α -GalA. Also described are uses of the pharmacological chaperones for treating Fabry disease and compositions for use in treating Fabry disease.SELECTED DRAWING: None

The present invention generally relates to tRNA-based effector molecules used to insert missense mutations into open reading frames (ORFs) of genes, for example, for the purpose of treating repeat elongation disorders. This disclosure features modified tRNA-based effector molecules (TREMs, e.g., TREM or TREM fragments), as well as related compositions and their use, for inserting missense mutations into open reading frames (ORFs) within genes. In some embodiments, the ORF comprises a missense mutation associated with repeat elongation disorder (RED).

The invention provides application of a genetic marker associated with the shank girth of a 13-week-old chicken in chicken genetic breeding, and belongs to the technical field of animal genetic breeding and genetic marker detection, and the genetic marker associated with the shank girth of the 13-week-old chicken comprises SCtag181 and / or SCtag182; the SCtag181 corresponds to the 10017293 site of the physical position of a chromosome 18 in the sequence information of a chicken reference genome bGalGal1. Mat.broil.GRCg7b version published in NCBI (National Center of Biotechnology Information), and belongs to the 19 intron sequence of a gene RPTOR, and the basic group at the position is A or G; the SCtag182 corresponds to the 10125815th site of the physical position of the No.18 chromosome in the same version of sequence information and belongs to the 67 exon missense mutation of the gene RNF213, and the basic group at the site is T or C. The SCtag181 and the SCtag182 are both helpful for genetically improving the shin girth of the chicken, and when the SCtag181 and the SCtag182 are applied to genetic breeding of the chicken, the uniformity of growth traits can be improved, and the incidence frequency of osteoporosis can be reduced.

This invention relates to the field of biotechnology, specifically to the FAM166A gene missense mutation molecular marker and its application in esophageal cancer risk assessment or prognosis. It was found that the expression level of FAM166A in esophageal cancer patient tissues was significantly higher than that in normal controls, and its expression level was positively correlated with the occurrence and development of esophageal cancer. In vitro cell function experiments confirmed that the FAM166A gene P84L missense mutant, compared with wild-type FAM166A, significantly enhanced the proliferation, invasion, and migration abilities of esophageal cancer KYSE150 cells. Upregulation of wild-type FAM166A significantly promoted the malignant phenotype of esophageal cancer cells, while upregulation of the P84L mutant enhanced this effect. An esophageal cancer cell model stably overexpressing wild-type FAM166A and the P84L mutant was constructed, which can serve as a drug screening platform for high-throughput screening of anti-tumor candidate drugs targeting FAM166A or its mutants.

This invention provides a method for identifying or predicting missense mutations that pose a risk of causing disease. [Solution] A method for predicting whether a missense mutation is pathogenic or benign includes: (1) creating a pathogenic mutation population and a benign mutation population for the target protein; (2) calculating the mutation energy (△△Gmut), standardized solvent-accessible surface area (nSASA), and predicted local distance difference test (pLDDT) score for each individual mutation constituting each population, and calculating the average values ​​of △△Gmut, nSASA, and pLDDT score for each population; (3) calculating △△Gmut, nSASA, and pLDDT score for the missense mutation to be predicted; and (4) calculating the Mahalanobis distance of the missense mutation to be predicted from the pathogenic mutation population and the benign mutation population, respectively.