46 results about "Pathogenic mutation" patented technology

The invention belongs to the technical field of medical software development, and particularly relates to a plateau newborn inherited metabolic disease screening system, a computer readable storage medium and application of the plateau newborn inherited metabolic disease screening system. According to the screening system, an altitude hierarchical multi-level reference value database based on a local healthy newborn queue is established, and the problem that the false positive rate of a plain area screening model in a plateau area is too high is solved by fitting an altitude metabolism marker reference median and a standard deviation curve. By designing a'biochemical primary screening-risk scoring-targeted sequencing automatic triggering 'three-level joint control data processing flow, targeted sequencing guided by a crowd specific pathogenic mutation library is started only when the biochemical risk is high, unnecessary whole genome sequencing is avoided, and the screening cost is remarkably reduced. The system can continuously iterate a reference curve and a risk threshold value according to definite diagnosis data, and closed-loop dynamic optimization from sample collection to report generation is achieved. The method has plateau adaptability, crowd specificity and cost controllability, and has a good clinical application prospect.

The invention discloses an editing system for repairing amyotrophic lateral sclerosis pathogenic mutant genes, and relates to an IS621-bridge-RNA gene editing system capable of being applied to eukaryotic cells, an AAV9 virus vector mediated IS621-bridge-RNA gene editing system and application of the AAV9 virus vector mediated IS621-bridge-RNA gene editing system, and the IS621-bridge-RNA gene editing system, a recombinant expression vector and a gene therapy mode are included.

A duchenne muscular dystrophy-related exonic splicing enhancer, sgRNA and gene editing tool can be applied in the preparation of drugs for treating duchenne muscular dystrophy. The gene editing tool designed on the basis of cytosine deaminase AID mutants and Cas9 mutants can perform site-specific modification on a mammalian genome by using an adeno-associated virus (AAV) as a vector. By optimizing an encoding nucleic acid sequence and an element composition structure of the editing tool, site-specific targeted modification of mammalian genetic material DNA can be efficiently achieved; and by performing targeted genetic manipulation on the nucleic acid sequence carrying disease mutations, a pathogenic mutation cannot be retained in a mature protein amino acid sequence or the pathogenic mutation cannot perform its function, so that the purpose of treating various gene mutation type genetic rare diseases is achieved, and the advantages of high efficiency, safety and stability are achieved.

The application relates to the technical field of gene sequencing data processing and bioinformation analysis, in particular to a Web-based whole-exome sequencing tumor gene mutation detection visual analysis method and system. The system collects user sequencing data and a reference genome version through a Web interactive interface; a program is called to perform quality control cleaning and evaluation on the data, and a visual report is generated; sequence alignment is completed based on the reference genome, and a variation site is identified through algorithm iteration; biological annotation of the variation is combined with a database, a candidate pathogenic mutation set is screened out in multiple levels according to a strategy, the candidate set is projected to a visual interface, a site state is confirmed or removed in response to a manual checking instruction, and a final gene mutation detection report is generated. The application greatly simplifies the whole-exome sequencing data processing procedure, makes it easy for clinical doctors or researchers without bioinformation background to start, and improves the popularization rate and work efficiency of tumor gene detection work.

Methods and systems for predicting the pathogenicity of variant sequences detected in a sample from a subject are described. The disclosed methods may comprise, for example, receiving sequence read data for a plurality of sequence reads obtained from a sample from a subject; identifying one or more variant sequences based on the sequence read data; providing a variant sequence from the one or more identified variant sequences as input to a trained machine learning model configured to determine a pathogenicity prediction score for the identified variant sequence based on the variant sequence and at least one of additional genomic profiling, demographic pathogenicity prediction score determined for the variant sequence identified in the sample from the subject.

This application belongs to the field of biotechnology and relates to an efficient and specific editing system, method, and application for A-G base substitution. The fusion protein described in this application comprises, from the N-terminus to the C-terminus, a first SaCas9 nickase fragment, a chimeric deaminase fragment, and a second SaCas9 nickase fragment. The deaminase is selected from adenosine deaminase or a variant thereof, specifically ecTadA8e. The amino acid sequence of ecTadA8e is shown in SEQ ID NO. 20, or has more than 80% sequence identity with the amino acid sequence shown in SEQ ID NO. 20, and possesses the function or activity of ecTadA8e. The fusion protein provided in this application, combined with the corresponding guide RNA, can efficiently and specifically replace the base A with G at the target site, providing an effective tool for repairing pathogenic mutations, studying gene function, and improving cell function, and has promising application prospects.

The invention discloses a system for screening Reiye's syndrome based on NOD2 gene new pathogenic mutation. The invention provides a computer device. The computer device comprises a memory, a processor and a computer program stored in the memory, the processor executes the computer program to implement the following steps: receiving NOD2 gene data (cDNA sequence) of a person to be tested; the method comprises the following steps: reacting the NOD2 gene with any one of the following mutations in SEQ ID No.2 stored in a computer: c.380Cgt; t, c, 2657Cgt; t, c.328Ggt; a, c.1295Cgt is selected from the group consisting of the T, c, 1981Ggt; c, and c, 2452Agt; c) performing comparison; and according to a comparison result, outputting information about whether the to-be-detected person is or is suspected to be a patient with the Reiderson's syndrome or about the risk of suffering from the Reiderson's syndrome. The novel pathogenic gene mutation form related to the NOD2 gene of the patient with the Reidersi syndrome is found, the novel pathogenic gene mutation form can serve as a target object to be used for developing a reagent and a computer device for diagnosing or screening the Reidersi syndrome, and the novel pathogenic gene mutation form has important significance on diagnosis and screening of the Reidersi syndrome.

This invention belongs to the field of biopharmaceuticals and relates to a gene therapy drug for hereditary retinal dystrophy related to RLBP1 gene mutations and its application. Specifically, it involves constructing a recombinant AAV-RLBP1 gene therapy drug, which is then injected intravitreally to infect retinal pigment epithelial cells and Müller cells, causing them to express complete and active RLBP1 protein. This invention utilizes a modified AAV vector to package codon-optimized human RLBP1-cDNA, enabling the expression of complete and active RLBP1 protein, which participates in the visual circulation pathway, rescuing retinal dysfunction caused by pathogenic mutations in the RLBP1 gene, improving visual function in patients, or delaying disease progression.

The invention discloses application of disulfiram in preparation of a medicine for treating UMOD gene mutation type autosomal dominant renal tubulointerstitial nephropathy, and belongs to the field of biomedicine. The application comprises the application of the disulfiram in preparation of the medicine for treating the hereditary tubulointerstitial nephropathy. According to the invention, a new pathogenic mutation UMOD c.106Cgt is identified; according to the invention, the pathogenicity of the gene is verified through a UMODH36Y mouse model constructed by CRISPR / Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats / CRISPR associated 9). DSF intervention is adopted, the serum creatinine and glomerular filtration rate (tGFR) of mice can be remarkably improved, and renal interstitial inflammation and fibrosis are relieved. The discovery prompts that the DSF realizes the therapeutic effect of renal function protection-inflammation inhibition-fibrosis relief in an ADTKD-UMOD animal model through targeted regulation of a pyroptosis pathway, a novel therapeutic strategy is provided for ADTKD-UMOD, and the clinical transformation period can be remarkably shortened due to the characteristic of new use of old medicines. The discovery lays an experimental foundation for developing a precise treatment scheme for the hereditary renal tubulointerstitial disease.

The invention discloses a scoring and sorting method and system for pathogenic mutation of a single-gene genetic disease, and relates to the technical field of biomedical treatment, the method comprises the following steps: based on pre-acquired phenotypic data and literature abstracts, performing standardized phenotypic term extraction on pre-acquired symptom description by using a mixed strategy, performing phenotype and gene association degree scoring on the standardized phenotype terms and pre-acquired gene mutation data through a similarity comparison method; performing gene variation annotation on a pre-acquired gene variation database, and performing gene variation scoring on the pre-acquired gene variation data according to a gene variation annotation result; and performing multi-dimensional pathogenicity comprehensive scoring evaluation by using a supervised learning model and a weighted summation method to obtain a pathogenic mutation sorting scoring result. By recommending the most probable pathogenic mutation, the grading and sorting of the pathogenic mutation of the genetic disease have the advantages of high detection recall rate and high automation degree.

The invention discloses a method for improving human alpha-globin expression through double-site gene editing and application of the method, and belongs to the technical field of gene editing. The method comprises the following steps: editing an HBA1 gene regulatory region and / or an HBA2 gene regulatory region and an HBA1 gene pathogenic mutation site and / or an HBA2 gene pathogenic mutation site by using a gene editing system, so that at least one cytosine in the HBA1 gene regulatory region and / or the HBA2 gene regulatory region is converted into thymine, and the pathogenic mutation site of the HBA1 gene and / or the pathogenic mutation site of the HBA2 gene are / is repaired. By performing double-site editing on the gene regulation region and the gene pathogenic mutation site, on one hand, the pathogenic mutation site is repaired, and normal translation of part of alpha-globin is recovered; on the other hand, an HBA1 gene regulation region and / or an HBA2 gene regulation region of the alpha-globin can be edited, transcription or translation of the alpha-globin can be promoted, the HBA1 gene regulation region and the HBA2 gene regulation region generate a synergistic effect, and finally the purpose of further improving the expression quantity of the alpha-globin is achieved.

The invention discloses a mutant gene of a gm15262 gene and application of the mutant gene, and belongs to the technical field of molecular biology and medicine. The CDS sequence of the mutant gene of the gm15262 gene is shown as SEQ ID NO.1, and compared with the CDS sequence of a normal human source gm15262 gene, the CDS sequence of the mutant gene of the gm15262 gene is subjected to c.C338T (p.P113L) mutation. A male sterility animal model can be constructed by enabling corresponding sites of the animal gm15262 gene to be subjected to same mutation, when the animal model is a mouse model, a male sterility mouse model can be obtained by enabling the gm15262 gene of a mouse to be subjected to c.C305T (p.P102L) mutation, and the mouse model is used for accurately simulating pathogenic mutation of human genetic diseases. And a key experimental platform is provided for development of gene therapy, targeted drug screening and germ cell editing research. The invention has important significance in diagnosis and treatment of male infertility.

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 discloses a method, device and storage medium for correcting mitochondrial genome sequencing mutations. The mitochondrial genome sequencing mutation correction method of the application comprises the following steps: firstly, retaining possible pathogenic mutations through a known mutation whitelist; and then, removing false positives caused by experimental errors and sequencing errors by using 11 filtering indexes, such as the average value of the position of a read in which the mutation is located, the chain distribution deviation of the mutation and the average base quality value of the mutation, so as to obtain a high-credibility mutation set. The correction method of the application can reduce the workload of mutation interpretation and improve the accuracy of analysis results. Moreover, the correction method of the application is not limited by the number of samples and can be used for correcting single samples or a small number of samples.

The application discloses an ncRNA gene mutation interpretation method, a storage medium and a terminal, and relates to the field of ncRNA gene mutation interpretation.The ncRNA gene mutation interpretation method comprises the following steps: constructing an ncRNA gene pathogenic mutation standard dataset, an ncRNA gene benign variation standard dataset and an ncRNA gene variation harmfulness standard dataset for experimental verification; constructing a scoring model for training ncRNA gene variation harmfulness and an ncRNA gene related disease phenotype similarity scoring model by using the aforementioned datasets; performing logistic regression modeling on harmfulness scoring files and ncRNA gene disease phenotype similarity scoring files containing the same number of pathogenic and benign ncRNA gene variation sites by using data mining software; obtaining an algorithm model for screening and identifying specific evaluation of ncRNA gene pathogenic mutations; training the algorithm model; and interpreting and reporting ncRNA gene mutations by using the trained algorithm model.The ncRNA gene mutation interpretation method can realize standardized, automatic, intelligent and high-throughput clinical interpretation reports for ncRNA gene mutations, greatly improves the interpretation efficiency and the accuracy of the interpretation.

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 application belongs to the technical field of gene detection, and particularly relates to a primer pair, a kit and a detection method for CHD7 mutation. The application can detect 10 potential CHD7 pathogenic mutation sites in a sample to be detected in one PCR reaction by aiming at 10 frequently-occurring CHD7 pathogenic mutation sites selected in a specific manner, and has the characteristic of wide coverage. In addition, the primer pair of the application can further combine with high-resolution melting curve analysis to omit steps such as product recovery after amplification, plasmid construction, sequencing detection and the like in traditional technology, greatly accelerating the detection process and reducing the detection cost, and improving the timeliness of subsequent medical intervention. On the other hand, the primer pair of the application can simultaneously detect 10 sites, and the single detection throughput is several times that of traditional technology, greatly reducing the sample requirement and the number of repeated experiments.

Disclosed herein is a system for discovering a drug active site of protein, to which a drug binds, in a protein containing a pathogenic mutation. The system includes: a pathogenic mutation position de

The invention relates to the technical field of gene editing, in particular to a method for synchronously constructing a mouse model with the point mutation (Knockin, KI) of a Clcn3 gene p.T570I and the knockout (Knockout, KO) of the Clcn3 gene by utilizing a CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-associated protein 9) system and application of the mouse model. By optimizing a gRNA targeting site and a donor oligonucleotide sequence, efficient introduction of Clcn3 gene p.T570I point mutation is achieved, and the mutation efficiency is improved by 30% or above compared with a traditional method; the constructed Clcn3 gene p.T570I KI and KO mouse models can be used for stably inheriting target mutation. The method is short in period, low in cost and suitable for large-scale gene editing animal model construction, the first Clcn3 gene p.T570I KI mouse model carrying the human pathogenic mutation site in the world is constructed, and an ideal and reliable genetic tool is provided for deep analysis of the physiological function of the CLCN3 gene and related disease mechanisms.

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 invention provides a tent5d gene mutation and application thereof, and belongs to the technical field of molecular biology and medicine. The CDS sequence of the mutant gene of the tent5d gene is as shown in SEQ ID NO.1, and compared with the CDS sequence of a normal human TENT5D gene, the CDS sequence of the mutant gene of the tent5d gene has c.C555G (p.D185E) mutation. A male sterility animal model can be constructed by enabling corresponding sites of animal tent5d genes to be subjected to same mutation, when the animal model is a mouse model, the tent5d genes of a mouse are subjected to c.T555G (p.D185E) mutation to obtain a male sterility mouse model, and the mouse model can be used for accurately simulating pathogenic mutation of human genetic diseases. And a key experimental platform is provided for development of gene therapy, targeted drug screening and germ cell editing research. The invention has important significance in diagnosis and treatment of male infertility.

The invention provides a screening method for establishing a model by using a whole exome sequencing technology. The screening method comprises the following steps: collecting a sample; extracting all DNA molecules in the sample, and carrying out quality inspection on the DNA molecules; if the DNA molecule quality inspection is qualified, adding a sequencing linker to the DNA molecule, and sequencing the DNA molecule to obtain original data; the original data is preprocessed to obtain effective data, the preprocessing comprises the steps of filtering out sites on mitochondria and patch sequences, screening out point locations with the mass value smaller than 30, point locations with the maximum value of GQ values of the same batch smaller than 20 and point locations with the maximum value of depth of the same batch smaller than 8, splitting multi-allele sites, filtering out known benign point locations, and obtaining the effective data through the screening of the point locations with the mass value smaller than 30, the maximum value of GQ values of the same batch smaller than 20 and the maximum value of depth of the same batch smaller than 8; retaining points of known pathogenic mutation or sites possibly influencing splicing, including annotating and screening effective data by using VEP (Vascular Endothelial Potential) and Gnomad; and performing differential expression gene analysis on the effective data, and establishing an evaluation and prediction model. According to the method, efficient and effective data are obtained through efficient and strict processing and are specifically analyzed.

The invention discloses a base editing system and application thereof. The base editing system comprises a guide RNA (Ribonucleic Acid) and a base editor; the guide RNA is targeted to an exon 4 of the KCNQ4 gene; the guide RNA and the base editor form a nuclear glycoprotein compound and perform base editing on the exon 4 of the KCNQ4 gene, so that the 229 amino acid of the protein expressed by the KCNQ4 after base editing is glycine. The base editing system disclosed by the invention can correct pathogenic mutation sites of cochlear hair cells, obviously improve auditory functions of Kcnq4 + / G229D mice and Kcnq4G229D / G229D mice, increase the survival of the hair cells, improve the electrophysiological functions of the hair cells, and have a good application prospect.

A biomarker for Tuberous sclerosis complex (TSC) with no mutation identified (NMI) in the TSC1 or TSC2 gene and a use thereof is provided. The biomarker is the expression level of IQGAP2 gene. The present disclosure analyzed and compared the whole-exon sequencing / clinical whole-exon sequencing results of TSC-NMI (No Mutation Identified, i.e., tuberous sclerosis complex with no mutation identified (NMI) in the TSC1 or TSC2 gene) patients with those of TSC patients having pathogenic mutations in TSC1 and TSC2 gene, and found a number of potential pathogenic candidate genes for TSC-NMI. Based on the long-term accumulated experience and experimental validation in this field, it was finally found that the IQGAP2 gene is related to TSC-NMI. Thus, IQGAP2 gene can be detected, and used as a detection marker for TSC-NMI and has potential as a drug target for treating the TSC-NMI patients.

The invention discloses a WASF1 mutation pathogenic mechanism model construction and lead compound screening method, and belongs to the field of biological medicine. The problem that the WASF1 gene c.1516Cgt can be solved; the pathogenic mechanism of T truncation mutation is not clear; and targeted drugs are lacked. According to the technical scheme, the method comprises the following steps: comparing the non-phenotypic mutation of the c.873delA of the WASF1 gene with the non-phenotypic mutation of the c.1516Cgt of the WASF1 gene; determining a pathogenic mechanism as a dominant negative effect or function acquisition mechanism according to a protein expression mode of T pathogenic mutation; on the basis of the mechanism, a multi-parameter optimization Python script is adopted to call AutoDock Vina to perform batch virtual screening on the ZINC20 database small molecule compounds; by combining a comprehensive scoring system of energy score (40%), ADMET score (30%) and dynamic stability score (30%), a lead compound targeting the WASF1 mutant protein is screened out. The method is suitable for mechanism research and drug development of WASF1-related neurodevelopmental disorder diseases.

The invention discloses application of an MYRF gene mutation detection method in preparation of a conical artery trunk deformity diagnostic reagent, and relates to the technical field of biology, and the technical key point is that the risk of conical artery trunk deformity of a subject is judged by detecting pathogenic mutation of an MYRF gene in a biological sample of the subject. Studies are developed from the aspects of clinical samples, stem cell levels, animal models and the like, the pathogenic mutation of the MYRF gene in the CTA sample is analyzed by utilizing a high-throughput sequencing technology, and the correlation between the gene mutation and disease occurrence is determined; molecular mechanisms of abnormal regulation axes or signal pathways of downstream target genes and heart development related genes caused by MYRF gene defects are analyzed in stem cell and animal models by using modern molecular biology technologies such as ChIP-Seq and RNA-Seq, and an efficient method is provided for diagnosing conic artery trunk deformity.

The application discloses a PTPRQ gene mutation site related to non-syndrome deafness, the mutation site is a novel pathogenic mutation site on a human PTPRQ gene, and is one or more combinations selected from c.4723C>T, c.6040C>T, c.1811T>C, c.5687-6del and c.6560C>T. A specific probe set for detecting a PTPRQ gene mutation, the probe set is a double-stranded DNA probe, is designed according to a PTPRQ gene 45-exon sequence of a transcript NM_001145026 and a flanking region of each 5' end and 3' end of each exon with an extension of 50 bp, contains 169 probes in total, the length of a single probe is 120 bp, a shingled design is adopted, there is an overlapping region between adjacent probes, and the probe density is dynamically adjusted according to the GC content of a target sequence. A detection method of a PTPRQ gene mutation, with peripheral blood or a blood sheet of a to-be-tested person as a sample, extracting genomic DNA, performing targeted capture enrichment by using the specific probe set, combining high-throughput sequencing with standardized bioinformatics analysis, and judging whether the PTPRQ gene mutation exists in the to-be-tested sample.

The present application relates to a SIGMA+ prediction mutation pathogenicity analysis method, system and device. It comprises: obtaining a mutation of a gene to be predicted; mapping the mutation of the gene to be predicted onto a protein structure of the gene to be predicted to obtain a protein structure with the mutation mapped; inputting the protein structure with the mutation mapped into a SIGMA model to obtain a structure feature score of the gene to be predicted; inputting the mutation of the gene to be predicted into a predictor to obtain a variation effect score of the gene to be predicted; and inputting the structure feature score and the variation effect score of the gene to be predicted into a classifier to obtain a classification result of the mutation being a pathogenic mutation or a benign mutation. The method aims to combine SIGMA with other predictors based on the mutation of the gene to be predicted and the protein structure information with the mutation mapped, to explore the high prediction ability and potential application value of SIGMA for mutation pathogenicity.

The application discloses sgRNA targeting GUCY2D mutation and application thereof in preparation of an eye disease treatment drug, and relates to the technical field of biological medicine. A nucleotide sequence of the sgRNA targeting GUCY2D mutation is shown in SEQ ID NO. 1-6 or SEQ ID NO. 8. Based on the screened sgRNA, the sgRNA is loaded into a recombinant AAV expression vector together with a compact adenine base editor, and in-situ precise repair is performed on pathogenic single base mutations in photoreceptor cells through eye local delivery. The application can efficiently correct pathogenic mutations, has no significant off-target risk, can effectively protect the structural integrity of photoreceptor cells, significantly restore the retinal electrophysiological function and overall visual perception ability of a model mouse, and has stable treatment effect, no obvious toxic side effects and good safety.

The invention relates to the technical field of gene detection, and particularly discloses a construction method and application of a spinal muscular atrophy pathogenic mutant gene copy number analysis model. Based on a nanopore sequencing technology, SMN1 and SMN2 copy number variation and intragene mutation can be simultaneously detected through a long and short amplicon combination method. Experimental operation and data analysis are rapid and simple, copy number variation of SMN1 and SMN2 and mutation in SMN1 and SMN2 genes can be accurately detected at the same time, tiny pathogenic mutation can be found easily, and more comprehensive and accurate SMA screening and diagnosis can be carried out. Meanwhile, the long amplicon system disclosed by the invention can be used for detecting g.27134Tgt; the SMN1 '2 + 0' genotype can be detected through detection of a G site, and the problem that comprehensive detection cannot be achieved in the prior art is solved.