51 results about "Genetics disease" patented technology

The invention relates to the technical field of biomedical data analysis, and discloses a data analysis method and system for genetic disease gene detection and a storage medium, and the method comprises the following steps: collecting a patient sample, and carrying out high-throughput sequencing to obtain original data; performing quality control and comparison processing on the data to generate variation detection data, and calculating variation information amount; suspicious variation sites are automatically screened, variation information amount is analyzed based on information entropy, and key variation is screened according to a preset threshold; performing Bayesian inference analysis on the key variation, calculating pathogenicity probability, and performing pathogenicity judgment based on an ACMG standard; calculating the matching degree of the key variation and the phenotype in combination with the phenotype information of the patient, and screening the variation conforming to phenotype characteristics; submitting the screening result to a doctor for auditing, and generating a final screening result; and generating a standardized gene detection report according to a final result. According to the method, pathogenic variation is efficiently and accurately recognized, and the automation level and clinical application value of genetic disease gene detection are improved.

The invention relates to the technical field of data analysis, and particularly discloses a Down's syndrome screening system based on multiple key indicators, which comprises the following steps: analyzing historical sample data including pregnant woman age, body weight, race background, pregnancy history record, serum PAPP-A concentration, free beta-hCG concentration, neck transparent layer thickness and the like; mining a chromosome abnormality risk distribution rule; standardizing detection data by adopting a principal component analysis method, grouping pregnant woman features by utilizing a clustering algorithm, and determining a feature offset coefficient; establishing a personalized index reference interval by combining factors such as fetal structure abnormality, chromosome abnormality and family genetic disease history; generating personalized risk probability distribution by fusing individual features and ultrasonic measurement data; according to the method, the risk value is calculated and the dynamically adjusted risk prediction curve is generated according to the real-time detection data and the personalized reference interval, so that an accurate Down's syndrome risk assessment basis is provided for clinical decisions.

The invention discloses a method for extracting mesenchymal stem cells from urine. The method comprises the following steps: (1) sampling and inoculating urine; (2) amplification and passage of mesenchymal stem cells; (3) identifying the urine stem cells; and (4) a cryopreservation and resuscitation method of the urine stem cells. And performing biological phenotype identification according to the standard formulated by the International Cell Therapy Association to confirm the mesenchymal stem cells. The method is low in cost, simple and rapid, and the used culture solutions are all commercialized and are very convenient to purchase and use. The culture solution special for the stem cells is used in the first two weeks of the extraction period, after passage, when enough stem cells are obtained, the culture medium can be replaced with a common DMEM culture medium, and the manufacturing cost is greatly reduced. And secondly, the materials are simple, rapid and non-invasive, and the sample of the method for extracting the mesenchymal stem cells from urine comes from a patient, so that the problem of heterogeneity of cell sources is reduced. And a foundation is laid for stem cell treatment and gene editing treatment of genetic diseases and major difficult diseases.

the present invention relates to peptides, in particular cell-penetrating peptides, having a first hydrophobic domain positioned at the C-terminus of the peptide and a second hydrophobic domain positioned at the N-terminus of the peptide, and to conjugates of such cell-penetrating peptides with a therapeutic molecule. The present invention further relates to use of such peptides or conjugates in methods of treatment or as a medicament, especially in the treatment of genetic disorders and in particular muscular dystrophies such as Duchenne muscular dystrophy.

The invention relates to the technical field of auxiliary diagnosis, and particularly discloses a genetic disease auxiliary diagnosis system based on biological characteristic information, which comprises a data arrangement module, a path analysis module, a characteristic analysis module and a path determination module, the data arrangement module extracts historical diagnosis data of the single-gene hereditary disease, constructs a diagnosis feature table and extracts a diagnosis path; the path analysis module is used for performing specific analysis on the diagnosis path and the single-gene hereditary disease and determining an independent diagnosis path; the feature analysis module performs quantitative analysis on the biological feature information of the diagnosis independent path to obtain a feature time index and construct a feature time sequence; and the path determination module performs quantitative analysis on the instability of each piece of biological characteristic information of the diagnosis independent path, and determines a stable diagnosis path. According to the method, the diagnosis process can be optimized, clinical decision and research can be assisted, the unnecessary detection cost is reduced, and the medical resource utilization efficiency is improved.

The invention belongs to the technical field of biological detection, and relates to a target area amplification method suitable for long-read-long three-generation sequencing, which comprises the following steps: designing at least one pair of amplification primers, and enabling the amplification primers to cover a target area; if the length of the target area is less than or equal to 20kb, designing a pair of amplification primers; if the length of the target area is larger than 20 kb, multiple pairs of amplification primers are designed, the adjacent amplification primers have overlapped areas, the multiple pairs of amplification primers are divided into two groups, and the coverage areas of the amplification primers in each group are not overlapped; performing long fragment amplification on the gDNA of the detection sample by adopting the amplification primer to obtain a to-be-detected product; carrying out library building and third-generation sequencing on the to-be-detected product; and carrying out single-gene genetic disease detection and / or haplotype analysis to obtain single-gene genetic disease information and / or haplotype information of the target gene. According to the method disclosed by the invention, the sequencing cost and the analysis time are remarkably reduced, and the method has relatively high detection accuracy.

The invention discloses a method and a system for assisting in inputting clinical information of rare diseases and analyzing gene mutation based on phenotypes. The method comprises the following steps: firstly, acquiring clinical information in voice, text and image forms of a patient through a multi-source data acquisition module, converting the clinical information into characters, and performing entity recognition and standardization processing to generate structured medical record data; secondly, extracting clinical phenotypes from the structured data; furthermore, a candidate gene list is obtained according to the gene-disease relationship, comprehensive scoring and sorting are carried out, and a concerned gene list is output. According to the method, efficient structured input and standardization of clinical information are realized, the accuracy and automation level of phenotype-gene matching are remarkably improved, the gene variation interpretation period is effectively shortened, and intelligent support is provided for precise diagnosis of genetic diseases.

The invention discloses a genetic disease pathogenic site sorting and diagnosis auxiliary method and system based on multi-modal artificial intelligence. The method comprises the following steps: firstly, collecting genetic disease data to construct a heterogeneous knowledge graph; the method comprises the following steps: acquiring patient data, and executing an analysis process: generating multi-modal feature representation of candidate pathogenic sites from four dimensions of variation features based on rules, a tissue specificity mechanism, a protein three-dimensional structure and real-time literature evidence; carrying out fusion sorting on the features by using a sorting model, and generating an interpretable report and a clinical examination suggestion based on the uncertainty of a sorting result; and after the doctor executes examination according to the suggestion and feeds back newly added data, the analysis process is repeated until a preset iteration target is achieved. According to the method, the limitation of a static analysis model is broken through, multi-dimensional evidence fusion and clinical workflow embedding are realized, and the interpretation accuracy and diagnosis efficiency of the pathogenic site of the genetic disease are remarkably improved.

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 invention belongs to the technical field of biological information detection, provides a genetic detection method, system, product and equipment before embryo implantation, and aims to solve the problems that a conventional genetic detection process before embryo implantation is complicated, depends on a complete family sample, is difficult to distinguish equilibrium translocation and unbalanced translocation, is low in linkage analysis efficiency, needs to independently detect items and the like. According to the method provided by the invention, parent haplotypes can be constructed on the basis of monomolecular length reading sequencing data of male parents, female parents and to-be-implanted embryo samples in families, sequence similarity is analyzed on the basis of the parent haplotypes, and the to-be-implanted embryo samples can be obtained by tracing genetic sources of the haplotypes of the to-be-implanted embryo samples. And determining whether the to-be-implanted embryo carries the single-gene genetic disease and / or chromosome structure rearrangement or not. According to the method, integrated detection of aneuploidy, monogenic hereditary diseases and chromosome structure rearrangement before embryo implantation can be completed on a single platform, and whether the embryo to be implanted has genetic defects or not can be quickly, simply, efficiently and accurately judged in a one-stop manner.

The present disclosure provides compositions related to binding of various sarcoglycan proteins, which are relevant for their role in numerous genetic disorders, including limb girdle muscular dystrophy. The disclosure includes proteins, antibodies and / or fragments thereof and associated polynucleotide constructs. The disclosure further provides methods for manufacturing said compositions and other uses for the same.

The invention discloses a reagent for editing a pig INSL3 gene and application of the reagent. The reagent for editing the pig INSL3 gene contains an INSL3-sgRNA A and an INSL3-sgRNA B, wherein the INSL3-sgRNA A and the INSL3-sgRNA The target sequence of the INSL3-sgRNA A is as shown in SEQ ID No.5; the target sequence of the INSL3-sgRNA B is shown in SEQ ID No. 6. Experiments prove that the INSL3-sgRNA A and the INSL3-sgRNA B are combined with a CRISPR (clustered regularly interspaced short palindromic repeats) / Cas9 system, so that the pig INSL3 gene can be efficiently edited, and the editing efficiency of the INSL3 gene of pig testicular cells and the editing efficiency of the INSL3 gene of pig fetal fibroblasts can reach 8.47% and 11.45% respectively. The invention has important significance on the function research of the INSL3 gene of pig cells or individuals and the breeding of pig genetic disease resistance.

The present application belongs to the technical field of biological information detection, and provides a pre-implantation genetic diagnosis method, system, product and equipment. The present application is aimed at the problems of complex traditional pre-implantation genetic diagnosis process, dependence on complete family sample, difficulty in distinguishing balanced translocation and unbalanced translocation, low linkage analysis efficiency, and the need for independent detection, etc. The method provided by the present application can be based on single molecule long read sequencing data of the paternal sample, the maternal sample and the to-be-implanted embryo sample in the family, construct the parental haplotype, and analyze the sequence similarity based on the same. By tracing the genetic source of the haplotype of the to-be-implanted embryo sample, it is determined whether the to-be-implanted embryo carries a monogenic genetic disease and / or a chromosome structure rearrangement. The present application can complete the integrated detection of pre-implantation aneuploidy, monogenic genetic disease and chromosome structure rearrangement on a single platform, and quickly, simply, efficiently and accurately determine whether the to-be-implanted embryo has genetic defects.

The present invention relates to a novel method of treating pulmonary emphysema in patients suffering from alpha-1 antitrypsin deficiency (AATD), a genetic disorder that causes low levels of alpha-1 antitrypsin (AAT), a protein that protects the lungs from damage by neutrophil elastase. The invention consists of aerosolizing nanoparticles composed of apolipoprotein A1 enriched with AAT (A1NP). The invention aims to deliver these nanoparticles directly to the lungs, where they can interact with the alveolar surface and modulate the inflammatory and proteolytic processes that lead to emphysema. In particular, the inventors report that said nanoparticles are not cytotoxic, have anti-inflammatory and anti-elastase properties, can cross alveolar epithelial cells, and are not immunogenic in mice.

The invention discloses a mutant gene enrichment method, a mutant gene detection method and a mutant gene detection kit based on Cas9 specific cleavage and isonucleotide magnetic beads. The method comprises the following steps: firstly, extracting free DNA; then identifying and cutting a completely matched wild type sequence by using Cas9 protein and specific sgRNA, and reserving the mutant DNA due to base mismatch; cas9 treated DNA and streptavidin magnetic beads containing a biotinylated oligonucleotide probe are incubated, guanine and cytosine in the probe are substituted by isoguanine and isocytosine respectively, and adenine and thymine are modified by locked nucleic acid, so that high-stability homodromous pairing is realized, and mutation DNA is selectively enriched; and finally, carrying out qPCR or sequencing detection on the enriched DNA. The kit has the characteristics of simplicity and convenience in operation, high specificity and high sensitivity, can be used for detecting single-base-level mutation, and is suitable for liquid biopsy, tumor early screening and genetic disease mutation detection.

The present disclosure relates to an engineered hematopoietic cell comprising a very late antigen-4 (VLA-4) variant and uses thereof in treating an inherited genetic disorder or an acquired disorder.

Disclosed are methods for preparing a non-naturally occurring composition, comprising: extracting cell-free DNA from a plasma fraction of a blood sample of a pregnant person, wherein the pregnant person is a heterozygous carrier of at least one pathogenic variant in at least one target gene associated with autosomal recessive disorders, wherein the extracted cell-free DNA comprises a mixture of maternal cell-free DNA and fetal cell-free DNA; performing targeted enrichment on the extracted cell-free DNA or DNA derived therefrom to enrich a plurality of target variant loci in a plurality of target genes and generating enriched DNA, wherein the target variant loci comprise the at least one pathogenic variant; performing high-throughput sequencing on the enriched DNA or DNA derived thereof and generating sequence reads, and determining fetal genotypes of one or more of the target genes from the sequence reads.

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.

This invention relates to the fields of molecular biology and human genetic disease detection; specifically, it relates to a reference standard for methylmalonic acidemia and its application. The reference standard comprises positive reference cells with MMACHC gene mutation sites. The genome of the positive reference cells contains one or more combinations of specific mutation sites of the following MMACHC genes: c.609G>A, c.567insT, c.658_660delAAG, c.482G>A, c.1A>G, c.80A>G, c.217C>T, c.315C>G, and c.394C>T. This reference standard provides reliable technical support for the accurate detection of methylmalonic acidemia, especially MMACHC gene-related mutations, and is of great significance in improving detection accuracy and promoting detection standardization.

A dual component system for treating a genetic disorder is provided. The system includes (a) a gene editing vector comprising an expression cassette comprising a nucleic acid sequence encoding a nuclease and regulatory sequences that direct expression of the nuclease in a target cell comprising a PCSK9 gene; and (b) a donor vector comprising a nucleic acid sequence encoding an exogenous product for expression from the PCSK9 locus, wherein the inserted nucleic acid sequence does not encode PCSK9, wherein the system further comprises sequences that direct the nuclease to specifically targets the native PCSK9 gene locus; and wherein the native PCSK9 in the target cell is optionally ablated or reduced post-dosing with the dual component system.

The invention discloses application of a mutant gene related to ASD, the mutant gene is at least one of the following genes: RAB5A, EFNB2, NEDD9, WNT9B, LIN7C, FOLR1, BNIP3, CAMSAP2, ADCY10, FCSK, UGDH and PIGH, the genes are related to ASD phenotype related pathways, but the genes are not recorded in an SFARI / HPO database before. The findings are beneficial to clarification of genetic causes of ASD and provide favorable help for early diagnosis and treatment research of ASD.

Hypomelanosis of Ito is a clinical term for patients with mosaic syndromes characterized by skin hypopigmentation and developmental disorders. The genetic causes of these rare diseases remain largely unclear. Here, we report that GNA13 is a new gene that causes Hypomelanosis of Ito. We identified an identical mutation in this gene in four unrelated patients exhibiting pigmentary mosaicism. In depth functional investigations revealed that this is an activatory mutation that alters the cytoskeleton and morphology of melanocytes via a hyperactivation of the RHOA / ROCK signalling pathway. Our results also indicate that this pathology does not necessarily originate from a decreased production of melanin, but can originate from a defect in melanosome transfer to keratinocytes due to cell shape alterations. Thus, our findings suggest for the first time a mechanism by which the clinical symptoms of patients with Hypomelanosis of Ito appear, and pave the path for new therapeutic approaches. Altogether, the present invention relates to a method for treating a patient suffering from hypomelanosis of Ito by administering a ROCK inhibitor and / or RHOA inhibitor.

The present invention relates to peptides, in particular cell penetrating peptides, of 40 amino acid residues or less comprising at least one directly glycosylated amino residue and one or more arginine rich arm domains, and to conjugates of such cell penetrating peptides with a therapeutic molecule. The present invention further relates to the use of the peptides or conjugates in methods of treatment or as a medicament, especially in the treatment of genetic disorders of the central nervous system.

The invention provides a probe composition, a gene chip, a reagent, a kit and application. The probe composition is designed based on capture areas of 34 genes related to dominant single-gene genetic diseases, can be used for non-invasive prenatal genetics screening, and is suitable for prenatal screening of genetic variation positive family history, bad fertility history, fetal ultrasound examination abnormality, pregnant woman elderly, father elderly and the like. The omission ratio and the birth rate of fetuses suffering from the dominant single-gene hereditary disease are effectively reduced.

The present disclosure relates to compositions and methods for treating genetic disorders caused by nonsense mutations using anticodon-engineered transfer RNA (ACE-tRNA) constructs. These DNA-based ACE-tRNA constructs are designed to suppress premature termination codons (PTCs) and restore the expression of full-length, functional proteins. The disclosure further provides formulations of ACE-tRNA constructs with poly(amine-co-ester) (PACE) polymeric nanoparticles to improve stability, protect nucleic acids, and enhance delivery to airway epithelial cells. Also described are functionalized ACE-tRNA Picovectors (sLPVs) incorporating targeting elements such as nuclear localization signals (NLSs), nucleolar localization sequences (NoLSs), and DNA nuclear targeting sequences (DTSs) to improve nuclear import and localization.

The invention provides an irritable bowel syndrome risk marker based on genomics. The risk marker comprises the following six pathogenic genes: CADM2, PHF2, PCLO, SHISA6, LRP1B and TANK. According to the invention, not only is the effect of the latest large-scale whole genome association research (GWAS) on the aspect of analyzing the genetic cause of the irritable bowel syndrome shown, but also five new genetic risk variation, potential unreported pathogenic genes and treatment targets of the irritable bowel syndrome are found; a new insight is provided for the cause of the irritable bowel syndrome, and a potential therapeutic intervention target is highlighted. The invention also provides an application based on the risk marker of the irritable bowel syndrome and a corresponding early screening kit.

The current invention provides an improved oligonucleotide and its use for treating, ameliorating, preventing, delaying and / or treating a human genetic disorder, said oligonucleotide comprising an internucleoside linkage of the following formula (I).

The present invention relates to the technical field of data analysis, and specifically discloses a Down syndrome screening system based on multiple key indicators. The system comprises: mining the risk distribution pattern of chromosomal abnormality by analyzing historical sample data, including maternal age, weight, ethnic background, pregnancy history, serum PAPP-A concentration, free β-hCG concentration, and nuchal translucency thickness; standardizing test data using principal component analysis, and grouping maternal characteristics using a clustering algorithm to determine a characteristic shift coefficient; establishing personalized indicator reference intervals based on factors such as fetal structural abnormalities, chromosomal abnormalities, and family genetic disease history; generating a personalized risk probability distribution by fusing individual characteristics with ultrasound measurement data; and calculating risk values ​​and generating a dynamically adjusted risk prediction curve based on real-time test data and the personalized reference intervals, thereby providing an accurate Down syndrome risk assessment basis for clinical decision-making.

The invention relates to a method for accurately analyzing whole genome sequencing data copy number variation, and belongs to the technical field of biological information analysis and genome data processing. The method comprises the following steps: constructing a target interval file based on a 1kb window and exon annotation information; performing quality control, comparison and duplicate removal on the sequencing data to generate a comparison file; calculating and standardizing the target interval sequencing depth under different quality thresholds, and establishing a multi-sample depth baseline; through comparison with a base line, identifying a candidate copy number variation region in combination with a difference multiple and Z-score; and further extracting abnormal comparison information of the candidate region, judging the position of the breaking point and evaluating the credibility of variation. According to the method, the comparison interference of homologous regions is remarkably reduced, the detection resolution and the fracture point positioning precision are improved, and the method can be widely applied to the scenes of genetic disease screening, tumor variation detection and the like.

The invention provides a method for the automated calculation of the reproductive risk of genetic disorders from Next Generation Sequencing (NGS) data of male and female subjects. The method includes (i) online data collection from male and female subjects; (ii) processing raw sequencing data to detect genetic variants; (iii) assessing variant pathogenicity using a scoring metric that comprises multiple types of supporting evidence; (iv) text mining of male and female family history and phenotype description; (v) association of genetic disorders to the identified pathogenic variants based on a comprehensive database with automated updating functionalities; (vi) calculation of the reproductive risks using data from male and female subjects; (vii) digital report generation. The method enables efficient and accurate identification of pathogenic variants in a wide range of gene-disease associations, which can be scaled in a computer system.