65 results about "Mutant allele" patented technology

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

To provide a technique that enables direct seeding cultivation of seed potatoes in the field of production of sweet potato tuberous roots (sweet potato cultivation), which offers significant labor-saving benefits, wherein the technique enables efficient development of sweet potato plants having desired traits and exhibiting low enlargement of seed potatoes.SOLUTION: A method for identifying a sweet potato plant exhibiting low enlargement of seed potatoes, includes the steps of: detecting a nucleotide site indicating the "Kyushu 199-type variant allele" associated with a DNA marker from a genomic DNA of the sweet potato plant to be identified, with respect to "the DNA marker that shows relevance to the phenotype of low enlargement of seed potatoes" in the genomic DNA of sweet potato plants; and determining that the sweet potato plant to be identified is a sweet potato plant exhibiting low enlargement of seed potatoes if a nucleotide site indicating the "Kyushu 199-type variant allele" associated with the DNA marker is detected in the detection step.SELECTED DRAWING: Figure 2

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

The invention is applicable to the technical field of biomedicine, and provides a method and a kit for detecting KCNJ5 gene mutation, and the method comprises the following steps: extracting a cfDNA sample; the method comprises the following steps: carrying out PCR (Polymerase Chain Reaction) amplification reaction by using a specific primer and a probe aiming at a KCNJ5 gene mutation site and taking a sample as a template; the specific primers and probes aiming at the mutation site of the KCNJ5 gene comprise specific primers and probes aiming at the mutation site of the G151R (c.451Ggt; the invention relates to a specific primer and a probe for G151R (c.451Ggt; the invention relates to a specific primer and a probe of L168R (c.503Tgt; C), aiming at L168R (c.503Tgt; g), a specific primer and a probe; sequencing a PCR amplification product, analyzing a sequencing result, and determining whether the KCNJ5 gene mutation exists or not. According to the invention, high-sensitivity and high-specificity detection of KCNJ5 gene mutation is realized by combining the specific primer and the probe with a digital PCR technology, and three main mutation types of the KCNJ5 gene can be detected at 0.01% mutation allele frequency level.

The present disclosure provides compositions and methods for altering auxin accumulation in corn or maize plants. Methods and compositions are also provided for altering the expression of genes related to auxin efflux through editing or mutagenesis of a brachytic2 (br2) gene to introduce a premature stop codon or a deletion into the gene such that a truncated Br2 protein encoded by the mutant allele of the br2 gene, which may be a dominant or semi-dominant allele, has at least part of a transmembrane domain without a nucleotide binding domain or motif. Modified plant, plant parts and cells having such a mutant allele with reduced or altered expression or activity of a br2 gene product can have improved characteristics, such as reduced plant height and increased lodging resistance, but without off-types in the plant.

The disclosure relates to soybean genes and mutant alleles thereof associated with improved flavor characteristics. Also disclosed are soybean plants comprising combinations of the mutant alleles along with related methods of improving one or more flavor characteristics of soybean seed.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Cancer immunology provides promising new avenues for cancer treatment but validation of potential neoantigens to target is costly and expensive. Analysis of MHC binding affinity, antigen processing, similarity to known antigens, predicted expression levels (as mRNA or proteins), self-similarity, and mutant allele frequency, provides screening method to identify and prioritize candidate neoantigens using sequencing data. Methods of the invention thereby save time and money by identifying the priority candidate neoantigens for further experimental validation.

The invention discloses a rice photo-thermo-sensitive male sterility mutant Osgpat6.1, a corresponding gene locus OsGPAT6.1 of the rice photo-thermo-sensitive male sterility mutant Osgpat6.1 and application of a coding protein of the rice photo-thermo-sensitive male sterility mutant The phenotypic gene OsGPAT6.1 for controlling the photo-thermo-sensitive male sterility of the rice is obtained by cloning through phenotypic analysis of a mutant and preliminary positioning of a target gene, an amino acid sequence of the phenotypic gene OsGPAT6.1 is encoded as shown in SEQ ID NO.1 to form a protein, and the gene affects the development process of rice pollen by affecting tapetum degradation. The OsGPAT6.1 gene is subjected to gene editing, or a mutant allele of the OsGPAT6.1 gene is introduced into a conventional rice variety in a hybridization manner, so that a photo-thermo-sensitive male sterile material for a two-line sterile line can be obtained. The gene and the encoding protein thereof can be applied to creation of photo-thermo-sensitive sterile rice and germplasm genetic improvement of the photo-thermo-sensitive sterile rice.

The present disclosure provides methods and systems for detecting an allelic imbalance molecular response in a sample from a subject. By determining allelic imbalance in single nucleotide polymorphisms (SNPs), a mutant allele fraction (MAF) measurement and divergence for SNPs in surrounding cluster and at gene level for all SNPs supporting determination of an allelic imbalance molecular response. Such determination increases evaluable samples that may otherwise be uninformative.

The invention discloses an ultra-sensitive target nucleic acid enrichment detection method based on programmable nuclease, and belongs to the technical field of biology. According to the enrichment method disclosed by the invention, on the basis of specific cutting of programmable nuclease, wild type nucleic acid can be continuously removed while isothermal amplification is carried out, so that the number of mutant alleles in a sample is continuously and exponentially increased, and low-abundance mutant genes or methylated DNA are enriched or detected. According to the present invention, sgRNA, guide DNA or guide RNA are designed and optimized, the sgRNA, the guide DNA or the guide RNA and a Cas protein or an Ago protein are used to form a ribonucleoprotein complex, the isothermal amplification is performed while the specific cutting is performed on the target gene, the mutation-containing gene is not cut, and the low-abundance mutation gene is enriched;

The invention discloses an ultra-sensitive target nucleic acid enrichment detection method based on programmable nuclease, and belongs to the technical field of biology. According to the enrichment method disclosed by the invention, on the basis of specific cutting of programmable nuclease, wild type nucleic acid can be continuously removed while isothermal amplification is carried out, so that the number of mutant alleles in a sample is continuously and exponentially increased, and low-abundance mutant genes or methylated DNA are enriched or detected. According to the present invention, sgRNA, guide DNA or guide RNA are designed and optimized, the sgRNA, the guide DNA or the guide RNA and a Cas protein or an Ago protein are used to form a ribonucleoprotein complex, the isothermal amplification is performed while the specific cutting is performed on the target gene, the mutation-containing gene is not cut, and the low-abundance mutation gene is enriched;

The invention relates to a mutant calreticulin for diagnosis of myeloid malignant tumors. A method for diagnosing myeloid malignancies comprising determining the presence of a mutant allele of a calreticulin gene is disclosed. In addition, genomic sequences, cDNA sequences, mRNA sequences and protein sequences of the mutant calreticulin are also subject matter of the invention. Furthermore, the invention relates to the medical use of inhibitors of the mutant calreticulin.

Methods and compositions are provided for modifying the flowering time and / or maturity time of soybean plants to enable them to be cultivated in a variety of geographical locations having different day lengths. Modified soybean plants are disclosed comprising non-natural mutant alleles at the E1 and / or E1Lb locus. The modified plants have a shorter flowering and / or maturity time than control plants.

Provided herein are highly transformable maize plants, referred to as HI-NA plants, and methods of their production and use. A HI-NA plant, as disclosed herein, is homozygous for a loss-of-function mutant allele in the patatin-like phospholipase A2α (MATL) gene and at least heterozygous for one or more QTL and / or gene alleles that are responsible for increased haploid induction and / or transformation frequency in plants. A HI-NA plant, as disclosed herein, may also have a cytotype A background, which may render it highly transformable. Also provided are methods of producing I-NA plants and methods of using a HI-NA plant for editing plant genomic DNA.

Methods and compositions are provided for modifying the flowering time and / or maturity time of soybean plants to enable them to be cultivated in a variety of geographical locations having different day lengths. Modified soybean plants are disclosed comprising non-natural mutant alleles at the E1, E2, E3, E4, E1La and / or E1Lb locus. The modified plants have a shorter flowering and / or maturity time than control plants.

Disclosed is an agent for the treatment of a common form of autosomal dominant retinitis pigmentosa (ADRP) wherein the agent comprises a first nucleotide sequence encoding a CRISPR-related (Cas) endonuclease bound to an NG or NNGRRT PAM (Primal Spacer Adjacent Motif) sequence, and a second nucleotide sequence encoding or comprising a guide RNA (gRNA) capable of forming a CRISPR-Cas complex with the Cas endonuclease, wherein the gRNA specifically targets a target mutant allele selected from the group consisting of RHOP23H and NR2E3G56R.

Methods and compositions are provided for modifying the flowering time and / or maturity time of soybean plants to enable them to be cultivated in a variety of geographical locations having different day lengths. Modified soybean plants are disclosed comprising non-natural mutant alleles at the E1, E2, E3, E4, E1La and / or E1Lb locus. The modified plants have a shorter flowering and / or maturity time than control plants.

The invention provides a construction method of a prediction model for prostate cancer malignancy risk and a prediction system, and the method comprises the following steps: S1, collecting sample data of hereditary variation of a subject, including mutation allelic dose of variation; s2, taking an intersection of the sample data of the heritable variation of the subject in the step S1 and a prostatic cancer GWAS site SNP set in UKBB; s3, calculating the correlation between the genetic mutation of the intersection in S2 and the activity of 3beta HSD1; s4, calculating the risk score of the subject; and S5, randomly selecting a plurality of genetic variations for multiple times, repeating the step S4, calculating to obtain a plurality of PRSs, and calculating a genetic variation fingerprint score. According to the construction method of the prediction model for the malignant risk of the prostate cancer and the prediction system, the tissue with high 3beta HSD1 enzyme activity and the tissue with low 3beta HSD1 enzyme activity are subjected to multi-omics sequencing, and genetic variation fingerprints are established to represent the metabolic activity of the 3beta HSD1 of the prostate tissue; the biomarker can be provided for doctors as an efficient biomarker for early diagnosis of prostatic cancer.

The invention provides application of combination of an mTOR inhibitor and an EPAS1 inhibitor in preparation of a medicine for treating myeloproliferative tumors, through combined use of the mTOR inhibitor everolimus and the EPAS1 inhibitor PT2385, JAK2V617F mutation-driven metabolic disorder is targeted, metabolic reprogramming is effectively reversed (the lactic acid level is reduced, the alpha-ketoglutaric acid level is increased, and the lactic acid / alpha-KG ratio is corrected), and the treatment effect on myeloproliferative tumors is improved. The JAK inhibitor can be used for treating MPN, synergistically relieving splenomegaly, reversing myelofibrosis and reducing mutation allele load, the curative effect is remarkably superior to that of existing JAK inhibitor single-drug treatment, and an innovative scheme with disease modification potential is provided for MPN.

Methods and compositions for detecting genetic instability using digital amplification assays. The methods may be performed in a set of isolated volumes and generally may involve competitive hybridization of a competitor and a probe / primer with a normal allele and one or more mutant alleles of a microsatellite locus. The competitor may be configured to compete similarly with, or to outcompete, the primer / probe for hybridization with the normal allele. The primer / probe may be configured to outcompete the competitor for hybridization with various mutant alleles of the locus that alter the length of the repetitive sequence by different amounts. Isolated volumes in which the primer / probe outcompetes the competitor may be enumerated, and represent one or more of the mutant alleles. The methods may enable diagnosing microsatellite instability and treating a subject based on the diagnosis.

The invention discloses a method for detecting KCNJ8 gene c.263Cgt; according to the technical scheme provided by the invention, the prevention and treatment efficiency of the hereditary arrhythmia is remarkably improved on the clinical diagnosis and treatment level. KCNJ8-A88G mutation detection is completed within 45 minutes through the ARMS-PCR technology, the mutation allele frequency as low as 0.1% can be accurately recognized through the sensitivity of 99.8%, and the diagnosis period is greatly shortened compared with traditional sequencing. On the treatment level, the KATP channel inhibitor is screened, and arrhythmia after myocardial infarction can be effectively prevented. According to the established'genotype-phenotype-treatment response 'correlation model, not only is the prevention and treatment level of diseases such as the J-wave syndrome improved, but also a conversion benchmark from laboratory basic research to clinical application is established.

An oligonucleotide probe for detecting a genomic alteration includes a first complementary region, a second complementary region, and a semi-complementary region. The first complementary region includes at least three nucleotides that are completely complementary to a mutant allele of a portion of a genomic sequence, the includes at least three nucleotides that are completely complementary to the mutant allele and to the wild type allele, and the semi-complementary region is adjacently flanked by the first complementary region and the second complementary region. The nucleotides of the semi-complementary region are completely complementary to the mutant allele and are not completely complementary to the wild type allele, the first complementary region comprises a first locked nucleic acid adjacent to the semi-complementary region, the second complementary region comprises a second locked nucleic acid adjacent to the semi-complementary region, and the semi-complementary region comprises a third locked nucleic acid.

To provide a method for efficiently and accurately distinguishing two similar diseases that differ in the presence or absence of a mutant allele in the same gene region.SOLUTION: A method for distinguishing between a genetic disease caused by a codon mutation in a gene and another disease includes the steps of: performing an amplification reaction to amplify a genetic region containing the codon, the amplification reaction including adding a DNA primer for amplifying the genetic region containing the codon and a PNA that inhibits the amplification of a normal allele containing the codon; and treating a product obtained by the amplification reaction with a restriction enzyme that specifically recognizes and cleaves either a base sequence containing the codon with the mutation or a base sequence containing the codon without the mutation, thereby obtaining a restriction enzyme-treated product.SELECTED DRAWING: Figure 3

The invention discloses a kit for detecting circulating tumor DNA (deoxyribonucleic acid) of portal vein and branch vein blood of portal vein. The kit comprises: a nucleic acid extraction assembly comprising an optimized lysate and selectively bound magnetic beads; the library construction component comprises a terminal repair / tailing fusion enzyme and a Y-shaped linker with a molecular identifier; the targeted enrichment assembly comprises a specific primer group and a probe group and is used for enriching related gene targets of the abdominal organ tumors; and necessary reaction components. Through an optimized nucleic acid extraction method, an efficient library construction system and a precise targeted enrichment technology, high-sensitivity detection of low-abundance ctDNA in portal venous blood is achieved, and the lower detection limit reaches 0.1% of mutation allele frequency. The kit is particularly suitable for early diagnosis, curative effect monitoring and prognosis evaluation of abdominal organ tumors such as intestinal cancer, liver cancer and pancreatic cancer.

An agent for treating a common form of autosomal dominant retinitis pigmentosa (ADRP) is disclosed, wherein the agent comprises a first nucleotide sequence encoding a CRISPR-associated (Cas) endonuclease which binds to an NG or NNGRRT PAM (protospacer adjacent motif) sequence, and a second nucleotide sequence encoding or comprising a guide RNA (gRNA) capable of forming a CRISPR-Cas complex with said Cas endonuclease, wherein the gRNA is specifically targeted to a target mutant allele selected from RHOP23H and NR2E3G56R.

The invention discloses an NtPPO gene heterozygous mutant and application thereof. The application comprises the following steps: (1) reducing polyphenol oxidase activity of tobacco leaves; (2) the browning degree of the flue-cured tobacco during baking is reduced; the NtPPO gene mutant comprises mutant types of NtPPO1, NtPPO2, NtPPO3, NtPPO4, NtPPO9, NtPPO10, NtPPO11, NtPPO12 and NtPPO13, and the mutant types of the NtPPO4 are limited as follows: a mutant allele NtPPO4-1 positioned on a first chromosome and a second chromosome and a mutant allele NtPPO4-2 positioned on a third chromosome and a fourth chromosome; the mutant type of the NtPPO9 is limited as follows: a mutant allele NtPPO9-1 positioned on a first chromosome and a second chromosome, and a mutant allele NtPPO9-2 positioned on a third chromosome and a fourth chromosome; the mutant type of the NtPPO10 is limited as follows: a mutant allele NtPPO10-1 positioned on a first chromosome and a second chromosome, and a mutant allele NtPPO10-2 positioned on a third chromosome and a fourth chromosome.

The application provides a circulating tumor DNA-based mutant gene detection method and application thereof, and relates to the technical field of biological detection.The application provides a circulating tumor DNA-based mutant gene detection method, adopts a customized panel technical route, adopts a single-stranded library construction method, preliminarily amplifies free DNA, and then performs target enrichment based on UMI multiplex PCR, so that the detection sensitivity and specificity are effectively improved.It is proved through tests that the method can simultaneously analyze multiple gene mutation results of the same patient, has a sensitivity of more than 70% and a specificity of more than 90% on the mutation allele ratio (AF), and has a good application prospect for MRD monitoring.

Methods and compositions are provided for modifying the flowering time and / or maturity time of soybean plants to enable them to be cultivated in a variety of geographical locations having different day lengths. Modified soybean plants are disclosed comprising non-natural mutant alleles at the FT2a, FT2b, FT5a, and / or ELF3 locus. The modified plants have a shorter flowering and / or maturity time than control plants.