26 results about "Mutant allele" patented technology

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 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.

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.

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.

This invention relates to adjustable carrying capacity COL6A1 The invention relates to an oligonucleotide expressing a dominant mutant allele, wherein the downregulation is achieved by hybridization of the oligonucleotide with the RNA transcript of the allele at the dominant mutation site, and the oligonucleotide does not inhibit the expression of the wild-type allele, or downregulates the expression of the wild-type allele to a lesser extent than it downregulates the expression of the allele carrying the dominant mutant. The invention also relates to the use of compositions to treat patients with muscular dystrophy, particularly those with malnutrition related to type VI collagen.

Aspects of the present disclosure relate to conjugates, and other aspects relate to formulations (e.g., aqueous, lyophilized forms) comprising such conjugates (e.g., each conjugate represented by the exemplary formula below) comprising a phosphorodiamidate morpholino oligomer (e.g., useful for targeting DMD) covalently linked to an antibody (e.g., an anti-TfR1 antibody). Also provided is the use of these formulations for treating subjects with a mutated DMD allele associated with Duchenne muscular dystrophy. JPEG2026503873000028.jpg63163

A pharmaceutical composition useful for the treatment of a cancer characterized by the presence of a mutant allele of IDH1 / 2 is provided, comprising a compound of the following formula:

The invention relates to a magnetic bead, a kit and a method for extracting short-fragment DNA (deoxyribonucleic acid). The magnetic beads are prepared by the following method: (1) taking magnetic beads, and adding a water-soluble carbodiimide activator and an activation synergist for activation; (2) taking the activated magnetic beads, and adding polyethyleneimine for reaction to obtain polyethyleneimine modified magnetic beads; and (3) taking the polyethyleneimine modified magnetic beads, adding poly N-isopropylacrylamide, the water-soluble carbodiimide activator and the activation synergist, and carrying out a reaction so as to obtain the magnetic beads. The surface of the magnetic bead is coated with a double-layer functional polymer to construct double channels, traditional chemical competition is replaced with physical screening, the enrichment efficiency and selectivity of short-fragment DNA with the average length of 166 bp are remarkably improved, and the magnetic bead is very suitable for cffDNA capture. By using the magnetic bead and the method, the usage amount of maternal plasma can be effectively reduced, the fetal fraction is increased, and the detection limit of mutant alleles is reduced.

The present invention is directed to a gene which, when mutated, results in presence of many male flowers and absence of female flowers in watermelon. Plants comprising mutant alleles of this gene are useful as pollenizers in the production of triploid, seedless watermelon fruits.

Cancer immunology provides a desirable new approach for cancer treatment, but verifies that the potential neoantigens to be directed against targets are cost-effective 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 methods for identifying and prioritizing candidate neoantigens using sequencing data. The methods of the invention save time and money by identifying preferential candidate neoantigens for further experimental verification.

Aspects of the disclosure relate to complexes and other aspects relate to formulations (e.g., aqueous, lyophilized forms) comprising such complexes (e.g, wherein each complex is of the exemplary formula shown below) comprising a phosphorodiamidate morpholino oligomer (e.g, useful for targeting DMD) covalently linked to an antibody (e.g., anti-TfR1 antibody). Also provided are uses of these formulations for treating a subject having a mutated DMD allele associated with Duchenne Muscular Dystrophy. (I)

This invention provides a SNP site, identification kit, identification method, and application for the Jk(a+w) blood type, which triggers immune hemolytic transfusion reactions. The SNP site is the c.613C>T mutation at position 613, starting from the start codon of the SLC14A1 gene coding region. In the proband, the c.613C>T mutation was detected in one allele, while the other allele carried other known inactivating mutations. The allele carrying the c.613C>T mutation resulted in reduced expression of the Kidd protein in the proband's erythrocytes; the other allele, carrying other inactivating mutations, did not express the Kidd protein. The combined effect of these two mutated alleles resulted in the Jk(a+w) phenotype. This provides a genetic variation basis for the establishment of rare blood type banks and the assurance of transfusion compatibility.

The present invention relates to a plant of the family Solanaceae comprising in its genome at least one copy of a mutant allele which causes stenospermocarpic fruit formation when present in homozygous form. The present invention further relates to pollen and seed produced by the plant of the present invention, seed from which the plant of the present invention can be grown and a part from the plant according to the present invention. The present invention further re- lates to a method of identifying and / or selecting a plant according to the present invention and a method of producing a plant according to the present invention. The present invention further relates to the use of the plant of the present invention as a crop for consumption or as a source of propagation material. The present invention further relates to the use of a nucleic acid for the identification of a plant of the present invention or for breeding plants of the present invention.

The application relates to a KASP molecular marker of an NbEDS1 gene, a detection method and application, and belongs to the technical field of plant molecular breeding. The KASP molecular marker is designed according to a specific 97 bp InDel site in a Nicotiana benthamiana NbEDS1 gene mutant, the wild-type allele is C (containing a 97 bp insertion sequence), the mutant allele is A (the insertion sequence is deleted), the marker has the advantages of high specificity, fast detection speed, low cost, high throughput and high accuracy, and can be applied to genotype identification of the NbEDS1 gene mutant of the Nicotiana benthamiana, rapid screening of mutant materials in related research on a TNL type immune receptor disease resistance pathway, and genetic analysis and breeding selection related to the NbEDS1 gene.

The invention belongs to the technical field of biomedical detection, and provides a prostatic cancer olaparione response marker determination system and a determination method and application thereof. A multifunctional polymer brush is grafted on the surface of a core-shell magnetic polymer microsphere, an HRR gene oligonucleotide probe is coupled through carbodiimide-mediated amidation reaction, and efficient enrichment and accurate quantitative detection of ultralow-abundance mutant alleles are achieved by combining a digital PCR technology. The use amount of the magnetic oligonucleotide probe in a single 20L reaction system is 0.5-200g, and the positive detection rate of HRR gene mutation sites with allele frequency of 0.10%-0.50% is not less than 95%. The problems that in the prior art, low-abundance target capturing efficiency is low, non-specific adsorption is high, and digital PCR quantitative accuracy is poor are solved, a high-sensitivity and high-specificity molecular diagnosis tool is provided for olapara utilization drug decision-making of castration-resistant metastatic prostate cancer patients, and wide clinical application value is achieved.

Methods for inactivating in a cell a mutant allele of the elastase, neutrophil expressed gene (ELANE gene) gene having a mutation associated with severe congenital neutropenia (SCN) or cyclic neutropenia (CyN) and which cell is heterozygous at one or more polymorphic sites selected from the group consisting of: rs10414837, rs3761005, rs1683564, rs9749274, rs740021, rs201048029, rs199720952, rs28591229, rs71335276, rs58082177, rs3826946, rs10413889, rs761481944, rs3761008, rs10409474, rs3761007, rs17216649, rs10469327, rs8107095, rs10424470 and rs78302854, the method comprisingintroducing to the cell a composition comprising:a CRISPR nuclease or a sequence encoding the CRISPR nuclease; anda first RNA molecule comprising a guide sequence portion having 17-20 nucleotides,wherein a complex of the CRISPR nuclease and the first RNA molecule affects a double strand break in the mutant allele of the ELANE gene,the method optionally further comprising introduction of a second RNA molecule comprising a guide sequence portion capable of complexing with a CRISPR nuclease, wherein the complex of the second RNA molecule and CRISPR nuclease affects a second double strand break in the ELANE gene.

RNA, compositions, and methods for inactivating in a cell a mutant allele of the elastase, neutrophil expressed gene (ELANE gene) gene having a mutation associated with severe congenital neutropenia (SCN) or cyclic neutropenia (CyN) and which cell is heterozygous at the polymorphic site rs1683564, the method comprisingintroducing to the cell a composition comprising:a CRISPR nuclease or a sequence encoding the CRISPR nuclease; anda first RNA molecule comprising a guide sequence portion having 17-30 nucleotides,wherein a complex of the CRISPR nuclease and the first RNA molecule affects a double strand break in the mutant allele of the ELANE genethe method optionally further comprising introduction of a second RNA molecule comprising a guide sequence portion capable of complexing with a CRISPR nuclease, wherein the complex of the second RNA molecule and CRISPR nuclease affects a second double strand break in the ELANE gene.

An oligonucleotide probe for detecting genomic alteration includes a semi-complementary region, a first complementary region, a second complementary region, and a minor groove binder moiety attached to a 3' end of the second complementary region. The semi-complementary region includes nucleotides that are completely complementary to a mutant allele of a portion of a genomic sequence and is not completely complementary to a wild type allele of the portion of the genomic sequence. The first complementary region extends from a 5' end of the semi-complementary region and includes nucleotides that are completely complementary to both the mutant allele and to a wild type allele of the gene. The second complementary region extends from a 3' end of the semi-complementary region and consists of four to seven nucleotides that are completely complementary to both the mutant allele and to the wild type allele.

The application discloses a method for improving feed utilization efficiency of yellow catfish by changing biological rhythm, and belongs to the technical field of fish genetic breeding. The application provides a mutant allele for changing biological rhythm of yellow catfish, which is obtained by targeted editing of a coding region of a yellow catfish rbmx gene through CRISPR / Cas9 technology, and the sequence feature is that a shift mutation occurs in a target region, resulting in early termination of protein translation, and the specific mutant allele of the rbmx gene is shown as SEQ ID NO: 2 or SEQ ID NO: 3. The homozygous yellow catfish mutant provided by the application and containing the mutant allele shows a significant improvement in feed utilization efficiency, and the female and male individuals are respectively increased by about 20.2% and 17.8% compared with wild type. The mutant allele and the yellow catfish mutant can be used for cultivating a new strain of yellow catfish with high feed utilization efficiency, and have important industrial application value.

The present invention is directed to provide novel RNA molecules, chimeric NA molecules, double-stranded RNA molecules, and double-stranded chimeric NA molecules. Specifically, an embodiment of the present invention is an RNA molecule for RNA interference to target a mutant allele with a point mutation, in which (1) the molecule has a nucleotide sequence complementary to a nucleotide sequence of a coding region of the mutant allele; and (2) when counted from the base at the 5′-end in a nucleotide sequence complementary to a nucleotide sequence of the mutant allele, (2-1) a base at position 5 or 6 is mismatched to a base in the mutant allele; (2-2) a position 10 or 11 corresponds to the position of the point mutation; and (2-3) a group at the 2′-position of a pentose at positions 6-8 or positions 7 and 8 is modified with, e.g., OCH3. In this RNA molecule, one or more ribonucleotides may be replaced by, e.g., a deoxyribonucleotide. The molecule may form a double-stranded RNA with a complementary strand.

Provided herein is a composition comprising a set of allele-specific primers. Further provided are methods of amplifying a mutant allele, comprising forming a mixture comprising at least one nucleic acid molecule having the mutant allele, and a set of allele-specific primers and subjecting the mixture to a condition sufficient to amplify the at least one nucleic acid molecule. Further provided herein is a method of determining a disease status of a subject.

The invention discloses a mutant allele of an OsGT1 gene and application thereof, relates to the technical field of molecular breeding of crops, and aims to provide the mutant allele of the OsGT1 gene, an encoding protein of the mutant allele and application of the encoding protein. The nucleotide sequence of the mutant allele is shown as SEQ ID NO. 1 in a sequence table. The amino acid sequence of the coding protein of the mutant allele is shown as SEQ ID NO.2 in the sequence table. Compared with a rice wild type OsGT1 gene, the mutant allele provided by the invention has mutation that the 581th nucleotide in a gene coding region is changed into T from C. The mutant allele of the OsGT1 gene is used for cultivating multi-tillering high-yield rice, and has important practical significance and agricultural utilization value.