67 results about "Missense mutation" patented technology

The invention relates to methods and compositions of matter for determining or predicting aggressiveness of a subject's tumor, for determining a subject's predisposition to cancer, for diagnosing cancer in a subject, and for selecting a therapy for a subject with cancer. Also provided are methods and compositions of matter for determining a Rabphillin-3A-Like gene genotype in a subject and for characterizing a Rabphillin-3A-Like gene in a subject.

Canavan disease, an autosomal recessive leukodystrophy, is caused by deficiency of aspartoacylase and accumulation of N-acetylaspartic acid in brain. Human aspartoacylase (ASP) cDNA spanning 1,435 bp has been cloned and expressed in E. coli. A base change, a854>c, has been found in 85% of the 34 Canavan alleles tested so far, which results in a missense glu285>ala mutation that is predicted to be part of the catalytic domain of aspartoacylase. The invention therefore provides nucleic acid sequences, genes, polypeptides, antibodies, vectors containing the gene, host cells transformed with vectors containing the gene, animal models for the disease, methods for expressing the polypeptide, genetic screening methods and kits, diagnostic methods and kits, methods of treating Canavan disease and methods of genetic therapy for the disease.

Tyrosine phosphorylation, regulated by protein tyrosine phosphatases (PTPs) and kinases (PTKs), is important in signaling pathways underlying tumorigenesis. A mutational analysis of the tyrosine phosphatase gene superfamily in human cancers identified 83 somatic mutations in six PTPs (PTPRF, PTPRG, PTPRT, PTPN3, PTPN13, PTPN14) affecting 26% of colorectal cancers and a smaller fraction of lung, breast and gastric cancers. Fifteen mutations were nonsense, frameshift or splice site alterations predicted to result in truncated proteins lacking phosphatase activity. Five missense mutations in the most commonly altered PTP (PTPRP) were biochemically examined and found to reduce phosphatase activity. Expression of wild-type but not a mutant PTPRT in human cancer cells inhibited cell growth. These observations suggest that the tyrosine phosphatase genes are tumor suppressor genes, regulating cellular pathways that may be amenable to therapeutic intervention.

Focal and segmental glomerulosclerosis (FSGS) is a kidney disorder of unknown etiology and up to 20% of patients on dialysis have this diagnosis. A large family with hereditary FSGS carries a missense mutation in the TRPC6 gene on chromosome 11q, encoding the ion channel protein Transient Receptor Potential Cation Channel 6. The missense mutation is a P112Q substitution, which occurs in a highly conserved region of the protein, enhances TRPC6-mediated calcium signals in response to agonists such as angiotensin II, and alters the intracellular distribution of TRPC6 protein. Previous work has emphasized the importance of cytoskeletal and structural proteins in proteinuric kidney diseases. Our findings suggest a novel mechanism for glomerular disease pathogenesis.

The invention discloses a method for predicting a tumor neoantigen and its application. The prediction method includes the following steps: S1, obtaining a tumor sample and a plasma leukocyte sample of a tumor patient, constructing a sequencing library, and performing whole genome, whole exome or targeted capture RNA, DNA sequencing; S2, using the plasma leukocyte DNA as a contrast, comparing thetumor sample DNA and detecting somatic mutation, filtering out a missense mutation site, and annotating the filtered missense mutation site; S3, using the plasma leukocyte DNA sequencing data to typeHLA-I and HLA-II alleles; and S4, predicting antigenic polypeptides that can bind to HLA-I and HLA-II alleles. The method of the present invention can more accurately screen out an antigen that can beexpressed genes and that can bind to HLA-I and HLA-II alleles and cause antitumor immune response.

Mitofusin genes and encoded polypeptides are provided, including the Drosophila Fzo protein and its homologs from insects, other invertebrates, yeast, and vertebrates including mouse and humans. Mitofusins are large predicted GTPases with a predicted trans-membrane domain, coiled-coil regions, and a C-terminal region showing a high pI. The mitofusins are the first known protein mediator of mitochondrial fusion, and mediate developmentally regulated post-meiotic fusion of mitochondria. Missense mutations that alter conserved residues required for GTP binding in other GTPases inhibit the in vivo fusogenic activity of Fzo but do not affect its localization. Fusion proteins having amino acid sequences from mitofusin transmembrane regions localize to mitochondria. Mitofusins may be used in methods of identifying anti-insect and antifungal agents. Functional derivatives of mitofusins useful for such methods are described.

A method of detecting in an individual an increased risk of hyperplastic vasculomyopathy, or a vascular disease resulting therefrom is disclosed. The method comprises obtaining a DNA genome sample from the individual and detecting in the sample a missense mutation in a gene which is a component of a smooth muscle cell contractile unit. In some embodiments the gene is ACTA2 and in some embodiments the gene is MYH11. In some embodiments, the gene is sequenced and then compared to a panel of control gene sequences which are representative of the same gene in individuals without vascular disease or who are at low risk of developing hyperplastic vasculomyopathy, to detect any missense mutations in the gene. The presence of a missense mutation in the gene indicates an increased risk of hyperplastic vasculomyopathy.

The present invention relates to a β-catenin oligonucleotide microchip for detecting mutation in the mutational hot spot regions of β-catenin gene, a manufacturing process thereof and a method for detecting the β-catenin mutation employing same, wherein specific oligonucleotides are selectively designed to detect various missense mutations and in-frame deletion at the mutational hot spots of β-catenin gene. The β-catenin oligo chip of the present invention can be used in studies to detect β-catenin mutations and unravel the signal transduction mechanism and tumorigenesis related to β-catenin gene.

Provided herein are methods and systems for targeted gene disruption (knock-out, missense mutation) and targeted gene knock-in in mammalian cells using base editors and guide RNAs (gRNAs) designed to target splice acceptor-splice donor sites. Also provided herein are universally acceptable genetically engineered cells comprising targeted disruptions in immunotherapy-related genes and comprising a CAR/TCR for therapeutic applications.

The present invention relates to a polypeptide comprising at least one at least one deletion selected from the group consisting of ΔHNH (Δ775-909), ARuvCIII-b (Δ1002-1074), AREC1-a (Δ510-655), AREC1-b (Δ525-587), AREC1-c (Δ662-710), AREC2 (Δ180-308), AREC2-a (Δ212-244), AREC2-b (Δ244-276), AREC2-c (Δ276-308), AREC2-d (Δ199-283), AREC2-e (Δ198-257), AREC2-f (Δ235-286), AREC2-g (Δ217-266), AREC3 (Δ498-712) and combinations thereof, wherein the position numbering is in accordance with SEQ ID NO: 1 encoding for S. pyogenes Cas9, and wherein the polypeptide has CRISPR-Cas DNA-binding activity. The polypeptide may further comprises a missense mutations selected from G12R, T13K, T13R, N14K, N497K, T657K, T657R, N767K, T770K, T770R, Q920K, Q920R, S1109R, D1135K, D1135R, S1338R and combinations thereof. Also claimed are nucleic acid molecules encoding for said polypeptides, compositions and method of site-directed engineering of a target DNA thereof.

The invention discloses a construction method, a construction kit and an application of an optic atrophy animal model, and relates to the biotechnical field. The construction method is characterized in that a base at the 277th locus of an exon 2 of an animal OPA3 gene mutates from G to A to cause missense mutation, an amino acid residue mutating from G to S, of the 93rd position of an encoded OPA3protein, and an animal containing the mutation exhibits typical optic atrophy disease characteristics and can be used as the optic atrophy animal model. The animal model fills a gap in human autosomal dominant optic atrophy animal models, enriches the type of existing optic atrophy animal models, and facilitates the development of researches on ophthalmic diseases.

The present invention relates to PRKAG2 gene mutation of hypertrophic cardiomyopathy and its detection method. The PRKAG2 gene mutation is the G-->A heterozygous mutation of the No. 298 place base in the 3rd exon of PRKAG2 gene, and causes the coded amino acid in No. 100 place to change from glycine (G) to serine (S). Its detection method includes the following steps: 1. extracting peripheral blood DNA; 2. in vitro PCR amplification of PRKAG2 gene exon; and 3. DNA sequencing analysis. The discovery of the PRKAG2 gene mutation can define the molecular genetic mechanism of Chinese familial hypertrophic cardiomyopathy combined with conducting system abnormality and ventricle pre-exciting disease further.

The invention relates generally to new prostate cancer markers, and particularly to a class of cancer marked by the presence of missense mutations in SPOP, an E3 ubiquitin ligase component. The invention provides methods and materials for detecting and diagnosing prostate cancer by detecting these mutations and may be useful in predicting disease progression and response to therapy.

The invention discloses an RFLP (Restriction Fragment Length Polymorphism) method for rapidly detecting single nucleotide polymorphism (SNP) of bovine PNPLA3 (Patatin Like Phospholipase Domain-Containing 3) gene. The RFLP method comprises the steps of by taking PNPLA3 gene-containing to-be-detected whole-genome DNA as a template, and human-designed primer pairs P1-P5 as primers, carrying out PCR (Polymerase Chain Reaction) amplification on the bovine PNPLA3 gene, and discovering 27 SNP loci; selecting four missense mutation loci and respectively designing primer pairs P2-Bg1I, P2-RsaI, P3-BmgT120I and P3-MspI; carrying out PCR amplification by using the four primer pairs, respectively performing enzyme digestion to the PCR amplified product by using the four restriction endonuclease, and then detecting the enzyme digestion product by using agarose gel electrophoresis, wherein the electrophoresis result shows the SNP at the 2062th locus, the 2078th locus, the 35800th locus and the 35932th locus of the PNPLA3 gene of the Qinchuan bovine gene. The PNPLA3 gene relates to the growth traits of weight, average daily gain and the like, the PNPLA3 gene has the activity of lipase and acyltransferase and plays an important role in aspects of maintaining energy balance, the detection method can be used for marker assisted selection (MAS) breeding of the growth traits of China cattle, thus being beneficial to fast setting cattle population with excellent genetic resources.

A method is provided for identifying a subject likely to have, or at risk of developing a disease condition correlated with increased reactive oxygen species (ROS), including cancer, by identifying in the subject a missense mutation in a nucleic acid of Complex III, IV and/or V of the OXPHOS system. This invention also provides a method of identifying a likelihood of having a heritable predisposition to cancer by detecting a homoplasmic missense mutation in non-tumor tissue of an OXPHOS system gene. This invention also provides a method for detecting likelihood of having cancer, predisposition to cancer, and likelihood of passing a predisposition to cancer to progeny involving identifying in non-tumor tissue of the subject a missense mutation in a complex III, IV and/or V gene of the mitochondrial OXPHOS system. The mutation may be a nuclear or mitochondrial mutation. The invention has been exemplified with respect to prostate cancer. When the mutation is homoplasmic in non-tumor tissue this is an indication it is an inherited and inheritable trait, and that the subject is likely to pass on the mutation to her progeny in the case of mutations in mitochondrial DNA or his or her progeny in the case of mutations in nuclear DNA. Both homoplasmic and heteroplasmic mutations in non-tumor tissue can indicate the presence of cancer.

The invention provides an application of a Smoc2 gene and an SNP marker thereof in multiple epiphyseal dysplasia, and relates to the technical field of biomedicine. According to the invention, a family with skeletal dysplasia is collected in Shandong, and final screening tests prove that SMOC2 c.1076T is greater than G; and p.L359R missense mutation is pathogenic mutation of a family with autosomal dominant multiple epiphyseal dysplasia, and the SMOC2 gene is a new pathogenic gene of the multiple epiphyseal dysplasia. A new pathogenic theoretical basis is provided for revealing a multiple epiphyseal dysplasia occurrence mechanism, and a foundation is laid for developing a disease early warning model suitable for people in China, so that the Smoc2 gene has good practical application value.

The invention relates to the field of molecular genetics, in particular to a molecular marking method for a mutation site of a coding region of a porcine SERPINA1 gene and application of the method to anti-PCV (porcine circovirus) pig breeding. The inventor finds that SERPINA1 coding regions of different varieties of pigs have multiple mutations, wherein a G>A mutation exists at the 445th base of the coding region to further cause a missense mutation: glutamic acid>lysine. Enzyme linked immunosorbent assay shows that an AA type individual has highest SERPINA1 serum content, an AG type individual has the second highest SERPINA1 serum content and a GG type individual has the lowest SERPINA1 serum content in a healthy state. After infection with PCV2, the SERPINA1 serum content of the GG type individual rapidly increases, while the content of the AG type and AA type individuals rapidly decreases, and such a result is consistent with that a Laiwu pig population with a higher anti-PCV capability is more likely to comprise GG type pigs compared with a western population and an mRNA expression level of the SERPINA1 gene is high. Obviously, a genotype of the 445th site of a coding region of an SERPINA1 gene in a porcine genome can be detected as a molecular marker associated with an anti-PCV character of a pig, so that the method is convenient, rapid and free of environmental influence, and early breeding can be implemented.

The invention provides an SNP molecular marker related to residual feed intake of pigs, the site of the SNP molecular marker is the 51519932th nucleotide site on chromosome 14 of international pig reference genome version 11.1, the site is a missense mutation site on a gene CCDC188, and the basic group of the site is T or C. By optimizing the dominant alleles of the SNP, the frequency of the dominant alleles can be increased generation by generation, the remaining feed intake of the boars can be reduced, the excellent boars with the characters can be bred, and the genetic improvement progress of the boars can be accelerated, so that the economic benefit of breeding of the boars can be effectively improved.

The invention discloses a marker assisting epilepsy diagnosis and a detection kit of the marker, and relates to the field of epilepsy diagnosis. According to the research, it is found from detection on an FASN gene of a member of an epilepsy family patient that the FASN gene of the member of the epilepsy family patient has a mutation c.G2998A, the gene mutation causes that the 1,000 amino acidof the corresponding FASN protein mutates into asparagine (N) from aspartic acid (D) and is a missense mutation. An nucleic acid molecule containing the c.G2998A mutation or protein containing a mutation p.D1000N can both serve as a biomarker of epilepsy diagnosis, and the rapid and reliable detection assistance marker is provided for epilepsy diagnosis on the molecular level.

The invention discloses a marker assisting in epilepsy diagnosis and a detection kit thereof, and relates to the field of epilepsy diagnosis. According to the study of the marker assisting in epilepsydiagnosis and the detection kit thereof, by detecting KCNT1 genes of family members of an epilepsy patient, the KCNT1 gene of the epilepsy patient in the family has a mutational c.G1955T, and mutation of the gene causes that the amino acid in the 652 site of KCNT1 protein corresponding to the c.G1955T changes from glutamic acid (G) to valine (V), which is missense mutation. Both nucleic acid molecules containing c.G1955T mutation or protein containing mutational p.G652V can be used as a biomarker for epilepsy diagnosis, so that a fast and reliable detection assisting marker is provided for epilepsy diagnosis at the molecular level.

The invention discloses a marker for assisting epilepsy diagnosis and a detection kit of the marker, and relates to the field of the epilepsy diagnosis. Research for detecting an ERBB4 gene of membersof an epilepsy family discovers that the ERBB4 gene of the members suffering from epilepsy in the family has mutant c.A1972T; the gene mutation results in variation of 658th amino acid of the corresponding ERBB4 gene protein from isoleucine (I) to phenylalanine (F), and the variation is missense mutation; nucleic acid molecules containing the mutant c.A1972T or protein containing mutant p.I658F can be used as a biomarker for the epilepsy diagnosis, and a quick and reliable detection auxiliary marker is provided for the epilepsy diagnosis in molecular level.

This invention relates to methods and compositions useful for detecting mutations which cause Familial Dysautonomia. Familial dysautonomia (FD; Riley-Day syndrome), an Ashkenazi Jewish disorder, is the best known and most frequent of a group of congenital sensory neuropathies and is characterized by widespread sensory and variable autonomic dysfunction. Previously, we mapped the FD gene, DYS, to a 0.5 cM region of chromosome 9q31 and showed that the ethnic bias is due to a founder effect, with >99.5% of disease alleles sharing a common ancestral haplotype. To investigate the molecular basis of FD, we sequenced the minimal candidate region and cloned and characterized its 5 genes. One of these, IKBKAP, harbors two mutations that can cause FD. The major haplotype mutation is located in the donor splice site of intron 20. This mutation can result in skipping of exon 20 in the mRNA from FD patients, although they continue to express varying levels of wild-type message in a tissue-specific manner. RNA isolated from patient lymphoblasts is primarily wild-type, whereas only the deleted message is seen in RNA isolated from brain. The mutation associated with the minor haplotype in four patients is a missense (R696P) mutation in exon 19 that is predicted to disrupt a potential phosphorylation site. Our findings indicate that almost all cases of FD are caused by an unusual splice defect that displays tissue-specific expression; and they also provide the basis for rapid carrier screening in the Ashkenazi Jewish population.