42 results about "Autosomal recessive inheritance" patented technology

This invention provides primers for in vitro diagnosis of mutation of autosomal recessive nonsyndromic hearing loss gene GJB2. The primers can be used for completely amplifying the coding region and upstream or downstream important splicing sequences of GJB2 gene. This invention also provides a test kit for containing the primers and ApaI restriction endonuclease and their application for in vitro detection of 233-235delC mutation of the complete GJB2 coding region. The test kit can also be used for detecting the mutation sites of the GJB2 coding region through sequencing by the forward primer, and detecting deletion or insertion heterozygous mutation through sequencing by the reverse primer. The test kit is suitable for large-scale screening of autosomal recessive nonsyndromic hearing loss gene GJB2 mutation and genetic counseling.

The present disclosure relates to methods for detecting unique genetic signatures derived from markers such as, for example, mutations, somatic or germ-line, in nucleic acids obtained from biological samples. The sensitivity of the methods provides for detection of mutations associated with a disease, e.g., cancer mutations, or with inherited disease, e.g., an autosomal recessive disease, in a noninvasive manner at ultra-low proportions of sequences carrying mutations to sequences carrying normal, e.g., non-cancer sequences, or a reference sequence, e.g., a human reference genome.

The invention relates to a real-time fluorescence quantitative probe and a kit for detecting IVS7-2A>G, which is one of 10 common mutations of an autosomal recessive inheritance large vestibular aqueduct-related deafness gene SLC26A4, wherein the kit comprises the real-time fluorescence quantitative probe. The wild-type probe is positioned at a site of 23403bp-23425bp; the mutant-type probe is positioned is positioned at a site of 23404bp-23425bp. In allusion to the Taqman mutant-type probe and the wild-type probe at mutation points and a pair of primers, the probes are high in specificity, high in sensitivity, and intuitive, accurate and reliable in test results, applicable to mass screening of the common mutation IVS7-2A>G of the autosomal recessive inheritance large vestibular aqueduct-related deafness gene SLC26A4 and rapid diagnosis of a SLC26A4 gene-related large vestibular aqueduct deafness.

The invention provides a genetic risk early-warning method for auxiliary reproduction sperm supplying strategy and a system. According to the method and the system, an autosome recessive genetic disease reproduction genetic risk of a to-be-pregnant women is evaluated and predicted, and a sperm donation volunteer who has relatively high gene pairing degree and low genetic disease risk as a to-be-selected object. Quantification and automation for risk evaluation of a reproduction autosome recessive genetic disease are comprehensively realized. The method and the system have advantages of greatlyreducing manpower cost and time cost, realizing high reasonability, and greatly improving analysis accuracy.

It is intended to provide an agent for regulating axon extension during neuranagenesis by regulating ephrin-Eph receptor signaling mechanisms and to provide a mouse having abnormal ephrin-Eph receptor signaling mechanisms. The present invention relates to a regulator of axon extension, comprising an agent for promoting or suppressing the function of α-chimerin, and to a miffy (mfy) mouse derived from a B6 strain, which displays autosomal recessive inheritance of an abnormal walking trait exhibiting a hopping gait with left-right synchronized movement of limbs and has mutation in an α-chimerin gene.

The invention discloses an oculocutaneous albinism type 1 related mutated TYR gene and application thereof to gene diagnosis. By collection of a 4-generation oculocutaneous albinism type 1 family, a transmission manner of 4-generation oculocutaneous albinism type 1 in the family is an autosomal recessive inheritance manner according to judgment; by reading of documents and online databases, possible pathogenic candidate genes are selected, then a propositus and other members in the family are subjected to PCR (polymerase chain reaction) amplification and Sanger sequencing to determine mutant gene loci, and consequently a TYR pathogenic gene (mutant c.107G) which is a novel pathogenic mutation is discovered. Discovery of the novel TYR pathogenic gene mutation locus enriches a pathogenic gene mutation spectrum, and the novel TYR pathogenic gene mutation locus can be used as a prenatal diagnosis screening locus for oculocutaneous albinism type 1 which is a serious recessive hereditary disease to guide prenatal and postnatal care. By providing of the oculocutaneous albinism type 1 related mutated TYR gene, data support is provided for design of prenatal diagnosis chips, and especially,important significance to prenatal gene diagnosis screening of seriously-harmful rare genetic diseases is achieved.

The present invention relates to the field of detection technology in medical molecular physiology, it is a kit for detecting autosomal dominant inheritance polycystic kidney disease. According to the structure property of pathogenic gene type A and type B of patient said invention can synthesize correspondent primer, adopt molecular physiological techonlogy and combine it with single-strand conformation polymorphism analysis method or high-pressure liquid-phase chromatography analysis method to make detection, and can directly detect out the mutant site and mutation type of pathogenic gene of the autosomal recessive inheritance polycystic kidney disease for preventing and curing said disease.

Described herein are guide RNAs and modified guide RNAs suitable for biallelic correction of Pompe disease. Also included are methods of modifying a target gene in a patient or in a patient-derived cell, wherein the patient has an autosomal recessive disorder with compound heterozygous mutations, the methods including delivering a first modified guide RNA, a second modified guide RNA, a Cas9 polypeptide, a biotin-binding molecule, a first biotinylated donor polynucleotide, and a second biotinylated donor polynucleotide. The first modified guide RNA and the first biotinylated donor polynucleotide correct a first diseased allele, and the second modified guide RNA and the second biotinylated donor polynucleotide correct a second diseased allele.

The invention belongs to the field of gene detection, relates to a gene detection panel related to autosomal recessive genetic diseases and an application of the gene detection panel, and particularlyrelates to a gene detection panel for distinguishing methylmalonic acidemia, methylmalonic acidemia combined homocysteinemia and propionaemia. The application comprises the following steps: detecting43 mutation sites of four genes related to three diseases aiming at samples with high genetic metabolic disease screening preliminary screening (tandem mass spectrometry) C3, designing amplificationprimers aiming at the 43 mutation sites to amplify a target sequence, and designing a single-base extension primer to detect target SNP, through multiple PCR and multiple single-base extension reactions, carrying out mass spectrometry according to different genotype masses, and determining the genotype of each site, so that diseases with different prognosis and treatment means are distinguished ata time.

The invention discloses an application of NVP-BGJ398 in preparation of a medicine for treating rMED (recombinant epiphyseal dysplasia). The inhibitor NVP-BGJ398 can be used for treating an SLC26A2 mutant autosome recessive hereditary multiple epiphyseal dysplasia rMED disease; the NVP-BGJ398 intervenes the phenotype of the postnatal dysplasia disease, can improve the cartilage cell differentiation and collagen secretion conditions of a limb cartilage growth plate, and improves the development bending malformation conditions of lower limbs.

The invention provides a high-throughput sequencing variation risk grouping and screening method. The method comprises the following steps: setting pathogenicity high-risk variation screening conditions, and screening gene data according to the pathogenicity high-risk variation screening conditions; setting pathogenicity high-risk variation screening conditions and medium-risk variation screening conditions with extremely low crowd frequency, and screening the gene data; setting pathogenicity medium-high risk variation screening conditions, and screening the gene data; setting gene variation screening conditions of pathogenicity medium and high risk autosomal dominant heredity, and screening the gene data; setting conditions of pathogenicity medium-high-risk autosomal recessive inheritance and the same gene, and screening the gene data; setting variation screening conditions of high-risk sex-linked inheritance in pathogenicity, and screening the gene data; and setting screening conditions for determining pathogenicity variation or suspicious pathogenicity variation with high risk in pathogenicity, and screening the gene data.

The invention provides the primary familial cerebral calcification pathogenic gene JAM2 and its application. Specifically, the present invention provides a use of the JAM2 gene, or its protein, or its detection reagent, for preparing a detection reagent or kit, which is used to detect primary familial brain calcification and / or its susceptibility. The present invention identifies JAM2 gene as a new pathogenic gene of autosomal recessive primary familial brain calcification for the first time; and, primary familial brain calcification can be diagnosed by detecting the mutation of JAM2 gene or its protein patients and / or their susceptibility.

The invention provides primary familial brain calcification pathogenic gene JAM2 and application thereof. Specifically, the invention provides application of JAM2 gene, or a protein thereof or a detection reagent thereof in preparation of a detection agent or a kit. The detection agent or the kit is used for detecting primary familial brain calcification and / or susceptibility of primary familial brain calcification. According to the invention, the JAM2 gene is identified as a new pathogenic gene for autosomal recessive inheritance of primary familial brain calcification for the first time; inaddition, a patient suffering from primary familial brain calcification and / or susceptibility thereof can be diagnosed by detecting the mutation of the JAM2 gene or the protein of the JAM2 gene.

The invention provides a high-throughput sequencing variation risk grouping screening method and system, and the method comprises the steps: setting pathogenicity high-risk variation screening conditions, and screening gene data according to the pathogenicity high-risk variation screening conditions; setting pathogenicity high-risk variation screening conditions and medium-risk variation screening conditions with extremely low crowd frequency, and screening gene data; setting pathogenicity medium-high risk variation screening conditions, and screening gene data; setting gene variation screening conditions of pathogenicity medium and high risk autosomal dominant heredity, and screening gene data; setting screening conditions of pathogenicity medium-high-risk autosomal recessive inheritance and the same gene, and screening the gene data; setting variation screening conditions of high-risk sex-linked inheritance in pathogenicity, and screening the gene data; and setting screening conditions for determining pathogenicity variation or suspicious pathogenicity variation with high risk in pathogenicity, and screening the gene data.

The present invention relates to the field of detection technology in medical molecular physiology, it is a kit for detecting autosomal dominant inheritance polycystic kidney disease. According to the structure property of pathogenic gene type A and type B of patient said invention can synthesize correspondent primer, adopt molecular physiological techonlogy and combine it with single-strand conformation polymorphism analysis method or high-pressure liquid-phase chromatography analysis method to make detection, and can directly detect out the mutant site and mutation type of pathogenic gene of the autosomal recessive inheritance polycystic kidney disease for preventing and curing said disease.

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.

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders that result in enzyme deficiencies that alter the production of adrenal steroids, due to 21-hydroxylase deficiency (a condition in which little or no cortisol biosynthesis occurs). A method is provided for administering 4-(2-chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-N-propa-2-inyl-1,3-thiazole-2-amine, or a pharmaceutically acceptable salt thereof, to adult subjects with congenital adrenal hyperplasia.

The invention provides a genetic risk early-warning method for auxiliary reproduction sperm supplying strategy and a system. According to the method and the system, an autosome recessive genetic disease reproduction genetic risk of a to-be-pregnant women is evaluated and predicted, and a sperm donation volunteer who has relatively high gene pairing degree and low genetic disease risk as a to-be-selected object. Quantification and automation for risk evaluation of a reproduction autosome recessive genetic disease are comprehensively realized. The method and the system have advantages of greatlyreducing manpower cost and time cost, realizing high reasonability, and greatly improving analysis accuracy.

An object of the present invention is to provide a mouse which has the characteristics of early developing visceral fat type obesity and also has concurrent diabetes and hyperlipemia and in which the trait is genetically established and recessively inherited. An ICR-derived mouse strain, Daruma, spontaneously developing obesity, exhibiting autosomal recessive inheritance for the trait of spontaneously developing obesity, and becoming obese only in the homozygous type is provided.

The invention discloses primers and method for detecting PKLR gene mutation of autosomal recessive inherited disease pyruvate kinase deficiency patients. The primers comprise primers for amplifying all exon sequences of the PKLR gene, and the Sanger sequencing technique and sequencing primers are adopted. Mutation of all exons of the PKLR gene in pyruvate kinase deficiency patients can be detected quickly. A detection result is accurate, assistant diagnosis of pyruvate kinase deficiency can be achieved, and reference is provided for early intervention, early treatment and prenatal diagnosis.

Novel methods are provided for identifying heterozygous carriers of autosomal recessive disorders such as Ataxia telangiectasia.

The present invention relates to a dual vector system for expressing Otoferlin protein, comprising a first nucleic acid vector and a second nucleic acid vector wherein the first nucleic acid vector comprises a first nucleotide sequence; the second nucleic acid vector comprises a second nucleotide sequence; the first nucleotide sequence comprises an expression cassette inserted between two first ITR sequences; the second nucleotide sequence comprises an expression cassette inserted between two second ITR sequences; the expression cassette of the first nucleotide sequence comprises a promoter, an N-terminal coding sequence of Otoferlin, an N-terminal coding sequence of intein and polyA; the expression cassette of the second nucleotide sequence comprises a promoter, a C-terminal coding sequence of intein, a C-terminal coding sequence of Otoferlin and polyA, wherein the first amino acid of the C-terminal coding sequence of Otoferlin is mutated into serine (S), threonine (T) or cysteine (C). The invention also relates to a packaging carrier system of the adeno-associated virus, a packaging method of the adeno-associated virus and the adeno-associated virus obtained by the method. The dual vector system or adeno-associated virus for expressing the Otoferlin protein of the present invention can be used in gene therapy, particularly in the treatment of hearing loss, such as in the treatment of Oof gene mutation associated autosomal recessive hereditary hearing loss 9 (DFNB9).

An object of the present invention is to provide a mouse which has the characteristics of early developing visceral fat type obesity and also has concurrent diabetes and hyperlipemia and in which the trait is genetically established and recessively inherited. An ICR-derived mouse strain, Daruma, spontaneously developing obesity, exhibiting autosomal recessive inheritance for the trait of spontaneously developing obesity, and becoming obese only in the homozygous type is provided.

A dual-vector system expressing Otoferlin protein, comprising a first nucleic acid vector and a second nucleic acid vector, the first nucleic acid vector comprising a first nucleotide sequence, and the second nucleic acid vector comprising a second nucleotide sequence; the first nucleotide sequence comprises an expression cassette inserted between two first ITR sequences; the second nucleotide sequence comprises an expression cassette inserted between two second ITR sequences; the expression cassette of the first nucleotide sequence comprises a promoter, an N-terminal coding sequence of Otoferlin, an N-terminal coding sequence of an intein, and polyA; the expression cassette of the second nucleotide sequence comprises a promoter, a C-terminal coding sequence of an intein, a C-terminal coding sequence of Otoferlin, and polyA, the first amino acid of the C-terminal coding sequence of Otoferlin being mutated to serine (S), threonine (T) or cysteine (C). An adeno-associated virus packaging vector system, an adeno-associated virus packaging method, and an adeno-associated virus obtained therefrom are also provided. The dual-vector system or adeno-associated virus for expressing Otoferlin protein can be used for gene therapy, particularly for treating hearing loss, such as for treating Otof gene mutation-related autosomal recessive nonsyndromic deafness 9 (DFNB9).

The present invention discloses that the MSH6 mutant gene with g.[12759inTTAAG] mutation is a new pathogenic gene of HR, and the sequence of the mutant fragment of the MSH6 mutant gene is shown in SEQ ID NO:3. The diploid homozygous genotype of the MSH6 mutant gene having the sequence shown in SEQ ID NO: 3 can lead to the occurrence of hypophosphatemic rickets in humans, and has SEQ ID NO: 3 and SEQ ID NO: 1, SEQ ID NO: 2, The diploid heterozygous genotype composed of any MSH6 mutation gene in the sequence shown in SEQ ID NO: 4 can also cause the occurrence of human hypophosphatemic rickets, and all of them are autosomal recessive inheritance. On this basis, the present invention provides two mutation detection kits based on PCR capture sequencing and conventional PCR and Sanger sequencing, which are of great significance for HR screening, diagnosis, and fertility guidance, and are especially helpful for Prevent the birth of children with HR at the source. In addition, the discovery of specific mutations in the MSH6 gene is also helpful for the exploration of the pathogenesis of HR and the development of therapeutic drugs and methods.

The present invention relates to a dual-vector system for expressing an OTOF protein. The dual-vector system comprises a first nucleic acid vector and a second nucleic acid vector, wherein the first nucleic acid vector comprises a first nucleotide sequence, and the second nucleic acid vector comprises a second nucleotide sequence; the first nucleotide sequence comprises an expression cassette inserted between two first ITR sequences, and the second nucleotide sequence comprises an expression cassette inserted between two second ITR sequences; and the expression cassette of the first nucleotide sequence comprises a promoter, an N-terminal coding sequence of OTOF, a splice donor sequence, a sequence undergoing homologous recombination with the second nucleotide sequence, and a polyA, and the expression cassette of the second nucleotide sequence comprises a promoter, a sequence undergoing homologous recombination with the first nucleotide sequence, a splice receptor sequence, a C-terminal coding sequence of OTOF, and a polyA. The present invention further relates to a packaging vector system for an adeno-associated virus, a method for packaging an adeno-associated virus, and an adeno-associated virus obtained thereby. The dual-vector system or adeno-associated virus for expressing an OTOF protein of the present invention can be used for treating autosomal recessive hereditary hearing loss associated with OTOF mutations.