WO2017222248A1 - Composition de diagnostic d'un dysfonctionnement congénital et son utilisation - Google Patents

Composition de diagnostic d'un dysfonctionnement congénital et son utilisation Download PDF

Info

Publication number
WO2017222248A1
WO2017222248A1 PCT/KR2017/006345 KR2017006345W WO2017222248A1 WO 2017222248 A1 WO2017222248 A1 WO 2017222248A1 KR 2017006345 W KR2017006345 W KR 2017006345W WO 2017222248 A1 WO2017222248 A1 WO 2017222248A1
Authority
WO
WIPO (PCT)
Prior art keywords
disease
glycogen storage
syndrome
composition
storage disease
Prior art date
Application number
PCT/KR2017/006345
Other languages
English (en)
Korean (ko)
Inventor
조은해
장자현
이태헌
전영주
유한욱
김구환
김기수
이소영
Original Assignee
주식회사 녹십자지놈
주식회사 녹십자엠에스
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 주식회사 녹십자지놈, 주식회사 녹십자엠에스 filed Critical 주식회사 녹십자지놈
Publication of WO2017222248A1 publication Critical patent/WO2017222248A1/fr

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/156—Polymorphic or mutational markers
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers

Definitions

  • the present invention relates to a composition for diagnosing congenital dysfunction and its use. More particularly, the present invention relates to mutation of genes related to congenital dysfunction of a newborn or fetus selected from the group consisting of hereditary lysosomal accumulation disease, Wilson's disease and autosomal 1A recessive hearing loss. It relates to a detectable composition and its use.
  • Neonatal or fetal screening was introduced to reduce complications and mortality by early detection and treatment of hereditary metabolic and rare diseases in newborns or fetuses with no symptoms. It has made significant technological progress over the past decades and has made significant contributions to the early diagnosis and treatment of diseases. Recently, the Centers for Disease Control and Prevention (CDC) has been selected as one of the 10 most important public health outcomes. (Centers for Disease Control and Prevention.Ten great public health achievements--United States, 2001-2010.MMWR Morb Mortal Wkly Rep 2011; 60: 619-23.). Neonatal screening was initiated by Robert Guthrie in 1963, based on a bacterial inhibition assay based on the bacterial phenylketonuria group screening test.
  • Radioimmunoassays, enzyme colorimetric methods, tandem mass spectrometry, and molecular genetic testing methods have been devised and popularized in early 1990 by using tandem mass spectrometry for neonatal screening (Millington DS, Kodo N, Norwood DL, Roe CR, Tandem mass spectrometry).
  • NGS Next-Generation Sequencing
  • Lysosomal accumulating disease occurs at a rate of 1 to 1 in 10,000 live births and shows significantly higher clinical and biochemical heterogeneity.
  • Hunter's syndrome (MPS II) and Fabry's disease are X chromosome-associated diseases, the majority of lysosomal accumulation diseases are inherited as common chromosomal recessive diseases. The extent and severity of lysosomal accumulation disease depends on the type and amount of substrate accumulated by the disease, but almost all diseases are progressive. Most diseases show both aspects of central nervous system expression and systemic expression, while some affect only tissues outside the central nervous system or nervous system. Many patients with lysosomal accumulation disorders die in infants or childhood, and those who survive to adulthood often have short life spans and high morbidity.
  • lysosomal accumulation diseases include Metachromatic leukodystrophy, Maroteaux-Lamy Syndrome, Mucopolysaccharidosis VI, Pompe Disease (Glycogen storage disease type II), and Krabbe Disease.
  • Goche disease is the most common lysosomal accumulation disease, affecting about 8,000 to 10,000 people worldwide.
  • the activity of a lysosomal enzyme known as acid-beta-glucosidase or GlcCerase is severely reduced due to one of approximately 200 mutations in the GBA gene encoding this enzyme. .
  • the disease is inherited in a common chromosomal recessive pattern, which means that Gosch disease occurs in people whose two copies of the GBA gene are mutated.
  • Decreased Glc serase activity results in the accumulation of glucocerebrosides (also called glucosyl ceramides) in tissues, including the spleen, liver, lungs, bone marrow and sometimes the brain.
  • glucocerebroside is believed to cause a variety of symptoms and signs of liver and spleen hypertrophy (splenomegaly), skeletal disease and sometimes Gosche disease, including lung, kidney and central nervous system damage.
  • Goche disease and Parkinson's disease or Parkinson's disease (Parkinson's disease), which affects mobility and balance. Parkinsonism has been observed in patients with Gosch disease and the gene carriers of the disease (Lesage et al., 2011).
  • the signs and symptoms of Parkinsonism in these individuals include: tremors, stiffness and bradykinesis, facial expressions, slurred or monotonous speech, myoclonic jerks, loss of smell and noness.
  • Vascular bone necrosis (Neudofer et al., 1996; Bultron et al., 2010).
  • Lewy body dementia has also been reported in some subjects. Effective dietary and / or pharmaceutical interventions for one or more of these signs and symptoms will significantly improve the quality of life in these individuals.
  • ERT enzyme-replacement therapy
  • substrate reduction therapy is the only approved therapeutic options in patients with Goche disease (see Harmanci, 2008 for details).
  • ERT using recombinant imiglucerase improves the vesceral and hematologic manifestations of the disease, but is ineffective in the neuropathic form of Goche disease.
  • the cost of ERT amounts to about $ 200,000 per patient per year, making the therapy difficult to use for many patients and insufficient supply of recombinant enzymes to meet the medical needs on the market.
  • recombinant imiglucerase is disadvantageous because it must be administered intravenously.
  • the first oral treatment of Goche disease is miglustat (N-butyldeoxynojirimycin), an iminosugar inhibitor of glucosyl ceramide synthase, used in substrate reduction therapy.
  • Miglostat has shown clinical improvement in selected patients with mild or moderate symptoms, but the response is slower and less robust than that observed with ERT.
  • Other potential treatments for Goche disease are still under development (Futerman, 2004).
  • the present inventors have made efforts to develop a composition for diagnosing neonatal or fetal rare diseases with high sensitivity and accuracy, particularly lysosome accumulation disease, Wilson's disease or autosomal 1A recessive hearing loss, and include mutations occurring in newborn or fetal rare diseases.
  • a composition for diagnosing neonatal or fetal rare diseases with high sensitivity and accuracy particularly lysosome accumulation disease, Wilson's disease or autosomal 1A recessive hearing loss, and include mutations occurring in newborn or fetal rare diseases.
  • Another object of the present invention is to provide a genetic mutation detection method for detecting a congenital dysfunction of a newborn or fetus using the diagnostic composition.
  • PEX10 GALE, AGL, GBA, GBE1, SLC2A2, IDUA, ARSB, PEX1, GALT, ALDOB, LIPA, SMPD1, PYGM, SLC37A4, GJB2, ATP7B, PYGL, NPC2, GALC, GALK2, GALNS, G6PC, GALK1, GAA
  • Hereditary lysosomal storage disease through genetic mutation detection including polynucleotides containing sequences complementary to one or more gene exon region sequences consisting of NPC1, MCOLN1, ARSA, PHKA2, ATP7A, GLA, HPRT1, IDS and ABCD1 Disease, LSD), Wilson disease (Wilson Disease) and autosomal 1A deafness (Autosomal Recessive 1A) provides a composition for diagnosing congenital dysfunction of the newborn or fetus selected from the group consisting of.
  • the present invention also comprises the steps of: (a) capturing a target gene using the composition in a biological sample; (b) determining the sequence of the captured gene; Genetic variability related genetic variation of the newborn or fetus selected from the group consisting of hereditary lysosomal accumulation disease, Wilson's disease and autosomal 1A recessive hearing loss, and (c) analyzing the determined nucleotide sequences. It provides a detection method of.
  • the invention also relates to a congenital dysfunction of a newborn or fetus selected from the group consisting of hereditary lysosomal storage disease (LSD), Wilson disease and autosomal 1A deafness (Autosomal Recessive 1A). Provided is the use of the composition for diagnosis.
  • LSD hereditary lysosomal storage disease
  • Wilson disease Wilson disease
  • autosomal 1A deafness Autosomal Recessive 1A
  • the present invention also provides a newborn or fetus selected from the group consisting of hereditary lysosomal storage disease (LSD), Wilson disease, and autosomal 1A deafness using the composition.
  • LSD hereditary lysosomal storage disease
  • Wilson disease Wilson disease
  • autosomal 1A deafness using the composition.
  • FIG. 1 is a diagram illustrating a method for detecting genetic variation in a sample using a composition for diagnosing congenital dysfunction of a newborn or fetus according to the present invention.
  • NGS Next Generation Sequencing
  • next generation sequencing and next generation sequencing This refers to a technique for fragmenting the whole genome and sequencing the fragment at a large capacity based on chemical hybridization, and includes technologies from Agilent, Illumina, Roche, and Life Technologies, and has a broad meaning.
  • the furnace is defined as including a technology of Pacificbio, a third generation technology, a technology such as Nanopore Technology, and a fourth generation technology.
  • SNV Single Nucleotide Variation
  • insertion / deletion mutation means an insertion or deletion variation that can change the number of nucleic acids in a gene.
  • the mutation of the gene associated with congenital dysfunction such as lysosomal accumulation disease, Wilson disease and autosomal 1A recessive hearing loss with high sensitivity and accuracy, it was intended to confirm that it can be accurately diagnosed.
  • the present invention PEX10, GALE, AGL, GBA, GBE1, SLC2A2, IDUA, ARSB, PEX1, GALT, ALDOB, LIPA, SMPD1, PYGM, SLC37A4, GJB2, ATP7B, PYGL, NPC2, GALC, GALK2 Detecting gene mutations comprising polynucleotides containing sequences complementary to one or more gene exon region sequences consisting of, GALNS, G6PC, GALK1, GAA, NPC1, MCOLN1, ARSA, PHKA2, ATP7A, GLA, HPRT1, IDS, and ABCD1
  • LSD Lysosomal Storage Disease
  • Wilson Disease Wilson Disease
  • Autosomal 1A Deafness Autosomal Recessive 1A
  • the polynucleotide may be a primer or a probe, but is not limited thereto.
  • the “gene exon region” of the present invention includes an intron sequence of ⁇ 100 bp, specifically ⁇ 50 bp, more specifically ⁇ 20 bp in the exon region and exon region translated into protein.
  • probe refers to an oligonucleotide specific for a single strand having a base sequence that is sufficiently complementary to the target base sequence to be detected to hybridize.
  • 'Oligonucleotide' of the present invention generally refers to a nucleotide polymer consisting of about 10 to about 100 nucleotides. However, the length of the nucleotides may be 100 or more or 10 or less.
  • the 'nucleotide' of the present invention is the basic unit of nucleic acid consisting of phosphate groups, 5-carbosaccharides and nitrogen bases.
  • 5-Tanose in RNA is ribose.
  • the 5-saccharide in DNA is 2-deoxyribose.
  • the sugars contain hydroxyl groups (-OH) in 5-saccharide-2.
  • the term also includes analogs of these basic units, such as methoxy groups at the 2 position of ribose.
  • 'hybridization' of the present invention is meant the annealing of the complementary sequence to the target nucleic acid (the sequence to be detected).
  • the ability of two nucleic acid polymers, including complementary sequences, to find each other and hybridize through base pair interactions is a well known phenomenon.
  • a 'hybrid' of the present invention is a complex formed between two single-stranded nucleotide sequences by Watson-Crick base pair or non-standard base pair between complementary bases.
  • the 'label' of the present invention refers to any atom or molecule capable of providing a detectable (specifically quantifiable) signal and binding to a nucleic acid.
  • the label can provide a detectable signal by fluorescence, radioactivity, chromaticity, X-ray diffraction or absorption, magnetism, or the like.
  • the 'specificity' of the present invention refers to the characteristics of the probe to describe the ability to distinguish between target and nontarget sequences.
  • the specificity of a probe means that the nucleotide sequence hybridizes with a given target sequence and is substantially free of hybridization with the nontarget sequence or with minimal hybridization with the nontarget sequence. Probe specificity depends on sequence and assay conditions.
  • the polynucleotide of the present invention can be cloned using a conventional cloning method (Maniatis, T., et al. Molecular Cloning: A Laboratory Manual, Cold Spring Harbor, New York, 1982) or using a commercially available DNA synthesizer. Chemically synthesized to obtain a large amount.
  • the probes of the present invention may be specific for any conventional label, e.g., radioisotopes such as 32P, 35S, 125I, 3H and 14C, residues with immune properties (e.g., antigens or haptens), specific for some reagents.
  • residues that provide a detectable enzymatic reaction e.g., enzymes, coenzymes, enzyme substrates or substrates participating in the enzyme reaction
  • residues that provide a detectable enzymatic reaction e.g., enzymes, coenzymes, enzyme substrates or substrates participating in the enzyme reaction
  • a non-radioactive material containing a residue and the like.
  • the gene list used in one embodiment of the present invention is shown in Table 1 below.
  • the polynucleotide may be characterized in that it can detect exon mutations of each gene, maintain a GC ratio in the range of 40 to 60%, and complementary to the gene sequence without the repeat sequence.
  • gene fragments satisfying the above conditions were constructed as shown in Table 2 below.
  • the mutation of the gene may be characterized in that it occurs at one or more positions selected from the group consisting of the exon region described in Table 2.
  • the polynucleotide may be characterized by complementary to part or all of one or more gene sequences selected from the group consisting of SEQ ID NOs: 1 to 458.
  • the polynucleotide may be characterized in that it comprises one or more polynucleotides specifically selected from the group consisting of SEQ ID NOs: 459 to 2114.
  • nucleotide sequences represented by SEQ ID Nos: 459 to 2114 of the polynucleotides are shown in Table 4 below.
  • the gene mutation may be any mutation occurring in the gene or chromosome, specifically, in the group consisting of single nucleotide variation (SNV), insertion / deletion mutation (Indel) and inversion (inversion) It may be characterized as one or more variations selected.
  • SNV single nucleotide variation
  • Indel insertion / deletion mutation
  • inversion inversion
  • the hereditary lysosomal accumulation disease may be any disease that occurs due to abnormalities in the function of the lysosomal enzymes due to genetic mutations from birth, specifically, chromosome leukodystrophy, Maro Maroteaux-Lamy Syndrome (Mucopolysaccharidosis VI), Pompe Disease (Glycogen storage disease type II), Krabbe Disease, Gaucher Disease, Fabry Disease, Hunter Disease (Hunter Disease, Mucopolysaccharidosis II), Mucopolysaccharidosis I, Niemann-Pick Disease Type C, Niemann-Pick Disease Type B, Niemann-Pick Disease Type A Pick Disease Type A), Cholesteryl ester storage disease / Wolman disease, Morquio syndrome (MPS IVa), Menkes disease, Galactosemia, galactosinase Galactokinase deficiency, Galactose epimerase deficiency, Glycogen storage disease 1a, Glycogen storage disease 1b,
  • the present invention provides a method of preparing a biocompatible sample comprising: (a) capturing a target gene using the composition in a biological sample; (b) determining the sequence of the captured gene; And (c) genetic mutations related to congenital dysfunction of the newborn or fetus selected from the group consisting of hereditary lysosomal accumulation disease, Wilson's disease, and autosomal 1A recessive deafness comprising analyzing the determined base sequences. It relates to a detection method of.
  • the step of capturing the gene of the present invention means fragmenting the whole genome of a sample, and then hybridizing specifically to the fragmented gene using polynucleotides complementary to the gene sequence to be analyzed. Detecting the mutation of the gene is a method of amplifying the captured gene fragment, and then determine the sequence by multiplex parallel sequencing method, specifically, it can be performed by the NGS method, but is not limited thereto. It doesn't happen.
  • the biological sample may be selected from the group consisting of blood, hair, saliva, urine, oral cells, and mixtures thereof, but is not limited thereto.
  • the detection performance of gene mutations in a total of 16 positive samples was confirmed.
  • the experimental method was a targeted NGS test and the equipment used for the experiment was NextSeq500 or MiSeq.
  • the variation information of the sample is shown in Table 5, and the sequence detection performance of the samples is shown in Table 6.
  • the raw data of the FASTQ file format was obtained from a MiSeq or NextSeq 500 device.
  • the FASTQ file was sorted into the hg19 sequence by the BWA-MEM algorithm, and the Duplicated Reads were removed using Picard.
  • composition for diagnosing pre-hearing dysfunction can detect gene mutations related to neonatal or fetal rare diseases with high sensitivity and accuracy, and thus, it is possible to detect rare neonatal diseases, especially lysosomal accumulation diseases, Wilson's disease or autosomal 1A recessive hearing loss. It is useful for diagnosis.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Analytical Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Microbiology (AREA)
  • Molecular Biology (AREA)
  • Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Biophysics (AREA)
  • Pathology (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

La présente invention concerne une composition de diagnostic d'un dysfonctionnement congénital et, plus spécifiquement, une composition de diagnostic d'un dysfonctionnement congénital et son utilisation, le dysfonctionnement congénital étant sélectionné dans le groupe constitué de la maladie d'accumulation lysosomale, de la maladie de Wilson, et de la surdité récessive autosomique (1A), la composition comprenant un polynucléotide contenant une séquence complémentaire d'une séquence d'une région particulière d'exon d'un gène. L'utilisation de la composition selon la présente invention peut détecter, avec une sensibilité et une précision élevées, une mutation génétique associée à un dysfonctionnement congénital chez les nouveau-nés ou les fœtus, et ainsi la composition de la présente invention est utile.
PCT/KR2017/006345 2016-06-24 2017-06-16 Composition de diagnostic d'un dysfonctionnement congénital et son utilisation WO2017222248A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2016-0079413 2016-06-24
KR1020160079413A KR101743211B1 (ko) 2016-06-24 2016-06-24 선천성 기능장애 진단용 조성물 및 이의 용도

Publications (1)

Publication Number Publication Date
WO2017222248A1 true WO2017222248A1 (fr) 2017-12-28

Family

ID=59217412

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2017/006345 WO2017222248A1 (fr) 2016-06-24 2017-06-16 Composition de diagnostic d'un dysfonctionnement congénital et son utilisation

Country Status (2)

Country Link
KR (1) KR101743211B1 (fr)
WO (1) WO2017222248A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113265461A (zh) * 2021-07-02 2021-08-17 北京华诺奥美医学检验实验室有限公司 一种用于检测高频基因致病变异的引物组和探针组及试剂盒
WO2021216622A1 (fr) * 2020-04-21 2021-10-28 Aspen Neuroscience, Inc. Édition génique de gba1 dans des cellules souches et procédé d'utilisation de cellules différenciées à partir de celles-ci
US11578327B2 (en) 2018-02-14 2023-02-14 Deep Genomics Incorporated Oligonucleotide therapy for Wilson disease

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101743211B1 (ko) * 2016-06-24 2017-06-15 주식회사 녹십자지놈 선천성 기능장애 진단용 조성물 및 이의 용도

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20130098749A (ko) * 2012-02-28 2013-09-05 사회복지법인 삼성생명공익재단 상염색체 열성질환 진단용 키트
KR20140000439A (ko) * 2012-06-22 2014-01-03 주식회사 진인 유전성 난청 관련 유전자의 돌연변이 유무를 감별하기 위한 올리고뉴클레오티드, ｄｎａ칩, 진단 키트 및 감별 방법
KR20140140386A (ko) * 2013-05-29 2014-12-09 주식회사 랩 지노믹스 실시간 중합효소연쇄반응을 이용한 ａｔｐ７ｂ 유전자의 돌연변이 검출
KR101743211B1 (ko) * 2016-06-24 2017-06-15 주식회사 녹십자지놈 선천성 기능장애 진단용 조성물 및 이의 용도

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20130098749A (ko) * 2012-02-28 2013-09-05 사회복지법인 삼성생명공익재단 상염색체 열성질환 진단용 키트
KR20140000439A (ko) * 2012-06-22 2014-01-03 주식회사 진인 유전성 난청 관련 유전자의 돌연변이 유무를 감별하기 위한 올리고뉴클레오티드, ｄｎａ칩, 진단 키트 및 감별 방법
KR20140140386A (ko) * 2013-05-29 2014-12-09 주식회사 랩 지노믹스 실시간 중합효소연쇄반응을 이용한 ａｔｐ７ｂ 유전자의 돌연변이 검출
KR101743211B1 (ko) * 2016-06-24 2017-06-15 주식회사 녹십자지놈 선천성 기능장애 진단용 조성물 및 이의 용도

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
BARASHKOV ET AL.: "Autosomal Recessive Deafness 1A (DFNB1A) in Yakut Population Isolate in Eastern Siberia: Extensive Accumulation of the Splice Site Mutation IVS1+1G>A in GJB2 Gene as a Result of Founder Effect", JOURNAL OF HUMAN GENETICS, vol. 56, 2011, pages 631 - 639, XP055447861 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11578327B2 (en) 2018-02-14 2023-02-14 Deep Genomics Incorporated Oligonucleotide therapy for Wilson disease
WO2021216622A1 (fr) * 2020-04-21 2021-10-28 Aspen Neuroscience, Inc. Édition génique de gba1 dans des cellules souches et procédé d'utilisation de cellules différenciées à partir de celles-ci
CN113265461A (zh) * 2021-07-02 2021-08-17 北京华诺奥美医学检验实验室有限公司 一种用于检测高频基因致病变异的引物组和探针组及试剂盒

Also Published As

Publication number Publication date
KR101743211B1 (ko) 2017-06-15

Similar Documents

Publication Publication Date Title
WO2017222248A1 (fr) Composition de diagnostic d'un dysfonctionnement congénital et son utilisation
WO2016167408A1 (fr) Procédé permettant de prédire le rejet d'une greffe d'organe au moyen d'un séquençage de nouvelle génération
Gusella et al. DNA markers for nervous system diseases
Tyler-Smith et al. Structure of a hypervariable tandemly repeated DNA sequence on the short arm of the human Y chromosome
Montenegro et al. Exome sequencing allows for rapid gene identification in a Charcot‐Marie‐Tooth family
Sahiratmadja et al. Association of polymorphisms in IL-12/IFN-γ pathway genes with susceptibility to pulmonary tuberculosis in Indonesia
Halgren et al. Risks and recommendations in prenatally detected de novo balanced chromosomal rearrangements from assessment of long-term outcomes
WO2019199105A1 (fr) Procédé d'évaluation du risque de maladie d'alzheimer
Gordon et al. Significant evidence for linkage disequilibrium over a 5-cM region among Afrikaners
Wilson et al. Genetic diversity and gene family expansions in members of the genus Entamoeba
Attardi Role of mitochondrial DNA in human aging
WO2017094941A1 (fr) Procédé de détermination de la variation du nombre de copies dans un échantillon comprenant un mélange d'acides nucléiques
Ikeda et al. Identification of sequence polymorphisms in two sulfation-related genes, PAPSS2 and SLC26A2, and an association analysis with knee osteoarthritis
WO2019132581A1 (fr) Composition de diagnostic du cancer, tel que du cancer du sein et du cancer de l'ovaire, et son utilisation
WO2017191871A1 (fr) Procédé et dispositif permettant de déterminer la fiabilité d'un marqueur de détection de variation
WO2022039565A1 (fr) Biomarqueur pour le diagnostic d'une dégénérescence maculaire liée à l'âge et utilisation associée
Li et al. Cordblood-based high-throughput screening for deafness gene of 646 newborns in Jinan area of China
WO2021107713A1 (fr) Procédé de diagnostic de la sclérose latérale amyotrophique sur la base d'un marqueur de mutation du gène lats1
WO2022108407A1 (fr) Procédé de diagnostic du cancer et de prédiction de pronostic utilisant un rapport de longueur d'acides nucléiques
Tsai et al. Distribution of genome-wide linkage disequilibrium based on microsatellite loci in the Samoan population
McCarthy et al. Genetics of type 2 diabetes
Zhu et al. Utility of trio‐based prenatal exome sequencing incorporating splice‐site and mitochondrial genome assessment in pregnancies with fetal ultrasound anomalies: prospective cohort study
WO2020204313A1 (fr) Marqueur snp pour diagnostiquer un anévrisme cérébral, comprenant un polymorphisme monobasique du gène gba
WO2022119327A1 (fr) Procédé de mesure du risque de maladie cardio-cérébro-vasculaire à l'aide d'un score de risque de maladie métabolique congénitale
Brintnell et al. Evidence for a novel rheumatoid arthritis susceptibility locus on chromosome 6p

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 17815661

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 17815661

Country of ref document: EP

Kind code of ref document: A1