CN107419028B - Kit for detecting variable hyperkeratosis rubra and application thereof - Google Patents
Kit for detecting variable hyperkeratosis rubra and application thereof Download PDFInfo
- Publication number
- CN107419028B CN107419028B CN201710816094.3A CN201710816094A CN107419028B CN 107419028 B CN107419028 B CN 107419028B CN 201710816094 A CN201710816094 A CN 201710816094A CN 107419028 B CN107419028 B CN 107419028B
- Authority
- CN
- China
- Prior art keywords
- sequence
- site
- gjb3
- variable
- gene
- Prior art date
- Legal status (The legal status 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 status listed.)
- Active
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
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/156—Polymorphic or mutational markers
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Wood Science & Technology (AREA)
- Analytical Chemistry (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Pathology (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
The invention discloses a kit for detecting variable erythema keratosis and application thereof. The invention discovers that by analyzing GJB3 and GJB4 genes of a family with 3 cases of variable Erythema Keratosis (EKV) patients: 2 missense mutation points c.34G > A and c.474G > A are found in all 3 patients from the pathogenic gene GJB3, and 1 mutation is carried in 4 of the other 9 members of the family. The polymorphism at the 34 th site and the 474 th site of the GJB3 gene is related to EKV pathogenicity, the composite hybrid mutation is firstly reported at home and abroad, and the site c.474G > A is firstly reported at home and abroad. The c.34G > A and c.474G > A loci discovered by the invention can be used for diagnosing or assisting in diagnosing the variable erythema keratosis, evaluating the possibility of future diseases of members who are not attacked in the family, and providing a gene diagnosis basis for normal mating and healthy offspring breeding of family members.
Description
Technical Field
The invention belongs to the technical field of biology, and particularly relates to a kit for detecting variable hyperkeratosis rubra and application thereof.
Background
Variable Erythema Keratosis (EKV) is a rare autosomal dominant skin disease, and sporadic and autosomal recessive cases were reported and first described by Mendes da Costa in 1925. The disease is thought to be caused by GJB4 and CJB3 gene mutations of Cx30.3, Cx3l and CX43 coding connexins.
At present, 14 GJB3 gene mutations and 7 GJB4 gene mutations are reported at home and abroad, wherein the 7 GJB4 gene mutations are all autosomal dominant inheritance, the 3 GJB3 mutations are autosomal recessive inheritance, and the rest GJB3 mutations are all dominant inheritance. Mutations in the GJB3 gene often result in extensive and severe keratinizing lesions, with more severe disease, than localized keratosis due to mutations in the GJB4 gene. Most patients with this disease develop the disease in the first year after birth, and the disease tends to be stable with the increase of age, but not to be cured for a long time, and the disease can be aggravated by trauma, mechanical friction, mood fluctuation, temperature change and the like, and the main characteristics of the disease are migratory and variable erythema and relatively fixed keratotic plaque.
Disclosure of Invention
An object of the present invention is to provide a novel use of a substance for detecting single nucleotide polymorphisms at positions 34 and 474 of the second exon of the GJB3 gene.
The invention provides an application of a substance for detecting the polymorphism of single nucleotides at 34 th and 474 th sites of a second exon of a GJB3 gene in preparation of a product for detecting or assisting in detecting variable erythema keratosis.
The invention also provides application of the substance for detecting the polymorphism of the mononucleotide at the 34 th site and the 474 th site of the second exon of the GJB3 gene in detecting or assisting in detecting the variable erythema keratosis.
In the application, the substance for detecting the single nucleotide polymorphisms at the 34 th site and the 474 th site of the second exon of the GJB3 gene is a primer pair for amplifying DNA fragments containing the 34 th site and the 474 th site of the second exon of the GJB3 gene.
In the above application, the primer pair is 1) or 2):
1) a primer pair A consisting of a single-stranded DNA molecule shown in a sequence 2 in the sequence table and a single-stranded DNA molecule shown in a sequence 3 in the sequence table;
2) a primer pair B consisting of a single-stranded DNA molecule shown in a sequence A and a single-stranded DNA molecule shown in a sequence B;
the sequence A is a nucleotide which is obtained by deleting or adding or changing one or more nucleotides in the sequence 2 and has the same function as the sequence 2;
and the sequence B is a nucleotide which is obtained by deleting or adding or changing one or more nucleotides in the sequence 3 and has the same function as the sequence 3.
It is another object of the present invention to provide a kit for detecting or aiding in the detection of variable erythematous keratoderma.
The kit for detecting or assisting in detecting the variable erythema keratosis provided by the invention comprises a substance for detecting the single nucleotide polymorphism at the 34 th site and the 474 th site of the second exon of the GJB3 gene.
In the kit, the substances for detecting the mononucleotide polymorphism at 34 th and 474 th sites of the second exon of the GJB3 gene are primer pairs for amplifying DNA fragments containing the 34 th and the 474 th sites of the second exon of the GJB3 gene.
In the kit, the primer pair is 1) or 2):
1) a primer pair A consisting of a single-stranded DNA molecule shown in a sequence 2 in the sequence table and a single-stranded DNA molecule shown in a sequence 3 in the sequence table;
2) a primer pair B consisting of a single-stranded DNA molecule shown in a sequence A and a single-stranded DNA molecule shown in a sequence B;
the sequence A is a nucleotide which is obtained by deleting or adding or changing one or more nucleotides in the sequence 2 and has the same function as the sequence 2;
and the sequence B is a nucleotide which is obtained by deleting or adding or changing one or more nucleotides in the sequence 3 and has the same function as the sequence 3.
In the kit, the kit further comprises a data processing device; the data processing apparatus has functions as shown in (a1) and (a 2):
(a1) detecting the single nucleotide polymorphism at 34 th and 474 th sites of a second exon of a GJB3 gene of a subject;
(a2) determining whether the subject is a patient with variable erythema keratosis according to the detection result: if the 34 th site and the 474 th site of the second exon of the GJB3 gene of the subject are both mutated from the base G to the base A, the subject is or is selected to be the patient with the degenerative erythema keratosis; otherwise, the subject is not, or is not candidate for, a variable erythema keratosis patient.
In the kit, the 34 th site and the 474 th site of the second exon of the GJB3 gene of the subject are mutated from the base G to the base A, the 34 th site and the 474 th site of the second exon of the GJB3 gene can be heterozygous mutation, the 34 th site and the 474 th site of the second exon of the GJB3 gene can be homozygous mutation, or one of the 34 th site and the 474 th site of the second exon of the GJB3 gene is homozygous mutation, and the other is heterozygous mutation.
In the application or the kit, the second exon of the GJB3 gene is sequence 1.
The application of the above-mentioned kit in diagnosing or assisting to diagnose whether the subject is a patient with variable erythema keratosis also belongs to the protection scope of the invention.
The invention discovers that by analyzing GJB3 and GJB4 genes of a family with 3 cases of variable Erythema Keratosis (EKV) patients: 2 missense mutation points c.34G > A and c.474G > A are found in all 3 patients from the pathogenic gene GJB3, and 1 mutation is carried in 4 of the other 9 members of the family. The polymorphism of the GJB3 gene at the 34 th site and the 474 th site is related to the pathogenicity of the EKV, the composite hybrid mutation is firstly reported at home and abroad, and the site c.474G > A is firstly reported at home and abroad. The sites c.34G > A and c.474G > A discovered by the invention can be used for diagnosing or assisting in diagnosing the degenerative erythema keratosis, evaluating the possibility of future diseases of members who are not attacked in the family, and providing a gene diagnosis basis for normal mating and healthy offspring breeding of family members.
Drawings
FIG. 1 is a standard family diagram.
FIG. 2 shows that the 34 th site of the second exon of the pathogenic gene GJB3 is an A/G heterozygous mutation.
FIG. 3 shows the 474 th A/G heterozygous mutation of the second exon of the pathogenic gene GJB 3.
Detailed Description
The experimental procedures used in the following examples are all conventional procedures unless otherwise specified.
Materials, reagents and the like used in the following examples are commercially available unless otherwise specified.
In the quantitative tests in the following examples, three replicates were set up and the results averaged.
Example 1 discovery and application of pathogenic sites associated with variable erythema keratosis
First, the study object and the clinical examination result
1. Variable erythematous keratosis sample
(1) Sample composition
A non-closely matched family of variable Erythema Keratosis (EKV) with a total of 12 members was selected as the subject and a standard family plot was prepared as shown in FIG. 1. The member information is shown in table 1.
TABLE 1, 12 family Member information
| Family serial number | Age (age) | Sex | Whether it is EKV patient |
| III-3 | 34 | For male | Whether or not |
| III-11 | 21 | Woman | Whether or not |
| III-10 | 26 | Woman | Whether or not |
| III-6 | 17 | Woman | Whether or not |
| III-9 | 26 | Woman | Whether or not |
| III-4 | 32 | For male | Whether or not |
| II-1 | 67 | For male | Whether or not |
| II-4 | 61 | Woman | Whether or not |
| II-7 | 48 | Woman | Whether or not |
| II-5 | 57 | Woman | Is that |
| II-6 | 52 | For male | Is that |
| II-2 | 64 | Woman | Is that |
(2) Results of clinical examination
After informed consent of the patients, physical examination and dermatology specialist physical examination were performed on the selected 12 family members.
The history of proband II-5 in EKV patients is as follows: full body reddish-brown keratotic plaques for 49 years. The red plaque appears at the ankle 3 months after birth, and the skin lesion gradually expands to the whole body and is relatively fixed with the age, and the color gradually deepens. Red speck-like edges are occasionally visible around the plaque. The condition of the disease is aggravated by cold stimulation, the disease is severe in winter and mild in summer, and the disease feels slight pruritus.
The pathological examination results of proband II-5 in EKV patients were as follows: hyperkeratosis, papilloma-like hyperplasia, hypertrophy of the spinous layer, infiltration of lymphocytes around the superficial dermal blood vessels.
The physical examination of proband II-5 in EKV patients was as follows: the system physical examination is not abnormal.
The skin specialties of proband II-5 in EKV patients were as follows: reddish brown keratotic plaques are visible on the limbs, buttocks, breasts and faces, and scales are adhered on the plaques, so that the plaques are not easy to peel off. The skin lesion is relatively fixed and is in a pattern shape, and the boundary is completely like a knife cutting sample. Keratinized thickening of both palms and soles, normal teeth and nails.
Laboratory examination of proband II-5 in EKV patients: the normal function of the liver and kidney is normal.
The diagnosis result shows that: proband II-5 is a patient with variable Erythema Keratosis (EKV), and the patient has a disease history, clinical symptoms and physical signs similar to those of another brother and sister 2. Therefore, it is known from diagnosis that: of the 12 members, EKV patients were 3 (proband II-5), EKV patients were 3 siblings, EKV patients were 1 child, EKV patients were 5 children of siblings. No other patients were found in the family.
2. Normal sample
100 normal individuals without relationship outside the family were selected as a control group.
Second, detection of pathogenic genes
Sanger sequencing was performed on the disease-causing genes GJB3 and GJB4 from DNA samples of 12 family members to confirm the presence of disease-causing mutations, and to verify whether the mutant genotypes were co-segregated with clinical manifestations within the families. And (3) detecting whether the mutation exists in the normal population by taking 100 normal individuals without relationship of blood outside the family as a control group, and further analyzing the association between the mutation site and the variable erythema keratosis. The method comprises the following specific steps:
1. peripheral blood samples were taken and DNA was extracted using Qiagen DNA extraction kit. And the DNA concentration was measured using a full wavelength ultraviolet/visible light scanning spectrophotometer DN-2000(NanoDrop Co., USA).
2. And (3) performing PCR amplification by using the DNA obtained in the step (1) as a template and adopting primers in the table 2 to obtain a PCR product. The PCR amplification system and the PCR reaction procedure are shown in Table 3 and Table 4, respectively.
TABLE 2 primer sequences
TABLE 3 PCR amplification System (5. mu.l)
| Stencil (ul) | 1 |
| Primer Fi (ul) | 0.5 |
| Primer Ri (μ l) | 0.5 |
| dNTP 10mM(μl) | 0.5 |
| Taq Buffer(μl) | 2.5 |
| Taq enzyme (. mu.l) 5U/. mu.l | 0.2 |
| Water (ul) | 20 |
TABLE 4 PCR reaction conditions
3. Sequencing and sequence analysis
And (3) purifying and recovering the PCR product by using a PCR product purification and recovery kit (worker B518131) and delivering to sequencing. Sequencing maps can be opened using either Chromas software or SeqMan software and analyzed using SeqMan software for sequence alignment.
The detection of family member mutations is shown in table 5. The sequence analysis result shows that: in the family members, no pathogenic mutation is found in a pathogenic gene GJB 4; 2 missense mutation points are found in a pathogenic gene GJB3 in 3 patients with variable erythema keratosis: c.34g > a (fig. 2) and c.474g > a (fig. 3). Wherein c.34G > A and c.474G > A are respectively positioned at the 34 th site and the 474 th site of the second exon (sequence 1) of the GJB3 gene, and the 34 th site and the 474 th site of the second exon of the GJB3 gene of 3 patients with variable erythema keratosis are heterozygous mutated, and both the base G and the base A are mutated. Of the other 9 members of the family, 4 members (III-11, III-10III-9 and II-1) carried only 1 mutation in c.34G > A and c.474G > A, and none of the other members found the c.34G > A and c.474G > A mutations. No c.34G > A or c.474G > A site mutation is found in 100 normal healthy human pathogenic genes GJB 3.
TABLE 5 family Member mutation detection
Foreign dominant inheritance families which are pathogenic to GJB3 gene c.34G > A mutation have been reported, but in the family, two patient offspring (III-11 and III-9) carry c.34G > A, but no variable erythema keratosis is shown, while 3 patients with the degenerative erythema keratosis simultaneously carry two mutations of c.34G > A and c.474G > A, and parents of the patients do not suffer from the diseases, and the family characteristics are also compounded with autosomal recessive inheritance.
In practical application, whether the subject is the patient with the variable erythema keratosis can be diagnosed or assisted to diagnose according to the mutation condition of c.34G > A and c.474G > A sites of the GJB3 gene:
if the 34 th site and the 474 th site of the second exon of the GJB3 gene of the subject are both mutated from the base G to the base A, the subject is or is selected as the patient with the variable erythema keratosis; otherwise, the subject is not, or is not candidate for, a variable erythema keratosis patient.
Sequence listing
<110> subsidiary hospital of southwest medical university
<120> kit for detecting variable erythema keratosis and application thereof
<160>3
<210>1
<211>1627bp
<212>DNA
<213> Artificial sequence
<220>
<223>
<400>1
gtaggcacgg cccccaccag gcgccatgga ctggaagaca ctccaggccc tactgagcgg 60
tgtgaacaag tactccacag cgttcgggcg catctggctg tccgtggtgt tcgtcttccg 120
ggtgctggta tacgtggtgg ctgcagagcg cgtgtggggg gatgagcaga aggactttga 180
ctgcaacacc aagcagcccg gctgcaccaa cgtctgctac gacaactact tccccatctc 240
caacatccgc ctctgggccc tgcagctcat cttcgtcaca tgcccctcgc tgctggtcat 300
cctgcacgtg gcctaccgtg aggagcggga gcgccggcac cgccagaaac acggggacca 360
gtgcgccaag ctgtacgaca acgcaggcaa gaagcacgga ggcctgtggt ggacctacct 420
gttcagcctc atcttcaagc tcatcattga gttcctcttc ctctacctgc tgcacactct 480
ctggcatggc ttcaatatgc cgcgcctggt gcagtgtgcc aacgtggccc cctgccccaa 540
catcgtggac tgctacattg cccgacctac cgagaagaaa atcttcacct acttcatggt 600
gggcgcctcc gccgtctgca tcgtactcac catctgtgag ctctgctacc tcatctgcca 660
cagggtcctg cgaggcctgc acaaggacaa gcctcgaggg ggttgcagcc cctcgtcctc 720
cgccagccga gcttccacct gccgctgcca ccacaagctg gtggaggctg gggaggtgga 780
tccagaccca ggcaataaca agctgcaggc ttcagcaccc aacctgaccc ccatctgacc 840
acagggcagg ggtggggcaa catgcgggct gccaatggga catgcagggc ggtgtggcag 900
gtggagaggt cctacagggg ctgagtgacc ccactctgag ttcactaagt tatgcaactt 960
tcgttttggc agatattttt tgacactggg aactgggctg tctagccggg tataggtaac 1020
ccacaggccc agtgccagcc ctcaaaggac atagactttg aaacaagcga attaactatc 1080
tacgctgcct gcaaggggcc acttagggca ctgctagcag ggcttcaacc aggaagggat 1140
caacccagga agggatgatc aggagaggct tccctgagga cataatgtgt aagagaggtg 1200
agaagtgctc ccaagcagac acaacagcag cacagaggtc tggaggccac acaaaaagtg 1260
atgctcgccc tgggctagcc tcagcagacc taaggcatct ctactccctc cagaggagcc 1320
gcccagattc ctgcagtgga gaggaggtct tccagcagca gcaggtctgg agggctgaga 1380
atgaacctga ctagaggttc tggagatacc cagaggtccc ccaggtcatc acttggctca 1440
gtggaagccc tctttcccca aatcctactc cctcagcctc aggcagtggt gctcccatct 1500
tcctccccac aactgtgctc aggctggtgc cagcctttca gaccctgctc ccagggactt 1560
gggtggatgc gctgatagaa catcctcaag acagtttcct tgaaatcaat aaatactgtg 1620
ttttata 1627
<210>2
<211>25bp
<212>DNA
<213> Artificial sequence
<220>
<223>
<400>2
aactcagaac actgcctggt acata 25
<210>3
<211>21bp
<212>DNA
<213> Artificial sequence
<220>
<223>
<400>3
gcttgttatt gcctgggtct g 21
Claims (3)
1. The application of the substance for detecting the single nucleotide polymorphism at the 59 th site and the 499 th site of the second exon of the GJB3 gene in preparing products for detecting or assisting in detecting the variable erythema keratosis;
the second exon of the GJB3 gene is a sequence 1.
2. Use according to claim 1, characterized in that: the substance for detecting the single nucleotide polymorphisms at the 59 th and 499 th sites of the second exon of the GJB3 gene is a primer pair for amplifying DNA fragments containing the 59 th and 499 th sites of the second exon of the GJB3 gene.
3. Use according to claim 2, characterized in that:
the primer pair is 1) or 2) as follows:
1) a primer pair A consisting of a single-stranded DNA molecule shown in a sequence 2 in the sequence table and a single-stranded DNA molecule shown in a sequence 3 in the sequence table;
2) a primer pair B consisting of a single-stranded DNA molecule shown in a sequence A and a single-stranded DNA molecule shown in a sequence B;
the sequence A is a nucleotide which is obtained by deleting or adding or changing one or more nucleotides in the sequence 2 and has the same function with the sequence 2; and the sequence B is a nucleotide which is obtained by deleting or adding or changing one or more nucleotides in the sequence 3 and has the same function as the sequence 3.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710816094.3A CN107419028B (en) | 2017-09-12 | 2017-09-12 | Kit for detecting variable hyperkeratosis rubra and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710816094.3A CN107419028B (en) | 2017-09-12 | 2017-09-12 | Kit for detecting variable hyperkeratosis rubra and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107419028A CN107419028A (en) | 2017-12-01 |
| CN107419028B true CN107419028B (en) | 2021-01-05 |
Family
ID=60432005
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710816094.3A Active CN107419028B (en) | 2017-09-12 | 2017-09-12 | Kit for detecting variable hyperkeratosis rubra and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107419028B (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102634579A (en) * | 2012-03-28 | 2012-08-15 | 上海艾迪康医学检验所有限公司 | Kit for detecting genic mutation of deafness associated genes GJB3 |
| WO2012158780A2 (en) * | 2011-05-16 | 2012-11-22 | The Regents Of The University Of Michigan | Lung cancer signature |
-
2017
- 2017-09-12 CN CN201710816094.3A patent/CN107419028B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012158780A2 (en) * | 2011-05-16 | 2012-11-22 | The Regents Of The University Of Michigan | Lung cancer signature |
| CN102634579A (en) * | 2012-03-28 | 2012-08-15 | 上海艾迪康医学检验所有限公司 | Kit for detecting genic mutation of deafness associated genes GJB3 |
Non-Patent Citations (1)
| Title |
|---|
| Mutations in the human connexin gene GJB3 cause erythrokeratodermia variabilis;Gabriele Richard等;《nature genetics》;19981231;第366-369页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107419028A (en) | 2017-12-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Blanco et al. | Evidence of a sex-dependent association between the MSX1 locus and nonsyndromic cleft lip with or without cleft palate in the Chilean population | |
| Bazzi et al. | Association between FTO, MC4R, SLC30A8, and KCNQ1 gene variants and type 2 diabetes in Saudi population | |
| US20110008773A1 (en) | Method for the determination of data for the preparation of the diagnosis of phakomatosis | |
| Beicht et al. | Next generation sequencing as a useful tool in the diagnostics of mosaicism in Alport syndrome | |
| CN111560428B (en) | Application of substance for detecting single nucleotide polymorphism of mitochondrial DNA rs3937033 | |
| CN111676283B (en) | Application of mitochondrial DNA single nucleotide polymorphism related to occurrence of high altitude pulmonary edema | |
| KR20130043107A (en) | Genetic marker for the diagnosis of dementia with lewy bodies | |
| Saravani et al. | Association of catalase (rs7943316) and glutathione peroxidase-1 (rs1050450) polymorphisms with the risk of type 2 diabetes (T2DM) | |
| Abramzon et al. | Investigating RFC1 expansions in sporadic amyotrophic lateral sclerosis | |
| Wang et al. | Optimizing RNA extraction yield from whole blood for microarray gene expression analysis | |
| Arefi et al. | Diverse presentations of cutaneous mosaicism occur in CYLD cutaneous syndrome and may result in parent-to-child transmission | |
| CN107419028B (en) | Kit for detecting variable hyperkeratosis rubra and application thereof | |
| JP6053681B2 (en) | Method and kit for diagnosing glaucoma in dogs | |
| JPH10500860A (en) | Detection method and probe for marker linked to pediatric spinal muscular atrophy locus | |
| CN109234282A (en) | BRCA1 gene g.43063754T > G mutant and its application in Computer-aided Diagnosis of Breast Cancer | |
| CN109321658B (en) | Kit for detecting susceptibility of cervical cancer | |
| JP5828499B2 (en) | Primer set for detecting mutation of EYS gene, probe, microarray, detection kit provided with these, and method for examining gene mutation causing retinitis pigmentosa | |
| CN105316393A (en) | Rapid detection method for detecting deletion mutation of cell apoptosis regulator gene (BIM) and detection kit thereof | |
| CN114606311B (en) | Application of SLC39A13 gene rs755555 locus, detection primer and probe combination thereof and kit | |
| CN105765077B (en) | Detection method for determining risk of anti-thyroid drug-induced agranulocytosis and kit for determination | |
| CN103725687B (en) | DRD (Dope-Reactive Dystonia)-related gene mutation and detecting method and usage thereof | |
| KR102180941B1 (en) | A composition for diagnosing glioblastoma | |
| Alberts et al. | Isolation of a cytochrome oxidase gene overexpressed in Alzheimer's disease brain | |
| CN104946738B (en) | Method for determining visceral fat accumulation susceptibility | |
| CN114774552A (en) | Diagnosis marker and diagnosis reagent for nevoid basal cell carcinoma syndrome and application |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |