CN105274236B - The application of ABCA3 genes - Google Patents
The application of ABCA3 genes Download PDFInfo
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- CN105274236B CN105274236B CN201510789275.2A CN201510789275A CN105274236B CN 105274236 B CN105274236 B CN 105274236B CN 201510789275 A CN201510789275 A CN 201510789275A CN 105274236 B CN105274236 B CN 105274236B
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- 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
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/156—Polymorphic or mutational markers
Abstract
It is an object of the invention to provide a kind of ABCA3 genes to prepare the application in detecting congenital cataract microcornea syndrome (CCMC) diagnostic product, the invention provides the new purposes of ABCA3 genes, so as to provide a kind of approach for effectively carrying out congenital CCMC disease genes diagnosis, prenatal gene examination and genetic counselling, application effect shows the SNP site of gene provided by the present invention and detection primer can be effectively used for clinical patients and fetus fine hair or amniotic fluid carries out the quick detection of ABCA3 gene mutation sites.
Description
Technical field
The invention belongs to gene diagnosis and the correlative technology field of prenatal gene diagnosis, and in particular to ATP connection boxes (ABC)
Transport sub- A3 (ABCA3) and prepare the application in detecting congenital cataract-microcornea syndrome (CCMC) gene diagnosis product.
Background of invention
Congenital cataract is to cause the common illness in eye of low vision children and blinding, the incidence of disease is about 0.01%~
0.06%, wherein about 50% is relevant with heredity, its mode of inheritance is most commonly seen with autosomal dominant inheritance.Congenital cataract
Can independently it occur, also can be as eye or the concomitant symptom of whole body syndrome, wherein 12%-18% patients with congenital cataract
Often occur to merge microcornea symptom.Cataract-microcornea syndrome (Cataract-microcornea syndrome, CCMC,
OMIM 116200) it is a kind of congenital dysplasia illness in eye, often involve eyes, show as not isophenic cataract and cornea
Transverse diameter is less than 10mm, and the anterior ocular segment that often occurs together depauperation, such as iridocoloboma, Peters are abnormal, corectopia and nystagmus,
These Poly-monstrosities often make Most patients loss of sight, are one of the major reasons of congenital blinding.It is and and simple congenital
Cataract is compared, and the patient for the microcornea that occurs together more is susceptible to suffer from glaucoma, and causes irreversible visual impairment.At present for
CCMC treatment means are limited, blind rate is very high, and heavy financial burden is brought to the whole society.
The congenital CCMC cause of disease and pathomechanism is unclear, studies in the world at present less.Science of heredity both domestic and external
Result of study shows that the disease is largely because caused by inherent cause.So far, existing 7 Disease-causing genes are proved
(referring to table 1).
Table 1：Cataract-microcornea syndrome Disease-causing gene positioning and clone's situation
CCMC has significant genetic heterogeneity, multiple candidate disease causing genes be present.Up to the present CCMC is caused a disease
The understanding of gene is still limited, and 7 knowns so far are only capable of explaining the morbidity of the patient less than 30%.This has become
The research of CCMC pathogenesis and the bottleneck of etiotropic diagnosis and Therapy study.This present situation promotes further to go to send out
The now Disease-causing gene new with the disease is understood, basis is provided for follow-up gene diagnosis, pre-natal diagnosis and gene therapy.
The content of the invention
It is an object of the invention to provide a kind of ABCA3 genes to prepare detection congenital cataract-microcornea syndrome
(CCMC) application in diagnostic product, so as to make up the deficiencies in the prior art.
Applicants have discovered that 4 generations are in the CCMC familys of autosomal dominant inheritance, it is sequenced, excludes by candidate gene
The pathogenic possibility of known 7 candidate genes mutation；Meanwhile extron group further is carried out to the core member of the family
Sequencing, the Disease-causing gene ATP connection boxes (ABC) that have found the family transport sub- A3 (ABCA3), so as to facilitate the present invention.
Present invention firstly provides the new purposes of ABCA3 genes, is comprehensive for detecting congenital cataract-microcornea in preparation
Application in simulator sickness (CCMC) diagnostic product；
The present invention also provides a kind of primer pair for being used to detect congenital cataract-microcornea syndrome (CCMC), described
The upstream and downstream primer sequence of primer pair be SEQ ID NO:1-38, its primer information are as follows：
ABCA3-1L:AGAAATGGAAAGTGACTCCTCT SEQ ID NO:1
ABCA3-1R:GTCTGTGGGTTACTGGAAGTT SEQ ID NO:2
ABCA3-2L:AACTTCCAGTAACCCACAGAC SEQ ID NO:3
ABCA3-2R:AGAGTGGAGTCAGAATCAAGGT SEQ ID NO:4
ABCA3-3L:ACCTTGATTCTGACTCCACTCT SEQ ID NO:5
ABCA3-3R:GAAAGAGTCCTAGCACATCAGA SEQ ID NO:6
ABCA3-4L:AGCTTTAGCTCATTACCTTGTC SEQ ID NO:7
ABCA3-4R:CCTGGTCAATCAGACAGAATTA SEQ ID NO:8
ABCA3-5L:ACATCAGAGCTGATTCTGTGAC SEQ ID NO:9
ABCA3-5R:ATAGTTTATGTCTCCTGGATGC SEQ ID NO:10
ABCA3-6L:CGTACAGTGGGAGACCATC SEQ ID NO:11
ABCA3-6R:CACTAATCCAGTGTCTCACCTT SEQ ID NO:12
ABCA3-7L:GCTGGGACACTCACTATATTTC SEQ ID NO:13
ABCA3-7R:CTGATGAACTTCTTCTTCTTGG SEQ ID NO:14
ABCA3-8L:GTTCTCGTAGAAACTGCTGACT SEQ ID NO:15
ABCA3-8R:GTCTGAGGACCTCCAAATG SEQ ID NO:16
ABCA3-9L:CATTTGGAGGTCCTCAGAC SEQ ID NO:17
ABCA3-9R:ATTGTCACATGGTCAGCATAG SEQ ID NO:18
ABCA3-10L:ACTCTGTCACATCTGACTTTGG SEQ ID NO:19
ABCA3-10R:GAGACACTGATGAGTGAGGAAA SEQ ID NO:20
ABCA3-11L:GTGAGTCAGATACGTGCTTCTC SEQ ID NO:21
ABCA3-11R:CTTCCTAGAACCACACCATAAC SEQ ID NO:22
ABCA3-12L:GTTGCACAGTACAGTCAGAGGT SEQ ID NO:23
ABCA3-12R:GACTGTGTCTCTCCCTCCAG SEQ ID NO:24
ABCA3-13L:CGCTGAGATGGTGTTAAAG SEQ ID NO:25
ABCA3-13R:AGAAAGCACTCAGAAACGAGTA SEQ ID NO:26
ABCA3-14L:GTTGAGGTTCAGGTCTCTGAC SEQ ID NO:27
ABCA3-14R:ATCTAGTGTGTCTGCTGGTTGT SEQ ID NO:28
ABCA3-15L:GAGGTAAAAGGCACTACAGAAG SEQ ID NO:29
ABCA3-15R:AACTTTGTGGTCAGAGACTTCA SEQ ID NO:30
ABCA3-16L:CTAAATTACGCTGACTTTCCTC SEQ ID NO:31
ABCA3-16R:GACATAGTAAGACCCTGTCGAA SEQ ID NO:32
ABCA3-17L:AGGAGTGACTGCTATTGACTTG SEQ ID NO:33
ABCA3-17R:TGTTAAGGAGTGTCCAGATGAT SEQ ID NO:34
ABCA3-18L:GCCTTTTACAGGTTGAAGTAGT SEQ ID NO:35
ABCA3-18R:CACAAAAGAAGGTGAGAGACAT SEQ ID NO:36
ABCA3-19L:GCCTTTTACAGGTTGAAGTAGT SEQ ID NO:37
ABCA3-19R:CACAAAAGAAGGTGAGAGACAT SEQ ID NO:38。
The present invention also provides a kind of kit for being used to detect congenital cataract-microcornea syndrome (CCMC), comprising
There is any of above-mentioned primer pair or several.
The present invention also provides a kind of SNP site related to congenital cataract-microcornea syndrome (CCMC) disease, is
The 4393rd by initiation codon, its base is G or A for ABCA3 gene coding regions；
The present invention also provides another SNP site related to congenital cataract-microcornea syndrome (CCMC) disease,
It is ABCA3 gene coding regions the 2408th by initiation codon, its base is C or T；
The present invention also provides another SNP site related to congenital cataract-microcornea syndrome (CCMC) disease,
It is ABCA3 gene coding regions the 4253rd by initiation codon, its base is A or T；
The invention provides the new purposes of ABCA3 genes, and congenital CCMC diseases are effectively carried out so as to provide one kind
The approach of ospc gene diagnosis, prenatal gene examination and genetic counselling, application effect show the SNP positions of gene provided by the present invention
Point and detection primer can be effectively used for clinical patients and fetus fine hair or amniotic fluid carries out the fast of ABCA3 gene mutation sites
Speed detection.
Brief description of the drawings
Fig. 1：ABCA3 gene coding regions the 4393rd SNP site information by initiation codon, its base are G or A.
Fig. 2：ABCA3 gene coding regions the 2408th SNP site information by initiation codon, its base are C or T.
Fig. 3：ABCA3 gene coding regions the 4253rd SNP site information by initiation codon, its base are A or T.
Fig. 4：Patient and normal person's ABCA3 sequencer maps, wherein A- in the cataract of embodiment 1-microcornea syndrome family
C:Patient；D-F:Normal person.The ABCA3 gene coding regions of three patients the 4393rd alkali by initiation codon in the family
Base sports A, the sequencing result of its reverse primer shows that the site is heterozygous mutant, is mutated by C there occurs heterozygous mutant by G
For T.
Fig. 5：Patient and normal person's ABCA3 sequencing results in the cataract of embodiment 2-microcornea syndrome family.A-E:
Patient；F-J:Normal person.The ABCA3 gene coding regions of five patients the 2408th base by initiation codon in the family
There occurs heterozygous mutant, and T is sported by C, and the sequencing result of its reverse primer shows that the site is heterozygous mutant, is sported by G
A。
Fig. 6：A cataract-microcornea syndrome patient of embodiment 3 and its mother (normal person) ABCA3 sequencing knots
Fruit.A:Patient；B:Normal person.There occurs miscellaneous for the 4253rd base by initiation codon for the patient ABCA3 gene coding regions
Mutation is closed, T is sported by A, the sequencing result of its reverse primer shows that the site is heterozygous mutant, and A is sported by T.
Embodiment
Applicant of the present invention has found the mutational site of ABCA3 genes in a geneogenous CCMC family, and another
One geneogenous CCMC family and several distribute confirm that the mutation of the gene is the sick Disease-causing gene in patient, so as to facilitate
The present invention.
ABCA3 belongs to the member of ABCA subfamilies in abc transport sub-family, and its gene is by more than 80000 nucleosides soda acids
Base forms, and positioned at 16p13.3, the transcribed mRNA (NM_001089) into about 6500bp, directly translation form 1704 amino
The protein of acid composition.
The present invention is described in detail below.
First, the screening in the mutational site of ABCA3 genes is found in congenital CCMC familys
Embodiment 1：The mutational site of ABCA3 genes is screened from congenital CCMC familys
1st, peripheral blood genomic DNA is extracted：
Meeting national relevant policies regulation, and on the basis of sampling object is agreed to, extracting outside first family member
All venous blood 2-5ml, are put into EDTA anticoagulant tubes, -80 DEG C freeze it is standby；The EDTA anticoagulations frozen take after room temperature thawing
500 μ L are put in centrifuge tube, add isometric TE (pH8.0), mix, 4 DEG C, and 10000rpm is centrifuged 10 minutes, abandons supernatant.
Add 180 μ L TE, 20 μ LSDS (10%), 8 μ L Proteinase Ks (l0mg/ml) to mix, be placed in 37 DEG C of water-baths and stay overnight.
Sample, brief centrifugation precipitation sample are taken out from water-bath.Isometric Tris- saturated phenols (about 300 μ L) are added in reaction tube,
Fully mix, 10000rpm is centrifuged 10 minutes at room temperature, and Aspirate supernatant (about 300 μ L) is into a new centrifuge tube.Phenol is repeated to take out
Carry once, Aspirate supernatant is into a new centrifuge tube.
Add isometric Tris saturated phenols:Chloroform mixed liquor (each 150 μ L of phenol, chloroform), mix, room temperature 10000rpm from
The heart 10 minutes, transfer supernatant to a new centrifuge tube.
Add isometric Tris saturated phenols:Chloroform:Isoamyl alcohol mixed liquor (each 100 μ L of phenol, chloroform, isoamyl alcohol), mix,
Room temperature 10000rpm is centrifuged 10 minutes, transfer supernatant to a new centrifuge tube.
L/10 volumes 3mol/L, pH5.2 sodium acetate (about 30 μ L) is added, 2 times of ethanol of volume precooling 100%, is gently mixed,
Visible white flocculent deposit.Room temperature 10000rpm is centrifuged 10 minutes, DNA is deposited in ttom of pipe, is abandoned supernatant.
Precipitated to DNA and add 70% ethanol, once, room temperature 7000rpm is centrifuged 5 minutes, is abandoned supernatant, is placed in room temperature for rinsing
Volatilize remaining ethanol, is eventually adding 50 μ L TE (pH8.0), 4 DEG C of overnight dissolving DNAs.
To the DNA row agarose gel electrophoresis of extraction, and application ultraviolet specrophotometer is in 260nm and 280nm colorimetrics, detection
DNA purity and concentration.
2. sequencing of extron group：Sequencing of extron group (Exome Sequencing) is a kind of new genome analysis skill
Art, the DNA in full genome extron (exon) region need to be only directed to, the genomic DNA of 3 patients in the family be taken, by depth
Human gene is collected using NimbleGen (44Mb) target enrichment system by ditch between fields Hua Da Gene Tech. Company Limited
The exon region of group, the extron library of enrichment is carried out using Illumina Genome Analyzer II platforms
Illumina GA high-flux sequences, 18283 (99.6%) captured altogether in 18357 target gene are individual.By these mutation filters
Cross 4 data of normal people storehouses：SNP database (dbSNP 129, http://www.ncbi.nlm.nih.gov/
), projects/SNP/snp_summary.cgi/ thousand human genome plans (February 28,2011releases for
SNPs,and February 16,2011releases for indels http://www.1000genome.org/),
Hapmap8 databases (http://hapmap.ncbi.nlm.nih.gov/), and Yan Di and Huang Di, two legendary rulers of remote antiquity's database, further filter out 3 trouble
106, the non-synonymous unknown mutation site that person shares, screened and pathogenic haplotype in the family using direct sequencing
The Disease-causing gene ABCA3 isolated, and carry out the site in 200 normal local crowd's peripheral blood genomic DNA samples
Mutation Screening, the mutation is not found.
3. direct sequencing verifies the mutation of patient ABCA3 genes in the family
PCR expands purpose fragment：Reaction condition and reaction system：
(1) PCR reaction conditions：94℃3min；94 DEG C of 40sec, 55 ± 3 DEG C of 40se, 72 DEG C of 60sec, 30-35cycles；
72℃10min。
(2) reaction system：(TAKARA LA Taq polymerase)
Carry out the genomic DNA template of every family member and the amplification of the ABCA3 primers respectively using the reaction system
Reaction.
PCR primer is sequenced：Above-mentioned PCR primer is sequenced using conventional Sanger PCR sequencing PCRs, three trouble in the family
The ABCA3 gene coding regions of person the 4393rd base by initiation codon there occurs heterozygous mutant, sports A, its is anti-by G
Show that the site is heterozygous mutant to the sequencing result of primer, T (Fig. 4) sported by C, cause the 1465th, ABCA3 albumen by
Aspartic acid mutations are asparagine, point of application mutation forecasting program SIFT (Sorting Intolerant From
Tolerant) prediction finds that the mutation result in the damage of ABCA3 protein functions " damaging " level, so as to cause the family
CCMC generation in system.Multiple sequencing result shows that the mutational site is not because amplification or sequencing mistake are introduced.200
The Mutation Screening in the site is carried out in the normal local crowd of example and the family in the peripheral blood genomic DNA sample of normal person, not
It was found that the mutation.
Pass through above-mentioned analysis, it was demonstrated that ABCA3 genes can be used for detecting whether patient has the potential danger for suffering from CCMC.
By the way that each extron fragment of the ABCA3 genes of tester is compared in normal homologous segment, the illness of person to be detected is determined
Risk.
The primer pair for expanding its each extron, the sequence information of its positive anti-primer are designed according to ABCA3 genome sequence
It is as follows：
ABCA3-1L:AGAAATGGAAAGTGACTCCTCT
ABCA3-1R:GTCTGTGGGTTACTGGAAGTT
ABCA3-2L:AACTTCCAGTAACCCACAGAC
ABCA3-2R:AGAGTGGAGTCAGAATCAAGGT
ABCA3-3L:ACCTTGATTCTGACTCCACTCT
ABCA3-3R:GAAAGAGTCCTAGCACATCAGA
ABCA3-4L:AGCTTTAGCTCATTACCTTGTC
ABCA3-4R:CCTGGTCAATCAGACAGAATTA
ABCA3-5L:ACATCAGAGCTGATTCTGTGAC
ABCA3-5R:ATAGTTTATGTCTCCTGGATGC
ABCA3-6L:CGTACAGTGGGAGACCATC
ABCA3-6R:CACTAATCCAGTGTCTCACCTT
ABCA3-7L:GCTGGGACACTCACTATATTTC
ABCA3-7R:CTGATGAACTTCTTCTTCTTGG
ABCA3-8L:GTTCTCGTAGAAACTGCTGACT
ABCA3-8R:GTCTGAGGACCTCCAAATG
ABCA3-9L:CATTTGGAGGTCCTCAGAC
ABCA3-9R:ATTGTCACATGGTCAGCATAG
ABCA3-10L:ACTCTGTCACATCTGACTTTGG
ABCA3-10R:GAGACACTGATGAGTGAGGAAA
ABCA3-11L:GTGAGTCAGATACGTGCTTCTC
ABCA3-11R:CTTCCTAGAACCACACCATAAC
ABCA3-12L:GTTGCACAGTACAGTCAGAGGT
ABCA3-12R:GACTGTGTCTCTCCCTCCAG
ABCA3-13L:CGCTGAGATGGTGTTAAAG
ABCA3-13R:AGAAAGCACTCAGAAACGAGTA
ABCA3-14L:GTTGAGGTTCAGGTCTCTGAC
ABCA3-14R:ATCTAGTGTGTCTGCTGGTTGT
ABCA3-15L:GAGGTAAAAGGCACTACAGAAG
ABCA3-15R:AACTTTGTGGTCAGAGACTTCA
ABCA3-16L:CTAAATTACGCTGACTTTCCTC
ABCA3-16R:GACATAGTAAGACCCTGTCGAA
ABCA3-17L:AGGAGTGACTGCTATTGACTTG
ABCA3-17R:TGTTAAGGAGTGTCCAGATGAT
ABCA3-18L:GCCTTTTACAGGTTGAAGTAGT
ABCA3-18R:CACAAAAGAAGGTGAGAGACAT
ABCA3-19L:GCCTTTTACAGGTTGAAGTAGT
ABCA3-19R:CACAAAAGAAGGTGAGAGACAT
The above-mentioned every pair of primers of application carries out the detection of ABCA3 genes respectively.
Embodiment 2：The mutational site of ABCA3 genes is screened from another congenital CCMC family
1. extract peripheral blood genomic DNA：The conventional phenol chloroform method narrated in Application Example 1 is out of family outside each member
Genomic DNA is extracted in all blood.
2.PCR expands purpose fragment：Reaction condition and reaction system：
(1) PCR reaction conditions：94℃3min；94 DEG C of 40sec, 55 ± 3 DEG C of 40se, 72 DEG C of 60sec, 30-35cycle；72
℃10min。
(2) reaction system：(TAKARA LA Taq polymerase)
19 couple of the genomic DNA template of every patient respectively with ABCA3 genes is carried out respectively using the reaction system to draw
The amplified reaction of thing.
3.PCR products are sequenced：Using conventional Sanger PCR sequencing PCRs to the genomic DNA template of patient in family respectively with
The amplified production of 19 pairs of primers of ABCA3 genes is sequenced, the results showed that the ABCA3 gene codes of five patients in the family
Region the 2408th base by initiation codon there occurs heterozygous mutant, sports T, the sequencing result of its reverse primer by C
It is heterozygous mutant to show the site, and A (Fig. 5) is sported by G, causes the 803rd, ABCA3 albumen to sport first sulphur ammonia by threonine
Acid, point of application mutation forecasting program SIFT predictions find that the mutation result in the damage of ABCA3 protein functions " damaging " level
It is bad, so as to cause the generation of CCMC in the family.Reproducible results demonstrates the authenticity in the site.And normally work as at 200
The Mutation Screening in the site is carried out in ground crowd and the family in the peripheral blood genomic DNA sample of normal person, does not find that this is prominent
Become.
Embodiment 3：From the another 2 congenital mutational sites for distributing screening ABCA3 genes in CCMC patient
Collection distributes CCMC patient：It is clear and definite to collect 2 diagnosis altogether in Shandong eye institute and Qingdao ophthalmologic hospital
CCMC distributes patient.
Extract peripheral blood genomic DNA：
Respectively extract 2 peripheric venous blood 2-5ml for distributing CCMC patient, be put into EDTA anticoagulant tubes, -80 DEG C freeze it is standby
With；The EDTA anticoagulations frozen take 500 μ L to be put in centrifuge tube, the conventional phenol chlorine narrated in Application Example 1 after room temperature thawing
Imitative method extracts genomic DNA out of family in each member's peripheral blood.
PCR expands purpose fragment：Reaction condition and reaction system：
(1) PCR reaction conditions：94℃3min；94 DEG C of 40sec, 55 ± 3 DEG C of 40se, 72 DEG C of 60sec, 30-35cycles；
72℃10min。
(2) reaction system：(TAKARA LA Taq polymerase)
19 couple of the genomic DNA template of every patient respectively with ABCA3 genes is carried out respectively using the reaction system to draw
The amplified reaction of thing.
PCR primer is sequenced：Using conventional Sanger PCR sequencing PCRs to the genomic DNA template of every patient respectively with ABCA3
The amplified production of 19 pairs of primers of gene is sequenced, and is distributed at 2 and the heterozygosis of ABCA3 genes is detected in patient dashes forward
Become：ABCA3 gene coding regions the 4253rd base by initiation codon there occurs heterozygous mutant, sports T, its is anti-by A
Show that the site is heterozygous mutant to the sequencing result of primer, A (Fig. 6) sported by T, cause the 1418th, ABCA3 albumen by
Asparagine sports isoleucine, and point of application mutation forecasting program SIFT predictions find that the mutation result in ABCA3 albumen
The damage of function " damaging " level, so as to cause patient CCMC generation.And in 200 normal local crowds and the family
The Mutation Screening in the site is carried out in the peripheral blood genomic DNA sample of middle normal person, does not find the mutation.
Claims (2)
1. a kind of application of the SNP site of ABCA3 genes, it is characterised in that described application is to prepare congenital cataract-small
The diagnostic product of cornea syndrome (CCMC)；Wherein SNP site is the ABCA3 gene coding regions that NCBI numberings are NM_001089
The 2408th by initiation codon, its base is C or T in domain.
2. application as claimed in claim 1, it is characterised in that described diagnostic product is PCR detection primers.
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| CN106521020B (en) * | 2017-01-04 | 2019-07-19 | 青岛大学 | A kind of SNP site of CRYBB1 gene |
| CN113362900A (en) * | 2021-06-15 | 2021-09-07 | 邵阳学院 | Mixed model for predicting N4-acetylcytidine |
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Non-Patent Citations (3)
| Title |
|---|
| Homo sapiens ATP-binding cassette, sub-family A (ABC1), member 3 (ABCA3), mRNA，NCBI Reference Sequence: NM_001089.2;Hupfeld,T.等;《NCBI GenBank》;20130526;1-7 * |
| Homo sapiens ATP-binding cassette, sub-family A (ABC1), member 3 (ABCA3), RefSeqGene on chromosome 16，NCBI Reference Sequence: NG_011790.1;NCBI GenBank;《NCBI GenBank》;20130708;1-18 * |
| Tyrosinekinase inhibition facilitates cooperation of transcription factor SALL4 and ABC transporter A3 towards intrinsic CML cell drug resistance;Hupfeld,T.等;《Br. J. Haematol.》;20130221;第161卷(第2期);204-213 * |
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| CN103589787A (en) | 2014-02-19 |
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