CN104745708A - LAMP (loop-mediated isothermal amplification) detection kit and detection method for transgenic corn NK603 strain - Google Patents

LAMP (loop-mediated isothermal amplification) detection kit and detection method for transgenic corn NK603 strain Download PDF

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CN104745708A
CN104745708A CN201510164657.6A CN201510164657A CN104745708A CN 104745708 A CN104745708 A CN 104745708A CN 201510164657 A CN201510164657 A CN 201510164657A CN 104745708 A CN104745708 A CN 104745708A
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杨丽霞
彭新凯
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HUNAN FOOD SAFETY PRODUCTION ENGINEERING TECHNOLOGY RESEARCH CENTER
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Abstract

The invention provides a LAMP (loop-mediated isothermal amplification) detection kit for transgenic corn NK603 strain. The LAMP kit contains amplification primers of SEQ ID NO:1-6 and also comprises betaine, dNTP, a Bst DNA polymerase buffer solution, a fluorescent dye SYTO-9, Bst DNA polymerase, Mg<2+>, a positive control and a negative control. By adopting the kit provided by the invention to perform loop-mediated isothermal amplification, an amplification product is combined with the fluorescent dye SYTO-9 in a reaction solution, and the amplification result is judged by adopting a real-time fluorescent image after reaction. The kit provided by the invention is good in specificity and high in sensitivity, can detect out NK6-3 of which the content is as low as 0.1% in a mixed sample, and is suitable for performing fast and accurate detection in a basic laboratory.

Description

A kind of LAMP detection kit of transgenic corns NK603 strain and detection method
Technical field
The present invention relates to the detection field of Transgenic corn lines, be specifically related to a kind of LAMP kit and detection method of transgenic corns NK603 strain.
Background technology
Genetically modified crops or genetic modification crop are by importing foreign gene be incorporated in genome, make a certain or some proterties obtain the crop of improveing.Genetically modified crops play important effect in raising resistance and improvement quality.But because transgenic technology may produce the reason such as new toxin and anaphylactogen, the genetic drift causing resistant gene, the security of international community to genetically modified food still has sizable dispute.European Union, the U.S., Japan and other countries have promulgated relevant decree all in succession, carry out identity management, and made relevant regulations to threshold value to genetically modified crops and derivative food thereof.The Ministry of Health of China has also put into effect " genetically modified food hygiene control way " in 2002.Should " way " specify: must identify " food being raw material production with genetically modified animals and plants, microorganism or its direct processed goods and foodstuff additive ".Therefore setting up a set of technology of GMO detection is easily and efficiently implement the important prerequisite of mark system.
Transgenic corns NK603 strain is developed by About Monsanto Chemicals (Monsanto Company), and imported in corn by Bar gene CP4 EPSPS, the CP4 EPSPS albumen of this genes encoding, can make the anti-careless ammonium phosphine of corn.Though this transgenic corns European Union's official approval is at present used for food and feed, its security still receives much concern.
At present the detection of transgenic product is mainly detected based on the PCR of nucleic acid level, comprise multiplex PCR (Multiplex PCR), real-time quantitative PCR (Real-time PCR) etc., but these methods need the heat circulating equipment with real-time fluorescence measuring ability, there is complex operation step, detection time is longer, is not suitable for on-the-spot detection in real time and tracing detection.2000, Japanese scholars Notomi etc. develops a kind of constant temperature nucleic acid amplification method---loop-mediated isothermal amplification technique (loop-mediatedisothermal amplification of novelty, LAMP), the method is for 6 zone design 4 species-specific primers of target gene, improve the specificity of detection, comparatively regular-PCR is high for its amplification efficiency simultaneously, improve sensitivity largely, LAMP technology has simply, fast, the advantage such as high specificity, in detecting for pathogenic bacterium, virus, parasite, anaphylactogen, species identification etc.
Along with increasing transgenic product large-scale commercial is produced, the rapid detection of transgenosis component is subject to extensive concern, and LAMP amplification technique is constant-temperature amplification, can not rely on thermal cycler, and common thermostatical instrument both can detect.Therefore fast and convenient LAMP has been successfully applied to the detection of the crops such as genetically engineered soybean, cotton, corn, paddy rice.
Summary of the invention
The object of the present invention is to provide a kind of LAMP detection kit and detection method of transgenic corns NK603 strain.
A LAMP detection kit for transgenic corns NK603 strain, its reaction system comprises: trimethyl-glycine, dNTP, Bst DNA polymerase buffer liquid, fluorescence dye SYTO-9, Bst archaeal dna polymerase, Mg2+, positive control, negative control; It is characterized in that, also comprise following primer, the base sequence of described primer is as follows:
Outer primer F3:5 '-GACCAGGTAATCTTACCTTTGT-3 '
Outer primer B3:5 '-TGAAACCGCTTTCAAGAGAA-3 '
Inner primer FIP:5 '-GGCCGCGTTAACAAGCTTACTTTTTGGACTATCCCGACTCTCT-3 '
Inner primer BIP:5 '-CTTGGTACCACGCGACACATTTTCTGTTATGGTTCGAGAAGAGAT-3 '
Ring primer LF:5 '-TCGAGGTCATTCATATGCTTGA-3 '
Ring primer LB:5 '-AGTGTTTGAGTGGATCCTGTT-3 '.
Preferably, in described reaction system, trimethyl-glycine concentration is 0.3-1.5mM, dNTP concentration be 0.2-3.5mM, Mg2+ concentration is 2-18mM.
Preferably, the ratio of the concentration of the inner primer described in described reaction system and outer primer is 1-8: 1; The ratio of ring primer and outer primer concentration is 1-2: 1.
Preferably, described reaction system contains 0.2 μM of outer primer, 1.6 μMs of inner primers, 0.4 μM of ring primer.
Preferably, Bst archaeal dna polymerase content is 4-10U, and more preferably, Bst archaeal dna polymerase content is 8U.
Preferably, it is characterized in that described positive control is the genomic dna of transgenic corns NK603 strain.
Preferably, described positive control is the recombinant plasmid containing NK603 strain Bar gene CP4EPSPS gene.
Described positive control recombinant plasmid preparation method is as described below: extract transgenic corns NK603 strain genomic dna, primers F 3/B3 is utilized to carry out PCR, increase and reclaim CP4EPSPS gene and be cloned in vector plasmid, transformation of E. coli competent cell, extract plasmid, DNA sequencing confirms the plasmid that sequence is correct.
Present invention also offers a kind of detection method applying LAMP detection kit detection transgenic corns NK603 strain, comprise following key step:
(1) detected sample genomic dna is extracted, with sample gene group DNA for template;
(2) according to detection sample number, LAMP amplification reaction solution is prepared: get 2 × LAMP reaction mixture 12.5 μ L according to every sample 25 microlitre reaction system, comprising 40mmol/L Tris-HClpH 8.8,20mmol/L KCl, 16mmol/L MgSO 4, 20mmol/L (NH 4) 2sO 4, 0.2%Tween-20,0.8mol/L Betaine, 2.8mmol/L of dNTPs; Add the outer primer B3 solution 0.5 μ L of the outer primer F3 solution 0.5 μ L of 10 μm of ol/L, 10 μm of ol/L; Add the inner primer BIP solution 2 μ L of the inner primer FIP solution 2 μ L of 20 μm of ol/L, 20 μm of ol/L; Add the ring primer LB solution 2 μ L of the ring primer LF solution 2 μ L of 5 μm of ol/L, 5 μm of ol/L; Add fluorescence dye SYTO-9 0.5 μ L, 8U/ μ L Bst archaeal dna polymerase 1 μ L, mixing;
(3) sample DNA template 2 μ L to be detected is added, mixing reaction system;
(4) isothermal duplication: add 20 μ L sealing liquids at PCR pipe inwall; 63 DEG C of isothermal reaction 45min, after reaction terminates, compared with showing fluorescence with positive control;
(5) result interpretation: reaction terminates rear employing real-time fluorescence figure to judge amplification, and the dyestuff used in reaction is fluorescence dye SYTO-9.Described result of determination be according to fluorescence dye SYTO-9 formed amplification curve as the conclusion detecting Transgenic corn lines NK603, otherwise result is not for detect Transgenic corn lines NK603.
The invention provides a kind of stopped pipe fluorescent detection system, the present invention is according to LAMP technology principle, the method is combined with real-time fluorescence technology, in LAMP reaction system, adds fluorescence dye, after amplification terminates, the DNA obtained that increases combines with fluorescence dye, does not need electrophoresis, naked eyes or fluorescence detector conveniently can observe amplification, this real-time fluorescence LAMP method for quick, is adapted at basic unit and detects promoting the use of in unit and on-the-spot fast inspection work.
Beneficial effect of the present invention is: the LAMP detection kit of the transgenic corns NK603 strain of the present invention's development and detection method, be applicable to the detection of transgenic corns NK603 strain, specificity is good, detection sensitivity high (0.1% sample can detect), method quick and precisely, is particularly useful for the promotion and application of basic unit one line laboratory and Site Detection.
Accompanying drawing explanation
The LAMP detection method specificity experiments result figure of Fig. 1: transgenic corns NK603 strain (1-6 be respectively transgenic corns NK603, MON863, MON810, transgenic paddy rice Bt63, transgenic corns biased sample (containing MIR604, Bt11, GA21,59122, Bt176), negative control).
The LAMP detection method sensitivity experiment result figure (1-7 is the transgenic corns of 5%, 1%, 0.5%, 0.1%, 0.05%, 0% respectively, negative control) of Fig. 2: transgenic corns NK603 strain.
Embodiment
In the present invention, transgenic corns standard substance NK603, MON863, MON810 are purchased from national standard material information center, transgenic paddy rice Bt63 and transgenic corns biased sample (containing MIR604, Bt11, GA21,59122, Bt176) presented by Entry-Exit Inspection and Quarantine Bureau of Hunan Province, non-transgenic corn sample is purchased from market.
The design of embodiment 1:LAMP primer sets
According to transgenic corns NK603 strain-specific gene sequence (GenBank sequence number AX342369), design LAMP primer group, LAMP primer group is made up of outer primer F3, outer primer B3, inner primer FIP, inner primer BIP, ring primer LF, ring primer LB, and the concrete sequence of each primer is in table 1.
Table 1 LAMP primer sequence
Above-mentioned primer is synthesized by Shanghai Sheng Gong biotechnology limited-liability company.Be mixed with respectively concentration be the outer primer F3 solution of 10 μm of ol/L, the outer primer B3 solution of 10 μm of ol/L, the inner primer FIP solution of 20 μm of ol/L, the inner primer BIP solution of 20 μm of ol/L, the ring primer LF solution of 5 μm of ol/L, 5 μm of ol/L ring primer LB solution as test kit, for subsequent use.
Embodiment 2: the preparation of positive control recombinant plasmid T-NK
Extract transgenic corns NK603 strain genomic dna according to CTAB method, utilize forward outer primer F3, oppositely outer primer B3 to carry out PCR, amplification object band, reaction conditions is as follows:
PCR reaction system (50 μ L): primer NK603-F3/NK603-B3 1 μ L, ddH respectively of 10 × PCR buffer 5 μ L, 5U/ μ L Taq archaeal dna polymerase 1 μ L, 10 μm of ol/L 2o 37 μ L, genomic dna 5 μ L; Be placed in PCR amplification instrument to react, response procedures: 94 DEG C of 4min denaturations; 95 DEG C of sex change 30sec, 58 DEG C of annealing 30sec, 72 DEG C of extensions 30sec, totally 30 circulations; 72 DEG C extend 5min.
Reclaim object band, be connected with carrier pMD18-T, transform DH5 α competent cell, extract plasmid, PCR sends to the order-checking of Shanghai Sheng Gong biotechnology company limited after identifying the positive.The plasmid markers that sequence is correct is the positive control of T-NK as transgenic corns NK603 strain.
The preparation of recombinant plasmid, is not limited only to the pMD18-T carrier in the present embodiment, and any common molecular clone common carrier, intestinal bacteria all can be used for preparing positive control plasmid.
Transgenic corns NK603 strain genomic dna also can use as the positive control in the present invention.
Embodiment 3: the reaction system of isothermal duplication and reaction condition optimization
In the present invention, sample gene group DNA is extracted by conventional CTAB method, for carrying out isothermal amplification.In an experiment, we are optimized the primer proportioning of isothermal duplication, be 0.3-1.5mM, dNTP concentration be 0.2-3.5mM, Mg2+ concentration are 2-18mM in trimethyl-glycine concentration.The ratio of described inner primer and the concentration of outer primer is 1-8: 1; The ratio of ring primer and outer primer concentration is 1-2: 1, all effectively augmentation detection can go out NK603 strain sample.Most preferred embodiment is as follows:
Isothermal amplification system is 25 μ L, namely adds in the PCR reaction tubes of 0.2mL: 2 × LAMPreaction mixture (40mmol/L Tris-HCl pH 8.8,20mmol/L KCl, 16mmol/LMgSO 4, 20mmol/L (NH 4) 2sO 40.2%Tween-20,0.8mol/L Betaine, 2.8mmol/Lof dNTPs) 12.5 μ L, the outer primer F3 solution 0.5 μ L of 10 μm of ol/L, the outer primer B3 solution 0.5 μ L of 10 μm of ol/L, the inner primer FIP solution 2 μ L of 20 μm of ol/L, the inner primer BIP solution 2 μ L of 20 μm of ol/L, the ring primer LF solution 2 μ L of 5 μm of ol/L, ring primer LB solution 2 μ L, the fluorescence dye SYTO-90.5 μ L of 5 μm of ol/L, 8U/ μ L Bst archaeal dna polymerase 1 μ L, recombinant plasmid T-NK DNA 2 μ L, add 20 μ L sealing liquids at PCR pipe inwall after mixing.Isothermal amplification condition is: 63 DEG C of isothermal reaction 45-60min.
Reaction terminates rear employing real-time fluorescence figure to judge amplification, and the dyestuff used in reaction is fluorescence dye SYTO-9.Described result of determination be according to fluorescence dye SYTO-9 formed amplification curve as the conclusion detecting transgenic corns NK603 strain, otherwise for not detect transgenic corns NK603 strain.
Embodiment 4: the LAMP detection kit preparing transgenic corns NK603 strain
For convenience of using, according to embodiment 1,2,3, assembling detection kit (50 times), with easy to use.
A test solution, is LAMP reaction system, contains: 2 × LAMP reaction mixture, fluorescence dye SYTO-9, Bst archaeal dna polymerase, LAMP detection primer group; Every agent A test solution contains 2 × LAMPreaction mixture 625 μ L, fluorescence dye SYTO-9 25 μ L, 8U/ μ L Bst archaeal dna polymerase 50 μ L, LAMP primer group 450 μ L, wherein outer primer F3 and each 25 μ L of B3 solution; Inner primer FIP and each 100 μ L of BIP solution; Ring primer LF and each 100 μ L of LB solution; Primers F 3, B3, FIP, BIP, LF, LB have the base sequence of sequence table SEQ .ID.No.1 to SEQ.ID.No.6 respectively.
B test solution is recombinant plasmid T-NK603 100 μ L, and concentration is 0.1ng/ μ L, as positive control;
C test solution is deionized water 100 μ L, as negative control.
Embodiment 5: the specificity experiments of the LAMP kit that transgenic corns NK603 strain detects
Get transgenic corns NK603, MON863, MON810, transgenic paddy rice Bt63 and transgenic corns biased sample (containing MIR604, Bt11, GA21,59122, Bt176) 1 part respectively, genomic dna is extracted respectively by CTAB method, and carry out LAMP isothermal duplication, for determining the specificity of test kit.
Fig. 1 is the experimental result picture that application primer sets of the present invention and detection method detect transgenic corns NK603 strain and other 5 kinds of samples, 1-6 be respectively transgenic corns NK603, MON863, MON810, transgenic paddy rice Bt63, transgenic corns biased sample (containing MIR604, Bt11, GA21,59122, Bt176), negative control, judge amplification according to real-time fluorescence figure, only transgenic corns NK603 genome has amplification curve.
As can be seen from the result of Fig. 1, all not there is specific amplification in other Transgenic corn lines, other plant and non-transgenic corn.Experimental result shows that the LAMP method set up has good specificity, can be used for the detection of transgenic corns NK603 strain.
Embodiment 6: the sensitivity experiment of the LAMP kit that transgenic corns NK603 strain detects
Transgenic corns NK603 strain standard substance are mixed with non-transgenic corn sample, be mixed with the corn seed sample that transgenic corns NK603 strain percentage contents (w/w) is 5%, 1%, 0.5%, 0.1%, 0.05%, 0%, CTAB method extracts genomic dna respectively, carries out isothermal duplication according to embodiment 3 most preferred embodiment.
Fig. 2 is the LAMP detection method sensitivity experiment result figure of transgenic corns NK603 strain of the present invention, 1-7 is the transgenic corns of 5%, 1%, 0.5%, 0.1%, 0.05%, 0%, the LAMP detected result of negative control corn sample respectively.
Experimental result show: transgenic corns NK603 content be 5%, 1%, 0.5%, 0.1% sample all have amplification curve to occur, illustrate that the LAMP method set up can be successfully detect transgenic corns NK603 the sample of 0.1% from transgenic corns NK603 strain content, there is higher sensitivity, can be used for the detection containing transgenic corns NK603 strain sample.
Above embodiment is only the preferred embodiment of this creation, and not in order to limit this creation, any amendment made within all spirit in this creation and principle, equivalent replacement, improvement etc., within the protection domain that all should be included in this creation.

Claims (10)

1. the LAMP detection kit of a transgenic corns NK603 strain, it is characterized in that, its reaction system comprises trimethyl-glycine, dNTP, Bst DNA polymerase buffer liquid, fluorescence dye SYTO-9, BstDNA polysaccharase, Mg2+, positive control, negative control and primer sets, and its base sequence is as follows:
Outer primer F3:5 '-GACCAGGTAATCTTACCTTTGT-3 '
Outer primer B3:5 '-TGAAACCGCTTTCAAGAGAA-3 '
Inner primer FIP:5 '-GGCCGCGTTAACAAGCTTACTTTTTGGACTATCCCGACTCTCT-3 '
Inner primer BIP:5 '-CTTGGTACCACGCGACACATTTTCTGTTATGGTTCGAGAAGAGAT-3 '
Ring primer LF:5 '-TCGAGGTCATTCATATGCTTGA-3 '
Ring primer LB:5 '-AGTGTTTGAGTGGATCCTGTT-3 '.
2. the LAMP detection kit of transgenic corns NK603 strain as claimed in claim 1, is characterized in that: in described reaction system, trimethyl-glycine concentration is 0.3-1.5mM, dNTP concentration be 0.2-3.5mM, Mg2+ concentration is 2-18mM.
3. the LAMP detection kit of transgenic corns NK603 strain as claimed in claim 1, is characterized in that: the ratio of the concentration of the inner primer described in described reaction system and outer primer is 1-8: 1; The ratio of ring primer and outer primer concentration is 1-2: 1.
4. the LAMP detection kit of transgenic corns NK603 strain as claimed in claim 3, is characterized in that: described reaction system contains 0.2 μM of outer primer, 1.6 μMs of inner primers, 0.4 μM of ring primer.
5. the LAMP detection kit of the transgenic corns NK603 strain as described in as arbitrary in Claims 1-4, is characterized in that: Bst archaeal dna polymerase content is 4-10U.
6. the LAMP detection kit of transgenic corns NK603 strain as claimed in claim 5, is characterized in that: Bst archaeal dna polymerase content is 8U.
7. the LAMP detection kit of transgenic corns NK603 strain as claimed in claim 1, is characterized in that: described positive control is the genomic dna of transgenic corns NK603 strain.
8. the LAMP detection kit of transgenic corns NK603 strain as claimed in claim 1, is characterized in that: described positive control is the recombinant plasmid containing NK603 strain Bar gene CP4EPSPS gene.
9. the LAMP detection kit of transgenic corns NK603 strain as claimed in claim 8, described positive control recombinant plasmid preparation method is as described below: extract transgenic corns NK603 strain genomic dna, primers F 3/B3 is utilized to carry out PCR, increase and reclaim CP4EPSPS gene and be cloned in vector plasmid, transformation of E. coli competent cell, extract plasmid, DNA sequencing confirms the plasmid that sequence is correct.
10. application rights requires that described in 1, LAMP detection kit detects a detection method for transgenic corns NK603 strain, comprises following key step:
(1) detected sample genomic dna is extracted, with sample gene group DNA for template;
(2) according to detection sample number, LAMP amplification reaction solution is prepared: get 2 × LAMP reaction mixture 12.5 μ L according to every sample 25 microlitre reaction system, comprising 40mmol/L Tris-HClpH 8.8,20mmol/L KCl, 16mmol/L MgSO 4, 20mmol/L (NH 4) 2sO 4, 0.2%Tween-20,0.8mol/L Betaine, 2.8mmol/L of dNTPs; Add the outer primer B3 solution 0.5 μ L of the outer primer F3 solution 0.5 μ L of 10 μm of ol/L, 10 μm of ol/L; Add the inner primer BIP solution 2 μ L of the inner primer FIP solution 2 μ L of 20 μm of ol/L, 20 μm of ol/L; Add the ring primer LB solution 2 μ L of the ring primer LF solution 2 μ L of 5 μm of ol/L, 5 μm of ol/L; Add fluorescence dye SYTO-9 0.5 μ L, 8U/ μ L Bst archaeal dna polymerase 1 μ L, mixing;
(3) sample DNA template 2 μ L to be detected is added, mixing reaction system;
(4) isothermal duplication: add 20 μ L sealing liquids at PCR pipe inwall, 63 DEG C of isothermal reaction 45min, after reaction terminates, compared with showing fluorescence with positive control;
(5) result interpretation: reaction terminates rear employing real-time fluorescence figure to judge amplification, and the dyestuff used in reaction is fluorescence dye SYTO-9.Described result of determination be according to fluorescence dye SYTO-9 formed amplification curve as the conclusion detecting Transgenic corn lines NK603, otherwise result is not for detect Transgenic corn lines NK603.
CN201510164657.6A 2015-04-02 2015-04-02 LAMP (loop-mediated isothermal amplification) detection kit and detection method for transgenic corn NK603 strain Pending CN104745708A (en)

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1332246A (en) * 2000-06-22 2002-01-23 孟山都技术有限公司 Maize Individual PV-IMGT32(NK603) and Compositions and Methods for its Detection

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1332246A (en) * 2000-06-22 2002-01-23 孟山都技术有限公司 Maize Individual PV-IMGT32(NK603) and Compositions and Methods for its Detection

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
RAJESH K. BHOGE ET AL.: "Event-specific analytical methods for six genetically modified maize events using visual and real-time loop-mediated isothermal amplification", 《FOOD CONTROL》 *
兰青阔等: "环状等温扩增技术快速检测转基因玉米MON863的研究", 《玉米科学》 *

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