CN110157793A - For detecting the kit and method of depressed individuals medication related gene - Google Patents
For detecting the kit and method of depressed individuals medication related gene Download PDFInfo
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Abstract
Primer sets, kit and the detection method that the invention discloses a kind of for detecting depressed individuals medication related gene, primer sets are selected from SEQ ID NO.1~SEQ ID NO.154 nucleotide sequence.Detection kit of the invention covers the relevant gene of 8 major class antidepressant curative effects of a clinical line, two wires, is related to drug metabolism, target spot, transporter gene site, and detection is comprehensively accurate；The present invention increases the relevant genetic test of antidepression synergism medicine curative effect for part Patients with Refractory Depression, and the selection for refractory depression therapeutic scheme provides strong support.
Description
Technical field
The present invention relates to technical field of gene detection, especially a kind of for detecting depressed individuals medication related gene
Kit and method.
Background technique
Depression is also known as depressive disorder, is common mental disease.Data are shown according to the statistics of the World Health Organization, to 2020
Year, depression, which will become, is only second to the cardiopathic second largest disease.The whole world has more than 300,000,000 people just to perplex by depression at present, in
The illness rate of state's depression is 6.1%, 3 percentage points higher than global average level, and disease incidence is in rise year by year in recent years
Trend is converted according to 6.1% disease incidence, and domestic patients with depression has reached 90,000,000.
Currently, the treatment most effective means of depression are drug therapy, but still in the stage of trial and error pricing, curative effect of medication
Significant individuation difference is shown with adverse reaction.Only 30%~45% patient can obtain under the treatment of antidepressant
The alleviation of clinical symptoms is obtained, 10% patient is invalid to any anti depressant medication, occurs at least one more than 80% patient
Kind adverse reaction, including Nausea and vomiting, dysarteriotony, dizziness, headache etc.；And antidepressants onset time is long, needs long-term
Medication.Therefore, curative effect and adverse reaction of the prediction patient to antidepressants, selection, raising therapeutic effect, reduction for drug
Adverse reaction, shortening treatment time and saving medical expense have a very important significance.
Cause drug therapy occur huge individuation difference the reason of, in addition to traditionally pathology, physiology, gender, the age,
Height, weight, compliance etc. are outer, and inherent cause is an important factor for influencing drug response difference.Wherein drug metabolic enzyme,
The gene pleiomorphism of transport protein, receptor and other drugs action target spot is cause drug effect and toxicity individual difference important
Reason.
Currently, the attention rate in society for depression is inadequate, depression medication is not instructed explicitly, so that more
Patients with depression selects therapeutic agent according to trial and error pricing, bears extra medical expense, the extended treatment time, causes curative effect of medication
It is undesirable, or even there is the case where adverse reaction.Especially, the intractable middle major depressive disorder patient in part recommends clinic
First-line treatment drug is also reactionless, and the therapeutic scheme selection of next step would be more difficult.By being metabolized to Patient drug, target
To, transhipment and the detection of the related genes such as toxicity, possible active drug is found out, is for Patients with Refractory Depression
One new hope.
Existing testing product pays close attention to depressed drug itself, inadequate for the synergy treatment concern of depression, and to difficulty
Controlling for depression of sex patient this is a new possible orientation treatment；It is produced currently on the market for the detection of patients with depression
The drug and gene of product covering are less, predict it is not accurate enough, especially for lack for Patients with Refractory Depression it is new can
It can effective therapeutic scheme.
Summary of the invention
The present invention solves above-mentioned technical problem by following aspect:
Firstly, being selected from SEQ ID NO.1~SEQ ID NO.154 nucleotide sequence the present invention relates to primer sets.Wherein
The primer sets can use in pairs, and the primer pair is selected from: SEQ ID NO.1 and SEQ ID NO.2；SEQ ID NO.3 and
SEQ ID NO.4；SEQ ID NO.5 and SEQ ID NO.6；... SEQ ID NO.151 and SEQ ID NO.152；And SEQ
ID NO.153 and SEQ ID NO.154.
It should be noted that above-mentioned basic amplimer group is designed for depressed individuals medication related gene loci,
For each primer length for 40~48b, difficulty is that the amplification condition of 77 pairs of primers is consistent, while can effectively expand again
Target fragment out, and all the Tm value of primer is controlled at 60 DEG C, and difference is no more than 1 DEG C, and amplified production is in 100-350bp；Its
In, there is the fixed sequence program of one section of 23bp: CCTACACGACGCTGTTCCGATCT before upstream primer 5 ', also has before downstream primer 5 '
The fixed sequence program of one section of 22bp: CAGACGTGTGCTCTTCCGATCT forms multiplexed PCR amplification primer sets；Upstream primer is under
The fixed sequence program swum in primer is identical as 3 ' end primers in specific linkers P5 and P7 respectively, and the amplified production of multiplex PCR can
Directly by with P5 and P7 adapter-primer hybrid reaction, while reaching amplification library and tagged purpose, to reduce library structure
The operating procedure built and time reduce the requirement of butt joint primer or linker DNA segment, reduce reagent cost.
The invention further relates to the kits for detecting depressed individuals medication related gene, and it includes above-mentioned primers
Group.
In some preferred embodiments, the related gene include but is not limited to CYP2D6, CYP2C19, FKBP5,
HTR2A、HTR1A、SLC6A4、CYP2C9、CYP1A2、DRD3、CYP2B6、ABCB1、ACE、TPH2、GRIK4、BDNF、BMP5、
COMT、ADRA2A、GNB3、SACM1L、MC4R、HTR1B、HLA-B、HLA-A、UGT1A4、DRD1。
In some preferred embodiments, the medicine is antidepressant, including but not limited to selectivity 5-HT reuptake
Inhibitor, selectivity 5-HT and NE reuptaking inhibitor, NE and specificity 5-HT energy antidepressants (NaSSA), NE and DA take the photograph again
Take inhibitor (NDRI), 5-HT2A receptor antagonist and 5-HT reuptaking inhibitor (SARI), selective N E reuptaking inhibitor
(NRIs), clinical a line, Second line Drug such as tricyclic antidepressant (TCA), Fourth Ring class.Further, the antidepressant
It further include the antidepressions synergism medicines such as antipsychotic drug class, thyroid hormones, anticonvulsion class.
In some preferred embodiments, the kit includes the first reaction solution, the second reaction solution and specific linkers.
Wherein, the first reaction solution is multi-PRC reaction liquid, the amplification for multiplex PCR；Second reaction solution is amplification PCR reaction solution, this
The inventor of application is prepared through test of many times using the mixed solution of special ratios, referring to embodiment 2.
In some preferred embodiments, the specific linkers are P5 primer and P7 primer mixed liquor.It is highly preferred that institute
State the Index sequence that P7 primer contains the 6bp base composition of specificity.It is highly preferred that the P5 primer sequence such as SEQ ID
Shown in NO.155, P7 primer sequence is as shown in SEQ ID NO.156.Wherein, Index sequence includes but is not limited to table in the application
3 base sequence.
Moreover, it relates to which the method for detecting depressed individuals medication related gene, includes the following steps:
Extract the DNA of one or more samples；
Target fragment is amplified from sample DNA using above-mentioned primer sets；
Target fragment carries out magnetic beads for purifying, and above-mentioned specific linkers are added, is attached reaction, is built
DNA library；And
The genotype of depressed individuals medication related gene in sample is determined to the DNA library sequencing of quality inspection qualification.
The present invention is by detection antidepressant related gene, to predict that patient to the curative effect and adverse reaction of drug, is
Clinical application provides reference；Compared with current clinical status, have the advantages that
1, detection kit of the invention covers the relevant gene of 8 major class antidepressant curative effects of a clinical line, two wires,
It is related to drug metabolism, target spot, transporter gene site, detection is comprehensively accurate；
2, the present invention increases the relevant genetic test of antidepression synergism medicine curative effect for part Patients with Refractory Depression,
Selection for refractory depression therapeutic scheme provides strong support；
3, the present invention can also can realize that high-throughput, fast and accurately to detect hundreds of different genes prominent using NGS technology
Become, saves time, the cost of repeated detection.
Detailed description of the invention
Fig. 1 be full-automatic nucleic acid-protein analysis system detect library result figure, display library fragments distribution situation (
Multimodal is presented within the scope of 200bp~500bp).
Specific embodiment
Aiming at the problems existing in the prior art, it is provided for patients with depression especially Patients with Refractory Depression more accurate
Medication guide, the present invention provides a kind of gene testers and kit for depressed individuals medication.
In some embodiments, the present invention provides a kind of gene tester for depressed individuals medication,
Specific steps include:
(1) according to the polymorphic sequence in treating depression pharmaceutical relevant gene site, multiplexed PCR amplification primer is designed；
(2) library construction Kit is prepared；
(3) genomic DNA is extracted from blood sample, buccal swab, dried blood spot equal samples；
(4) using sample gene to be tested group DNA construct sequencing library, including target fragment amplification, adjunction head, purifying,
Quality check process；
(5) library of quality inspection qualification carries out high-flux sequence, obtains sequencing data；
(6) analysis sequencing data is as a result, provide examining report in conjunction with disease (depression) database.
In some preferred embodiments, above-mentioned antidepressant include selectivity 5-HT reuptaking inhibitor (SSRI),
Selective 5-HT and NE reuptaking inhibitor (SNRI), NE and specificity 5-HT can antidepressants (NaSSA), NE and DA reuptake
Inhibitor (NDRI), 5-HT2A receptor antagonist and 5-HT reuptaking inhibitor (SARI), selective N E reuptaking inhibitor
(NRIs), clinical a line, Second line Drug such as tricyclic antidepressant (TCA), Fourth Ring class；In some preferred embodiments, also
Including antidepressions synergism medicines such as antipsychotic drug class, thyroid hormones, anticonvulsion classes.
In some preferred embodiments, said medicine related gene include CYP2D6, CYP2C19, FKBP5, HTR2A,
HTR1A、SLC6A4、CYP2C9、CYP1A2、DRD3、CYP2B6、ABCB1、ACE、TPH2、GRIK4、BDNF、BMP5、COMT、
ADRA2A、GNB3、SACM1L、MC4R、HTR1B、HLA-B、HLA-A、UGT1A4、DRD1。
In some preferred embodiments, said gene site includes above-mentioned 26 gene polynorphisms sites, such as the following table 1
It is shown:
1 26 gene polynorphisms sites of table
In some preferred embodiments, said gene site primer primer includes SEQ ID NO.1~SEQ ID
NO.154 primer sequence, as shown in table 2 below:
2 primer sequence of table
Existing patients with depression detection data dispersion is single, does not form efficient database, fails to accomplish that early period is detected
It is blended with later period tracking follow-up, promotes data effective rate of utilization, increase the validity for the treatment of recommendations.The present invention is anti-by detection
Depressed pharmaceutical relevant gene establishes depression database, accomplishes that detection early period and later period tracking follow-up blend, promoting data has
Utilization rate is imitated, the validity for the treatment of recommendations is increased；In some preferred embodiments, the database be with reference to PharmGKB,
The well-known database such as CPIC, FDA, in conjunction with the data unscrambling data library that clinical expertise establishes, for being provided effectively for patient
Therapeutic scheme selection gist.
In some preferred embodiments, the present invention provide it is a kind of containing above-mentioned specific primer (SEQ ID NO.1~
SEQ ID NO.154) kit.
Further, the kit further includes reaction solution 1, amplimer, reaction solution 2, specific linkers.
Further, the amplimer is mixed by SEQ ID NO.1~SEQ ID NO.154.
Further, the reaction solution 1 carries out the program of target fragment amplified reaction with amplimer are as follows: and 95 DEG C of (I),
5min；(II) 95 DEG C, 15s；60 DEG C, 30s；72 DEG C, 30s；15-25 circulation；(III) 72 DEG C, 5min.
Further, the specific linkers are P5 primer and P7 primer mixed liquor.
Further, the P7 primer contains the Index sequence of the 6bp base composition of specificity.
Further, the reaction solution 2 carries out the response procedures of adjunction head with specific linkers are as follows: 95 DEG C of (I), 5min；
(II) 95 DEG C, 15s；60 DEG C, 30s；72 DEG C, 30s；5-20 circulation；(III) 72 DEG C, 5min.
It should be pointed out that not related to the present invention relates to the detection to antidepressant curative effect and the prediction of adverse reaction
And antidepressant is specifically used.Kit test result of the invention can be used as the reference of clinical application, but some non-
Inherent cause (such as food, drug) may also influence the curative effect and adverse reaction of drug.Therefore, conditions of patients, life should be combined
The clinical information such as habit living and other laboratory parameters determine dosage regimen.
To better illustrate the object, technical solutions and advantages of the present invention, below in conjunction with the drawings and specific embodiments pair
The present invention is described further.
Embodiment 1
A kind of embodiment of the detection method of depressed individuals medication related gene of the invention, is mainly used for library structure
It builds and result is reported, covering antidepressant and increasing can simply, quickly be constructed using library constructing method of the invention
The sequencing library of the gene loci of drug is imitated, while detecting the catastrophe of 26 related genes.Meanwhile the depression number of foundation
It can be provided according to genetic test as a result, in conjunction with patient's concrete condition comprising a line, two wires antidepressants and synergy according to library system
The therapeutic scheme of drug provides feasibility high therapeutic scheme, especially provides for Patients with Refractory Depression new for patient
Possible effective scheme.The method of the present invention cannot be only used for illumina microarray dataset, it can also be used to which Ion Torrent sequencing is flat
Platform.
Below by taking illumina microarray dataset MiSeq sequencing system as an example, detection scheme of the invention, specific steps are introduced
It is as follows:
(1) design of primers.
Antidepressant and synergism medicine related gene include CYP2D6, CYP2C19, FKBP5, HTR2A, HTR1A,
SLC6A4、CYP2C9、CYP1A2、DRD3、CYP2B6、ABCB1、ACE、TPH2、GRIK4、BDNF、BMP5、COMT、ADRA2A、
GNB3、SACM1L、MC4R、HTR1B、HLA-B、HLA-A、UGT1A4、DRD1。
Said gene site includes above-mentioned 26 gene polynorphisms sites, as shown in table 1.
Basic amplimer group is designed for said gene site, each primer length is in 18~25bp (plus fixed sequence
Primer length is 40~48bp after column), Tm value is at 60 DEG C, and difference is no more than 1 DEG C, and amplified production draws in 100-350bp in upstream
Add the fixed sequence program of the preceding paragraph 23bp before object 5 ': CCTACACGACGCTGTTCCGATCT adds the preceding paragraph before downstream primer 5 '
The fixed sequence program of 22bp: CAGACGTGTGCTCTTCCGATCT forms multiplexed PCR amplification primer sets, specific primer sequence such as SEQ
Shown in NO.1~SEQ NO.154.Fixed sequence program in upstream primer and downstream primer is respectively and in specific linkers P5 and P7
3 ' end primers are identical, the amplified production of multiplex PCR can directly by with P5 and P7 adapter-primer hybrid reaction, while reaching amplification
Library and tagged purpose reduce butt joint primer or linker DNA segment to reduce operating procedure and the time of library construction
Requirement, reduce reagent cost.
(2) prepared by kit, selects the multi-PRC reaction liquid of suitable producer's production to prepare reaction solution 1, synthesizes amplimer
Group mixed preparing is amplimer, and the general P5 primer (fixed sequence program containing upstream amplification primer) of synthesis illmina platform and P7 draw
Object (fixed sequence program containing downstream amplification primer and index sequence label) mixed configuration is specific linkers, and suitable PCR is selected to react
Buffer, dNTP mix, Taq enzyme prepare reaction solution 2.
(3) nucleic acid extraction, the sample of the diversified forms such as the applicable blood of the present invention, buccal swab, dried blood spot, using correspondence
Nucleic acid extracting reagent extract genomic DNA, and using ultramicron ultraviolet specrophotometer measurement DNA concentration and purity.
(4) library construction, the sample DNA of quality inspection qualification carry out library construction using the kit of preparation, and specific steps are such as
Under:
1) target fragment expands
Reagent and sample DNA are sequentially added according to sequence, carry out the amplification enrichment of target gene: 112.5 μ L of reaction solution expands
Increase primer 2 μ L, sample DNA 1-10.5 μ L, nuclease-free water is mended to 25 μ L.
The program of target fragment amplified reaction are as follows: 95 DEG C of (I), 5min；(II) 95 DEG C, 15s；60 DEG C, 30s；72 DEG C, 30s；
15-25 circulation；(III) 72 DEG C, 5min.
2) magnetic beads for purifying
AMPure XP Beads vortex concussion is taken to make its suspension, equilibrium at room temperature 30min；
PCR reaction solution is shifted into 1.5mL centrifuge tube, the Agencourt AMPure XP that 25 μ L (1X) suspend is added
Beads is mixed with turbula shaker or is at least blown and beaten 10 times up and down with pipettor；
It is stored at room temperature 5 minutes；
Centrifuge tube is placed in magnetic frame, 5min is stood, to separate magnetic bead and supernatant.After solution clarification, in removal
(note clearly: not encounter magnetic bead)；
The 80% ethyl alcohol Yu Guanzhong that 200 μ L newly match is added, is placed at room temperature for 30 seconds, then carefully removes supernatant；
Repetition is cleaned once with 80% ethyl alcohol；
To centrifuge tube brief centrifugation, pipe is placed in magnetic frame, opens pipe lid, air-dried 5 minutes and (note: should not excessive wind
Dry magnetic bead influences DNA yield)；
23 μ L sterile waters are added in centrifuge tube, mixed well with turbula shaker or are blown and beaten up and down with pipettor, room temperature is put
It sets 2 minutes, transfer supernatant is into new PCR pipe after solution clarification；
Production concentration is detected using Qubit 3.0.
3) connector connects
Reagent and sample are sequentially added according to sequence, carries out connector connection: reaction solution 2 13.5 μ L, specific linkers 1-3 μ
L, PCR purified product 1-10.5 μ L, nuclease-free water are mended to 25 μ L.
Response procedures are as follows: 95 DEG C of (I), 5min；(II) 95 DEG C, 15s；60 DEG C, 30s；72 DEG C, 30s；5-20 circulation；
(III) 72 DEG C, 5min.
4) magnetic beads for purifying
Same step 2.
5) quality inspection
Feelings are distributed using Qubit 3.0 and the full-automatic nucleic acid-protein analysis system of Qsep 100 detection library concentration and segment
Condition.
(6) high-flux sequence carries out 2X 300bp sequencing using the library of quality inspection qualification on MiSeq sequenator, obtains
Sequencing data.
(7) data analysis and report, analyze sequencing data, obtain sample gene mutation feelings with reference to genome alignment with the mankind
Condition, input database, the information according to the reliable sources such as CPIC, PharmGKB, Consensus of experts, practice guidelines, drug specification
And the diagnosis and treatment experience of clinical expert, the treatment recommendations of reasonable are provided, so as to reference for clinicians.
The preparation of 2 kit of embodiment
For detecting a kind of embodiment of the kit of depressed individuals medication related gene, the kit in the present invention
26 gene pleiomorphisms can be detected simultaneously, include reaction solution 1, amplimer (as shown in SEQ NO.1~SEQ NO.154), reaction
Liquid 2, specific linkers and quality-control product.
According to Experimental comparison, reaction solution 1 is multi-PRC reaction liquid, is purchased from Kapa Biosystems；
Groped according to experiment, amplimer is SEQ NO.1~SEQ NO.154 primer that embodiment 1 designs, raw by raw work
Object engineering (Shanghai) Co., Ltd. is synthesized, and 10 μM of working solution is formulated as using sterilizing purified water, is mixed into each primer
Mixed liquor of the concentration at 0.01-0.05 μM；
According to Experimental comparison, reaction solution 2 is amplification PCR reaction solution, and by 2 × Phanta Max Buffer, (Nanjing promise is only praised
Biotechnology Co., Ltd) 12.5 μ L, dNTP Mix (10mM each) (Thermo Fisher Scientific) 0.5 μ L,
Phanta Max Super-Fidelity DNA Polymerase (Nanjing Vazyme Biotechnology Co., Ltd.) 0.5 μ L is prepared
It forms.
Specific linkers are P5 primer and P7 primer mixed liquor, are closed by Sangon Biotech (Shanghai) Co., Ltd.
At being formulated as 10 μM of working solution using sterilizing purified water, usage amount is 1-3 μ L.
P5 primer sequence:
5′-AATGATACGGCGACCACCGAGATCTACACTCTTTCCGTACACGACGCTGTTCCGATCT-3′(SEQ
ID NO.155)；
P7 primer sequence:
5′-CAAGCAGAAGACGGCATACGAGATNNNNNNGTGACTGGAGTTCAGACGTGTGCTCTTCCGATC-s-
T-3(SEQ ID NO.156)；
Wherein " NNNNNN " is index sequence.
P5 primer is made of 2 parts, the P5 sequence 35bp base complementary with sequence testing chip (i.e. flowcell) top connection and
Sequence 23bp identical with upstream primer fixed sequence program collectively forms the P5 primer of 58bp；P7 primer is made of 3 parts, with survey
The P7 sequence 32bp of sequence chip (flowcell) top connection complementation, specificity 6bp index sequence label are fixed with downstream primer
The identical sequence 22bp of sequence, collectively forms the P7 primer of 60bp.P5 primer and P7 primer cooperate amplifiable multi-PRC reaction
Target fragment, while sequencing sequence and label are added at segment both ends, the library that can be used for being sequenced is formed, library construction behaviour is reduced
Make step and time, improves sample process efficiency.
Index sequence is as shown in table 3 below.
3 Index sequence label of table
Index label is used for specimen discerning, and any of the above-described a index sequence can be used in each sample, in same once sequencing
The sample of middle detection cannot use identical index, otherwise can not carry out sample differentiation.
Quality-control product includes positive quality control product and negative quality-control product, positive quality control product by the site CYP2D6 gene rs1065852,
The site CYP2C19 gene rs4244285, FKBP5 gene rs4713916 site mutation plasmid and wild type DNA sample mixing system
At heterozygous mutation sample；Negative quality-control product is prepared by the sample DNA of all wild types of detection site.
32 blood sample detections of embodiment
The present invention can be used for detecting a variety of samples such as blood, buccal swab, dried blood spot, now by taking 2 anticoagulation samples as an example,
Illustrate the specifically used of kit in embodiment 2.
(1) sample DNA extracts
2 anticoagulation sample 1-2ml are taken, the poba gene group produced using TIANGEN Biotech (Beijing) Co., Ltd.
DNA extraction kit (centrifugal column type) (article No.: DP318 specification: 50/200 person-portion), operation to specifications carry out DNA and mention
It takes.
The DNA of extraction using ultramicron ultraviolet specrophotometer measurement DNA concentration (>=1ng/ μ L) and purity (1.6~
2.0)。
(2) library construction
1) target fragment expands
Reagent and sample DNA are sequentially added according to sequence, carry out the amplification enrichment of target gene: 112.5 μ L of reaction solution expands
Increase primer 2 μ L, sample DNA (10-100ng) 1-10.5 μ L, nuclease-free water is mended to 25 μ L.
The program of target fragment amplified reaction are as follows: 95 DEG C of (I), 5min；(II) 95 DEG C, 15s；60 DEG C, 30s；72 DEG C, 30s；
15-25 circulation；(III) 72 DEG C, 5min.
2) magnetic beads for purifying
AMPure XP Beads vortex concussion is taken to make its suspension, equilibrium at room temperature 30min；
PCR reaction solution is shifted into 1.5mL centrifuge tube, the Agencourt AMPure XP that 25 μ L (1X) suspend is added
Beads is mixed with turbula shaker or is at least blown and beaten 10 times up and down with pipettor；
It is stored at room temperature 5 minutes；
Centrifuge tube is placed in magnetic frame, 5min is stood, to separate magnetic bead and supernatant.After solution clarification, in removal
(note clearly: not encounter magnetic bead)；
The 80% ethyl alcohol Yu Guanzhong that 200 μ L newly match is added, is placed at room temperature for 30 seconds, then carefully removes supernatant；
Repetition is cleaned once with 80% ethyl alcohol；
To centrifuge tube brief centrifugation, pipe is placed in magnetic frame, opens pipe lid, air-dried 5 minutes and (note: should not excessive wind
Dry magnetic bead influences DNA yield)；
23 μ L sterile waters are added in centrifuge tube, mixed well with turbula shaker or are blown and beaten up and down with pipettor, room temperature is put
It sets 2 minutes, transfer supernatant is into new PCR pipe after solution clarification；
Production concentration (>=1ng/ μ L) is detected using Qubit 3.0.
3) connector connects
Reagent and sample are sequentially added according to sequence, carries out connector connection: reaction solution 2 13.5 μ L, specific linkers 1-3
μ L, PCR purified product (10ng) 1-10.5 μ L, nuclease-free water are mended to 25 μ L.
Response procedures are as follows: 95 DEG C of (I), 5min；(II) 95 DEG C, 15s；60 DEG C, 30s；72 DEG C, 30s；5-20 circulation；
(III) 72 DEG C, 5min.
4) magnetic beads for purifying
Same step 2.
5) quality inspection
Using Qubit 3.0 and Qsep100 full-automatic nucleic acid-protein analysis system detection library concentration (>=10ng/ μ L) and
Segment distribution situation (result is as shown in Figure 1).
(3) it is sequenced
2X 300bp sequencing is carried out using MiSeq sequenator to the library of quality inspection qualification.
Data analysis, sample sequencing depth meet Quality Control requirement in 500X or more, Q30 > 80%, 95% or more coverage rate.
Sample gene mutation analysis result is as shown in table 4 below.
4 Genotyping of table
4 20 clinical sample detections of embodiment
The blood sample of 20 known types is directed in present case, using in kit in embodiment 2 and embodiment 3
The application method of kit is detected.
Concrete operation step is with embodiment 3: depth is sequenced in 500X or more in sample, Q30 > 80%, coverage rate 95% with
On, meet Quality Control requirement.
Available experiment conclusion based on the analysis results, in 20 samples, 8, CYP2D6*1/*1 type (wild type), * 1/*
10 4, types, 3, * 10/*10 type, 2, * 2/*10 type, 1, * 1/*2 type, 1, * 5/*10 type, 1, * 1/*5 type, CYP2C19*
15,1/*1 type (wild type), 4, * 1/*2 type, 1, * 1/*3 type, FKBP5rs4713916 heterozygous mutant 1, HTR1A
Rs6295 heterozygous mutant 4, homozygous mutation 1, ABCB1rs1045642 heterozygous mutant 3, homozygous mutation 1,
ABCB1rs1128503 heterozygous mutant 1, MC4R rs489693 heterozygous mutant 2, with Sanger PCR sequencing PCR verification result phase
Together.
Finally it should be noted that the above embodiments are merely illustrative of the technical solutions of the present invention rather than protects to the present invention
The limitation of range, although the invention is described in detail with reference to the preferred embodiments, those skilled in the art should be managed
Solution, can with modification or equivalent replacement of the technical solution of the present invention are made, without departing from technical solution of the present invention essence and
Range.
Claims (10)
1. primer sets are selected from SEQ ID NO.1~SEQ ID NO.154 nucleotide sequence.
2. the primer sets of claim 1, wherein the primer sets use in pairs, and the primer pair is selected from: SEQ ID
NO.1 and SEQ ID NO.2；
SEQ ID NO.3 and SEQ ID NO.4；
SEQ ID NO.5 and SEQ ID NO.6；
……
SEQ ID NO.151 and SEQ ID NO.152；And
SEQ ID NO.153 and SEQ ID NO.154.
3. the kit for detecting depressed individuals medication related gene, it includes primers of any of claims 1 or 2
Group.
4. the kit of claim 3, wherein the related gene include CYP2D6, CYP2C19, FKBP5, HTR2A, HTR1A,
SLC6A4、CYP2C9、CYP1A2、DRD3、CYP2B6、ABCB1、ACE、TPH2、GRIK4、BDNF、BMP5、COMT、ADRA2A、
GNB3、SACM1L、MC4R、HTR1B、HLA-B、HLA-A、UGT1A4、DRD1。
5. the kit of claim 3 or 4, wherein the medicine is antidepressant, including selective 5-HT reuptaking inhibitor,
Selective 5-HT and NE reuptaking inhibitor, NE and specificity 5-HT can antidepressants (NaSSA), NE and DA reuptaking inhibitor
(NDRI), 5-HT2A receptor antagonist and 5-HT reuptaking inhibitor (SARI), selective N E reuptaking inhibitor (NRIs), three
Clinic one line, Second line Drug such as ring class antidepressants (TCA), Fourth Ring class.
6. the kit of claim 3 further includes the first reaction solution, the second reaction solution and specific linkers.
7. the kit of claim 6, wherein the specific linkers are P5 primer and P7 primer mixed liquor.
8. the kit of claim 7, wherein the P7 primer contains the Index sequence of the 6bp base composition of specificity.
9. the kit of claim 7, wherein the P5 primer sequence is as shown in SEQ ID NO.155, P7 primer sequence such as SEQ
Shown in ID NO.156.
10. the method for detecting depressed individuals medication related gene, includes the following steps:
Extract the DNA of one or more samples；
Target fragment is amplified from sample DNA using the primer sets of claims 1 or 22；
Target fragment carries out magnetic beads for purifying, and the specific linkers in any one of claim 6~9 are added, is attached reaction, obtains
To the DNA library built；And
The genotype of depressed individuals medication related gene in sample is determined to the DNA library sequencing of quality inspection qualification.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111321214A (en) * | 2020-03-04 | 2020-06-23 | 上海康黎医学检验所有限公司 | Kit for guiding human depression medication and application thereof |
| CN111899894A (en) * | 2020-08-03 | 2020-11-06 | 东南大学 | System and method for evaluating prognosis drug effect of depression patient |
| CN113584151A (en) * | 2021-07-17 | 2021-11-02 | 北京阅微基因技术股份有限公司 | Composite amplification system and kit for antipsychotic individualized medication related genotyping detection |
| CN115094128A (en) * | 2022-05-06 | 2022-09-23 | 四川大学华西医院 | Method for diagnosing curative effect of antidepressant through intestinal microbial analysis |
| CN117594119A (en) * | 2024-01-17 | 2024-02-23 | 北京大学第六医院 | Device for predicting the efficacy of paroxetine or a pharmaceutically acceptable salt thereof for patients suffering from depression or anxiety |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101338337A (en) * | 2007-07-04 | 2009-01-07 | 北京华安佛医药研究中心有限公司 | Polymorphism site genotype estimation depression, use and process of medicine effect and kit |
| AU2011211453A1 (en) * | 2004-06-21 | 2011-09-01 | The Board Of Trustees Of The Leland Stanford Junior University | Genes and pathways differentially expressed in bipolar disorder and/or major depressive disorder |
| CN106192021A (en) * | 2016-08-02 | 2016-12-07 | 中国海洋大学 | A kind of construction method in RAD label sequencing library of connecting |
| CN108342466A (en) * | 2018-05-04 | 2018-07-31 | 广州海思医疗科技有限公司 | A kind of high-flux sequence method and its application of psychoneural class pharmaceutical relevant gene |
| CN108823299A (en) * | 2018-06-11 | 2018-11-16 | 苏州艾达康医疗科技有限公司 | A kind of detection method and kit of depression medication related gene |
| CN108913766A (en) * | 2018-07-17 | 2018-11-30 | 浙江大学 | A kind of specific primer and probe and kit detecting depressed individuals chemical drug object therapeutic gene multisite mutation |
-
2019
- 2019-04-29 CN CN201910360575.7A patent/CN110157793A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2011211453A1 (en) * | 2004-06-21 | 2011-09-01 | The Board Of Trustees Of The Leland Stanford Junior University | Genes and pathways differentially expressed in bipolar disorder and/or major depressive disorder |
| CN101338337A (en) * | 2007-07-04 | 2009-01-07 | 北京华安佛医药研究中心有限公司 | Polymorphism site genotype estimation depression, use and process of medicine effect and kit |
| CN106192021A (en) * | 2016-08-02 | 2016-12-07 | 中国海洋大学 | A kind of construction method in RAD label sequencing library of connecting |
| CN108342466A (en) * | 2018-05-04 | 2018-07-31 | 广州海思医疗科技有限公司 | A kind of high-flux sequence method and its application of psychoneural class pharmaceutical relevant gene |
| CN108823299A (en) * | 2018-06-11 | 2018-11-16 | 苏州艾达康医疗科技有限公司 | A kind of detection method and kit of depression medication related gene |
| CN108913766A (en) * | 2018-07-17 | 2018-11-30 | 浙江大学 | A kind of specific primer and probe and kit detecting depressed individuals chemical drug object therapeutic gene multisite mutation |
Non-Patent Citations (4)
| Title |
|---|
| NAZAN YUCE-ARTUN等: "Influence of CYP2B6 and CYP2C19 polymorphisms on sertraline metabolism in major depression patients", 《INT J CLIN PHARM》 * |
| 喻妍等: "影响抗抑郁药物疗效的基因多态性研究进展", 《国际精神病学杂志》 * |
| 许杜鹃等: "《全国普通高等医学院校药学类专业十三五规划教材 药学服务实务》", 31 January 2016 * |
| 闵文蛟等: "基因多态性对抗抑郁药物疗效的影响", 《华西医学》 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111321214A (en) * | 2020-03-04 | 2020-06-23 | 上海康黎医学检验所有限公司 | Kit for guiding human depression medication and application thereof |
| CN111899894A (en) * | 2020-08-03 | 2020-11-06 | 东南大学 | System and method for evaluating prognosis drug effect of depression patient |
| CN113584151A (en) * | 2021-07-17 | 2021-11-02 | 北京阅微基因技术股份有限公司 | Composite amplification system and kit for antipsychotic individualized medication related genotyping detection |
| CN115094128A (en) * | 2022-05-06 | 2022-09-23 | 四川大学华西医院 | Method for diagnosing curative effect of antidepressant through intestinal microbial analysis |
| CN117594119A (en) * | 2024-01-17 | 2024-02-23 | 北京大学第六医院 | Device for predicting the efficacy of paroxetine or a pharmaceutically acceptable salt thereof for patients suffering from depression or anxiety |
| CN117594119B (en) * | 2024-01-17 | 2024-05-10 | 北京大学第六医院 | Device for predicting the efficacy of paroxetine or a pharmaceutically acceptable salt thereof for patients suffering from depression or anxiety |
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