CN108531569A - The gene marker screened for obsessive-compulsive disorder and schizophrenia, depression and its application - Google Patents
The gene marker screened for obsessive-compulsive disorder and schizophrenia, depression and its application Download PDFInfo
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Abstract
The invention discloses a kind of gene marker screened with schizophrenia, depression for obsessive-compulsive disorder, the gene marker includes：Obsessive-compulsive disorder characterizing gene sequence shown in SEQ ID NO.1~SEQ ID NO.10.The invention also discloses said gene markers to prepare the application in screening the product of diagnosis to obsessive-compulsive disorder and schizophrenia, depression.The gene marker of the present invention, examination for obsessive-compulsive disorder and schizophrenia, depression, sensibility height, high specificity, and with the peripheral blood that clinically most easily acquires it is detection sample, easy to detect, the examination for being suitable for obsessive-compulsive disorder and schizophrenia, depression diagnoses, and new objective molecular indexes are provided for the detection of the mental diseases such as obsessive-compulsive disorder, help to improve the problem of current mental disease diagnosis excessively relies on doctor's subjective judgement, have a extensive future.
Description
Technical field
The present invention relates to technical field of molecular biology, more particularly to one kind is for obsessive-compulsive disorder and schizophrenia, depression
The gene marker and its application that disease is screened.
Background technology
Mental disease be one group to show behavior, the nervous system disease based on the disorder in psychological activity.Due to big
Partial mental disease lacks objective diagnosis index, at present to the diagnosis of mental disease, the main or row by observing patient
It is linked up for and with patient, judges thinking, the cognitive ability of patient, also insight etc., understand the state of an illness.Because of different doctors couple
The understanding and cognition of disease often has differences, and causes the diagnosis consistency of mental disease poor, the research of different researcher's reports
As a result it is difficult to compare and explain between, has seriously affected the diagnosis and treatment of mental disease.Although using the methods of CT, MRI carry out brain at
The inspections such as picture, contribute to the state of an illness for judging organic psychiatric patient, but for this non-occupancy of functional mental disease
The nervous system disease, Image Examination is with regard to helpless.Because the early stage of most central nervous diseases, even in
Phase, clinical manifestation is much like, unless to the later stage, after the performance of disease specific occurs, can just clarify a diagnosis.Due to
The pathological biopsy for lacking brain tissue supports that the diagnosis of mental disease depends on psychoanalysis scale and doctor's subjective judgement,
Often specious for the diagnosis of mental disease, diagnosis consistency is poor, has seriously affected the symptomatic treatment of mental disease.
Although due to the presence of blood brain barrier, cerebral tissue is considered in high degree completely cutting off with blood very much, but has not
Few scholar expert is dedicated to the gene expression of blood cell, if the substitute that can find " brain tissue cell " carries out corresponding disease
The research of disease, such as the leucocyte of schizophreniac and the kinsfolk of its health culture just have the base of notable differential expression
Because existing.C.Liew in 2005 etc. successfully screen out in blood can significantly distinguish the two-way disturbance of emotion, schizophrenia and
Listless sick people.Schizophrenia is well-known severe psychiatric diseases, and the two-way disturbance of emotion is otherwise known as mania-suppression
Strongly fragrant syndrome, both diseases have many similar mental symptoms, their organic disease basis not to know, and absolutely not
Tissue biopsy assistance may be carried out to clarify a diagnosis.By the research to its blood expression of specific gene, becomes and can be claimed at present
For the method for " tissue examination " unique feasible.
According to newest American Psychiatric Association (APA)《The diagnostic and statistical manual of phrenoblabia》5th edition (referred to as
DSM-V), obsessive-compulsive disorder has certain similitude with schizophrenia/depression in phenotype, it is difficult to pass through psychoanalysis scale
Obsessive-compulsive disorder is screened Deng subjectivity method of discrimination, there is an urgent need to one kind can be used for obsessive-compulsive disorder and schizophrenia/depression Zhen
Other objective measure.
Invention content
The invention solves the lifes that current shortage can carry out obsessive-compulsive disorder and schizophrenia/depression objective and accurate examination
The technical issues of object marker, provides a kind of peripheral blood genetic marker screened with schizophrenia/depression for obsessive-compulsive disorder
Object, examination of the marker for obsessive-compulsive disorder diagnose, and have very high sensibility and specificity, and due to using clinically most
The peripheral blood easily acquired is detected, and detection process is easy, is suitable for obsessive-compulsive disorder and is screened diagnosis with schizophrenia/depression.
In order to solve the above-mentioned technical problem, the present invention is achieved through the following technical solutions:
In one aspect of the invention, a kind of combination product comprising multiple polynucleotides or its segment is provided, it is described
Multiple polynucleotides obsessive-compulsive disorder and schizophrenia, patients with depression peripheral blood in differential expression, multiple polynucleotides
For obsessive-compulsive disorder characterizing gene marker, nucleotide sequence is as shown in SEQ ID NO.1~SEQ ID NO.10.
In another aspect of this invention, a kind of composition is provided, it includes for detecting in obsessive-compulsive disorder and schizophrenia
The gene order of the primer and/or probe of gene differential expression in disease, patients with depression peripheral blood, the differential expression is SEQ
Obsessive-compulsive disorder characterizing gene sequence shown in ID NO.1~SEQ ID NO.10.
In another aspect of this invention, the use of the above-mentioned combination product comprising multiple polynucleotides or its segment is additionally provided
On the way, it is used to prepare the product that diagnosis is screened to obsessive-compulsive disorder and schizophrenia, depression.
Preferably, the product for screening diagnosis with schizophrenia, depression to obsessive-compulsive disorder includes：Use real-time quantitative
PCR, RNA are sequenced or genetic chip to obsessive-compulsive disorder and schizophrenia, depression screen the product of diagnosis.
The product for carrying out screening diagnosis to obsessive-compulsive disorder and schizophrenia, depression with real-time quantitative PCR includes spy
The primer of obsessive-compulsive disorder characterizing gene sequence shown in different amplification SEQ ID NO.1~SEQ ID NO.10.
The product for obsessive-compulsive disorder and schizophrenia, depression screen diagnosis with genetic chip includes：With SEQ
The probe of the hybridization of obsessive-compulsive disorder characterizing gene sequence shown in ID NO.1~SEQ ID NO.10.
In another aspect of this invention, a kind of inspection screened with schizophrenia, depression for obsessive-compulsive disorder is additionally provided
Test agent box, the kit include specificity for obsessive-compulsive disorder characterizing gene shown in SEQ ID NO.1~SEQ ID NO.10
The primer and/or probe of sequence.
Preferably, the sequence of the primer is as shown in SEQ ID NO.11~SEQ ID NO.30；The sequence of the probe
As shown in SEQ ID NO.31~SEQ ID NO.40.
In another aspect of this invention, a kind of inspection screened with schizophrenia, depression for obsessive-compulsive disorder is additionally provided
Survey chip, the spy that the chip includes with obsessive-compulsive disorder characterizing gene sequence hybridizes shown in SEQ ID NO.1~SEQ ID NO.10
Needle.
Using the kit or detection chip of the present invention, SEQ ID NO.1~SEQ in subject's peripheral blood can be detected
The expression of obsessive-compulsive disorder characterizing gene sequence shown in ID NO.10, the information for then raising or lowering according to these gene expressions
The probability that subject suffers from obsessive-compulsive disorder is differentiated, to realize that obsessive-compulsive disorder and the examination of schizophrenia, depression diagnose.
The gene marker of the present invention, the examination for obsessive-compulsive disorder and schizophrenia, depression diagnose, sensibility height,
High specificity, and be detection sample with the peripheral blood clinically most easily acquired due to being, it is easy to detect, it is suitable for similar to phenotype
The examination of obsessive-compulsive disorder and schizophrenia, depression diagnose, realize the symptomatic treatment of obsessive-compulsive disorder, diagnose and provide for obsessive-compulsive disorder
A kind of objective Testing index, is conducive to break that current obsessive-compulsive disorder clinical diagnosis excessively relies on psychoanalysis scale and doctor's subjectivity is sentenced
Disconnected limitation, has broad application prospects.
Description of the drawings
The present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments.
Fig. 1 is that the embodiment of the present invention 2 utilizes the characterizing gene filtered out to obsessive-compulsive disorder and schizophrenia, depression sample
Accuracy that grab sample is predicted, sensitivity and specificity distribution map；
Fig. 2 is that the embodiment of the present invention 2 schemes the ROC AUC that obsessive-compulsive disorder diagnoses using the characterizing gene filtered out.
Specific implementation mode
The present invention is built upon on the basis of mankind's full genome express spectra quantitative analysis, passes through quantitative analysis peripheral blood total serum IgE
Gene expression situation, compare the gene expression difference in obsessive-compulsive disorder and schizophrenia, depression peripheral blood sample, then pass through
Support vector machines (Support Vector Machine) method filters out 10 and difference occurs in patients with OCD peripheral blood
The gene signal of expression (gene expression is raised or lowered), the i.e. expression signal of obsessive-compulsive disorder characteristic gene (biomarker).
Then, using fluorescence quantitative RT-RCR, chip gene expression profile or RNA sequencing technologies quantitatively detect in subject's peripheral blood this 10
The relative expression quantity of a obsessive-compulsive disorder gene marker, and then differentiate the probability that subject suffers from obsessive-compulsive disorder.
The screening of 1 obsessive-compulsive disorder characterizing gene marker of embodiment
The screening of obsessive-compulsive disorder characterizing gene includes the following steps：
1) use Affymetrix Gene Expression Using Affymetrix 2.0 mankind of U133Plus complete
20 obsessive-compulsive disorders of chip gene expression profile pair make a definite diagnosis what patient, 20 schizophrenia and 20 patients with depression samples formed
Peripheral blood gene expression is composed, and above-mentioned 60 samples are as training set (Training set)；
2) utilize Affymetrix MAS5 methods to the chip gene expression profile testing result of each sample in training set into
Row normalized；
3) probe collection (Probeset) signal that expression signal is excessively high and too low in total serum IgE is rejected, is selected in training set institute
Having has the probe collection signal moderately expressed to carry out subsequent analysis in 60 samples；
4) the T methods of inspection are used to select the difference expression gene of obsessive-compulsive disorder and schizophrenia, depression, screening conditions are
Multiple changes FC>1.2 times, significance P<0.05 probe collection signal obtains 3631 groups of satisfactory probe collection；
5) gene order comparison is carried out to the probe collection filtered out, picks out the gene for including 2 and 2 or more probe collection
For subsequent analysis, 326 candidate genes are obtained；
6) it is screened from above-mentioned 326 candidate genes by force with support vector machine method (Support Vector Machine)
Compel disease characterizing gene, according to SFFS (Sequential Forward Floating Selection) screening strategy, builds two points
Class mathematical model carries out training set sample using LOOCV (leave-one-out cross validation) methods random
It samples and the sample cluster generated to sampling carries out classification prediction, pick out has highest prediction accuracy to obsessive-compulsive disorder
(accuracy) 10 genes establish the Zhen of obsessive-compulsive disorder and schizophrenia, depression as obsessive-compulsive disorder candidate feature gene
Other diagnostic model；
7) above-mentioned 10 obsessive-compulsive disorders candidate feature gene is detected using real time fluorescence quantifying PCR method, is as a result shown
Show that the expression variation tendency of 10 obsessive-compulsive disorder candidate feature genes is consistent with the gene expression trend that chip of expression spectrum detects, this 10
A characterizing gene sequence as obsessive-compulsive disorder characterizing gene marker is as shown in table 1 below.
The sequence of 1 obsessive-compulsive disorder characterizing gene marker of table
| Serial number | Obsessive-compulsive disorder characterizing gene title | Sequence table numbering |
| 1 | NONO genes | SEQ ID NO.1 |
| 2 | SDHC genes | SEQ ID NO.2 |
| 3 | SNX5 genes | SEQ ID NO.3 |
| 4 | HSPA8 genes | SEQ ID NO.4 |
| 5 | USF2 genes | SEQ ID NO.5 |
| 6 | RAB1B genes | SEQ ID NO.6 |
| 7 | UFL1 genes | SEQ ID NO.7 |
| 8 | MAPK1IP1L genes | SEQ ID NO.8 |
| 9 | PURB genes | SEQ ID NO.9 |
| 10 | TESPA1 genes | SEQ ID NO.10 |
Embodiment 2 using the obsessive-compulsive disorder characterizing gene marker that filters out to obsessive-compulsive disorder and schizophrenia, depression into
Row screens diagnosis
1. method and step：
1) collection of sample peripheral blood sample to be detected：It is collected using the BD PAXgeneRNA heparin tubes of QIAGEN companies
Patient's peripheral blood sample；
2) in sample peripheral blood sample to be detected total serum IgE extraction purification：Use the PAXgeneBlood of QIAGEN companies
Total serum IgE in RNA Kit extraction purification peripheral bloods is used in combination 2100 type microelectrophoresis analyzers of Agilent BioAnalyzer to reflect
Surely the total serum IgE fragment integrity and yield extracted；
3) reverse transcription reaction：Use the High-Capacity cDNA Reverse of Life Techonolgy companies
Transcription kit reverse transcription reagent box is that template is reversed with Olig (dT) for reverse transcriptase primer using total serum IgE
Record reaction synthesis cDNA；
4) fluorescence quantitative RT-RCR detects：According to 10 obsessive-compulsive disorder characterizing genes (SEQ ID NO.1~SEQ ID
NO.10) and the correlated series of reference gene GAPDH, specific primer SEQ ID NO.11~SEQ ID NO.30 (its is designed
In, primer SEQ ID NO.11~SEQ ID NO.12 are used for specific amplification SEQ ID NO.1 gene markers, primer SEQ
ID NO.13~SEQ ID NO.14 be used for specific amplification SEQ ID NO.2 gene markers, primer SEQ ID NO.15~
SEQ ID NO.16 are used for specific amplification SEQ ID NO.3 gene markers, primer SEQ ID NO.17~SEQ ID
NO.18 is used for specific amplification SEQ ID NO.4 gene markers, and primer SEQ ID NO.19~SEQ ID NO.20 are for spy
Specific amplification SEQ ID NO.5 gene markers, primer SEQ ID NO.21~SEQ ID NO.22 are used for specific amplification SEQ
ID NO.6 gene markers, primer SEQ ID NO.23~SEQ ID NO.24 are used for specific amplification SEQ ID NO.7 genes
Marker, primer SEQ ID NO.25~SEQ ID NO.26 are used for specific amplification SEQ ID NO.8 gene markers, primer
SEQ ID NO.27~SEQ ID NO.28 are used for specific amplification SEQ ID NO.9 gene markers, primer SEQ ID
NO.29~SEQ ID NO.30 are used for specific amplification SEQ ID NO.10 gene markers), and design specific probe SEQ
(wherein SEQ ID NO.31~SEQ ID NO.40 are respectively SEQ ID NO.1~SEQ to ID NO.31~SEQ ID NO.40
The probe sequence of ID NO.10 characterizing gene sequences), using SEQ ID NO.11~SEQ ID NO.30 as primer, with SEQ ID
NO.31~SEQ ID NO.40 be probe or using can with the SYBR Green dyestuffs of pcr amplified fragment non-specific binding,
The cDNA obtained using reverse transcription is carried out real-time fluorescence quantitative RT-PCR reaction, obtains 10 gene marks as amplification template
MRNA relative amount of the will object in peripheral blood sample；
Fluorescent quantitative PCR primer sequence is as follows：
NONO genes
Forward primer：5'GCTCCTGTGCCAGCTGGTA3'(SEQ ID NO.11)
Reverse primer：5'GGGTCAATCCCAAAGTTCCA 3'(SEQ ID NO.12)
SDHC genes
Forward primer：5'TGCCCACAGCTTGCCTACTC 3'(SEQ ID NO.13)
Reverse primer：5'AAATCAAAGCCCAATATGGAGAGA 3'(SEQ ID NO.14)
SNX5 genes
Forward primer：5'GCTCAACATTGAAGCTGCTAAGG 3'(SEQ ID NO.15)
Reverse primer：5'AGAGCTTTGTTTGAGTTCTCATAGTCA 3'(SEQ ID NO.16)
HSPA8 genes
Forward primer：5'GAAACTGCTGGTGGAGTCATGA 3'(SEQ ID NO.17)
Reverse primer：5'TGAAGGTCTGTGTCTGCTTGGT 3'(SEQ ID NO.18)
USF2 genes
Forward primer：5'ACTAAGCCCCGGCACTTCTAG 3'(SEQ ID NO.19)
Reverse primer：5'TTCCCATCAGCACCCTGTCT 3'(SEQ ID NO.20)
RAB1B genes
Forward primer：5'TCCTGCAAGAAAGCAAGTCTTTG 3'(SEQ ID NO.21)
Reverse primer：5'GGTGGGACAGGCAAGAGACA 3'(SEQ ID NO.22)
UFL1 genes
Forward primer：5'GTGAGTGGTCACAAAAAAGTAGTCACT 3'(SEQ ID NO.23)
Reverse primer：5'ACTGTTTTAACTGAATTGTGTGTGTATGA 3'(SEQ ID NO.24)
MAPK1IP1L genes
Forward primer：5'GACTCCCACCAAGTGCAACAC 3'(SEQ ID NO.25)
Reverse primer：5'GAGGCACGGAGGGATACATTC 3'(SEQ ID NO.26)
PURB genes
Forward primer：5'GTGGGCGGGTCAGTTCAG 3'(SEQ ID NO.27)
Reverse primer：5'ATGCCCGGCTAATTTTAGTATTTTT 3'(SEQ ID NO.28)
TESPA1 genes
Forward primer：5'GAAAACTCTACCCAGTAATCCAATCAC 3'(SEQ ID NO.29)
Reverse primer：5'TCATGTCAAACTGTAATCCCCATT 3'(SEQ ID NO.30)
Quantitative fluorescent PCR probe sequence is as follows：
NONO genes
Probe sequence：5'CCCAGCTCCTCCAGGACCTGCC 3'(SEQ ID NO.31)
SDHC genes
Probe sequence：5'CGGCCTAGAAGCAG 3'(SEQ ID NO.32)
SNX5 genes
Probe sequence：5'TCTCTTATACAGACGCACCAAAGCCCTCA 3'(SEQ ID NO.33) HSPA8 genes
Probe sequence：5'TGTCCTCATCAAGCGTAATACCACCATTCC 3'(SEQ ID NO.34)
USF2 genes
Probe sequence：5'CACGTCCCGCTGCCTCCTGC 3'(SEQ ID NO.35)
RAB1B genes
Probe sequence：5'TCTCCCTGAGAAGCCATGTCCCTCGT 3'(SEQ ID NO.36)
UFL1 genes
Probe sequence：5'TACAACTCCCCTCTCCCTGCAAAAACCA 3'(SEQ ID NO.37)
MAPK1IP1L genes
Probe sequence：5'CTCCACTGTGCCTTTTGGACCAGCA 3'(SEQ ID NO.38)
PURB genes
Probe sequence：5'TCAGCCTGGACAACATGGTGAAACCC 3'(SEQ ID NO.39)
TESPA1 genes
Probe sequence：5'ACCCACCAGGCCCCACCTCC 3'(SEQ ID NO.40)
5) diagnosis of sample donor result to be detected：Existed according to 10 obsessive-compulsive disorder gene markers in fluorescence quantitative RT-RCR
MRNA relative amounts in peripheral blood sample differentiate to whether subject suffers from obsessive-compulsive disorder.
2. result
82 obsessive-compulsive disorders (OCD), 46 schizophrenia (Schiz), 44 depressions are had detected with fluorescence quantitative RT-RCR
10 obsessive-compulsive disorder gene marker relative expression quantities in disease (Dep) peripheral blood in patients screen diagnostic model to upper using obsessive-compulsive disorder
It states 172 samples (including training set (Training set) and test set sample (Test set)) and carries out classification prediction, it will be pre-
Result is surveyed compared with the clinical diagnosis testing result of above-mentioned mental disease, obtains 10 obsessive-compulsive disorder gene markers of the invention to strong
Compel sensitivity (Sensitivity), specific (Specificity) and accuracy (Accuracy) that disease screens diagnosis, specifically
Testing result is shown in Fig. 1,2 and the following table 2.
Table 2 screens obsessive-compulsive disorder (OCD), schizophrenia (Schiz), depression (Dep) sensitivity, special of detection
Property, accuracy and ROC AUC value
Embodiments of the present invention above described embodiment only expresses, the description thereof is more specific and detailed, but can not
Therefore it is interpreted as the limitation to the scope of the claims of the present invention.It should be pointed out that for those of ordinary skill in the art,
Without departing from the inventive concept of the premise, various modifications and improvements can be made, these belong to the protection model of the present invention
It encloses.Therefore, the protection domain of patent of the present invention should be determined by the appended claims.
Sequence table
<110>Shanghai Co., Ltd of uncle's bold and unconstrained medical test institute
<120>The gene marker screened for obsessive-compulsive disorder and schizophrenia, depression and its application
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aaggccctca tcccctgccg ctacttctct ggggaatgtg ggttccatcc aggattgggg 120
gcctctctgc tcacccactc tgcacccagg atcctagtcc cctgccctct ggcacagctg 180
cttcctgcaa gaaagcaagt ctttggtctc cctgagaagc catgtccctc gtgctgtctc 240
ttgcctgtcc cacctgtgcc ctgccctcca gcttgtattt aagtccctgg gctgccccct 300
tggggtgccc cccgctccca ggttcccctc tggtgtcatg tcaggcattt tgcaaggaaa 360
agccacttgg ggaaagatgg aaaaggacaa aaaaaattaa taaatttcca ttggccctcg 420
ggtgagctga gggt 434
<210> 7
<211> 433
<212> DNA
<213> Homo sapiens
<400> 7
aagaccttgt tctcaaatct aggaaatcat ctgtgacgga agagtaatga tcttaattta 60
catttgtcat atagtaagca ttttccccca aggttgaagg tgagtggtca caaaaaagta 120
gtcactatac aactcccctc tccctgcaaa aaccacctca tacacacaca attcagttaa 180
aacagtagta ttgtattaaa tgtaaatctt aaaaagatgt gaatttttgt aaattgggtt 240
cttcatggaa gtttttttcc acctgatttt cacacaaata ctatatgaaa tttttcacat 300
tattttcaca taattttaaa aattacatat ttcaggtttg ttctctttcc aaatgttgaa 360
tgaaaaacaa attttccaat ccatttatcc ctggggaagg attcatttgt tgcgagtgcc 420
agtatactta aat 433
<210> 8
<211> 783
<212> DNA
<213> Homo sapiens
<400> 8
aacacttaag atctctgcat tttgttgagt gctaattaca cttcaattta aaaattggta 60
aaagtactcc aggacatcaa taaatttaaa tttgggagta cacacagtgg ctcatggcta 120
taatcccaat actttgggag gctgaggcag gagggtcctt tgatcccagg agtttgagac 180
cgggtctggg caacatagtg agacacctgt ctctgcaata aatttttaaa attttaagaa 240
atttgctggg catgatggca cacacctgta gtaccggcta ttagggagac tgaggcaaga 300
agatgacttg agcccaggag gtcaagattg cagtgagctg tgatctctct cgccactgca 360
ctccagcctg ggtgacagaa tgagaccctg tctccaaaaa aaagacgagg aaatgaaaat 420
gtctgatgaa ttttcgttgg cagatgcact acctgaacac tcccctgcca aaacctctgc 480
tgtgagcaat acaaaacctg gccaacctcc tcaaggctgg ccaggctcca acccttggaa 540
taatccgagt gctccatctt cagtgccatc tggactccca ccaagtgcaa caccctccac 600
tgtgcctttt ggaccagcac caacaggaat gtatccctcc gtgcctccca ccggaccacc 660
tccaggaccc ccagcaccct ttcctccttc cggaccatca tgtcccccac ctggtggtcc 720
ttatccagcc ccaactgtgc cgggccctgg ccccacaggg ccatatccta caccaaatat 780
gcc 783
<210> 9
<211> 1166
<212> DNA
<213> Homo sapiens
<400> 9
tggccttgat cagtgagaaa gggaaggaga aaagtgactt ttttgcttat gtagaaatga 60
ctcatttgct gagagtttgt ctttctgcag cactcttggt atatagtgat cggtctcctt 120
tttgattggg gaaagttaat gtttttgacc ctggagttaa ttcagttgag ttatcttata 180
tttttaggaa gtatcagaat tgctctgatg aataacaaag ttgactgttt tgatgtccaa 240
tctcaggttt tagaatatag tggtgtaaag tcccactatt tttaattctt aaaacaactt 300
taatttcgta caccctaaaa gtcacatgca taaggcctgt tcagagagca gagcctccat 360
ctttttgctc cttttctact ttgtacttca cttgaaaaaa tatcaagtga ctttacattg 420
tatatttcca ttgtaaccct gacatttctc aaagataaag cactttttga tcatgaaata 480
catgaaatct ttgtgtgatg tggatcatag tttctcaggc tcccttagat aattgcttat 540
gaatattgtt ctaactctgt gtaagaagag tagaaatctt tgctaatgtt agaaggtttg 600
tattattgat ccagaatgca ttttgctagt ttccaatgga tgggagagta aataatgctg 660
cattcacaat ttaataagtt actttccctt gagccttaag gtaacttttt ctttcctgtc 720
aactacagca ctgaagttat agtaagtgaa tgagattatc agttttcagg gttggtttta 780
gagtactgta aatcaattag ctgtcttcct aaagagttac aactcccatt cagtatactg 840
gataatgggt gtgtgggtgg ggctggggag ggcgggagat agtttgtaga aaagaaaaaa 900
gaaaaaaaaa aaaacacatt taccttaaga aaatacagac aaaaaagaat aaagtatgtg 960
tcatatgctc catttgagat tccaaatgcg gccgggcgtg gtggctcacg cctgtaatcc 1020
cagcactctg ggaggctgag gtgggcgggt cagttcaggt cagcctggac aacatggtga 1080
aaccccgtct ctactaaaaa tactaaaatt agccgggcat ggtggtgcat gcctgtagtc 1140
ccagctactt gggaggctga ggcagg 1166
<210> 10
<211> 474
<212> DNA
<213> Homo sapiens
<400> 10
gcaaagtggg agcaggcatc ttacctggta tgagcaggag gaacaaagga aaggggaggt 60
gctaacactt ttaaatgacc agatcttgta agaactcact cattatacag taccaagggg 120
agatggtgct aaacgattaa tgaaaactct acccagtaat ccaatcacca cccaccaggc 180
cccacctcca acaatgggga ttacagtttg acatgagatt tgggtgagga cacagatcca 240
aactgtcagg cctctgagcc caagctaagc catcatatcc cctgtgacct gcatgtatac 300
atccagatgg cctgaagcaa gtggagaatc acaaaagaag tgaaaatggc ctgttgctgc 360
cttaacagat gacattactt tgtgaaattc cttcttctgg ctcagaagct cccccactga 420
gcaccttgtg acccccaccc ctgcctgcca gagaataatc ccctttgact gtaa 474
<210> 11
<211> 19
<212> DNA
<213>Artificial sequence
<400> 11
gctcctgtgc cagctggta 19
<210> 12
<211> 20
<212> DNA
<213>Artificial sequence
<400> 12
gggtcaatcc caaagttcca 20
<210> 13
<211> 20
<212> DNA
<213>Artificial sequence
<400> 13
tgcccacagc ttgcctactc 20
<210> 14
<211> 24
<212> DNA
<213>Artificial sequence
<400> 14
aaatcaaagc ccaatatgga gaga 24
<210> 15
<211> 23
<212> DNA
<213>Artificial sequence
<400> 15
gctcaacatt gaagctgcta agg 23
<210> 16
<211> 27
<212> DNA
<213>Artificial sequence
<400> 16
agagctttgt ttgagttctc atagtca 27
<210> 17
<211> 22
<212> DNA
<213>Artificial sequence
<400> 17
gaaactgctg gtggagtcat ga 22
<210> 18
<211> 22
<212> DNA
<213>Artificial sequence
<400> 18
tgaaggtctg tgtctgcttg gt 22
<210> 19
<211> 21
<212> DNA
<213>Artificial sequence
<400> 19
actaagcccc ggcacttcta g 21
<210> 20
<211> 20
<212> DNA
<213>Artificial sequence
<400> 20
ttcccatcag caccctgtct 20
<210> 21
<211> 23
<212> DNA
<213>Artificial sequence
<400> 21
tcctgcaaga aagcaagtct ttg 23
<210> 22
<211> 20
<212> DNA
<213>Artificial sequence
<400> 22
ggtgggacag gcaagagaca 20
<210> 23
<211> 27
<212> DNA
<213>Artificial sequence
<400> 23
gtgagtggtc acaaaaaagt agtcact 27
<210> 24
<211> 29
<212> DNA
<213>Artificial sequence
<400> 24
actgttttaa ctgaattgtg tgtgtatga 29
<210> 25
<211> 21
<212> DNA
<213>Artificial sequence
<400> 25
gactcccacc aagtgcaaca c 21
<210> 26
<211> 21
<212> DNA
<213>Artificial sequence
<400> 26
gaggcacgga gggatacatt c 21
<210> 27
<211> 18
<212> DNA
<213>Artificial sequence
<400> 27
gtgggcgggt cagttcag 18
<210> 28
<211> 25
<212> DNA
<213>Artificial sequence
<400> 28
atgcccggct aattttagta ttttt 25
<210> 29
<211> 27
<212> DNA
<213>Artificial sequence
<400> 29
gaaaactcta cccagtaatc caatcac 27
<210> 30
<211> 24
<212> DNA
<213>Artificial sequence
<400> 30
tcatgtcaaa ctgtaatccc catt 24
<210> 31
<211> 22
<212> DNA
<213>Artificial sequence
<400> 31
cccagctcct ccaggacctg cc 22
<210> 32
<211> 14
<212> DNA
<213>Artificial sequence
<400> 32
cggcctagaa gcag 14
<210> 33
<211> 29
<212> DNA
<213>Artificial sequence
<400> 33
tctcttatac agacgcacca aagccctca 29
<210> 34
<211> 30
<212> DNA
<213>Artificial sequence
<400> 34
tgtcctcatc aagcgtaata ccaccattcc 30
<210> 35
<211> 20
<212> DNA
<213>Artificial sequence
<400> 35
cacgtcccgc tgcctcctgc 20
<210> 36
<211> 26
<212> DNA
<213>Artificial sequence
<400> 36
tctccctgag aagccatgtc cctcgt 26
<210> 37
<211> 28
<212> DNA
<213>Artificial sequence
<400> 37
tacaactccc ctctccctgc aaaaacca 28
<210> 38
<211> 25
<212> DNA
<213>Artificial sequence
<400> 38
ctccactgtg ccttttggac cagca 25
<210> 39
<211> 26
<212> DNA
<213>Artificial sequence
<400> 39
tcagcctgga caacatggtg aaaccc 26
<210> 40
<211> 20
<212> DNA
<213>Artificial sequence
<400> 40
acccaccagg ccccacctcc 20
Claims (10)
1. the combination product comprising multiple polynucleotides or its segment, the multiple polynucleotides are in obsessive-compulsive disorder and schizophrenia
Disease, patients with depression peripheral blood in differential expression, multiple polynucleotides be obsessive-compulsive disorder characterizing gene marker, nucleotide
Sequence is as shown in SEQ ID NO.1~SEQ ID NO.10.
2. composition, it includes for detecting the gene difference table in obsessive-compulsive disorder and schizophrenia, patients with depression peripheral blood
The gene order of the primer and/or probe reached, the differential expression is obsessive-compulsive disorder shown in SEQ ID NO.1~SEQ ID NO.10
Characterizing gene sequence.
3. the purposes of the combination product comprising multiple polynucleotides or its segment described in claim 1, is used to prepare to obsessive-compulsive disorder
The product of diagnosis is screened with schizophrenia, depression.
4. purposes according to claim 3, which is characterized in that described to be screened to obsessive-compulsive disorder and schizophrenia, depression
The product of diagnosis includes：Obsessive-compulsive disorder and schizophrenia, depression are carried out with real-time quantitative PCR, RNA sequencings or genetic chip
Screen the product of diagnosis.
5. purposes according to claim 4, which is characterized in that it is described with real-time quantitative PCR to obsessive-compulsive disorder and schizophrenia
The product that disease, depression carry out screening diagnosis includes that obsessive-compulsive disorder shown in specific amplified SEQ ID NO.1~SEQ ID NO.10 is special
Levy the primer of gene order.
6. purposes according to claim 4, which is characterized in that it is described with genetic chip to obsessive-compulsive disorder and schizophrenia,
Depression carry out screen diagnosis product include：With obsessive-compulsive disorder characterizing gene sequence shown in SEQ ID NO.1~SEQ ID NO.10
Arrange the probe of hybridization.
7. a kind of detection kit screened with schizophrenia, depression for obsessive-compulsive disorder, which is characterized in that the kit
Include primer and/or probe of the specificity for obsessive-compulsive disorder characterizing gene sequence shown in SEQ ID NO.1~SEQ ID NO.10.
8. detection kit according to claim 7, which is characterized in that the sequence of the primer includes SEQ ID NO.11
Nucleotide sequence shown in~SEQ ID NO.30.
9. detection kit according to claim 7, which is characterized in that the sequence of the probe includes SEQ ID NO.31
Nucleotide sequence shown in~SEQ ID NO.40.
10. a kind of detection chip screened with schizophrenia, depression for obsessive-compulsive disorder, which is characterized in that the chip packet
Containing with obsessive-compulsive disorder characterizing gene sequence hybridizes shown in SEQ ID NO.1~SEQ ID NO.10 probe.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201710123948.XA CN108531569B (en) | 2017-03-03 | 2017-03-03 | Gene marker for screening obsessive-compulsive disorder, schizophrenia and depression and application thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710123948.XA CN108531569B (en) | 2017-03-03 | 2017-03-03 | Gene marker for screening obsessive-compulsive disorder, schizophrenia and depression and application thereof |
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| CN108531569A true CN108531569A (en) | 2018-09-14 |
| CN108531569B CN108531569B (en) | 2021-05-07 |
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| CN112924685A (en) * | 2019-12-05 | 2021-06-08 | 中国科学院大连化学物理研究所 | Depression biomarker and diagnostic kit comprising same |
| CN113555118A (en) * | 2021-07-26 | 2021-10-26 | 内蒙古自治区人民医院 | Method and device for predicting disease degree, electronic equipment and storage medium |
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| CN112924685A (en) * | 2019-12-05 | 2021-06-08 | 中国科学院大连化学物理研究所 | Depression biomarker and diagnostic kit comprising same |
| CN112924685B (en) * | 2019-12-05 | 2022-09-13 | 中国科学院大连化学物理研究所 | Depression biomarker and diagnostic kit comprising same |
| CN113555118A (en) * | 2021-07-26 | 2021-10-26 | 内蒙古自治区人民医院 | Method and device for predicting disease degree, electronic equipment and storage medium |
| CN113555118B (en) * | 2021-07-26 | 2023-03-31 | 内蒙古自治区人民医院 | Method and device for predicting disease degree, electronic equipment and storage medium |
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| Publication number | Publication date |
|---|---|
| CN108531569B (en) | 2021-05-07 |
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