CN102154478A

CN102154478A - Subsyndromal symptomatic depression gene expression diagnosis chip

Info

Publication number: CN102154478A
Application number: CN2011100332997A
Authority: CN
Inventors: 方贻儒; 易正辉; 李则挚; 洪武
Original assignee: SHANGHAI MENTAL HEALTH CENTER
Current assignee: SHANGHAI MENTAL HEALTH CENTER
Priority date: 2010-09-21
Filing date: 2011-01-30
Publication date: 2011-08-17
Anticipated expiration: 2031-01-30
Also published as: CN102154478B

Abstract

The invention belongs to the field of biochips, and provides a subsyndromal symptomatic depression gene expression diagnosis chip. The chip consists of a solid phase vector, wherein the solid phase vector is provided with 46 gene probes; genes corresponding to the 46 probes are PSMB4, TMBIM6, PNN, CD84, PRKCB, PRKAR2A, KALRN, NRAS, NRAS, CTNS, GCHFR, TERF2, NOP56, SH3YL1, COG3, INPP4A, PURA, GINS4, ZCCHC3, STAT5B, SCFD2, TMEM97, SOCS4, SLC16A3, C19orf6, PIK3AP1, FGD3, VARS, KTI12, ZNF791, LHX9, NEK8, ZNF785, RHOQ, PA2G4, CCND2, WWP2, CAPRIN1, BRE, MEF2A, SENP1, STRN, ABL1, PDE6B, FDPS and RPL4 respectively; and the 46 gene probes are arrayed in a matrix form. By adopting the chip, biological basis is provided for subsyndromal symptomatic depression, and subsyndromal symptomatic depression can be diagnosed easily and quickly.

Description

The depressed genetic expression diagnosing chip of inferior syndrome

Technical field

The invention belongs to bioengineering field, relate in particular to a kind of diagnosing chip, the depressed genetic expression diagnosing chip of particularly a kind of inferior syndrome.

Background technology

Dysthymia disorders is a kind of serious harm human physical and mental health's a mental disorder, have high morbidity, high relapse rate, high disability rate, high homicide rate and disease characteristics such as overburden, therefore its great burden that causes to the able-bodied harm of individuality and to society causes the extensive concern of Chinese scholars, government and society and has carried out the research of a series of Clinics and Practices already for catching people's attention.Yet still have 2/3rds to 3/4ths to have depressive symptom but not meet at present " the 4th edition revised edition of Americanism medical diagnosis on disease handbook (Diagnostic and Statistical Manual at present, Fourth Edition, Text Revision, DSM-IV-TR) depressive patient under the threshold of dysthymia disorders diagnosis in, tangible social function infringement (Judd LL is arranged, Rapaport MH, Paulus MP, Brown JL.1994.Subsyndromal symptomatic depression:a new mood disorder? J Clin Psychiatry 55:18-28.).Wherein common also is that to hide what be difficult for being identified most be inferior syndrome depression.Inferior syndrome depression (Subsyndromal Symptomatic Depression, SSD) refer to have simultaneously 2 or multinomial depressive symptom, great majority or full time occur, continued at least 2 weeks, though do not meet " severe depression " and/or " dysthymia obstacle " Case definition of current diagnositc system, but can cause serious occupational function to descend equally, depressive state (Judd LL under a kind of threshold of harm such as social function infringement, Akiskal HS, Paulus MP.The role and cl inical significance of subsyndromal depressive symptoms (SSD) in unipolar major depressive disorder.J Affect Disorders, 1997,45:5-17.).Yet inferior syndrome depression (SSD) does not but cause real concern and enough attention, and a lot of people even professional know little about it.Discover with healthy people and compare, easier chronic depression and severe depression (the Judd LL of developing into of inferior syndrome depression, Akiskal HS, Maser JD, et al.Major depressive disorder:a prospective study of residual subthreshold depressive symptoms as predictor of rapid relapse.J Affect Disorders 1998; 50:97-108.), equally with dysthymia disorders can cause serious harm (Judd LL to patient's social function, Paulus MP, Wells KB, and Rapaport MH.Socioeconomic burden of subsyndromal depressive symptoms and major depression in a sample of the general population.Am J Psychiatry 1996; 153:1411-1417.), therefore to the depressed early discovery of inferior syndrome, early diagnosis and to carry out early intervention necessary.

Because inferior syndrome depressive illness because of not bright, mainly is by the clinical symptom diagnosis at present, so scientists is devoted to find its biology sign.Because the live body cerebral tissue is difficult to obtain, past people is attempted to study by corpse cerebral tissue difference expression gene and is sought its biology sign, yet the research of corpse cerebral tissue is subjected to influence of various factors again, and can't dynamically follow up a case by regular visits to.At present people generally believe that depressive disorder is not only neuropsychiatric disease, or a kind of physical disease, it was both relevant with central nervous system, relevant with neuroendocrine system, autonomic nervous system and immunity system again, owing to recycle system peripheral leukocytes is subjected to neuroendocrine system, autonomic nervous system and immunity system because of the depressed influence that changes, therefore increasing relevant depressive disorder gene expression research begins to turn in brain in the genetic expression of peripheral blood cells.

For the research of the gene expression profile of multigenic disease, mainly be in order to inquire into the biology pathogenesis of disease, the biology sign of disease and offer help for the classification of disease and diagnosis.And utilize biochip technology to detect the disease gene express spectra, thus make up the gene diagnosis chip mathematical model of disease, be the direction of disease gene expression study.Now explore making up medical diagnosis on disease models such as diabetes, hypertension and meningioma, obtained some successes, made up diabetes and hypertensive gene diagnosis chip.But at present the research of relevant mental disorder is less, and Ohmori T etc. has made up a kind of special detection and chip that stress related gene expression, and the genetic expression that is applied to dysthymia disorders detects, but does not set up the genetic expression diagnostic model of inferior syndrome depression.

Summary of the invention

The object of the present invention is to provide the depressed genetic expression diagnosing chip of a kind of inferior syndrome, the depressed genetic expression diagnosing chip of described this inferior syndrome will solve the technical problem of the biological method that the inferior syndrome depression of diagnosis is not arranged in the prior art as yet.

The invention provides the depressed genetic expression diagnosing chip of a kind of inferior syndrome, constitute by solid phase carrier, described solid phase carrier is provided with 46 gene probes, the pairing respectively gene of described 46 gene probes is PSMB4, TMBIM6, PNN, CD84, PRKCB, PRKAR2A, KALRN, NRAS, NRAS, CTNS, GCHFR, TERF2, NOP56, SH3YL1, COG3, INPP4A, PURA, GINS4, ZCCHC3, STAT5B, SCFD2, TMEM97, SOCS4, SLC16A3, C19orf6, PIK3AP 1, FGD3, VARS, KTI 12, ZNF791, LHX9, NEK8, ZNF785, RHOQ, PA2G4, CCND2, WWP2, CAPRIN1, BRE, MEF2A, SENP1, STRN, ABL1, PDE6B, FDPS, RPL4, described 46 gene probes are matrix form and arrange.

Further, also be provided with 2 gene probes on the described solid phase carrier, be respectively 18S and GAPDH.

Further, described solid phase carrier is selected from any one in slide glass, silicon chip, acetate film or the cellulose nitrate film.

The present invention at first takes out peripheral blood 15ml to the inferior syndrome depression of going into group and each 8 example of normal healthy controls group and extracts RNA and carry out Affymetrix U133plus 2.0 gene expression chips and detect, utilize the gene expression chip data simultaneously, adopt SVMs (SVM) sorter to make up the depressed genetic expression diagnosing chip of inferior syndrome model, we obtain the medical diagnosis on disease model of 46 genes at last.Pass through ABI

Inquire corresponding probe number (www.appliedbiosystems.com) among the Gene Expression Assays, be identified for designing 46 gene probes of diagnosing chip at last.We number transfer to u.s.a. applied biosystem (ABI) company with 46 gene probes, make the ABTaqMan low density chip of 48Assay Format--the depressed genetic expression diagnosing chip of----inferior syndrome.Secondly, in order to check the effect of the depressed genetic expression diagnosing chip of inferior syndrome that we invent, we have also designed the subsequent authentication experiment to this diagnosing chip, our confirmatory experiment is included sex, age be complementary inferior syndrome depression and each 50 example of normal healthy controls group altogether in, carrying out the depressed genetic expression diagnosing chip of inferior syndrome detects, found that the depressed prediction accuracy of inferior syndrome reaches 82.0%, in addition, we utilize the svm classifier device that the verification msg collection is carried out testing oneself of 10 times of cross validations (Cross-validation), and the classification bat reaches 87.0%.Wherein normal healthy controls group categories performance reaches 84.0%, and the depressed classifying quality of inferior syndrome reaches 90.0%.

Biology path and functional module that the corresponding gene of probe that chip of the present invention comprises mainly participates in comprise: the GnRH signal path, mitogen activated protein kinase (MAPK) signal path, vascular endothelial growth factor (VEGF) signal path, the CD40 signal path, Fc epsilon RI signal path, insulin signaling pathway, ErbB signal path, type ii diabetes, CREB transcriptional control path and Toll sample receptor signal path etc.

The relevant gonadotropin releasing hormone of the corresponding gene of probe that chip of the present invention comprises (gonadotropin releasing hormone, GnRH) signal path, insulin signaling pathway and type ii diabetes gene, these genes are all relevant with internal secretion, and also to have a pathomechanism of endocrine alteration consistent with dysthymia disorders and SSD for this.At present existing a large amount of evidences show that the interaction of hpa axis and HPG axle has participated in the morbidity of depressive disorder, and the excessive driving of the CRH of sex hormone receptor mediation has vital role in taking place, develop at depressive disorder probably.The excessive driving of CRH is the co-channel of depressive disorder morbidity, no matter be that the male sex or women's depressive disorder patient have this general character, the excessive activation of the CRH of estrogen receptor mediation may be one of women's reason of easily suffering from depressive disorder; And the regulation and control disorder of the CRH of androgen receptor mediation then may be the basis of male sex's depressive patient pathogeneticing characteristic.

The gene of the gene probe correspondence of diagnosing chip is relevant with the VEGF signal path, this path is relevant with somatomedin, somatomedin such as Brain Derived Neurotrophic Factor (BDNF), VEGF and fibroblast somatomedin (FGF) play an important role in cerebral nerve generation and vasculogenesis function.In depression research, these somatomedins are widely studied.VEGF is all influential to the formation of neurone and spongiocyte, recent studies have shown that it has neuroprotective.VEGF exerts an influence to the morphology of hippocampal tissue, therefore discovers that VEGF and depressive disorder have very big dependency.Discover in addition to the influential medicine of VEGF signal path may to dysthymia disorders and senile dementia (Alzheimer ' s disease, AD) effective.

In addition, candidate gene also relates to the CREB path.The existing CREB albumen of discovering is regulated many and depressive disorder gene expression related, and depressive disorder suicide patient corpse cerebral tissue CREB expresses obviously and descends, and CREB genetic expression of dysthymia disorders peripheral blood and protein level all descend.Employing can be used as the medicine of treatment dysthymia disorders to the influential medicine of CREB transcription factor.Long-term anti depressant therapy can cause CREB to raise, and CREB also has the Research of Animal Model for Study of a large amount of relevant depressive disorders to be confirmed in dysthymia disorders with effect in the antidepressant, has to discover that the level that increases CREB in rodent models will make animal model show as similar antidepressant behavior.

The gene of candidate diagnosis chip also includes erbB (epidermal growth factor receptor, EGFR, EGF-R ELISA) signal path, this signal path abnormal expression can cause few prominent spongiocyte (OL) unusual, the oligodendrocyte functional defect can cause dopaminergic unusual, therefore also may be relevant with depressive disorder.The transgenic mice experiment has confirmed that the erbB signal path among the OL is blocked causing quantity and the morphologic variation of OL, reduces myelinic thickness, and reduces the conduction velocity of CNS aixs cylinder.

Toll sample receptor signal path, CD40 signal path and Fc epsilon RI (high affinity immune globulin E acceptor) signal path is relevant with immunity.(Toll-like receptor TLR) is a quasi-mode identification receptor of discovered in recent years to Toll sample acceptor, and (pathogen-associated molecular pattern PAMP) activates the natural immunity by the identification pathogen-associated molecular pattern.The i type transmembrane protein that CD40 is made up of 277 amino acid belongs to tumor necrosis factor receptor super family.Although still there is not the research of this three classes signal path gene and depressive disorder relation at present, because depressive disorder may be relevant with dysimmunity, so they may be relevant with depressive disorder.

Mitogen activated protein kinase (MAPK) signal path is a bars transduction pathway that extensively is present in the various cells, is made up of one group of cascade activatory protein serine/threonine, has the important regulating and controlling effect for operation and the genetic expression of cell cycle.This signal path is relevant with neural plasticity, therefore also thinks to have dependency with depressive disorder.AlttoaA etc. have carried out the cerebral tissue gene chip at the dysthymia disorders animal model and have detected, and find MAPK signal path overexpression in the dysthymia disorders rat cerebral tissue.

In sum, it is main relevant with immunity, internal secretion, somatomedin and transcriptional regulator that the medical diagnosis on disease chip of the SSD that we make up comprises the pairing gene of probe, and these paths are most relevant with depressive disorder in discovering in the past.

The present invention compares with prior art, and its technical progress is conspicuous, and the present invention provides the biology foundation for diagnosing inferior syndrome depression, can be than being easier to and diagnosing fast inferior syndrome depression.

Description of drawings

Fig. 1 is the gene differential expression cluster analysis figure of depressed group of inferior syndrome (SSD) and control group (Control) peripheral blood leucocyte.

Embodiment

The process of 46 gene probes of embodiment 1 screening

1.1 depressed group of inferior syndrome and the examination of normal healthy controls group peripheral blood gene expression chip

Each 8 example of inferior syndrome depressive patient that selection sex and age all mate and normal healthy controls person are taken out peripheral blood 15ml extraction RNA and are carried out the detection of Affymetrix U133plus 2.0 gene expression chips, and this experiment is finished by Shanghai Bai Hao Bioisystech Co., Ltd.

1.2 chip differences expression analysis and cluster analysis

For the variance analysis of chip express spectra data, we adopt the method for multiple test of hypothesis.In analyzing and processing, we handle (MTP) based on the progressively multiple check that resamples and control class I type error rate widely.

Depressed group of inferior syndrome (SSD) and normal healthy controls (Control) group Affymatrix U133plus 2.0 chips are carried out pre-treatment, under the R language environment, adopt MAS5 that the original expression values of chip is carried out background noise and proofread and correct and standardization, make to have comparability between the chip.Difference expression gene to SSD screens then.We adopt the downward general threshold values (maxT) that FWER controlled in the multiple hypothesis testing method of foregoing description to handle and calculate the p value of resetting after proofreading and correct.This processing provides very strong FWER control, also combines the co-ordinative construction of test statistic simultaneously.

By Welch t check calculate maxT handle the rearrangement that obtains uncorrected and proofread and correct after the P value.P value that maxT obtains falling progressively and t statistic, number of times B parameter=10000 of Chong Paiing wherein, we obtain 46 difference expression genes of inferior syndrome depressed group vs. normal healthy controls group (p value＜1e-4).

At differential gene, we find can distinguish accurately sample (patient) by the method for hierarchical clustering.The express spectra that the probe of differential expression is tried in body and the reference group in correspondence in the hierarchical clustering SSD group carries out cluster analysis, and the result shows that these gene probes that screen by multiple test of hypothesis have the ability (as shown in Figure 1) that the pathological state of sample is distinguished.

1.3 determine 46 diagnostic probes

We select SVM (SVMs) that SSD group and Control group data are carried out 10 times of independent cross validations (10CV) test; The self-test result show sample attribute (the inferior depressed group of control group and SSD) all prediction accurately reach 100% based on the SSD model prediction accuracy of 46 selected difference expression gene express spectras.Therefore we determine the target gene chip probe of these 46 pairing probes of difference expression gene for diagnosing chip of the present invention, and Affymetrix probe, the AssayID of detailed 46 target gene chip probes, Gene Symbol and Locus Link see the following form.

ABI AssayID correspondence table in 46 target gene chip probes and the test set data in the training set data:

Test oneself 10CV classification capacity and make up in the model predictive ability referring to as following table-1 and show-2.In addition, the realization of SVM algorithm adopts weka software to realize; Being set to of parameter: C=1.0 wherein, L=0.0010, P=1.0E-12, N=0, V=-1, W=1, and select polynomial kernel function PolyKernel-C 250007-E 1.0.

The training dataset 10CV attributive classification situation of model of testing oneself of table-1.

The training dataset detailed accuracy cartogram of disaggregated model of testing oneself of table-2.

The depressed genetic expression diagnosing chip design of embodiment 2 inferior syndromes

We number transfer to u.s.a. applied biosystem (ABI) company with 46 gene probes, make AB TaqMan low density chip (the Applied Biosystems of 48Assay Format

Low Density Array)--the depressed genetic expression diagnosing chip of----inferior syndrome.This diagnosing chip is made of solid phase carrier, described solid phase carrier is provided with 46 gene probes, the pairing respectively gene of described 46 gene probes is PSMB4, TMBIM6, PNN, CD84, PRKCB, PRKAR2A, KALRN, NRAS, NRAS, CTNS, GCHFR, TERF2, NOP56, SH3YL1, COG3, INPP4A, PURA, GINS4, ZCCHC3, STAT5B, SCFD2, TMEM97, SOCS4, SLC16A3, C19orf6, PIK3AP1, FGD3, VARS, KTI 12, ZNF791, LHX9, NEK8, ZNF785, RHOQ, PA2G4, CCND2, WWP2, CAPRIN1, BRE, MEF2A, SENP1, STRN, ABL1, PDE6B, FDPS, RPL4, described 46 gene probes are matrix form and arrange.In addition, this diagnosing chip also comprises 2 gene probes, corresponding 2 house-keeping gene: 18S of its institute and GAPDH.

The depressed genetic expression diagnosing chip of embodiment 3 inferior syndromes validation verification

For the validity of the diagnosis of verifying chip of the present invention, we have made 100 parts of (entrusting ABI company) invention chips altogether, and have collected SSD patient and each 50 example of normal health person, carry out chip detection of the present invention, and concrete steps are as follows:

3.1 peripheral blood lymphocyte extracts:

The SSD patient that goes into group and each 50 example of normal health person are adopted DSM-IV-TR axle I obstacle fixed pattern clinical examination patient versions, and (Structured Clinical Interview for DSM-IV-TR Axis I Disorders-Patient Edition SCID-I/P) carries out interview.Extract ulnar vein blood 5ml morning on an empty stomach, the high grease food of diet the day before yesterday, 2% EDTA anti-freezing.(GE Sweden) presses product description and separates peripheral blood lymphocyte, is kept at and is sent to Shanghai Bai Hao Bioisystech Co., Ltd among the TRIzol to use Ficoll-PlaqueTM Plus.

3.2 go into to organize the preparation of experimenter's geneome RNA and carry out chip detection of the present invention (finishing) by Shanghai Bai Hao Bioisystech Co., Ltd:

Usually when using TRIzol method extracting total tissue RNA, because the restriction of method, cause the purity drop of total RNA, influence the mark and the chip hybridization of probe.So need to use the further purifying of QIAGEN RNeasy Kit.Measure OD value (OD numerical value is between 1.8-2.1 usually).Afterwards by RNA synthetic dsdna (table-3), and the purifying double-stranded DNA.Then synthesizing biotinylated mark cRNA (table-4), segment cRNA (table 3), hybridization (table 4), and wash-out (table 5), dyeing, scan chip.

Usually when using TRIzol method extracting total tissue RNA, because the restriction of method, cause the purity drop of total RNA, influence the mark and the chip hybridization of probe.So need to use the further purifying of QIAGEN RNeasy Kit.Measure OD value (OD numerical value is between 1.8-2.1 usually).Afterwards by RNA synthetic dsdna (table-3), and the purifying double-stranded DNA.Then synthesizing biotinylated mark cRNA (table-4), segment cRNA (table-5), hybridization (table-6), and wash-out (table-7), dyeing, scanning chip.

Table-3 is by the RNA synthetic dsdna

Table-4

4.1cDNA in-vitro transcription composition

Composition	Volume
		Template DNA	See Table 2
10×IVT?Labeling?Buffer?4μL	4μl
		IVT?Labeling?NTP?Mix	12μl
IVT?Labeling?Enzyme?Mix	4μl
		Add water to final volume	40μl

4.2 the volume of required template DNA (amount by total RNA is calculated)

Total RNA (μ g)	The template DNA volume
		1.0-8.0	12μl
8.1-16.0	6μl

Table-5 segment reactions

Composition	Volume
		20μg?cRNA	1-32μl

5×Fragmentation?Buffer	8μl
		RNase-free water	To 40 μ l

Table-6 hybridization solutions

20 * Eukaryotic Hybridization Controls is frozen, uses preceding 65 ℃ of temperature to bathe 5 minutes

Array	The hybridization volume	Cumulative volume
			Standard	200μl	250μl
Midi	130μl	160μl
			Mini	80μl	100μl
Micro	80μl	100μl

Table-7 wash-outs and dyeing

The elution program of 11 μ m eucaryon chips

The elution program of 〉=18 μ m eucaryon chips

3.3 chip detection of the present invention statistical study as a result:

According to the experiment of foregoing invention chip, obtain 48 expression of gene numerical quantities after every chip detection, 2 house-keeping gene: 18S and GAPDH are wherein arranged.As confidential reference items, we obtain the relative expression quantity increment (delta Ct) of 46 target disease genes according to the probe expression amount numerical value of 18S and GAPDH.The repeating data of each gene probe is made average handle, 46 target gene expression amount data in the output confirmatory experiment.Then, we utilize the sample attribute (be control group or SSD group) of the SSD model prediction of Affymetrix U133plus 2.0 gene expression chip data (obtaining) training acquisition from the individual authentication data set of ABI platform in the process of 46 gene probes of screening; Test data set (from Affymetrix chip express spectra) has identical target gene with individual authentication data set (from the ABI experiment porch).Wherein, the employed machine learning algorithm of classifying quality of checking independent data sets remains the SVM-SVMs identical with making up SSD model step, and the parameter setting is also identical; And the kernel function of selecting for use is the polynomial kernel function, and PolyKernel-C250007-E 1.0.Before realizing the SSD model construction and model being applied to experiment obtains to individual authentication genetic expression numerical classification, we finish 2 analytical procedures respectively: handle the missing values of individual authentication data set (1), and the processing of (2) data normalization.

Missing values to the individual authentication data set is handled: because there is the excalation value in the experiment of ABI individual authentication, we handle missing values; Select the disappearance position of the average expression amount assignment of this gene under the generic sample attribute to current gene expression amount; Although SVM supports to exist the situation of missing values, we consider subsequent normalization.

The processing of data normalization: because two groups of data (test data set and verification msg collection) are respectively from different batches, the different experiments platform), we calculate the Z-Score (all gene variances under (all gene averages under raw value-feature)/feature) of each gene respectively, promptly do two sets of data and carry out stdn (normalization) processing, make two groups of different platform data have comparability.

3.4 result's discriminatory analysis:

This individual authentication at the invention chip found that the SSD prediction accuracy reaches 82.0%.Table-8

Table-8. attributive classification the situation of individual authentication model:

In addition, we utilize the svm classifier device that the individual authentication data set has also been done testing oneself of 10 times of cross validations (Cross-validation), and the classification bat reaches 87.0%.Wherein the control group classification performance reaches 84.0%, and the SSD classifying quality reaches 90.0%.Table-9, table-10.

The 10CV attributive classification situation of the model of testing oneself of table-9 individual authentication data

Correctly?Classified?Instances	87	0.87
			Incorrectly?Classified?Instances	13	0.13
Kappa?statistic	0.74
			Mean?absolute?error	0.13
Root?mean?squared?error	0.3606
			Relative?absolute?error	0.26
Root?relative?squared?error	0.72111
			Total?Number?of?lnstances	100

The test oneself detailed accuracy cartogram of disaggregated model of table-10 individual authentication data sets

Therefore we think that chip of the present invention (the depressed genetic expression diagnosing chip of inferior syndrome) is that effectively its validity is 90.0%.

Claims

1. depressed genetic expression diagnosing chip of inferior syndrome, constitute by solid phase carrier, it is characterized in that: described solid phase carrier is provided with 46 gene probes, described 46 pairing genes of probe are respectively PSMB4, TMBIM6, PNN, CD84, PRKCB, PRKAR2A, KALRN, NRAS, NRAS, CTNS, GCHFR, TERF2, NOP56, SH3YL1, COG3, INPP4A, PURA, GINS4, ZCCHC3, STAT5B, SCFD2, TMEM97, SOCS4, SLC16A3, C19orf6, PIK3AP1, FGD3, VARS, KTI12, ZNF791, LHX9, NEK8, ZNF785, RHOQ, PA2G4, CCND2, WWP2, CAPRIN1, BRE, MEF2A, SENP1, STRN, ABL1, PDE6B, FDPS, RPL4, described 46 gene probes are matrix form and arrange.

2. the depressed genetic expression diagnosing chip of a kind of inferior syndrome as claimed in claim 1 is characterized in that: also be provided with 2 gene probes on the described solid phase carrier, be respectively 18S and GAPDH.

3. the depressed genetic expression diagnosing chip of a kind of inferior syndrome as claimed in claim 1, it is characterized in that: described solid phase carrier is selected from any one in slide glass, silicon chip, acetate film or the cellulose nitrate film.