CN103773880A - Application of substances for detecting rs6461563 site nucleotide in early evaluation of risk of schizophrenia - Google Patents
Application of substances for detecting rs6461563 site nucleotide in early evaluation of risk of schizophrenia Download PDFInfo
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- CN103773880A CN103773880A CN201410044742.4A CN201410044742A CN103773880A CN 103773880 A CN103773880 A CN 103773880A CN 201410044742 A CN201410044742 A CN 201410044742A CN 103773880 A CN103773880 A CN 103773880A
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/156—Polymorphic or mutational markers
Abstract
The invention discloses application of substances for detecting rs6461563 site nucleotide in early evaluation of risk of schizophrenia, and particularly relates to application of substances for detecting rs6461563 site nucleotide in early evaluation of risk of schizophrenia of children and adolescents. The invention has significant application value for preventing and controlling schizophrenia, especially schizophrenia of children and adolescents.
Description
Technical field
The present invention relates to evaluate in early days the application in the ill risk of schizophrenia for detection of the material of rs6461563 site Nucleotide, be specifically related to evaluate in early days the application in the ill risk of children and adolescents schizophrenia for detection of the material of rs6461563 site Nucleotide.
Background technology
Schizophrenia is one group of mental disease that the cause of disease is not bright, the how slow or subacute onset person between twenty and fifty, often show as clinically the different syndrome of symptom, relate to the inharmonious of many-sided obstacles such as sensory perception, thinking, emotion and behavior and cerebration, between individuality, symptom is widely different, even if same patient also may show different symptoms in different steps or stadium.
Schizoid clinical manifestation is as follows:
1, sensory perception obstacle
Can there is multiple sensory perception obstacle in schizophrenia, the most outstanding sensory perception obstacle is illusion, comprise phonism, photis, olfactory hallucination, gustatory hallucination and tactile hallucination etc., and phonism is the most common.
2, the disturbance of thought
The disturbance of thought is schizoid core symptom, mainly comprises form of thought obstacle and content of thought obstacle.Form of thought obstacle, take thinking associative process obstacle as main manifestations, comprises the obstacle of the aspects such as thinking association's active procedure (amount, speed and form), thinking association's continuity and logicality.Vain hope is the most common, most important content of thought obstacle.The vain hope the most often occurring has persecutory delusion, delusion of relation, delusion of influence, delusion of jealousy, the delusion of grandeur, non-descent delusion etc.According to estimates, there is persecutory delusion in the schizophreniac up to 80%, persecutory delusion can show as sense of insecurity in various degree, as be monitored, be ostracised, worry to be offerd medicine or murdered etc., under vain hope impact, patient can make defence or Aggression, in addition, feeling of passivity is also comparatively outstanding with it at some patients were, thinking, emotion and behavior generation impact on patient.
3, affective disorder
Apathy and emotional responses is inharmonious is the modal emotion symptom of schizophreniac, and in addition, the emotion symptoms such as incoordination excitement, irritability, depression and anxiety are also more common.
4, will and behavior disorder
The hypobulia of most of patients even lacks, and shows as movable minimizing, peels off and stay alone, and behavior is passive, lack due enthusiasm and initiative, working and learning interest is gone down, be indifferent to future, to clearly not intending in the future, some patient may have some plans and plan, but seldom carries out.
5, cognition dysfunction
In schizophreniac, the incidence of cognitive defect is high, and cognition dysfunction appears in approximately 85% patient, as cognitive defects such as information processing and selective attention, working memory, short-term memory and study, execution functions.Between cognitive defect symptom and other psychotic symptoms, there is certain dependency, as more obvious in the obvious patient's of form of thought obstacle cognitive defect symptom, the obvious patient's of negative symptoms cognitive defect symptom is more obvious, and cognitive defect may be relevant with the generation of some positive symptom etc.Cognitive defect may betide psychotic symptoms clear before (as prodromal stage), or sharply decline along with the appearance of psychotic symptoms, or along with the course of disease extends and progressively decline, tentatively think that Patients with Chronic Schizophrenia is more obvious than the cognitive defect of first episode schizophrenia.
Schizoid clinical classification is as follows:
1, intolerance style
This is in schizophrenia modal one type, take illusion, vain hope as main clinical manifestation.
2, hebephrenictype
In adolescence morbidity, take significant thinking, emotion and behavior disorder as main manifestations, typical performance is loosening of association, the split of thought, and emotion, behavior reaction naivety, may be with the illusion of fragment, vain hope; It is hyperfunction that some patients were can show as instinctive activity, as appetite, sexual desire enhancing etc.This type patient first-episode age is low, and onset is anxious, and social function is impaired obviously, and general prognosis is not good.
3, catatonic type
Take tension syndrome as main manifestations, patient can show as catatonic sqtupor, waxy flexibility, mechanical words and deeds, and incoordination psychomotor excitement, impulsive action.General this type patient onset is more anxious, and some patients were is alleviated rapidly.
4, simple form
This type is mainly in pubescence morbidity, and the negative symptom of main manifestations is shunk back as unsociable and eccentric, flat affect or indifferent etc.This type result for the treatment of is not good enough, and the decline of patient's social function is obvious, poor prognosis.
5, undifferentiated type
This type has the part feature of above-mentioned certain type, or has above-mentioned various Some features, but is difficult to be included into above-mentioned any type.
6, Residual-type
This type is stage, the change that main manifestations is personality or the decline of social function after schizophrenia acute phase.
External conventional Case definition comprises the classification of diseases of the U.S. and the International Classification of Diseases handbook ICD-10 of DSM DSM-IV-TR, WHO, and domestic conventional Case definition is Chinese Spirit Obstacles classification and Case definition CCMD-3.
Summary of the invention
The object of this invention is to provide for detection of the material of rs6461563 site Nucleotide and evaluate in early days the application in the ill risk of schizophrenia, be specifically related to evaluate in early days the application in the ill risk of children and adolescents schizophrenia for detection of the material of rs6461563 site Nucleotide.
The invention provides the application in preparing product of material for detection of the Nucleotide in rs6461563 site; The function of described product is suffered from schizoid risk for evaluating (particularly EARLY STAGE EVALUATION) or auxiliary evaluation (particularly early stage auxiliary evaluation) people to be measured.
The present invention also provides the application in preparing product of material for detection of the Nucleotide in rs6461563 site; The function of described product is for diagnosing whether (particularly early diagnosis) or auxiliary diagnosis (particularly early stage auxiliary diagnosis) patient to be measured is schizophreniac.
The present invention also protects a kind of product, contains the material for detection of the Nucleotide in rs6461563 site; The function of described product is that EARLY STAGE EVALUATION (particularly EARLY STAGE EVALUATION) or auxiliary evaluation (particularly early stage auxiliary evaluation) people to be measured suffer from schizoid risk.Described product also can comprise and records following (a) or carrier (b): if G allelotrope is carried in the rs6461563 site (a) in people's to be measured genomic dna, it is higher that people to be measured suffers from schizoid risk; If G allelotrope is not carried in the rs6461563 site in people's to be measured genomic dna, it is lower that people to be measured suffers from schizoid risk; (b) if the rs6461563 site in people's to be measured genomic dna is GG genotype or GT genotype, it is higher that people to be measured suffers from schizoid risk; If the rs6461563 site in people's to be measured genomic dna is TT genotype, it is lower that people to be measured suffers from schizoid risk.
The present invention also protects a kind of product, contains the material for detection of the Nucleotide in rs6461563 site; The function of described product is for diagnosing whether (particularly early diagnosis) or auxiliary diagnosis (particularly early stage auxiliary diagnosis) patient to be measured is schizophreniac.
Arbitrary described rs6461563 site specifically can be above: take people's to be measured genomic dna as template, adopt amplified production that special primer obtains amplification from the 44th Nucleotide of 5 ' end; Described special primer forms the single strand dna shown in the sequence 2 of the single strand dna shown in the sequence 1 by sequence table and sequence table.
Arbitrary described " for detection of the material of the Nucleotide in rs6461563 site " is made up of, probe first and probe second special primer above; Described special primer forms the single strand dna shown in the sequence 2 of the single strand dna shown in the sequence 1 by sequence table and sequence table; Described probe first is as shown in the sequence 3 of sequence table; Described probe second is as shown in the sequence 4 of sequence table.
Arbitrary described people to be measured specifically can be children to be measured or teenager to be measured above.
The present invention also protects a kind of test kit of the Nucleotide for detection of rs6461563 site, special primer,, probe first and probe second is made up of; Described special primer forms the single strand dna shown in the sequence 2 of the single strand dna shown in the sequence 1 by sequence table and sequence table; Described probe first is as shown in the sequence 3 of sequence table; Described probe second is as shown in the sequence 4 of sequence table.Described rs6461563 site specifically can be: take people's to be measured genomic dna as template, adopt amplified production that described special primer obtains amplification from the 44th Nucleotide of 5 ' end.
The present invention also protects the as a token of application of thing in the product of exploitation or design or the schizoid ill risk of preparation detection of rs6461563 site.Described rs6461563 site specifically can be: take people's to be measured genomic dna as template, adopt amplified production that described special primer obtains amplification from the 44th Nucleotide of 5 ' end.
The present invention, for the prevention and control of schizoid prevention and control, particularly children and Teenager with Schizophrenia, has great using value.
Embodiment
Following embodiment is convenient to understand better the present invention, but does not limit the present invention.Experimental technique in following embodiment, if no special instructions, is ordinary method.Test materials used in following embodiment, if no special instructions, is and purchases available from routine biochemistry reagent shop.Quantitative test in following examples, all arranges and repeats experiment, results averaged for three times.SNP site is mononucleotide polymorphism site, and each rs site is certain concrete SNP site.Rs6461563 site is positioned at No. 7 karyomit(e) (take human gene group DNA as template, adopt nucleotide sequence that single strand dna shown in the sequence 2 of single strand dna shown in the sequence 1 of sequence table and sequence table carries out the product that pcr amplification obtains specifically can be as shown in the sequence of sequence table 5).Schizoid Case definition is Chinese Spirit Obstacles classification and Case definition CCMD-3, and healthy person is the people who gets rid of relative disease by above-mentioned standard diagnostics.
The association analysis of embodiment 1, rs6461563 site Nucleotide and the ill risk of schizophrenia
For the crowd that carries out association analysis: 1127 of the schizophreniacs that hospital has made a definite diagnosis, 942 of Serious depression patients, 1164 of healthy persons, are the volunteer of informed consent, are Han nationality.
1, get respectively the blood of each individuality, extract genomic dna.
2, the genomic dna extracting take step 1 is template, adopts TaqMan real-time fluorescence PCR to identify rs6461563 site Nucleotide.
Upstream primer (sequence 1 of sequence table): 5'-CAGCACACGGTCTTAGGCTTT-3';
Downstream primer (sequence 2 of sequence table): 5'-CAGAGGAAATCCCAGACATATCACT-3';
TaqMan probe 1(5' → 3', its nucleotides sequence is classified the sequence 3 of sequence table as, for detection of allelotrope G):
FAM-TTCTCACAAGCCGCCT-MGB；
TaqMan probe 2(5' → 3', its nucleotides sequence is classified the sequence 4 of sequence table as, for detection of allelotrope T):
VIC-TTCTCACAAGCCTCCT-MGB。
VIC and FAM are fluorophor.MGB is fluorescent quenching group.
The results are shown in Table 1.
Table 1 detected result
After multiple hypothesis test is proofreaied and correct, find that the gene frequency distribution in rs6461563 site is relevant to schizophrenia (Pallele=0.0033 proofreaies and correct rear Pallele=0.0264).The G allelotrope in rs6461563 site is more common in schizophrenia crowd, may increase schizoid risk.This presentation of results, SP4 gene may be schizophreniac's tumor susceptibility gene, rs6461563 site is associated with schizophrenia, may be the risk site of this disease, or is associated with the risk site of this disease.Can assess or whether auxiliary diagnosis individuality to be measured is schizophreniac the ill risk of the schizophrenia of individuality to be measured by rs6461563 site being carried out to gene type.
Because children and adolescents is schizoid group of people at high risk, the present invention has outstanding value for evaluating the ill risk of children and adolescents schizophrenia.
Claims (10)
1. the application in preparing product for detection of the material of the Nucleotide in rs6461563 site; The function of described product is that evaluation or auxiliary evaluation people to be measured suffer from schizoid risk.
2. the application in preparing product for detection of the material of the Nucleotide in rs6461563 site; The function of described product is whether diagnosis or auxiliary diagnosis patient to be measured are schizophreniac.
3. application as claimed in claim 1 or 2, is characterized in that: described rs6461563 site is: take people's to be measured genomic dna as template, adopt amplified production that special primer obtains amplification from the 44th Nucleotide of 5 ' end; Described special primer forms the single strand dna shown in the sequence 2 of the single strand dna shown in the sequence 1 by sequence table and sequence table.
4. the application as described in claim 1 or 2 or 3, is characterized in that: described " for detection of the material of the Nucleotide in rs6461563 site " is made up of, probe first and probe second special primer; Described special primer forms the single strand dna shown in the sequence 2 of the single strand dna shown in the sequence 1 by sequence table and sequence table; Described probe first is as shown in the sequence 3 of sequence table; Described probe second is as shown in the sequence 4 of sequence table.
5. a product, contains the material for detection of the Nucleotide in rs6461563 site; The function of described product is that EARLY STAGE EVALUATION or auxiliary evaluation people to be measured suffer from schizoid risk.
6. a product, contains the material for detection of the Nucleotide in rs6461563 site; The function of described product is whether diagnosis or auxiliary diagnosis patient to be measured are schizophreniac.
7. the product as described in claim 5 or 6, is characterized in that: described rs6461563 site is: take people's to be measured genomic dna as template, adopt amplified production that special primer obtains amplification from the 44th Nucleotide of 5 ' end; Described special primer forms the single strand dna shown in the sequence 2 of the single strand dna shown in the sequence 1 by sequence table and sequence table.
8. the product as described in claim 5 or 6 or 7, is characterized in that: described " for detection of the material of the Nucleotide in rs6461563 site " is made up of, probe first and probe second special primer; Described special primer forms the single strand dna shown in the sequence 2 of the single strand dna shown in the sequence 1 by sequence table and sequence table; Described probe first is as shown in the sequence 3 of sequence table; Described probe second is as shown in the sequence 4 of sequence table.
9. for detection of the test kit of the Nucleotide in rs6461563 site, by special primer,, probe first and probe second are formed; Described special primer forms the single strand dna shown in the sequence 2 of the single strand dna shown in the sequence 1 by sequence table and sequence table; Described probe first is as shown in the sequence 3 of sequence table; Described probe second is as shown in the sequence 4 of sequence table.
The as a token of application of thing in the product of exploitation or design or the schizoid ill risk of preparation detection of 10.rs6461563 site.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1635142A (en) * | 2003-12-26 | 2005-07-06 | 中国医学科学院基础医学研究所 | Reagent kit for forecasting susceptibility of intolerance type dementia preaecox and primer used thereby |
| CN102146479A (en) * | 2011-04-15 | 2011-08-10 | 上海交通大学 | Primers and probes for detecting genes associated with schizophrenia, bipolar affective disorders and major depression and kits and preparation methods thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1635142A (en) * | 2003-12-26 | 2005-07-06 | 中国医学科学院基础医学研究所 | Reagent kit for forecasting susceptibility of intolerance type dementia preaecox and primer used thereby |
| CN102146479A (en) * | 2011-04-15 | 2011-08-10 | 上海交通大学 | Primers and probes for detecting genes associated with schizophrenia, bipolar affective disorders and major depression and kits and preparation methods thereof |
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