CN105821136A - Personalized genetic typing guidance body building and weight losing method and equipment application thereof - Google Patents
Personalized genetic typing guidance body building and weight losing method and equipment application thereof Download PDFInfo
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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
- C12Q1/6813—Hybridisation assays
- C12Q1/6834—Enzymatic or biochemical coupling of nucleic acids to a solid phase
- C12Q1/6837—Enzymatic or biochemical coupling of nucleic acids to a solid phase using probe arrays or probe chips
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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
- C12Q1/6813—Hybridisation assays
- C12Q1/6827—Hybridisation assays for detection of mutation or polymorphism
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- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
- G16B25/00—ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
Abstract
The invention relates to data related to influences of different kinds of fat intake on obesity and influences of different types of sports on weight reduction and blood glucose reduction in disclosed human genome single nucleotide polymorphism (SNP) data. According to genetic differences between individuals, a method suitable for determining main reasons of obesity and making personalized diet schemes or giving suggestions about lifestyles is built, and the method is applied to development of wearable mobile devices and application software. The invention further relates to preparation and application of genetic chips related to detection. The personalized weight losing and body building schemes can reasonably, efficiently and selectively use modern sports exercise means and diet regulation according to personal gene characteristics, so that individuals achieve the aims of diet regulation and exercise planning more scientifically and more quickly.
Description
Technical field
The present invention relates to a kind of method being suitable for the appropriate dietary regimen of experimenter or life style suggestion, the method, by associated SNP positions genotype and the accumulation computational analysis such as obesity-prone, fat measurement in detection experimenter, determines the weight loss program personalized for experimenter and diet and exercise guide.
Background technology
The investigation report numeral of McKinsey & Co. of the U.S. shows, the whole world is overweight, and (containing obesity) crowd reaches 2,100,000,000, accounts for population in the world 1/3, claims China to become the significant contribution strength of " fat cause ", and meanwhile, the trend of Adolescent Obesity is the most obvious.
Obesity is to ruin the cause of all kinds of wickedness of health.World Health Organization (WHO) (WHO) is thought, obesity is " epidemic diseases " already, and relevant with multiple uninfection, including type ii diabetes, cancer and heart disease.Every year to overweight relevant death toll more than 2,800,000.And occur with it, it is individual, family, the heavy financial burden of society's shared.
Along with the overweight of China and obese people are increasing, not only Direct economic burden increases, and the indirect economy cost that obesity is brought steeply rises especially.Zhang Yongjian points out, obesity becomes out-and-out economic problems already.In the world, from the origin cause of formation, obesity is initially positively related with affluence, but gradually spreads to relative poverty area.Later, the most rich crowd in relative areas of well-being, become fat main force.
Data show, have broken through 100,000,000 populations at the China BMI obese people more than more than 28, and obesity rates has broken through 10%, and urban adult overweight person has broken through 40%, and gathering way of China obese patient alreadys more than Systems in Certain Developed Countries.China has become second-biggest-in-the-world fat state at present, and fat number is only second to the U.S..And the important enemy of the biggest health of obesity, problem of obesity has been not only health problem, has become as great social problem.
According to individual, fat genetic predisposition is set up personalized fat-reducing scheme with the method improving the fat-reducing obtained by the similar scheme not accounting for hereditary information and body weight keeps result accordingly, it would be desirable to a kind of.Need a kind of method being associated by main body metabolic gene type with response diet and/or exercise.
Human genome single nucleotide variations (SNP) data major part disclosed in the magnanimity that international HapMap plan generates relates to disease susceptibility and individual characteristics.Data in terms of disease susceptibility can be applied to instructing individualized disease prevention aspect.And relevant fat intake fat, dissimilar is on fat impact, the data of the different types of movement impact on reducing body weight and blood glucose reduction in magnanimity public data, can potential be applied to exist on the individuality of hereditary difference, make individual more scientific, the more rapid purpose reaching dietary adjustments and exercise plan.
Currently without special detection and diet response and the gene of exercise response related SNP position.Current Wearable mobility device simply instructs quantity of motion and assessment sleeper effect.Do not consider quantity of motion and diet, and the comprehensive health of people is affected by sleep.
Therefore, develop detection and the analysis method of genome polymorphism of a nucleic acid mutation based on biochip, all possible heterozygous variance of specific gene in a large amount of Patient Sample A can be studied quickly and accurately.Coordinate diet guide, absorption or the absorption of fat of sugar can be controlled targetedly, it is easier to reach the effect kept good figure and lose weight.
Summary of the invention
What we developed is a kind of detection and the analysis method of genome polymorphism of nucleic acid mutation based on biochip.The all possible heterozygous variance of specific gene in a large amount of Patient Sample A can be studied quickly and accurately.Qualification, mapping and typing to single nucleotide polymorphisms among whole genome, the research etc. of human mitochondrion 16.6kb genome polymorphism.Unlike other these type of gene chips, other gene chips are full-length genome or for diagnosis cancer susceptibility person etc..Human genome single nucleotide variations (SNP) site on our chip is verified through us, and special detection and diet response and exercise respond the gene pleiomorphism of related SNP position.Meanwhile, after present invention discover that more than 20 SNP, degree of accuracy is higher.
Relevant obesity in human genome single nucleotide variations (SNP) data disclosed in the magnanimity that application international HapMap plan generates, dissimilar fat intake is on fat impact, the data of the different types of movement impact on reducing body weight and blood glucose reduction, according to the hereditary difference between individuality, in conjunction with Wearable mobility device and application software, instruct like to be beautiful exercise plan and dietary adjustments plan personalizedly；According to individual's genetic traits, rationally, effectively, optionally use Modern Physical Education exercise means and cuisines regulation, make individual more scientific, the more rapid purpose method and apparatus reaching dietary adjustments and exercise plan.
Wearer's exercising way is divided three classes: 1, control sugar and take in simultaneously；2, fat intake is controlled；3, positive motion response.Current Wearable mobility device can consider total calorie and the total calorie of absorption consumed when assessing train on.
Summary of the invention summation
The invention discloses a kind of method being suitable for the appropriate dietary regimen of experimenter or life style suggestion, wherein, the method includes extracting nucleic acid from the sample that experimenter obtains, and detect the obesity-prone associated SNP positions in described nucleic acid, fat measurement associated SNP positions, diet response associated SNP positions and the allelotype of exercise response associated SNP positions, by the relatively fat product increasing accumulative risk that comprehensive each SNP site genotype is corresponding, the body weight increment sum that fat measurement associated SNP positions is corresponding, diet or exercise Relevant phenotype are comprehensively analyzed, determine the weight loss program personalized for experimenter and diet and exercise guide.
In the present invention, described sample includes body fluid sample, tissue samples, it preferably includes saliva, blood sample.
In the present invention, described obesity-prone associated SNP positions includes at least one in rs3751812, rs10871777, rs6548238, rs13130484, rs7647305, rs925946, rs4788102, rs6232, rs7566605, rs574367, rs6545814, rs10938397, rs261967, rs4715210, rs9356744, rs6265, rs652722, rs4776970, rs17817449, rs12597579, rs6567160 and rs11671664.
In the present invention, described fat associated SNP positions of measuring includes at least one in rs6548238, rs925946, rs7138803, rs9939609, rs13130484, rs4788102, rs10838738, rs10871777, rs12970134.
In the present invention, described diet response associated SNP positions includes at least one in rs1801282, rs5082, rs662799.
In the present invention, described response associated SNP positions of taking exercise includes at least one in rs9939609, rs1801282, rs1800588, rs4994.
In one embodiment of the invention, the allelotype of described obesity-prone associated SNP positions can be to be the one in allele GG, GT, the TT existed in rs3751812 mode；With the one in allele GG, AG, AA that rs10871777 mode exists；One in allele C C that exists in rs6548238 mode, CT, TT；With the one in allele TT, CT, CC that rs13130484 mode exists；One in allele C C that exists in rs7647305 mode, CT, TT；With the one in allele TT, GT, GG that rs925946 mode exists；With the one in allele AA, AG, GG that rs4788102 mode exists；One in allele C C that exists in rs6232 mode, CT, TT；One in allele C C that exists in rs7566605 mode, CG, GG；With the one in allele TT, GT, GG that rs574367 mode exists；With the one in allele GG, AG, AA that rs6545814 mode exists；With the one in allele GG, AG, AA that rs10938397 mode exists；One in allele C C that exists in rs261967 mode, AC, AA；With the one in allele TT, CT, CC that rs4715210 mode exists；With the one in allele TT, CT, CC that rs9356744 mode exists；With the one of CC, CT, TT in the allele that rs6265 mode exists；One in allele C C that exists in rs652722 mode, CT, TT；With the one in allele AA, AT, TT that rs4776970 mode exists；With the one in allele GG, GT, TT that rs17817449 mode exists；One in allele C C that exists in rs12597579 mode, CT, TT；One in one in allele C C that exists in rs6567160 mode, CT, TT, allele GG, AG, the AA existed in rs11671664 mode.
In one embodiment of the invention, the described fat allelotype measuring associated SNP positions can be to be allele C C, the one in CT, TT existed in rs6548238 mode；With the one in allele TT, GT, GG that rs925946 mode exists；With the one in allele AA, AG, GG that rs7138803 mode exists；With the one in allele AA, AT, TT that rs9939609 mode exists；With the one in allele TT, CT, CC that rs13130484 mode exists；With the one in allele AA, AG, GG that rs4788102 mode exists；With the one in allele GG, AG, AA that rs10838738 mode exists；With the one in allele GG, AG, AA that rs10871777 mode exists；With the one in allele AA, AG, GG that rs12970134 mode exists.
In one embodiment of the invention, the allelotype of described diet response associated SNP positions can be to be the one in allele GG, CG, the CC existed in rs1801282 mode；With the one in allele GG, AG, AA that rs5082 mode exists；With the one in allele AA, AG, GG that rs662799 mode exists.
In one particular embodiment of the present invention, the allelotype of described diet response associated SNP positions has a following phenotype:
1) in allele GG, CG, CC that rs1801282 mode exists, GG or CG shows that low-fat diet may cause waistline to increase, unsaturated fatty acids in diet is possible to prevent waistline to increase and may cause reducing body weight, and CC shows that in diet, high unsaturated fatty acids seems do not reduce beneficial to BMI or prevent waistline from increasing；
2) in allele GG, AG, AA that rs5082 mode exists, wherein GG shows that high saturated fat diet can increase fat probability, low saturated fat diet will not increase fat probability, AG or AA shows the relevant high saturated and low saturated fat diet of the fat probability of typical case；
3) in allele AA, AG, GG that rs662799 mode exists, AA shows that high fat diet relevant higher BMI, AG or GG show that food fat consumes uncorrelated BMI change.
In one embodiment of the invention, the described allelotype tempering response associated SNP positions can be to be the one in allele AA, AT, the TT existed in rs9939609 mode；With the one in allele GG, CG, CC that rs1801282 mode exists；One in allele C C that exists in rs1800588 mode, CT, TT；With the one in allele AA, AG, GG that rs4994 mode exists.
In one particular embodiment of the present invention, the described allelotype tempering response associated SNP positions has a following phenotype:
1) in allele AA, AT, TT that rs9939609 mode exists, AA shows to tend to the people of high BMI, and taking exercise is correlated with is greatly reduced BMI, AT shows to tend to the people of typical case BMI, temper the relevant BMI, TT of typically reducing and show to tend to the people of relatively low BMI, take exercise and slightly reduce BMI；
2) in allele GG, CG, CC that rs1801282 mode exists, GG or CG shows to take regular exercise and improves glucose-tolerant, and CC shows to take regular exercise and changes glucose-tolerant hardly；
3) in allele C C that exists in rs1800588 mode, CT, TT, CC or CT shows that tempering relevant 5% improves insulin sensitivity, and TT shows to take exercise and uncorrelated improves insulin sensitivity；
4) in allele AA, AG, GG that rs4994 mode exists, AA shows, by walking, reduce energy absorption and increase physical exertion, relevant reduction body weight, AG or GG shows, by walking, reduce energy absorption and increase physical exertion, uncorrelated reduction body weight.
Present invention also offers a kind of gene chip for instructing body-building and weight-reducing, wherein, described gene chip includes solid phase carrier and is fixed on this solid phase carrier the specific oligonucleotide probe for SNP site detection, and described SNP site is obesity-prone associated SNP positions, the fat allelotype measured associated SNP positions, diet response associated SNP positions and temper response associated SNP positions.
In the gene chip of the present invention, described obesity-prone associated SNP positions includes at least one in rs3751812, rs10871777, rs6548238, rs13130484, rs7647305, rs925946, rs4788102, rs6232, rs7566605, rs574367, rs6545814, rs10938397, rs261967, rs4715210, rs9356744, rs6265, rs652722, rs4776970, rs17817449, rs12597579, rs6567160, rs11671664.
In the gene chip of the present invention, described fat associated SNP positions of measuring includes at least one in rs6548238, rs925946, rs7138803, rs9939609, rs13130484, rs4788102, rs10838738, rs10871777, rs12970134.
In the gene chip of the present invention, described diet response associated SNP positions includes at least one in rs1801282, rs5082, rs662799.
In the gene chip of the present invention, described response associated SNP positions of taking exercise includes at least one in rs9939609, rs1801282, rs1800588, rs4994.
The invention also discloses a kind of for instruct body-building and weight-reducing such as the present invention in the preparation method of gene chip, wherein, concrete steps include:
(1) by solid phase carrier pretreatment, microscope slide chromic acid lotion is washed, soaked overnight, washing, in the immersion of 20%-25% ammonia overnight, washing, is then immersed in the ethanol solution of aminopropyl trimethoxysilane, with glacial acetic acid regulation pH value to 4.0-6.0, EtOH Sonicate cleans, drying 4-5 hour, glutaraldehyde aldehyde radicalization processes, stand-by；
(2) artificial synthetic oligonucleotide's chip probe, wherein every oligonucleotide chip probe 5 ' ends when synthesis are modified through amino group；
(3) being dissolved in sampling liquid by above-mentioned each oligonucleotide chip probe, during point sample, every some point sample volume is about 0.4-0.6mL, and point sample spacing is 500-600 μm, point sample a diameter of 200-300 μm, and every probe repeats point sample 2-3 time；Room temperature is placed 24-26 hour cured and get final product.
The invention provides a kind of test kit, wherein, described test kit comprises the gene chip as described in any one of claim 13-17, and described test kit also includes PCR buffer, MgC12, dNTPmix and the Taq enzyme used by PCR amplification.
The invention also discloses the hardware device of the application program using the method being suitable for the appropriate dietary regimen of experimenter or life style suggestion of the present invention, wherein said application program is arranged in described hardware device.
In the present invention, at least one during described hardware device includes mobile phone, computer, Wearable mobility device, implantable devices or a combination thereof.
The invention provides the method using heretofore described hardware device to carry out health control, wherein, including step: the data that typing or reception are corresponding for SNP in being suitable for the method for the appropriate dietary regimen of experimenter or life style suggestion as described in the present invention in described hardware device；Described application program data based on typing and reception are that user comprehensively analyzes diet, exercise program；The data such as typing or reception user's real time kinematics situation, body weight, diet in described hardware device further；Described application program gives analyze and feed back health status.
The beneficial effect of the invention:
Make use of the data of world HapMap full-length genome correlation research plan；Rather than the selective data on genetics of classics, and systems biology global analysis chain from functional genomics calculates individual obesity-prone risk, individuality reduces the potentiality of body weight, impact and the individual exercises of whose body weight are moved to body weight control effect by diet.It is contemplated that the study on classics conclusion of physiology, biochemistry, molecular biology and threpsology, functional genomics is chain and the result precision of systems biology Whole genome analysis and reliability higher.Specifically include:
(1) gene chip for fitness guidance that the present invention provides provides each related gene polymorphism detecting system and algorithm, can quickly, accurately detect gene-correlation SNPs in sample to be tested, highly sensitive, wherein more than after 20 SNP, degree of accuracy is higher, there is important meaning for scientific guidance fitness, can be widely used for each crowd.
(2) this gene loci applies the data of world HapMap full-length genome correlation research plan, includes each race's conserved site (3) PCR primer specificity good, can ensure the success rate of experiment well.
(4) automaticity is high, it is simple to popularization and application.
(5) this test kit has stable, reliable, low price, advantage faster.
Accompanying drawing explanation
Fig. 1 is to illustrate the figure of relation between degree of accuracy and SNP quantity in the assessment of polygenes complex character.
Fig. 2 is to illustrate the figure of SNP site related gene correspondence obesity-prone relative risk in experimenter 1.
Fig. 3 is to illustrate the figure of SNP site related gene correspondence obesity-prone relative risk in experimenter 2.
Fig. 4 is to illustrate the figure of SNP site related gene correspondence obesity-prone relative risk in experimenter 3.
Detailed description of the invention
Below by detailed description of the invention and experimental data, the present invention is further illustrated.Although for purposes of clarity, proprietary term used below, but these terms are not meant to definition or limit the scope of the present invention.
As used herein, term " allele " refers to be positioned at the one pair of genes controlling relative character in the same position of pair of homologous chromosome.It possibly be present in the two or more genes in chromosome particular seat.
As used herein, term " BMI " (body-mass index) is a kind of based on height and body weight and the metering of the body fat being applicable to masculinity and femininity.When BMI is between 18.5-24.9, it is believed that BMI belongs to " typical " scope.According to this present invention, the BMI ＜ 18.5 of underweight main body；The BMI of one overweight main body between 25-29.9, the BMI of a fat main body between 30-39.9, BMI be the main body of 40 or bigger be considered as extreme obese.
As used herein, term " increase risk " refers to the statistical frequency that disease or situation occur in a main body carrying a kind of specific polymorphic allele and the frequency ratio of this disease or situation occurs relatively in a number of crowd not carrying this specific polymorphic allele.
Term used in the present invention " nucleic acid ", refers to polynucleotide or oligonucleotide, such as DNA (deoxyribonucleic acid) (DNA), and, in the appropriate case, ribonucleic acid (RNA).This word, it can be appreciated that include, as the analog of the equivalent of RNA or DNA prepared by nucleotide analog, and is applicable to list (justice or antisense) and the double stranded polynucleotide of embodiment of the present invention.
Term used in the present invention " SNP " refers to single nucleotide polymorphism (singlenucleotidepolymorphism), is primarily referred to as in genomic level the DNA sequence polymorphism caused by the variation by single core thuja acid.Polymorphism refers to a kind of gene or its fragment is multiple coexists (e.g., allelic variation) with more than one form.The fragment of one gene with at least two multi-form (e.g., two kinds of different nucleotide sequences), at least a part of which has two kinds of different forms, i.e. two different nucleotide sequences, be known as " a gene pleiomorphism region ".A specific gene order in a gene polynorphisms region is an allele.One polymorphic regions can be a mononucleotide, the feature of different allelic differences.One polymorphic regions, it is possibility to have several nucleotide are long.
Experimental technique in following embodiment, if no special instructions, is conventional method.
Specific embodiment:
The corresponding phenotype of allele of embodiment 1SNP
The data that world HapMap full-length genome correlation analysis (GWAS, GenomeWideAssociationStudy) plans are the most imperfect, just tend to complete, can carry out character assessment after 2014.This analysis is by extracting disease group individual (thousands of example) and the genomic DNA of normal group individual (thousands of example), utilize gene chip that each example is done full-length genome snp analysis, find out by statistical method and between two groups, have dramatically different SNP site, thus the cause of disease of disease is positioned in those SNP site, and the gene of those SNP is probably " tumor susceptibility gene " site of disease.Reselection independent sample is verified, best samples up to ten thousand.Finally determine that gene relevant for those SNP is disease " tumor susceptibility gene.Here the SNP site arranging acquisition is the site that at least two independent studies obtains repeating.
nullIt is analyzed according in human genome single nucleotide variations (SNP) data disclosed in the magnanimity that HapNap full-length genome correlation research plan in the world generates，In conjunction with obesity relevant in magnanimity public data、Dissimilar fat intake is on fat impact、The data of the different types of movement impact on reducing body weight and blood glucose reduction，And systems biology global analysis chain from functional genomics calculates individual obesity-prone risk、The individual potentiality reducing body weight、Impact and the individual exercises of whose body weight are moved to body weight control effect by diet，I.e. arrange the corresponding phenotype of allele obtaining SNP，And sort data into as obesity-prone associated SNP positions、Fat measurement associated SNP positions、Diet response associated SNP positions and exercise respond allelotype and the phenotype of correspondence thereof of associated SNP positions.OR value corresponding to each of which rs is calculated by the Testing Association in GWAS.The allele correspondence phenotype of concrete SNP refers to table 1 to table 4.
The corresponding phenotype of allele of table 1 obesity-prone associated SNP positions
The fat corresponding phenotype of allele measuring associated SNP positions of table 2
The corresponding phenotype of allele of table 3 diet response associated SNP positions
The corresponding phenotype of allelotype of response associated SNP positions tempered by table 4
It addition, the present invention finds, the assessment of polygenes complex character is in logarithmic relationship between degree of accuracy and SNP quantity, increases check and evaluation precision with SNP quantity and be greatly improved, as shown in Figure 1.
Meanwhile, 31 SNP lists in the present invention, the SNP of cross occurrence in analyzing including various trait.It is contemplated that physiology, biochemistry, the study on classics conclusion of molecular biology and threpsology, data results according to world HapMap full-length genome correlation research plan, it is rational and inevitable that minority single nucleotides variation (SNP) duplicates in various trait, but they risks and assumptions in various trait and functional effect are different, it might even be possible to the most contrary.Sharing 31 SNPs in the present invention, wherein 24 do not intersect；Wherein 7 have intersection (as shown in table 5) in various trait, and they risks and assumptions in various trait and functional effect can be different.
31 SNP lists in table 5 present invention, the SNP of cross occurrence in analyzing including various trait
Embodiment 2SNP gene chip, the preparation method of test kit and using method
The design principle of the gene chip being applied to vigorous and graceful guidance is, it includes solid phase carrier and is fixed on this solid phase carrier for responding with obesity-prone, the individual body weight that reduces at potentiality, diet and temper the specific oligonucleotide probe of response related gene mononucleotide polymorphism site detection, and related gene mononucleotide polymorphism site is:
With obesity-prone risk related SNP s
Body weight potentiality related SNP s is reduced with individuality
The gene SNP s relevant with diet response
The gene SNP s relevant with tempering response
Related gene mononucleotide polymorphism site, devises one group of oligonucleotide probe, the nucleotide sequence of described oligonucleotide probe, is specifically shown in Table 6:
Table 6 is for the sequence oligonucleotide probe of the gene chip of body weight control
By such scheme, described solid phase carrier is nitrocellulose filter, nylon membrane or microscope slide, and described solid phase carrier makes its surface with can be with the active group of immobilized nucleic acid molecule through different chemical modifications.The solid phase carrier that the gene chip of the present invention is used is selected from any material that can be used for preparing gene chip, include but not limited to nitrocellulose filter, nylon membrane or microscope slide, described solid phase carrier is through different chemical modifications, on its surface with can be with the active group of immobilized nucleic acid molecule such as aldehyde radical (-CHO) etc..
Based on above scheme, making is for the gene chip of body weight control, first,
(1) by solid phase carrier pretreatment, stand-by；
(2) according to the probe sequence designed by table 6, as shown in SEQIDNo.1-31, synthetic every oligonucleotide chip probe；
(3) being dissolved in sampling liquid by above-mentioned each oligonucleotide chip probe, point sample solidifies and get final product.
By such scheme, described solid phase carrier is microscope slide, and described pretreatment is to be washed by microscope slide chromic acid lotion, soaked overnight, washing, in the immersion of 20%-25% ammonia overnight, washing, it is then immersed in the ethanol solution of aminopropyl trimethoxysilane, with glacial acetic acid regulation pH value to 4.0-6.0, EtOH Sonicate cleans, and dries 4-5 hour, and glutaraldehyde aldehyde radicalization processes.
By such scheme, described every oligonucleotide chip probe 5 ' ends when synthesis are modified through amino group.During point sample, every some point sample volume is about 0.4-0.6mL, and point sample spacing is 500-600 μm, point sample a diameter of 200-300 μm, and every probe repeats point sample 2-3 time；Described cured is that room temperature places solidification in 24-26 hour.
Process prepared by sample, also includes the amplification of DNA sample.By such scheme, described DNA sample amplification kit also includes PCR buffer, MgC12, dNTPmix and the Taq enzyme used by PCR amplification.
Above-mentioned for the using method of gene chip instructed of losing weight, specifically include following steps:
(1) preparation of sample to be tested:
1. sample DNA is extracted；
2. use PCR method that DNA is expanded；
3. confirm through electrophoresis detection after PCR terminates, then reclaim purpose fragment band；
(2) fluorescein labelling
Fluorescent labeling is carried out to step 1 reclaims the purpose fragment obtained；
(3) chip hybridization experiment
Purpose fragment correspondence after labelling in step 2 is added drop-wise on gene chip, hybridizes with the oligonucleotide chip probe being fixed on said gene chip, then carry out carrying out washing treatment；
Scanning and result judge, scanning analysis obtains hybridization signal, it is determined that obtain result.
The fat analysis of causes of embodiment 3 experimenter 1 and motion diet guide
(1) sample DNA is extracted；
Can extract according to this area conventional method, sample behaviour saliva, the present invention uses saliva DNA extraction kit to extract a middle age micro-fat women saliva；
(2) use primer that DNA sample is expanded.Preparation 50u following PCR reaction system, and according to following reaction condition, carry out PCR amplification respectively.
PCR reaction system
| Component and concentration thereof | The addition of each component |
| 10×PCR Buffer | 5μl |
| MgCl2 | 3μl |
| dNTP mix(10mmol/μl) | 1μl |
| Forward primer, 10pmol/ μ l | 1μl |
| Downstream primer, 10pmol/ μ l | 1μl |
| Taq enzyme (10U/ μ l) | 0.5μl |
| Blood or saliva DNA | 1μl |
| H2O | 37.5μl |
| Cumulative volume | 50μl |
PCR reaction condition
(3) PCR amplification respectively takes product 5 μ l after terminating, and mass volume ratio is the agarose gel electrophoresis detection observation confirmation of 1%.Then use hundred Tyke DNA to reclaim test kit PCR primer is purified, reclaim purpose fragment.
(4) fluorescein labelling
By the purpose fragment of recovery in 25 μ l (potassiumcacodylate) Han 200mM potassium cacodylate, 25mMTris-HC1 buffer (pH7.2), 1mM cobalt dioxide (CoC12), 0.01% Triton X-100 (TritonX-100, v/v), in the labelling system of 20 μMs of Cy3-dCTP (20U) Deoxydization nucleotide terminal transferases, 37 DEG C of fluorescein labellings 1 hour.
(5) hybridization
It is added drop-wise to gene chip surface by corresponding with after the mixing of hybridization solution equal-volume respectively for the DNA cloning product after fluorescein labelling i.e. sampling liquid 2 μ l, hybridization solution is 5 × SSC (0.5wt%SDS, 50% (v/v) Methanamide), add coverslip, be then placed in hybridizing box 65 DEG C and hybridize 6 hours.
(6) washing
Develop a film with the solution of final concentration of 2 × SSC+0.2wt%SDS, each 2 minutes, then rinse 2 times with 2 × SSC, each 2 minutes, finally clean 2 times with tri-distilled water, each 2 minutes, then with the centrifugation 5 minutes of 1000 revolutions per.
(7) result detection and analysis
By scanner scanning: reasonable set laser intensity, photomultiplier tube (PMT) parameter.
The fluorescence intensity level of scanogram is analyzed with quantitative analysis software.Use the standardized method of gene chip according to each probe hybridization signal, and cluster (Cluster) method judges results of hybridization, i.e. draws the allelotype of SNP site.Testing result applies our HapMap large database concept qualitatively and quantitatively to analyze, and obtains relative risk (OR), is calculating synthetic risk rate (OR).Finally combine the average risk rate in crowd's correspondence site, carry out comprehensive assessment.
By genechip detection obesity-prone associated SNP positions, the fat allelotype measured associated SNP positions, diet response associated SNP positions and temper response associated SNP positions, in synopsis 1 to 4, the concrete phenotype of display, draws the data of this experimenter self.And data are analyzed.
(8) obesity-prone risk analysis is as shown in Fig. 2 and Biao 7.
Wherein the sickness rate (%) of colony's average risk=Chinese population, is 5%, and these data are from World Health Organization (WHO) WHO Epidemiological study result.
The computing formula of accumulative risk is: accumulative risk=OR1×OR2×OR3×OR4×…×ORn, wherein n is the number of SNP site, ORnFor the relative risk that each SNP is corresponding.
The sickness rate (%) of person under inspection's risk=person under inspection's accumulative risk rate × Chinese population.
Y-axis is risk index Beta value as shown in Figure 2, wherein Beta=Loge(OR), so OR and Beta value can convert.
The obesity-prone associated SNP positions genotype of table 7 experimenter 1 and risk analysis
OR=2.96 risk increases
Colony's average risk 5.0%
The risk 14.8% of this experimenter
The gene of increase risk of obesity: FTO on No. 16 chromosomes, fat mass and fat associated protein.
The gene of reduction risk of obesity: BDNF on No. 11 chromosomes, Brain Derived Neurotrophic Factor.
Conclusion: obesity-prone risk increases, and relevant with fat mass and 2 Mutations of leptin (FTO) gene-correlation, the linkage disequilibrium of possible FTO gene causes potential obesity-prone to increase.
Simultaneously, the present invention also provide a comparison the data of " 23andMe " test kit, with " 23andMe " test kit, the sample of experimenter 1 has been carried out obesity-prone risk analysis, found that (table 8), the accumulative risk only 1.42 of this test kit detection, the substantially less than result 2.96 of the present invention.And experimenter's in fact vivo carrying FTO gene, and the middle age is micro-fat, is badly in need of sensitiveer method pointing out.So, the method for multiple SNP Cooperative Analysis of the present invention is better than prior art, can analyze experimenter's obesity-prone risk more delicately.
Table 8 obesity-prone risk analysis (data of 23andMe)
(9) fat measurement is analyzed, and is shown in Table 9.
Each increased weight is corresponding Beta value, the increased weight of increased weight sum=corresponding for each SNP of ∑.
The reduction body weight potential ability of table 9 experimenter 1-obesity is measured and is analyzed
With relevant gene of putting on weight: GNPDA2 on No. 4 chromosomes, glucose 6 phosphatase.
The gene relevant with reducing body weight: BDNF-AS on No. 11 chromosomes, Brain Derived Neurotrophic Factor antisense RNA；BCDIN3D-RPL35AP28 on No. 12 chromosomes, containing BCDIN3 domain RNA transmethylase/ribosomal protein L 35a pseudogene 28；No. 16 chromosome SH2B1/NPIPB8, connect albumen/nuclear Pore Complex interaction protein family member B8.
Conclusion: the probability (depending on stature height) that more general Adults is about 5.50 pounds.
(10) temper response, be shown in Table 10.
The exercise associated SNP positions genotype of table 10 experimenter 1 and analysis
PPARG on No. 3 chromosomes, peroxisome proliferation-activated receptors；
ADRB3, adrenoreceptor B3 on No. 8 chromosomes；
FTO on No. 16 chromosomes, fat mass and fat associated protein；
LIPC, liver esterase C on No. 15 chromosomes.
(11) diet response, is shown in Table 11.
The diet associated SNP positions genotype of table 11 experimenter 1 and analysis
PPARG on No. 3 chromosomes, peroxisome proliferators activated receptor γ；
APOA5 on No. 11 chromosomes, ApoA5；
APOA2 on No. 1 chromosome, ApoA2.
Comprehensively analyze prompting: owing to the susceptibility risk of the potential obesity of experimenter 1 is mainly relevant with ob gene (FTO) with fat, obesity-prone risk is higher.High fat diet is correlated with higher Body Mass Index (BMI).But there is the potential of more general Adults about 5.5 pounds.
Measure 1: control the absorption of fat.In diet, high unsaturated fatty acids seems not reduce body weight to be beneficial to, and can not prevent waistline from increasing.
Measure 2: by walking, reduces energy absorption and increases physical exertion, being correlated with and reduce body weight.And, strengthen tempering relevant 5% and improve insulin sensitivity, taking exercise is correlated with typically reduces obesity about 8 pounds (5 feet of 7 inches of high individuals).
The fat analysis of causes of embodiment 3 experimenter 2 and motion diet guide
Experimenter 2 is a young women, and build is the thinnest, and sample extraction is identical with step (1)-(7) in embodiment 2 with detection method.Analysis result is as shown in following table 12-16.
(1) obesity-prone risk analysis, as shown in Fig. 3 and Biao 12.
Wherein the sickness rate (%) of colony's average risk=Chinese population, is 5%, and these data are from World Health Organization (WHO) WHO Epidemiological study result.
The computing formula of accumulative risk is: accumulative risk=OR1×OR2×OR3×OR4×…×ORn, wherein n is the number of SNP site, ORnFor the relative risk that each SNP is corresponding.
The sickness rate (%) of person under inspection's risk=person under inspection's accumulative risk rate × Chinese population.
Y-axis is risk index Beta value as shown in Figure 2, wherein Beta=Loge(OR), so OR and Beta value can convert.
The obesity-prone associated SNP positions genotype of table 12 experimenter 2 and risk analysis
Obesity-prone relative risk OR=0.86 normality risk
Colony's average risk 5.0%
The risk 4.3% of experimenter 2
Increase the gene of risk of obesity: there is no；
Reduce the gene of risk of obesity: there is no.
Conclusion: obesity-prone risk is similar to normal population.
Simultaneously, the present invention also provide a comparison the data of " 23andMe " test kit, with " 23andMe " test kit, the sample of experimenter 2 has been carried out obesity-prone risk analysis, found that (table 13), the accumulative risk of this test kit detection is 1.09, higher than the result 0.86 of the present invention.And experimenter's in fact build is the thinnest, 0.86 represents the build that experimenter belongs to thinner than normal population, does not has necessity of fat-reducing, and the test value of " 23andMe " test kit is higher than the present invention, and higher than the average level of crowd, belongs to the most fat.It is not inconsistent with the practical situation of experimenter.Therefore, illustrate that the method applied in the present invention is better than prior art, experimenter's obesity-prone risk can be analyzed more delicately, and more conform to practical situation.
Table 13 obesity-prone risk analysis (data of 23andMe)
(2) fat measurement is analyzed
The fat of table 14 experimenter 2 measures associated SNP positions genotype and analysis
With relevant gene of putting on weight: MC4R on No. 18 chromosomes, black cortin 4 receptor.
The gene relevant with reducing body weight:
BDNF-AS on No. 11 chromosomes, Brain Derived Neurotrophic Factor antisense RNA；
FTO on No. 16 chromosomes, fat mass and fat associated protein.
The probability (depending on stature height) that more general Adults is about 4 pounds.
(3) response analysis is tempered
The exercise associated SNP positions genotype of table 15 experimenter 2 and analysis
PPARG on No. 3 chromosomes, peroxisome proliferation-activated receptors；
ADRB3, adrenoreceptor B3 on No. 8 chromosomes；
FTO on No. 16 chromosomes, fat mass and fat associated protein；
LIPC, liver esterase C on No. 15 chromosomes.
(4) diet response analysis
The diet associated SNP positions genotype of table 16 experimenter 2 and analysis
PPARG on No. 3 chromosomes, peroxisome proliferators activated receptor γ；
APOA5 on No. 11 chromosomes, ApoA5；
APOA2 on No. 1 chromosome, ApoA2.
Comprehensively analyze prompting: the risk of the susceptibility risk of the potential obesity of experimenter 2 and normal population is known each other.And there is the potential of more general Adults about 4.0 pounds.Food fat consumes uncorrelated Body Mass Index (BMI) change.
Measure 1: in food, unsaturated fatty acids seems not reduce helpful to Body Mass Index, and nor affecting on waistline increases.
Measure 2: by walking, reduces energy absorption and increases physical exertion, being correlated with and reduce body weight.And, strengthen tempering relevant 5% and improve insulin sensitivity, taking exercise is correlated with typically reduces obesity about 5 pounds (5 feet of 7 inches of high individuals).
The fat analysis of causes of embodiment 4 experimenter 3 and motion diet guide
Experimenter 2 is that a young women, sample extraction and detection method are identical with step (1)-(7) in embodiment 2.Analysis result is as shown in following table 17-21:
The obesity-prone associated SNP positions genotype of table 17 experimenter 3 and risk analysis
OR=1.38 risk has increased slightly
Colony's average risk 5.0%
The risk 6.9% of this experimenter
The gene of increase risk of obesity: MC4R on No. 18 chromosomes, black cortin 4 receptor.
Reduce the gene of risk of obesity: there is no.
Conclusion: client's obesity-prone risk is slightly higher, relevant with black cortin 4 acceptor gene related locus variation.
Meanwhile, the present invention also provide a comparison the data of " 23andMe " test kit, with " 23andMe " test kit, the sample of experimenter 2 has carried out obesity-prone risk analysis (table 18).
Table 18 obesity-prone risk analysis (data of 23andMe)
(9) fat measurement is analyzed, and is shown in Table 19.
The reduction body weight potential ability of table 19 experimenter 3 and fat measurement are analyzed
Dramatically increase the gene that body weight is relevant: MC4R on No. 18 chromosomes, black cortin 4 receptor.
Significantly reduce the gene that body weight is relevant:
BDNF-AS on No. 11 chromosomes, Brain Derived Neurotrophic Factor antisense RNA；
FTO on No. 16 chromosomes, fat mass and fat associated protein；
TMEM18 on No. 2 chromosomes, membrane-spanning protein 18；
BCDIN3D/RPL35AP28 on No. 12 chromosomes, containing BCDIN3 domain territory RNA transmethylase/ribosomal protein L 35a pseudogene 28；
The probability (depending on stature height) that more general Adults is about 8 pounds.
Conclusion: the probability (depending on stature height) that more general Adults is about 5.50 pounds.
(10) temper response, be shown in Table 20.
The exercise associated SNP positions genotype of table 20 experimenter 3 and analysis
PPARG on No. 3 chromosomes, peroxisome proliferation-activated receptors；
ADRB3, adrenoreceptor B3 on No. 8 chromosomes；
FTO on No. 16 chromosomes, fat mass and fat associated protein；
LIPC, liver esterase C on No. 15 chromosomes.
(11) diet response, is shown in Table 21.
The diet associated SNP positions genotype of table 21 experimenter 3 and analysis
PPARG on No. 3 chromosomes, peroxisome proliferators activated receptor γ；
APOA5 on No. 11 chromosomes, ApoA5；
APOA2 on No. 1 chromosome, ApoA2.
Comprehensively analyze prompting: the susceptibility risk of the potential obesity of client is the most relevant with black cortin 4 acceptor gene related locus variation, and obesity-prone risk has increased slightly.High fat diet is correlated with higher Body Mass Index (BMI).But there is the potential of more general Adults about 8.0 pounds.
Feature: control the absorption of fat, in diet, high unsaturated fatty acids seems not reduce body weight to be beneficial to, and can not prevent waistline from increasing.
Measure: by walking, reduces energy absorption and increases physical exertion, being correlated with and reduce body weight.And, strengthen tempering relevant 5% and improve insulin sensitivity.Client is for tending to the people of relatively low Body Mass Index (BMI), and taking exercise is correlated with typically reduces obesity about 5 pounds (5 feet of 7 inches of high individuals).
Embodiment 5 hardware device and health control method
Data inputting or reception
Hardware device includes such as mobile phone, computer, wearable device, implantable devices etc., is provided with personalization gene type of the present invention and instructs the application program of ways of preventing obesity in this hardware device.The wearable device meeting related needs of the present invention can be to be more than one or a combination thereof in the forms such as Intelligent bracelet, wrist-watch, ring, necklace, glasses, heart rate band.
The amount of physical memory of the built-in certain capacity of described hardware device, and can have wired connection interface, the microUSB data-interface etc. that such as electronic product is conventional at present.
Before using, the test kit of the present invention is used to detect the SNP in the body fluid sample of user, it is thus achieved that corresponding data.Then, user can directly enter to described hardware device or Bluetooth data transfer module receives above-mentioned data.
Data analysis and output
Aggregation of data based on typing and the reception analysis of described application program, specifies the recommendation of dietary program, meals, exercise program for user and provides body weight to keep skill；
Data typing again or reception
User, based on specifying dietary program, exercise program etc., carries out body-building.The mobile phone of application program of ways of preventing obesity, computer, wearable device etc. can be instructed by being provided with personalization gene type of the present invention, the parameters such as full-time monitoring, data inputting or reception individual daily relevant body weight, motion, body temperature, diet information, as tempered the essential informations such as distance, diet sugar, fat consumption.The related datas such as individual human diet, motion are carried out actively by hardware device user, and typing mode includes the various ways such as word and photo.
Wherein, wearable device can include that with other smart machines the devices such as smart mobile phone, Intelligent flat computer or personal computer have the equipment of Bluetooth communication modules and corresponding software to carry out data transmission, can also be connected by wireless network and carry out communication, or by microUSB interface wired connection transmission data etc..
Data analysis and feedback
The diet of input, movable information can be analyzed by the application program in hardware device, propose the feedback to body-building and weight-reducing schemes such as current diet motions and advise.
The hardware device of the application program instructing ways of preventing obesity based on personalization gene type of the present invention of the present invention, and health control method is not limited to above-described embodiment, can carry out multiple modification.In a word, both falling within the scope of the invention without departing from all improvement in scope of the present invention.
Claims (22)
1. the method being suitable for the appropriate dietary regimen of experimenter or life style suggestion, wherein, the method includes extracting nucleic acid from the sample that experimenter obtains, and detect the obesity-prone associated SNP positions in described nucleic acid, fat measurement associated SNP positions, diet response associated SNP positions and the allelotype of exercise response associated SNP positions, by the relatively fat product increasing accumulative risk that comprehensive each SNP site genotype is corresponding, the body weight increment sum that fat measurement associated SNP positions is corresponding, diet or exercise Relevant phenotype are comprehensively analyzed, determine the weight loss program personalized for experimenter and diet and exercise guide.
The most described sample includes body fluid sample, tissue samples, it preferably includes saliva, blood sample.
null3. the method as described in any one of claim 1-2，Wherein，Described obesity-prone associated SNP positions includes rs3751812、rs10871777、rs6548238、rs13130484、rs7647305、rs925946、rs4788102、rs6232、rs7566605、rs574367、rs6545814、rs10938397、rs261967、rs4715210、rs9356744、rs6265、rs652722、rs4776970、rs17817449、rs12597579、At least one in rs6567160 and rs11671664.
4. the method as described in any one of claim 1-2, wherein, described fat associated SNP positions of measuring includes at least one in rs6548238, rs925946, rs7138803, rs9939609, rs13130484, rs4788102, rs10838738, rs10871777, rs12970134.
5. the method as described in any one of claim 1-2, wherein, described diet response associated SNP positions includes at least one in rs1801282, rs5082, rs662799.
6. the method as described in any one of claim 1-2, wherein, described response associated SNP positions of taking exercise includes at least one in rs9939609, rs1801282, rs1800588, rs4994.
7. method as claimed in claim 3, wherein, the allelotype of described obesity-prone associated SNP positions can be to be the one in allele GG, GT, the TT existed in rs3751812 mode；With the one in allele GG, AG, AA that rs10871777 mode exists；One in allele C C that exists in rs6548238 mode, CT, TT；With the one in allele TT, CT, CC that rs13130484 mode exists；One in allele C C that exists in rs7647305 mode, CT, TT；With the one in allele TT, GT, GG that rs925946 mode exists；With the one in allele AA, AG, GG that rs4788102 mode exists；One in allele C C that exists in rs6232 mode, CT, TT；One in allele C C that exists in rs7566605 mode, CG, GG；With the one in allele TT, GT, GG that rs574367 mode exists；With the one in allele GG, AG, AA that rs6545814 mode exists；With the one in allele GG, AG, AA that rs10938397 mode exists；One in allele C C that exists in rs261967 mode, AC, AA；With the one in allele TT, CT, CC that rs4715210 mode exists；With the one in allele TT, CT, CC that rs9356744 mode exists；With the one of CC, CT, TT in the allele that rs6265 mode exists；One in allele C C that exists in rs652722 mode, CT, TT；With the one in allele AA, AT, TT that rs4776970 mode exists；With the one in allele GG, GT, TT that rs17817449 mode exists；One in allele C C that exists in rs12597579 mode, CT, TT；One in one in allele C C that exists in rs6567160 mode, CT, TT, allele GG, AG, the AA existed in rs11671664 mode.
8. method as claimed in claim 4, wherein, the described fat allelotype measuring associated SNP positions can be to be allele C C, the one in CT, TT existed in rs6548238 mode；With the one in allele TT, GT, GG that rs925946 mode exists；With the one in allele AA, AG, GG that rs7138803 mode exists；With the one in allele AA, AT, TT that rs9939609 mode exists；With the one in allele TT, CT, CC that rs13130484 mode exists；With the one in allele AA, AG, GG that rs4788102 mode exists；With the one in allele GG, AG, AA that rs10838738 mode exists；With the one in allele GG, AG, AA that rs10871777 mode exists；With the one in allele AA, AG, GG that rs12970134 mode exists.
9. method as claimed in claim 5, wherein, the allelotype of described diet response associated SNP positions can be to be the one in allele GG, CG, the CC existed in rs1801282 mode；With the one in allele GG, AG, AA that rs5082 mode exists；With the one in allele AA, AG, GG that rs662799 mode exists.
10. method as claimed in claim 9, wherein, the allelotype of described diet response associated SNP positions has a following phenotype:
1) in allele GG, CG, CC that rs1801282 mode exists, GG or CG shows that low-fat diet may cause waistline to increase, unsaturated fatty acids in diet is possible to prevent waistline to increase and may cause reducing body weight, and CC shows that in diet, high unsaturated fatty acids seems do not reduce beneficial to BMI or prevent waistline from increasing；
2) in allele GG, AG, AA that rs5082 mode exists, wherein GG shows that high saturated fat diet can increase fat probability, low saturated fat diet will not increase fat probability, AG or AA shows the relevant high saturated and low saturated fat diet of the fat probability of typical case；
3) in allele AA, AG, GG that rs662799 mode exists, AA shows that high fat diet relevant higher BMI, AG or GG show that food fat consumes uncorrelated BMI change.
11. methods as claimed in claim 6, wherein, the described allelotype tempering response associated SNP positions can be to be the one in allele AA, AT, the TT existed in rs9939609 mode；With the one in allele GG, CG, CC that rs1801282 mode exists；One in allele C C that exists in rs1800588 mode, CT, TT；With the one in allele AA, AG, GG that rs4994 mode exists.
12. methods as claimed in claim 11, wherein, the described allelotype tempering response associated SNP positions has a following phenotype:
1) in allele AA, AT, TT that rs9939609 mode exists, AA shows to tend to the people of high BMI, and taking exercise is correlated with is greatly reduced BMI, AT shows to tend to the people of typical case BMI, temper the relevant BMI, TT of typically reducing and show to tend to the people of relatively low BMI, take exercise and slightly reduce BMI；
2) in allele GG, CG, CC that rs1801282 mode exists, GG or CG shows to take regular exercise and improves glucose-tolerant, and CC shows to take regular exercise and changes glucose-tolerant hardly；
3) in allele C C that exists in rs1800588 mode, CT, TT, CC or CT shows that tempering relevant 5% improves insulin sensitivity, and TT shows to take exercise and uncorrelated improves insulin sensitivity；
4) in allele AA, AG, GG that rs4994 mode exists, AA shows, by walking, reduce energy absorption and increase physical exertion, relevant reduction body weight, AG or GG shows, by walking, reduce energy absorption and increase physical exertion, uncorrelated reduction body weight.
13. 1 kinds for instructing the gene chip of body-building and weight-reducing, wherein, described gene chip includes solid phase carrier and is fixed on this solid phase carrier the specific oligonucleotide probe for SNP site detection, and described SNP site is obesity-prone associated SNP positions, the fat allelotype measured associated SNP positions, diet response associated SNP positions and temper response associated SNP positions.
null14. gene chips as claimed in claim 13，Wherein，Described obesity-prone associated SNP positions includes rs3751812、rs10871777、rs6548238、rs13130484、rs7647305、rs925946、rs4788102、rs6232、rs7566605、rs574367、rs6545814、rs10938397、rs261967、rs4715210、rs9356744、rs6265、rs652722、rs4776970、rs17817449、rs12597579、rs6567160、At least one in rs11671664.
15. gene chips as claimed in claim 13, wherein, described fat associated SNP positions of measuring includes at least one in rs6548238, rs925946, rs7138803, rs9939609, rs13130484, rs4788102, rs10838738, rs10871777, rs12970134.
16. gene chips as claimed in claim 13, wherein, described diet response associated SNP positions includes at least one in rs1801282, rs5082, rs662799.
17. gene chips as claimed in claim 13, wherein, described response associated SNP positions of taking exercise includes at least one in rs9939609, rs1801282, rs1800588, rs4994.
The preparation method of 18. 1 kinds of gene chips for instructing body-building and weight-reducing as described in claim 13-17, wherein, concrete steps include:
(1) by solid phase carrier pretreatment, microscope slide chromic acid lotion is washed, soaked overnight, washing, in the immersion of 20%-25% ammonia overnight, washing, is then immersed in the ethanol solution of aminopropyl trimethoxysilane, with glacial acetic acid regulation pH value to 4.0-6.0, EtOH Sonicate cleans, drying 4-5 hour, glutaraldehyde aldehyde radicalization processes, stand-by；
(2) artificial synthetic oligonucleotide's chip probe, wherein every oligonucleotide chip probe 5 ' ends when synthesis are modified through amino group；
(3) being dissolved in sampling liquid by above-mentioned each oligonucleotide chip probe, during point sample, every some point sample volume is about 0.4-0.6mL, and point sample spacing is 500-600 μm, point sample a diameter of 200-300 μm, and every probe repeats point sample 2-3 time；Room temperature is placed 24-26 hour cured and get final product.
19. 1 kinds of test kits, wherein, described test kit comprises the gene chip as described in any one of claim 13-17, and described test kit also includes PCR buffer, MgC12, dNTPmix and the Taq enzyme used by PCR amplification.
The hardware device of 20. application programs using the method as described in any one of claim 1-12, wherein said application program is arranged in described hardware device.
21. hardware devices as claimed in claim 20, wherein, described hardware device includes at least one in mobile phone, computer, Wearable mobility device, implantable devices or a combination thereof.
The method that 22. hardware devices as described in any one of claim 20-21 carry out health control, wherein, including step: data corresponding for SNP in typing or the method as described in any one of claim 1-12 of reception in described hardware device；Described application program data based on typing and reception are that user comprehensively analyzes diet, exercise program；The data such as typing or reception user's real time kinematics situation, body weight, diet in described hardware device further；Described application program gives analyze and feed back health status.
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