KR20140136744A - Method of Providing Recommended Dietary Information for New Born Infant Based on Genetic Test and System for the Same Method - Google Patents

Abstract

The present invention relates to a method for supplying food or nutriment information for preventing or treating an autistic disorder or developmental delay based on the obtained genetic variation information after the genetic variation information is obtained by the genetic test of a newborn infant, a system performing the same, and a computer readable recording medium with a program for performing the same. According to the present invention, provided is dietetic treatment information for preventing or treating the autistic disorder or developmental delay based on a genetic test result of the newborn infant with a high autistic disorder or developmental delay risk.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for providing recommended dietary information to a newborn based on genetic testing,

The present invention relates to a method for providing information on a recommended dietary information of a newborn based on genetic testing, a system used in the method, and a computer readable recording medium on which a program for executing the method is recorded.

The food we eat contains a variety of compounds with biological activity. Amino acids, nucleotides, etc., which are metabolites of low molecular substances or high molecular substances such as vitamins, minerals and fatty acids and phytochemicals, are taken into the body, and these biologically active substances regulate the expression of the body genes It can act as dietary signals. Nutrigenomics is a study to study the effect of biologically active substances, which are taken as nutrients of foods, on the expression of genes in the body. These nutritional genetics have been further explored and found that nutrients affect gene expression and affect disease outbreaks and healing to some extent. Therefore, studies have been made that the components of food can not only promote health, but also can contribute to the improvement and prevention of specific diseases by controlling the expression of genes.

Numerous papers and patent documents are referenced and cited throughout this specification. The disclosures of the cited papers and patent documents are incorporated herein by reference in their entirety to better understand the state of the art to which the present invention pertains and the content of the present invention.

The present inventors have examined the mutation of various genes related to diseases in neonates and integrated the information on the mutation of these genes, and based on the integrated gene mutation data, the recommended nutrients Or a method and system for providing food information, thereby completing the present invention.

Accordingly, it is an object of the present invention to provide a nutritional or food information requiring ingestion to improve or prevent a disease associated with a base mutated gene after obtaining information on base mutation by performing gene base sequence analysis on a newborn baby Method.

It is another object of the present invention to provide a nutritional or food information providing system for providing nutrient or food information to be consumed in order to improve or prevent disease associated with a base mutated gene after obtaining information on base mutation by performing gene base sequence analysis on a newborn baby .

It is still another object of the present invention to provide a computer readable recording medium on which a program for executing the above method is recorded.

The objects and advantages of the present invention will become more apparent from the following detailed description of the invention, claims and drawings.

According to one aspect of the present invention, there is provided a method for detecting a mutation in a nucleotide sequence of a neonatal, A method of providing information comprising the steps of: (a) obtaining base mutation information at a single base polymorphic position of genes to be tested; And (b) outputting a report describing the base mutation information obtained in the step (a), wherein when a single nucleotide polymorphic site base of the genes to be tested is judged to be a mutant base, a disease associated with the base mutated gene Record the nutrient or food information that needs to be ingested in the report to improve or prevent it.

According to a preferred embodiment of the present invention, the above step (A) is performed by a method of (i) sequencing, (ii) real time-polymerase chain reaction, or (iii) a combination of these methods .

According to another preferred embodiment of the present invention, step (a) comprises the following steps when (i) performing the method according to the method for sequencing:

(a) determining the nucleotide sequence of the DNA of the test subject gene from the biological sample of the newborn using the gene sequencer, inputting the determined nucleotide sequence of the DNA through the gene sequence inputting device, Converting into a suitable file format through a base sequence converter;

(b) constructing a reference gene database by storing the nucleotide sequence information including the single nucleotide polymorphism site of the genes to be tested, and comparing the single nucleotide polymorphism site of the genes to be tested with the up- stream region or a 5'-direction downstream region of the nucleotide sequence database to construct a border sequence database, and the converted nucleotide sequence file to be analyzed in the step (a) A base sequence to be analyzed, a base sequence stored in the boundary sequence database, and a base sequence of a single base polymorphic site stored in the reference gene database are retrieved through a gene base sequence comparator, The polymorphism site was identified as a base mutation, and the obtained base mutation The variations for the entire result if the entire inspection target gene through the table builder recorded based on the discrimination data, the steps to create a full-result table; And

(c) establishing a reference certificate database by storing information on the report form format, extracting the results from the entire result table created in the step (b) through the report result file creator, Generating a final result file for outputting a test report, and outputting a test report describing whether a single nucleotide polymorphism site of the test target genes has a base mutation using the generated final result file through a test report output unit, When the single nucleotide polymorphic site of the genes to be tested is determined to be a mutant base in step (b), the nutrition or food information necessary for ingesting to improve or prevent disease associated with the base mutated gene through the test report reader Record in the report.

Hereinafter, the method of the present invention will be described in detail for each step.

Step (a)

The subject of the gene test of the present invention is a newborn infant. In the present invention, the newborn preferably means a baby up to four weeks after birth. The gene sequencing analyzer in the present invention is a device capable of analyzing the DNA sequence of a specific gene region on a genome included in a biological sample obtained from a newborn, which is a test subject. The biological sample means a biological sample that can be obtained by easily separating from the newborn without injuring the body. Examples include blood, urine, saliva, synovial fluid, oral cells, hair follicle cells, and the like. Each sample is assigned a unique number according to the type of single nucleotide polymorphism of the genes to be tested, as well as the nucleotide sequence stored in the reference gene database shown below.

The data relating to the nucleotide sequence obtained from the gene sequence analyzer is inputted in a form accessible by the transducer through the gene sequencer. The input gene sequence is converted into a suitable file format so that it can be processed by a computer program through a gene sequencer. A suitable file format is not particularly limited, but may be, for example, a file format that is easy for graphic processing or sequence alignment processing using a computer program, for example, information of an inputted base sequence. seq. < / RTI > Gene sequences should be written in standard IUB / IUPAC amino acid and standard IUB / IUPAC amino acid and nucleic acid codes. As the base sequences stored in the reference gene database are inputted, the converted base sequences of the sample genes are assigned unique numbers according to each base single polymorphism of the genes to be tested.

Step (b)

Reference gene database

The reference gene database is constructed by storing the nucleotide sequence information including the single nucleotide polymorphic site of the genes to be tested. The nucleotide sequence stored in the reference gene database has a wild-type single nucleotide polymorphism gene. The wild-type single nucleotide polymorphic base information of the genes to be examined can be obtained from the NCBI dbSNP site (www.ncbi.nlm.nih.gov/snp). According to an embodiment of the present invention, the gene to be tested is a gene selected from the group consisting of the following genes:

ACAT (Acetyl-Coenzyme-A-acetyltransferase),

AHCY (S-adenosylhomocysteinehydrolase),

BHMT (Betaine < RTI ID = 0.0 > omocysteinemethytransferase)

Cystathionine-beta-synthase (CBS),

COMT (Catechol-O-methyltransferase),

MAOA (Monoamineoxidase A),

Methylenetetrahydrofolatereductase (MTHFR),

MTR (Methioninesynthase),

MTRR (Methioninesynthasereductase),

SHMT (Serine hydroxymethyltransferase),

VDR (VitaminDreceptor),

NOS (NitricOxidesynthase),

SUOX (Sulfiteoxidase),

TS (Thymidylate synthase),

GST_T1 (Glutathione S-transferase theta 1), and

GST_M1 (Glutathione S-transferase Mu 1).

The genes to be examined include genes involved in the methylation cycle in vivo, and include genes for detoxification, immune function, maintenance and repairing of DNA, energy production, mood balancing, It is known to be involved in controlling inflammation. Metabolic disorders such as cardiovascular disease, cancer, diabetes, obesity, and aging are caused by deficiency or damage of metabolic control function by mutation by single nucleotide polymorphism in the genes, and autism and autistic disorder, chronic fatigue syndrome, Alzheimer ' It is known to cause inflammatory diseases such as diseases, abortion and infertility, allergies, bronchial asthma, atopy, and psychiatric diseases.

The base sequence of the gene to be tested stored in the reference gene database is a base sequence including a single base polymorphic site. The term "single nucleotide polymorphism " in the present invention means a mutation of one base at a single base site constituting a chromosomal gene. By such mutation, genetic diversity among individuals in the same species and different susceptibility to diseases And different reactivity to the drug.

According to one embodiment of the present invention, the single nucleotide polymorphic site of the gene of interest is selected from the group consisting of the following single nucleotide polymorphic sites: ACAT-rs3741049 (SEQ ID NO: 1), AHCY-rs819147 (SEQ ID NO: 2) (SEQ ID NO: 3), BHMT-rs58580 (SEQ ID NO: 4), CBS-rs234706 (SEQ ID NO: 5), CBS-rs1801181 (SEQ ID NO: 6), COMT-rs4680 (SEQ ID NO: 10), MTRR-rs1801394 (SEQ ID NO: 13), NOS (SEQ ID NO: 14), SHMT-rs1979277 (SEQ ID NO: 15), VDR-rs731236 (SEQ ID NO: 16), VDR-rs10735810 19), and TS-rs16430 (SEQ ID NO: 20).

In the present invention, GST_T1 (Glutathione S-transferase theta 1) and GST_M1 (Glutathione S-transferase Mu 1) genes in the test subject do not mutate at a single nucleotide polymorphism site except for null mutation, . Analysis of deletion mutations in the GST_T1 and GST_M1 genes has been reported by Bellda et al., Genetic risk and carcinogen exposure: a common inherited defect of the carcinogen-metabolism gene glutathione S-transferase M1 (GSTM1) that increases susceptibility to bladder cancer . J Natl Cancer Inst 1993; 85: 1159-1164; Pemble S, et al., Human glutathione S-transferase theta (GSTT1): cDNA cloning and the characterization of a genetic polymorphism. Biochem J 1994; 300 (Pt 1): 271-276]. In the case of the TS (Thymidylate synthase) gene, the nucleotide sequence of SEQ ID NO: 20 is checked for insertion or deletion of a region consisting of the six bases from the 27th to the 32nd bases.

According to an embodiment of the present invention, the nucleotide sequence containing a single nucleotide polymorphic site stored in the reference gene database includes three nucleotides constituting one codon of a single nucleotide polymorphism site, and the nucleotide sequence of 3 nucleotides 3 ' Direction is a nucleotide sequence in which an arbitrary nucleotide sequence is added to an upstream (upstream) and a 5 'downstream (downstream) direction.

The length of any of the above base sequences is not particularly limited, but it is comprised of 20-50 nucleotides, more preferably 20-45 nucleotides, even more preferably 20-40 nucleotides, and most preferably 30 nucleotides. The nucleotide sequences containing the single nucleotide polymorphic sites stored in the reference gene database assign unique numbers to the single nucleotide polymorphisms of the genes to be tested.

Boundary sequence database

Based on the single nucleotide polymorphism site of the genes to be tested, the nucleotide sequence database of the upstream or downstream region is stored and the boundary sequence database is constructed.

In the present invention, the border sequence does not include a single nucleotide polymorphism site based on the single nucleotide polymorphism site of the genes to be examined described above, and is a nucleotide sequence in the 3 'upstream or 5' downstream region. The length of the border sequence is not particularly limited, but is preferably 10-30 nucleotides, more preferably 10-20 nucleotides, and even more preferably 12-15 nucleotides.

The border sequences stored in the border sequence database are assigned unique numbers according to the single nucleotide polymorphisms of the genes to be tested, as well as the nucleotide sequences stored in the reference gene database.

Gene sequence comparison

A file of the converted base sequence to be analyzed in the step (a) is inputted through a gene base sequence file inputting device, and the nucleotide sequence to be analyzed through the gene base sequence comparator and the nucleotide sequence And a nucleotide sequence of a single nucleotide polymorphic site stored in the reference gene database to discriminate whether a nucleotide sequence of a single nucleotide polymorphic site of the gene to be tested is a nucleotide variation.

According to an embodiment of the present invention, the determination of whether or not a single nucleotide polymorphism site of a gene to be tested in the gene base sequence comparator is a base mutation can be determined by sorting the nucleotide sequence to be analyzed and the nucleotide sequence stored in the boundary sequence database, And adding an arbitrary nucleotide sequence before and after the three nucleotides following the termini, and outputting the nucleotide sequence with a unique number attached thereto.

According to another embodiment of the present invention, the determination of whether or not a single nucleotide polymorphism site of the subject gene in the gene base sequence comparator is a base mutation may be determined by comparing the nucleotide sequence output with the unique number and the same unique number of the reference gene database And then performing sequence alignment to discriminate whether or not the single nucleotide polymorphic site of the gene to be tested is a base mutation.

More specifically, the gene base sequence comparator recalls the base sequence to be analyzed, reads the bound sequence having the same unique number in the boundary sequence stored in the boundary sequence database, And recognizes three nucleotide bases following the border sequence in the nucleotide sequence to be analyzed. A query sequence is output by adding an arbitrary nucleotide sequence to each of the 3'-direction upstream and 5'-direction downstream of the recognized three nucleotides. At this time, a unique number identical to the original number assigned at the beginning is retained in the output Query sequence. The arbitrary base sequence is the same base sequence as any base sequence described in the base sequence including a single base polymorphic site of the genes to be tested stored in the reference gene database.

The base sequence having the same unique number among the reference sequences stored in the reference gene database and the query sequence added with the arbitrary base sequence is called up to sort the base sequences of both base sequences and then the nucleotide sequence identity . The result of sorting the nucleotide sequence is output in the form of a result file. In the result file, if the base of the single nucleotide polymorphic site of the query sequence to be tested is not the same as the base of the wild type reference gene, the variant nucleotide is indicated.

Create full result table

Based on the discrimination data of the nucleotide variation obtained through the above-described gene base sequence comparator, a total result table in which the mutation of the whole of the gene to be examined is recorded is created through the whole result table generator. More specifically, based on the data on the base mutation of each of the tested single nucleotide polymorphisms obtained through the gene base sequence comparator, a complete result table recording the mutation of the entire gene to be tested is created. In the overall result table, the name of the single nucleotide polymorphism, as well as the name of the sample, the gene identifier, the name of the nucleotide sequence, three nucleotides of the single nucleotide polymorphism site, one nucleotide of the single nucleotide polymorphism site, Additional file names can be recorded.

Step (c)

(B), extracts the results from the overall result table created in the step (b), and compares the form with the report form form from the constructed reference report database unit A final result file for outputting a post-test report is generated, and a report describing whether or not the base polymorphism site of the subject genes undergoes base mutation is output using the final result file generated through a report writer.

Extracts data such as the base mutation in the single nucleotide polymorphism of the subject gene from the entire result table created in step (b), and generates a final result file for the report output according to the report form from the reference report database unit. Using the resultant final result file, a report describing whether or not a single nucleotide polymorphism site of the genes to be tested is mutated is output. When the single nucleotide polymorphic site of the genes to be tested is judged to be a mutant base in the step (b), the nutrient or food information required for ingestion to improve or prevent the disease associated with the base mutated gene through the test report reader In the report.

According to another preferred embodiment of the present invention, the method of the present invention comprises the following steps when performing the above step (A) by (ii) Real Time Polymerase Chain Reaction (PCR) method:

(a) an oligonucleotide probe capable of binding to a sequence containing a single nucleotide polymorphism (SNP) base of the genes to be tested, the probe comprising a base probe specifically binding to a mutation base of the SNP, And a wild type base probe that specifically binds to the wild type base of the SNP base is prepared, and the oligonucleotide primer capable of amplifying the sequence containing the SNP base is prepared by binding a different fluorescent substance to the mutated base probe and the wild type base probe, ;

(b) DNA nuclei obtained from a biological sample of a newborn using a mutagenic base probe, a wild type base probe and a primer prepared in the step (a) in a 'Real Time-Polymerase Chain Reaction' ;

(c) analyzing the real-time PCR result obtained in the step (b) in the real-time PCR result analyzer to check whether a single nucleotide polymorphic site of the gene to be tested has a base mutation;

(d) creating a complete result table in which the mutation status of the entire gene to be examined is recorded through the entire result table generator based on the discrimination data on whether the nucleotide polymorphism of the single nucleotide polymorphism site identified in the step (c) step;

(f) constructing a reference report database by storing information on the report form format, extracting the results from the entire result table created in the step (d) through the report result file creator, Generating a final result file for outputting a test report after comparing with a test report format and outputting a test report describing whether or not a base mutation of a single nucleotide polymorphism site of the genes to be tested is described using the generated final result file through a report writer , When the single nucleotide polymorphic site of the genes to be tested is judged to be a mutant nucleotide in the step (c) ', the nutrient necessary for ingesting to improve or prevent the disease associated with the gene mutated through the test report Record food information in a report.

Hereinafter, the method of the present invention will be described in detail for each step.

Step (a)

An oligonucleotide mutagenic probe that specifically binds to a mutated base of single nucleotide polymorphism (SNP) of the genes to be tested, and an oligonucleotide wild type base probe that specifically binds to the wild type base of SNP are prepared. A different fluorescent material binds to the SNP mutated base probe and the SNP wild type base probe, respectively. Also, an oligonucleotide primer capable of amplifying a sequence containing the SNP base is prepared.

The content of the single nucleotide polymorphism of the gene to be tested and the gene to be tested is the same as that described in the step (b) in the case of performing the step (a) by (i) the nucleotide sequence analysis method, I never do that.

Step (b)

A real-time PCR reaction is performed on a DNA nucleic acid obtained from a biological sample of a newborn using the SNP mutated base probe, the SNP wild type base probe and the primer prepared in the step (a). Details of real-time PCR are known in the art and can be found in the literature, ChemBioChem Volume 4, Issue 11, pages 1120-1128, November 7, 2003.

Step (c)

The real-time PCR result analyzer analyzes the real-time PCR result in the step (b) to determine whether a single nucleotide polymorphism site of the gene to be tested has a base mutation.

Step (d)

Based on the discrimination data for the presence or absence of base mutation of the single nucleotide polymorphism site identified in the step (c) ', the entire result table in which mutation to the whole of the gene to be examined is recorded is created through the entire result table generator.

Step (f)

First, a reference report database is constructed by storing information on the report form format, a result is extracted from the entire result table created in the step (d) through a report result file creator, and the report form data from the constructed reference report database And generates a final result file for outputting a test report, and outputs a report describing whether or not the single nucleotide polymorphism site of the genes to be tested has been mutated, using the final result file generated through the report writer. When the single nucleotide polymorphic site of the genes to be tested is judged to be a mutant base in the step (c) ', the nutrient or food necessary for ingestion to improve or prevent the disease associated with the base mutated gene through the test report reader Record the information in the report.

According to another aspect of the present invention, there is provided a computer-readable recording medium on which a program for executing the above-described method is recorded.

According to still another aspect of the present invention, there is provided a method for detecting a mutation in a nucleotide sequence, the method comprising: performing gene base sequence analysis on a newborn to obtain information on the base mutation; A system for providing food information, the system comprising a gene sequence analysis unit (10), a gene mutation discrimination unit (20), and a report preparation unit (40), wherein the gene sequence analysis unit (10) A nucleotide sequence analyzing unit 11 for determining the nucleotide sequence of the DNA of the subject gene from the biological sample, a gene base sequence input unit 12 for inputting the determined nucleotide sequence of the DNA, , And the gene mutation discriminator (20) comprises a gene mutation discriminator (20) A nucleotide sequence file input unit 21, a reference gene database unit 22 for storing nucleotide sequence information including a single nucleotide polymorphism site of the genes to be tested, a 3 'upstream direction or a 5' direction based on a single nucleotide polymorphism site of the gene to be tested A nucleotide sequence database 23 for storing nucleotide sequence information in the downstream downstream region, a base sequence database 23 for storing nucleotide sequence information in the downstream downstream region, a base sequence database 23 for storing the base sequence information, A nucleotide sequence comparison unit (24) for comparing the nucleotide sequence of the target gene with the nucleotide sequence of the target gene to determine whether the nucleotide sequence of the single nucleotide polymorphism site of the gene to be tested is mutated; Create a complete result table that records variations across all genes The report creating unit 40 includes a reference report database unit 41 that stores information on a report form format, a result extracting unit 42 that extracts a result from the created result table, A report result file creation unit 42 for generating a final result file for outputting a report after comparing it with the report form format from the database unit 41, If the base mutation status is described and the single nucleotide polymorphic site of the genes to be tested is determined to be a mutant nucleotide, the nutrition or food information required to be ingested in order to improve or prevent the disease associated with the gene mutated in the report And a report booklet output section 43 for outputting a report book.

According to still another aspect of the present invention, there is provided a method for detecting a mutation in a nucleotide sequence, the method comprising: performing gene base sequence analysis on a newborn to obtain information on the base mutation; A system for providing food information, the system comprising a gene sequence analysis and gene mutation discrimination unit (30) and a report writing unit (40), wherein the gene sequence analysis and gene mutation discrimination unit (30) Wherein the oligonucleotide probe is capable of binding to a sequence containing a single nucleotide polymorphism (SNP) base of the SNP, and a probe capable of binding specifically to the mutated base of the SNP, And an oligonucleotide capable of amplifying a sequence containing the SNP base A real-time PCR reaction unit 31 for performing real-time PCR on a DNA nucleic acid obtained from a biological sample of a neonate using an otide primer, and analyzing the real-time PCR result to confirm whether or not the base mutation of the single- A real-time PCR analysis unit 32, and an overall result table creation unit 32 for creating a complete result table in which variations of all of the genes to be tested are recorded based on the base-mutation determination data obtained in the real- The report creating unit 40 includes a reference report database 41 in which information on the report form format is stored, a result extracting unit 42 for extracting a result from the created total result table, Result report file that generates the final result file for outputting the report after comparing with the report form format When a single nucleotide polymorphism site of the genes to be tested is described using the final result file, and the single nucleotide polymorphism site of the genes to be tested is determined to be a mutation base, And a report output unit (43) for outputting a report describing the nutrient or food information required to be consumed in order to improve or prevent the disease associated with the base mutated gene.

According to an embodiment of the present invention, in the system, the gene to be tested is one or more genes selected from the group consisting of the following genes:

ACAT (Acetyl-Coenzyme-A-acetyltransferase),

AHCY (S-adenosylhomocysteinehydrolase),

BHMT (Betaine < RTI ID = 0.0 > omocysteinemethytransferase)

Cystathionine-beta-synthase (CBS),

COMT (Catechol-O-methyltransferase),

MAOA (Monoamineoxidase A),

Methylenetetrahydrofolatereductase (MTHFR),

MTR (Methioninesynthase),

MTRR (Methioninesynthasereductase),

SHMT (Serine hydroxymethyltransferase),

VDR (VitaminDreceptor),

NOS (NitricOxidesynthase),

SUOX (Sulfiteoxidase),

TS (Thymidylate synthase),

GST_T1 (Glutathione S-transferase theta 1), and

GST_M1 (Glutathione S-transferase Mu 1).

According to another embodiment of the present invention, the single nucleotide polymorphic site of the gene of interest is selected from the group consisting of the following single nucleotide polymorphic sites: ACAT-rs3741049 (SEQ ID NO: 1), AHCY-rs819147 (SEQ ID NO: (SEQ ID NO: 3), BHMT-rs58580 (SEQ ID NO: 4), CBS-rs234706 (SEQ ID NO: 5), CBS-rs1801181 (SEQ ID NO: 6), COMT-rs4680 (SEQ ID NO: 10), MTRR-rs1801394 (SEQ ID NO: 13), NOS (SEQ ID NO: 14), SHMT-rs1979277 (SEQ ID NO: 15), VDR-rs731236 (SEQ ID NO: 16), VDR-rs10735810 19), TS-rs16430 (SEQ ID NO: 20).

According to another embodiment of the present invention, the base sequence including the single nucleotide polymorphic site of the gene to be tested, which is stored in the reference gene database unit 22, includes three nucleotides constituting one codon at a single nucleotide polymorphism site , And is a nucleotide sequence in which an arbitrary nucleotide sequence is added to the 3 nucleotide 3'-direction upstream (up-stream) and 5'-direction downstream (down-stream).

According to another embodiment of the present invention, the determination of whether or not a single nucleotide polymorphism site of a gene to be tested in the gene base sequence comparison unit 24 is a base mutation can be determined by analyzing a nucleotide sequence to be analyzed and a nucleotide sequence And then adding an arbitrary nucleotide sequence before and after the three nucleotides next to the border sequence end, and outputting the nucleotide sequence with the unique number attached thereto.

According to another embodiment of the present invention, the determination of the base mutation of the single nucleotide polymorphic site of the gene to be tested in the gene base sequence comparison unit 24 may be performed by comparing the nucleotide sequence output with the unique number, And then performing sequence alignment to discriminate whether a single nucleotide polymorphic site of the gene to be tested is a base mutation or not.

The present invention relates to a method for providing nutrient or food information that requires ingestion to improve or prevent disease associated with a base mutated gene after obtaining information on base mutation by performing gene base sequence analysis on a newborn baby, And a computer-readable recording medium on which a program for executing the method is recorded. According to the present invention, it is possible to provide information on the dietary therapy for improving and preventing diseases that may occur based on the results of genetic tests on newborns.

FIG. 1 is a block diagram showing an overall configuration of an embodiment of the system of the present invention, which shows a configuration of a gene sequence analyzing unit 10, a gene mutation discriminating unit 20, and a report creating unit 40.
2 shows the construction of a gene sequence analyzer 11, a gene base sequence input unit 12 and a gene base sequence converter 13 constituting the gene sequence analyzer 10.
FIG. 3 is a block diagram showing the construction of a gene mutation discriminator 20 including a gene nucleotide sequence file input unit 21, a reference gene database 22, a boundary sequence database 23, a gene sequence comparison unit 24, And the table creating unit 25 shown in FIG.
FIG. 4 shows a process of extracting nucleotide sequences of three nucleotides of a single nucleotide polymorphic site of a gene to be analyzed using a border sequence and outputting an arbitrary nucleotide sequence added before and after the extracted three nucleotide sequences.
FIG. 5 shows an example of a result file generated through the multiple sequence sorting program in the gene sequence comparison part 24.
FIG. 6 shows an example of the entire result file generated through the overall result table creation unit 25. FIG.
FIG. 7 is an overall block diagram of another embodiment of the system of the present invention, showing the construction of a gene sequence analysis, gene mutation discrimination unit 30 and a report writing unit 40.
FIG. 8 is a diagram showing a real-time PCR reaction unit 31, a real-time PCR result analysis unit 32 and an overall result table preparation unit 33 constituting the gene sequence analysis and gene mutation discrimination unit 30 Configuration.
9 shows the configuration of the reference report database 41, the report result file creation unit 42, and the report output unit 43 constituting the report creation unit 40. As shown in FIG.
Figure 10 shows an example of the final result file for the report output.
Fig. 11 shows a cover page as an example of the report provided in the present invention.
FIG. 12 shows a page listing results of single nucleotide polymorphism test of a gene to be examined as an example of the test report provided in the present invention.
FIG. 13 shows an example of a test report provided in the present invention, which includes a page in which a methylation pathway in vivo is imaged, information on the function of a test item gene, a disease associated with it and a recommended nutrient and food Show the page listed.
FIG. 14 shows an example of a test report provided in the present invention, showing pages describing nutrient-containing foods, complex component elements, and roles of important internal components.

Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these embodiments are only for describing the present invention in more detail and that the scope of the present invention is not limited by these embodiments in accordance with the gist of the present invention .

Example

FIG. 1 is an overall block diagram of an embodiment of the system of the present invention, which shows a configuration of a gene sequence analyzing unit 10, a gene mutation discriminating unit 20, and a report creating unit 40.

Fig. 2 shows the structure of the gene sequence analyzer 10. The gene sequencing unit 11 may be configured by a device capable of analyzing the base sequence of the gene, for example, a 3730 XL DNA Analyzer (Applied Biosystems, Foster City, Calif., USA). The nucleotide sequence determination data generated by the gene sequence analyzing unit 11 is input to the gene base sequence converting unit 13 through the gene base sequence input unit 12, Converts sequence information to a suitable file format. The gene base sequence converter 13 can perform an input and a conversion using a suitable program such as Sequence Analysis (Applied Biosystems, Foster City, Calif., USA). Specifically, the Base Calling is performed using the Mixed Bases option 35%, and then the file is saved in two types of files in .ab1, .seq format. For heterozygosity, the nucleotide sequence should be written in standard IUB / IUPAC amino acid and standard IUB / IUPAC amino acid and nucleic acid codes. If the quality of input nucleotide sequence data is low and read as N, it is separated so that analysis is impossible. In other words, if the output of the gene sequencer is checked and a sample whose N-base calling result is found to correspond to the "Quality Threshold <15" condition is separated, it is returned to the step of inspecting the gene sequencer.

3 shows a configuration of the gene mutation discrimination unit 20. In FIG.

A file of the converted base sequence to be analyzed is inputted through the gene base sequence file input unit 21. The converted nucleotide sequence file to be inputted is a file outputted through the nucleotide sequence conversion unit 13. The reference gene database 22 stores nucleotide sequence information including a single nucleotide polymorphic site of the gene to be tested. Sequence information for single nucleotide polymorphisms can be obtained from the NCBI dbSNP site (www.ncbi.nlm.nih.gov/snp). In a specific example of the invention, the single nucleotide polymorphic site stored in the reference gene database portion 22 is the following single nucleotide polymorphic site: ACAT-rs3741049 (SEQ ID NO: 1), AHCY-rs819147 (SEQ ID NO: 2), BHMT rs58802 (SEQ ID NO: 3), BHMT-rs58580 (SEQ ID NO: 4), CBS-rs234706 (SEQ ID NO: 5), CBS-rs1801181 (SEQ ID NO: 6), COMT- (SEQ ID NO: 10), MTR-rs1801394 (SEQ ID NO: 13), NOS- (SEQ ID NO: 14), SHMT-rs1979277 (SEQ ID NO: 15), VDR-rs731236 (SEQ ID NO: 16), VDR-rs10735810 (SEQ ID NO: 17), VDR-rs1544410 ), TS-rs16430 (SEQ ID NO: 20).

Each single nucleotide polymorphic nucleotide sequence is assigned a unique number, and the nucleotide sequence information of the site is stored in FASTA format. For example, if the unique number of the ACAT gene test is assigned as 001 and the single nucleotide polymorphism of this gene is registered with NCBI as rs3741049, then store it as 001-ACAT-rs3741049. The nucleotide sequence containing a single nucleotide polymorphic site of the gene to be tested, which is stored in the reference gene database unit 22, comprises three nucleotides constituting one codon at a single nucleotide polymorphism site, and the 3 nucleotides in the 3 'direction Any base sequences are added upstream and downstream of the 5 'direction.

The boundary sequence database 23 stores sequence information of the upstream or downstream region based on the single nucleotide polymorphism site of the gene to be examined. The individual nucleotide polymorphisms of the individual nucleotide polymorphisms are assigned to the border sequences and stored therein. The border sequence is a sequence consisting of 12 to 15 nucleotides in either the 3 'direction or the 5' direction on the basis of the position of the single nucleotide polymorphism to be examined. Table 1 summarizes information on 35 SNPs (SNPs).

# Reference-name Single nucleotide polymorphism Border sequence 001 001-ACAT-rs3741049 G / A (+ T / -C) TATGCCTATTGCATC (SEQ ID NO: 21) 002 002-AHCY-rs819147 G / A (+ G / -A) AATAATCTTCATAGA (SEQ ID NO: 22) 009 009-BHMT-rs651852 A / G (+ T / -C) AGGAGGGTGAGAATT (SEQ ID NO: 23) 011 011-BHMT-RS58580 T / A (+ T / -A) TATGGAAATCACTGC (SEQ ID NO: 24) 012 012-CBS-rs234706 C699T (+ A / -G) AACCCCCTGGCTCAC (SEQ ID NO: 25) 013 013-CBS-RS1801181 A360A (+ A / -G) GCGGTGGCCGTGAAG (SEQ ID NO: 26) 015 015-COMT-rs4680 V158M (+ A / -G) GTGGATTTCGCTGGC (SEQ ID NO: 27) 020 020-COMT-rs4818 L136L (+ C / -G) TCACCAGGGGCGAGG (SEQ ID NO: 28) 023 023-MAOA-rs6323 R297R (+ T / -G) AACCAGTTAATTCAG (SEQ ID NO: 29) 025 025-MTHFR-rs1801133 A222V (C677T) AAGGTGTCTGCGGGA (SEQ ID NO: 30) 027 027-MTHFR-rs1801131 A1289C (+ C / -A) GTGTCTTTG (SEQ ID NO: 31) 028 028-MTR-RS1805087 A2756G (+ G / -A) GAAGATATTAGACAG (SEQ ID NO: 32) 029 029-MTRR-rs1801394 A66G (+ G / -A) GCCATCGCAGAAGAA (SEQ ID NO: 33) 038 038-VDR-rs731236 Taq (I352I) (+ T / -C) GAGGCCATCCAGGAC (SEQ ID NO: 34) 040 040-VDR-rs10735810 Fok (N: T) (+ T / -C) AGGCAATGGCGGCCA (SEQ ID NO: 35) 039 039-VDR-rs1544410 Bsm / Taq (+ A / -G) CCACAGACAGGCCTG (SEQ ID NO: 36) 035 035-NOS-rs1799983 D298E (+ T / -G) CTGCAGGCCCCAGAT (SEQ ID NO: 37) 036 036-SHMT-rs1979277 C1420T (+ A / -G) GAGAGCTTCGCCTCT (SEQ ID NO: 38) 037 037-SUOX-rs7731115 S370S (+ C / -T) GAACTTCCTGTCCAG (SEQ ID NO: 39) 050 050-TS-rs16430 TTAAAG (+ Del / -Ins) AGTGTGGTTATGAAC (SEQ ID NO: 40)

The nucleotide sequence comparison unit 24 retrieves the nucleotide sequence of the transformed nucleotide sequence to be analyzed, the nucleotide sequence stored in the border sequence database unit, and the nucleotide sequence of the single nucleotide polymorphism site stored in the reference gene database unit 22 Determine whether the polymorphic site of the single nucleotide polymorphism of the gene of interest is a base mutation.

The process in the above-described gene base sequence comparison unit will be described in detail as follows. First, after reading the converted base sequence file (.seq) to be analyzed, the base sequence having the same unique number is retrieved from the boundary sequence database unit 23, and the retrieved base sequence and the nucleotide sequence to be analyzed are aligned Three nucleotides following the posterior border sequence are extracted. The nucleotide sequence of the extracted 3 nucleotides and 30 nucleotides is attached to Query 1. For example, in the case of the single nucleotide polymorphic site of 015-COMT in Table 1, the nucleotide sequence 5'-GTGGATTTCGCTGGC-3 'corresponds to the border sequence, and after reading the nucleotide sequence file (.seq) , It can be seen that the boundary sequence corresponds to positions 29-43. The nucleotide sequence of the next three nucleotides, that is, the base sequence corresponding to the 44th, 45th, and 46th nucleotides, and then recognizing any base sequence consisting of arbitrary 30 nucleotides in front of the above three bases [GTG] And attaches a unique number to it and outputs it to Query 1 (see FIG. 4).

On the other hand, an arbitrary base sequence added before and after the three bases [GTG] is a nucleotide sequence of a single nucleotide polymorphic site in the nucleotide sequence containing a single nucleotide polymorphic site of the gene to be tested, which is stored in the reference gene database section 22 Is set to the same sequence as any base sequence added to the 3 'direction upstream and 5' direction downstream of the three nucleotides constituting the open codon.

Then, Query 1 is output in the FASTA format, the reference gene base sequence having the same unique number is loaded from the reference gene database unit 22, and a query sequence of Query 1 is analyzed using a multiple sequence sorting program such as clustalw 2 program (SEQ. ID. NO. 2) and the reference gene sequence to generate a resultant file (.alpha.) (See FIG. 5). In the resultant file, the presence of a mutant base in the query sequence of Query 1, as compared to the single base polymorphic base of the wild type reference gene sequence, is recorded (see FIG. 5) .

The overall result table creating unit 25 prepares a complete result table in which the mutation of the entirety of the gene to be examined is recorded based on the result file of the nucleotide mutation discrimination data obtained in the gene nucleotide sequence comparing unit. The overall result table is created as follows. (- / -) when there is no base mutation of the single nucleotide polymorphism in the resultant file .alph. When there is a base mutation, it outputs (+/-) or (+ / +) as a mutation type. When there is a degenerated base, it outputs (+/-) and a degenerated base If it does not exist, print (+ / +). Including degenerated bases, it is possible to denote all the amino acids that can be generated at the time of amino acid translation. The output is stored in a file of all_result_table.txt. The contents stored in the entire result file include "sample name, gene identification number - symbol, nucleotide sequence data name, three nucleotide DNA, one nucleotide DNA, amino acid translation, image file name" (See FIG. 6).

FIG. 7 is an overall configuration diagram of another embodiment of the system of the present invention, which shows a configuration of gene sequence analysis, gene mutation discrimination unit 30, and report generation unit 40.

FIG. 8 shows a structure of the gene sequence analysis and gene mutation discrimination unit 30. FIG. The gene sequence analysis and gene mutation discrimination unit 30 includes a real time PCR reaction unit 31, a real time PCR result analysis unit 32 and an overall result table preparation unit 33.

In the real-time PCR reaction unit 31, an oligonucleotide probe capable of binding to a sequence containing a single nucleotide polymorphism (SNP) base of the genes to be tested is used as a mutagenic probe that specifically binds to the mutation base of the SNP And real-time PCR using a DNA base nucleic acid obtained from a biological sample of a newborn using a wild-type base probe specifically binding to the wild type base of the SNP and an oligonucleotide primer capable of amplifying the sequence containing the SNP base, I do. The wild-type base probe and the mutated base probe of the SNP are bound to different fluorescent materials. The real-time PCR reaction unit can be configured with a device capable of performing real-time PCR, for example, an Applied Biosystems 7500 Fast Instrument (Applied Biosystems, Foster City, CA, USA).

The real-time PCR analysis unit 32 analyzes the real-time PCR result to check whether a single nucleotide polymorphic site of the gene to be tested has a base mutation. The real-time PCR result analyzing unit 32 can be performed using a suitable program such as a TaqMan Genotyper Software program (Life Technologies Corporation, Foster City, CA, USA). The results analyzed by the real-time PCR analysis unit 32 can be output to a txt format file using the Export function of the TaqMan Genotyper Software program. The output contents include Sample ID, Plate Barcode, Gene Symbol, NCBI SNP Reference , Assay Name or OD, Allele 1 Call, Allele 2 Call, and the like.

The overall result table creation unit 33 creates a complete result table in which the mutation status of all of the genes to be tested is recorded based on the base mutation determination data obtained in the real time PCR result analysis unit. The method and procedure for creating the overall result table are the same as those described above.

9 shows the configuration of the report creating unit 40. As shown in FIG.

The reference report database unit 41 stores information on the report form format. The result report creating unit 42 extracts the required result from the created result table, compares the result with the report form form from the reference report database 41, and generates a final result file for outputting the report. The report book output unit 43 finally outputs a report describing whether or not a single nucleotide polymorphism site of the genes to be tested is nucleotide mutation using the generated final result file. More specifically, the generated result table of all_result_table.txt is compared with the reference report form stored in the reference report database unit 31, and the result values of the DNA and the call are input according to the item order of the reference report And generates a final result file outcome_test.txt for outputting the report (see FIG. 10).

The report booklet output unit 33 outputs a report describing whether or not a single nucleotide polymorphism site of the genes to be tested is nucleotide mutation using the generated final result file. If the single nucleotide polymorphic site base of the genes to be tested is a mutated base, the report may record diseases related to the mutated gene and information on nutrients or foods to prevent or ameliorate these diseases.

Table 2 to Table 16 show examples of the diseases and the recommended nutrients or foods according to the mutation type of the gene to be tested according to the present invention.

ACAT (Acetyl Co-Enzyme A Acetyltransferase) In vivo energy production related genes gene
For polymorphism It causes vitamin B12 deficiency and decreases the production of Co-Q10 and cartininin due to damage to the methylation system, reducing the in vivo energy source. Related diseases Chronic Fatigue Syndrome, Chronic Leak Syndrome, Celiac Disease, Inflammatory Bowel Disease, Hypercholesterolemia, Neurological Symptoms, Tumor Recommended intake component Curcumin, Vitamin B12 (riboflavin), Co-Q10, Carnitine

AHCY (S-Adenosylhomocysteine Hydrolase) Genes that function to degrade S-AdenosylHomocysteine (SAH) into adenosine and homocysteine gene
For polymorphism Because it is the only pathway that produces homocysteine, mutations in the causative electrons will lower the concentration of homocysteine, causing problems with the overall functionality of the methylation circuit. Related diseases Developmental delay, digestive disorders, intellectual impairment, coronary artery disease, heart failure, lack of gene synthesis Recommended intake component Vitamin E, vitamin B12, selenium, folic acid, SAMe, milk, NADH, lactoferrin, soy, colostrum

BHMT (Betaine-Homocysteine methyltransferase) Genes that directly convert homocysteine into methionine gene
For polymorphism 011-BHMT shows a similar abnormality to that caused by overdosing of homocysteine due to CBS deficiency because homocysteine is not capable of converting to methionine and the whole function of methylation circuit is degraded and homocysteine is decomposed. It's possible. Therefore, if you have this gene polymorphism, you should avoid taurine ingestion and limit your exposure to toxins such as ammonia. 009-BHMT is associated with HVA, a product of the dopamine metabolism, and polymorphisms in this gene may increase MHPG levels, leading to symptoms associated with concentration disorders. Related diseases (ADD), attention deficit hyperactivity disorder (ADHD), liver cancer, tumor, abdominal aortic aneurysm, non-Hodgkin's lymphoma, congenital heart disease Recommended intake component Curcumin, carnitine, SAMe, policosanol, betaine, choline, zinc

Cystathionine-beta-synthase (CBS) Genes that convert homocysteine to cystathionine gene
For polymorphism The presence of 012-CBS gene polymorphism increases uptake of homocysteine in the body up to 10 times that of normal genes, resulting in rapid production of toxins such as ammonia and sulfur oxides. Because these human toxin detoxification uses a substance called BH4, the 027-MTHFR gene involved in BH4 synthesis needs to be analyzed together. In addition, SUOX gene analysis, which converts sulfite to sulfate, is highly recommended. If the polymorphisms of these genes are duplicated, the risk of the associated symptoms or illness may be higher. Related diseases Attention deficit hyperactivity disorder (ADHD), liver cancer, tumor, aphasia, intellectual disability, athletic disability Recommended intake component Curcumin, carnitine, SAMe, policosanol, betaine, choline, zinc

COMT (Catechol-O-methyltransferase) Genes involved in the degradation of neurotransmitters (dopamine, norepinephrine) gene
For polymorphism Due to the polymorphism of the 015-COMT gene, the activity of degrading neurotransmitters such as dopamine may be lower than in normal people. The polymorphism of the 020-COMT gene increases the activity of degrading dopamine. The increase or decrease of neurotransmitters such as dopamine is known to be one of the causes of frequent changes in emotions and related diseases such as when neurotransmitter balance is broken. Related diseases (ADD), attention deficit hyperactivity disorder (ADHD) learning disorder, conduct disorder, depression, tic disorder, bipolar disorder, emotional upset, bipolar disorder, Parkinson's disease, schizophrenia, fibromyalgia, borderline personality disorder Recommended intake component Vitamin B12, vitamin D, SAMe, curcumin

MAOE (Monoamine Oxidase A) The gene involved in the degradation of the neurotransmitter serotonin gene
For polymorphism Serotonin can be elevated in the body as it has a poor ability to break down serotonin produced from tryptophan (serotonin is a substance that causes drowsiness, lethargy, depression, etc.). Because the reasoning is located in the Xchromosome, When you have polymorphism, you do not have a homologous chromosome that can compensate for it, so the symptoms and the risk become higher. Related diseases Anxiety disorders, airport disturbances, depression, Brunner syndrome, Lesch-nyhan syndrome, obsessive compulsive disorder, attention deficit hyperactivity disorder, antisocial personality disorder, social phobia, borderline personality disorder, Intellectual disability, Alzheimer's disease Recommended intake component 5-HTP, zinc, NADH, trehalose, Niacinamide SeroMood Compound Supplement ²

MTHFR (5,10-Methylenetetrahydrofolate Reductase) A gene involved in the conversion of THF absorbed from folic acid to 5-methyl THF gene
For polymorphism The 025-MTHFR gene polymorphism can lower the conversion of THF to 5-MTHF (5-methyltetrahydrofolate), which in turn reduces the conversion of homocysteine to methionine. Lowering the amount of methionine degrades the overall function of the methylation circuit.
People with a polymorphism of the 027-MTHFR gene may have a lower production of BH4 than normal individuals. Related diseases 025-MTHFR: hyperactivity disorder, heart disease, stroke, heart arrhythmia, thrombosis, peripheral neuropathy, colorectal cancer, pulmonary embolism
027-MTHFR: Depression, Anxiety, Irritable Bowel Syndrome, Fibromyalgia, Chronic Fatigue, Dementia Recommended intake component BH4, L-5-MTHF, folic acid, vitamin B12, vitamin E, Krill oil, omega 3, zinc, silymarin,

MTR (Methionine synthase) Genes involved in the process of converting homoscedeses to methionine Methionine synthase reductase (MTRR) A gene involved in the methyl-B12 regeneration necessary for the smooth functioning of the MTR enzyme gene
For polymorphism The polymorphism of the MTR gene promotes 5-MTHF and homocysteine degradation and increases methionine production using methyl-B12. Therefore, methyl-B12 consumption is higher than normal people, so it may cause deficiency symptoms.
The MTRR gene allows the reuse of methyl-B12 in the body. Therefore, polymorphism of this gene will cause methyl-B12 deficiency. Related diseases Huntington's disease, autism, macrosomia, cancer, brain disease, homocystineuria, methylmalonic acid, multiple sclerosis Recommended intake component Methyl-B12 *, betaine, curcumin, carnitine, SAMe, policosanol, choline, zinc
* Since the supply of methyl-B12 is also related to the COMT gene, it is recommended to take hydroxyl-B12 for COMT (+ / +) and methyl-B12 for COMT (- / -).

Nitric Oxide Synthase Nitric Oxide (NOS) Genes involved in ammonia degradation and nitric acid production gene
For polymorphism Ammonia decomposition will be lower than normal people. Therefore, the CBS gene involved in ammonia production and the MTHFR analysis involved in the production of BH4 used for ammonia degradation should be combined. Having a polymorphism in all three genes can lead to a higher risk for the associated symptoms or illness. Related diseases Cardiovascular disease, hypertension, atherosclerosis, heart disease, diabetes, stroke, hypertension, hypercholesterolemia, renal disease, hyperglycemia Recommended intake component Omega3, BH4, vitamin B12, vitamin C (avoid foods with high sulfur content)

Serine hydroxymethyltransferase (SHMT) Genes responsible for 5-10-MethyleneTHF, a precursor for DNA synthesis gene
For polymorphism The amount of 5-formyl folate required for DNA synthesis may decrease. Related diseases Heart related diseases (hypertension, arteriosclerosis, stroke) Recommended intake component Vitamin B6, folic acid, vitamin B12, 5-MTHF (5-methyltetrahydrofolate), colostrum, protease, trehalose,
AHCY / SHMT-IronRelatedBacterialIssues60Capsules ³

SUOX (sulfite oxidase) Genes involved in the conversion of strong sulfites to sulfates gene
For polymorphism Since the ability to detoxify toxins in the body is reduced, exposure to toxins from the environment as well as toxins in the body can be more sensitive than normal people. Related diseases Asthma, allergies, inflammation, hereditary fulminant hyperglycemia, brain softening, dystonia, intellectual disability, Weill-Marchesani syndrome, leukemia Recommended intake component Molybdenum (Mo), boron, vitamin E, succinate, vitamin B12,
(Avoid foods with high sulfur content)

VDR (vitamin D receptor) Vitamin D receptor gene
For polymorphism The 039-VDR gene polymorphism may lower levels of vitamin D and dopamine in the body. The 040-VDR gene polymorphism has lower levels of glucose and pancreatic function in the blood than normal individuals. Related diseases (ADD), attention deficit hyperactivity disorder (ADHD), learning disorder, conduct disorder, depression, tic disorder, bipolar disorder, emotional relief, bipolar disorder, Parkinson's disease, schizophrenia, fibromyalgia, Disability) and rickets, osteoporosis, hair loss Recommended intake component Vitamin K, common pancreatic function adjuvant, glucose regulator (low-carbohydrate food, chromium supplement) COMT (- / -) and VDR Taq (+ / +): dopamine precursors such as quercetin or macunapuriens COMT (+ / +) And VDR Taq (- / -): If the polymorphisms of MTR / MTRR are present together, avoid feeding methyl-B12 and ingesting hydroxyl-B12. Do not administer dopamine precursors.

Thymidylate synthase (TS) Genes that convert deoxyuridylate to thymidylate gene
For polymorphism Due to the polymorphism, activity of the related enzymes may be decreased to increase the amount of dUTP, increase the instability of the genome, and there may be a problem in the synthesis of DNA containing genetic information. Related diseases Cerebrospinal fluid disorder, hereditary movement disorder, stomach cancer, colon cancer Recommended intake component L-5-MTHF, folic acid, vitamin B12, vitamin B2, vitamin B6

GST_M1 (Glutathione S-transferase Mu 1) Genes involved in facilitating the release of various toxic substances out of the body gene
For polymorphism Gene polymorphism in GSTM1 can reduce the ability of the body to excrete toxins in the body and prevent toxic substances from being released smoothly. Related diseases Bladder cancer, asthma, esophageal cancer, endometriosis, laryngeal cancer, prostate cancer, lung cancer, chronic obstructive pulmonary disease Recommended intake component Vitamin C, Vitamin E, Selenium, Beta Carotene

11 to 14 illustrate a report that is finally output and is provided to the examinee. The report page 1 in Fig. 11 is a cover page, and information such as a test date, a receipt number, and a name of a examinee is written. In the test report page 2 of Fig. 11, description contents of gene test related to autism and developmental delay are written. A schematized diagram that can be easily understood by the examinee can be inserted.

In the report page 3-4 of FIG. 12, a table created by converting outcome.txt into an HTML source is written.

In the test report page 5 of FIG. 13, an image of a methylation pathway in vivo is displayed, in which the names and signatures of inspectors, data analysis, and responsible persons are inserted. The report page 6-9 of FIG. 13 describes the characteristics according to the test item genes. In the case of a mutation base, if the gene is mutated, describe the disease related to the mutant gene, the recommended intake nutrients, and the food. On page 9-11 of the test report in Figure 14, reference is made to nutrition-containing foods, complex component elements and the role of important in vivo components.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the same is by way of illustration and example only and is not to be construed as limiting the scope of the present invention. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.

&Lt; 110 > Solgent Co., Ltd. <120> Method of Providing Recommended Dietary Information for New Born          Infant Based on Genetic Test and System for the Same Method <130> PN130136 <160> 40 <170> Kopatentin 2.0 <210> 1 <211> 51 <212> DNA <213> Homo sapiens <400> 1 aatttcttta atgactgagc catgcygatg caataggcat acaaaaatat t 51 <210> 2 <211> 52 <212> DNA <213> Homo sapiens <400> 2 tgctctatat aacgggatta cgtccayctc tatgaagatt attgtgtaaa ca 52 <210> 3 <211> 52 <212> DNA <213> Homo sapiens <400> 3 ttcatttagt acatttaggg actggcraaa ttctcaccct cctttgactg gt 52 <210> 4 <211> 52 <212> DNA <213> Homo sapiens <400> 4 gtgaaaagta ttatggaaat cactgcwgca caggaaaagt aattcagatg tt 52 <210> 5 <211> 52 <212> DNA <213> Homo sapiens <400> 5 tgcaggatct catcagcggt ggtgtcrtag tgagccaggg ggttgctggc gt 52 <210> 6 <211> 52 <212> DNA <213> Homo sapiens <400> 6 agcacggtgg cggtggccgt gaaggcygcg caggagctgc aggagggcca gc 52 <210> 7 <211> 52 <212> DNA <213> Homo sapiens <400> 7 cccagcggat ggtggatttc gctggcrtga aggacaaggt gtgcatgcct ga 52 <210> 8 <211> 52 <212> DNA <213> Homo sapiens <400> 8 cgcctgctgt caccaggggc gaggctbatc accatcgaga tcaaccccga ct 52 <210> 9 <211> 52 <212> DNA <213> Homo sapiens <400> 9 gcagagagaa accagttaat tcagcgkctt ccaatgggag ctgtcattaa gt 52 <210> 10 <211> 52 <212> DNA <213> Homo sapiens <400> 10 cttgaaggag aaggtgtctg cgggagycga tttcatcatc acgcagcttt tc 52 <210> 11 <211> 52 <212> DNA <213> Homo sapiens <400> 11 gtggggggag gagctgacca gtgaagmaag tgtctttgaa gtcttcgttc tt 52 <210> 12 <211> 52 <212> DNA <213> Homo sapiens <400> 12 ggaagaatat gaagatatta gacaggrcca ttatgagtct ctcaaggtaa gt 52 <210> 13 <211> 52 <212> DNA <213> Homo sapiens <400> 13 caggcaaagg ccatcgcaga agaaatrtgt gagcaagctg tggtacatgg at 52 <210> 14 <211> 52 <212> DNA <213> Homo sapiens <400> 14 cccctgctgc tgcaggcccc agatgakccc ccagaactct tccttctgcc cc 52 <210> 15 <211> 52 <212> DNA <213> Homo sapiens <400> 15 gtcaggcagg ccaggcagag ggaagaraga ggcgaagctc tcaacctcct cc 52 <210> 16 <211> 52 <212> DNA <213> Homo sapiens <400> 16 cctggggtgc aggacgccgc gctgatygag gccatccagg accgcctgtc ca 52 <210> 17 <211> 52 <212> DNA <213> Homo sapiens <400> 17 tggcctgctt gctgttctta cagggangga ggcaatggcg gccagcactt cc 52 <210> 18 <211> 52 <212> DNA <213> Homo sapiens <400> 18 gttcctgggg ccacagacag gcctgcrcat tcccaatact caggctctgc tc 52 <210> 19 <211> 52 <212> DNA <213> Homo sapiens <400> 19 tctccatccc ggggctctgt gatggcvgac tggacaggaa gttcctgaat gg 52 <210> 20 <211> 57 <212> DNA <213> Homo sapiens <400> 20 tatagcaaca tataaaacaa ctataacttt aaagttcata accacactct acatcat 57 <210> 21 <211> 15 <212> DNA <213> Homo sapiens <400> 21 tatgcctatt gcatc 15 <210> 22 <211> 15 <212> DNA <213> Homo sapiens <400> 22 aataatcttc ataga 15 <210> 23 <211> 15 <212> DNA <213> Homo sapiens <400> 23 aggagggtga gaatt 15 <210> 24 <211> 15 <212> DNA <213> Homo sapiens <400> 24 tatggaaatc actgc 15 <210> 25 <211> 15 <212> DNA <213> Homo sapiens <400> 25 aaccccctgg ctcac 15 <210> 26 <211> 15 <212> DNA <213> Homo sapiens <400> 26 gcggtggccg tgaag 15 <210> 27 <211> 15 <212> DNA <213> Homo sapiens <400> 27 gtggatttcg ctggc 15 <210> 28 <211> 15 <212> DNA <213> Homo sapiens <400> 28 tcaccagggg cgagg 15 <210> 29 <211> 15 <212> DNA <213> Homo sapiens <400> 29 aaccagttaa ttcag 15 <210> 30 <211> 15 <212> DNA <213> Homo sapiens <400> 30 aaggtgtctg cggga 15 <210> 31 <211> 9 <212> DNA <213> Homo sapiens <400> 31 gtgtctttg 9 <210> 32 <211> 15 <212> DNA <213> Homo sapiens <400> 32 gaagatatta gacag 15 <210> 33 <211> 15 <212> DNA <213> Homo sapiens <400> 33 gccatcgcag aagaa 15 <210> 34 <211> 15 <212> DNA <213> Homo sapiens <400> 34 gaggccatcc aggac 15 <210> 35 <211> 15 <212> DNA <213> Homo sapiens <400> 35 aggcaatggc ggcca 15 <210> 36 <211> 15 <212> DNA <213> Homo sapiens <400> 36 ccacagacag gcctg 15 <210> 37 <211> 15 <212> DNA <213> Homo sapiens <400> 37 ctgcaggccc cagat 15 <210> 38 <211> 15 <212> DNA <213> Homo sapiens <400> 38 gagagcttcg cctct 15 <210> 39 <211> 15 <212> DNA <213> Homo sapiens <400> 39 gaacttcctg tccag 15 <210> 40 <211> 15 <212> DNA <213> Homo sapiens <400> 40 agtgtggtta tgaac 15

Claims (17)

There is provided a method for providing nutrient or food information necessary for ingestion in order to improve or prevent a disease associated with a base mutated gene after obtaining information on base mutation by performing gene base sequence analysis on a newborn baby as follows How to:
(A) obtaining base mutation information at a single nucleotide polymorphism position of genes to be tested;
(B) a step of outputting a report describing the base mutation information obtained in the step (a), wherein when the single nucleotide polymorphic site base of the genes to be tested is judged to be a mutant base, the disease associated with the base mutated gene is improved Or to record the nutrient or food information required to be ingested in the report to prevent it.
The method of claim 1, wherein the step (a) is performed by a method of (i) sequencing, (ii) a real time PCR method, or (iii) How to.
3. The method according to claim 2, wherein said step (a) is performed by (i) a method of sequencing, comprising the steps of:
(a) determining the nucleotide sequence of the DNA of the test subject gene from the biological sample of the newborn using the gene sequencer, inputting the determined nucleotide sequence of the DNA through the gene sequence inputting device, Converting into a suitable file format through a base sequence converter;
(b) constructing a reference gene database by storing the nucleotide sequence information including the single nucleotide polymorphism site of the genes to be tested, and comparing the single nucleotide polymorphism site of the genes to be tested with the up- stream region or a 5'-direction downstream region of the nucleotide sequence database to construct a border sequence database, and the converted nucleotide sequence file to be analyzed in the step (a) A base sequence to be analyzed, a base sequence stored in the boundary sequence database, and a base sequence of a single base polymorphic site stored in the reference gene database are retrieved through a gene base sequence comparator, The polymorphism site was identified as a base mutation, and the obtained base mutation The variations for the entire result if the entire inspection target gene through the table builder recorded based on the discrimination data, the steps to create a full-result table; And
(c) establishing a reference certificate database by storing information on the report form format, extracting the results from the entire result table created in the step (b) through the report result file creator, Generating a final result file for outputting a test report, and outputting a test report describing whether a single nucleotide polymorphism site of the test target genes has a base mutation using the generated final result file through a test report output unit, When the single nucleotide polymorphic site of the genes to be tested is determined to be a mutant base in step (b), the nutrition or food information necessary for ingesting to improve or prevent disease associated with the base mutated gene through the test report reader Record in the report.
The method according to claim 2, wherein the step (a) is performed by (ii) a real time PCR (Real Time Polymerase Chain Reaction) method, comprising the steps of:
(a) an oligonucleotide probe capable of binding to a sequence containing a single nucleotide polymorphism (SNP) base of the genes to be tested, the probe comprising a base probe specifically binding to a mutation base of the SNP, And a wild type base probe that specifically binds to the wild type base of the SNP base is prepared, and the oligonucleotide primer capable of amplifying the sequence containing the SNP base is prepared by binding a different fluorescent substance to the mutated base probe and the wild type base probe, ;
(b) DNA nuclei obtained from a biological sample of a newborn using a mutagenic base probe, a wild type base probe and a primer prepared in the step (a) in a 'Real Time-Polymerase Chain Reaction';
(c) analyzing the real-time PCR result obtained in the step (b) in the real-time PCR result analyzer to check whether a single nucleotide polymorphic site of the gene to be tested has a base mutation;
(d) creating a complete result table in which the mutation status of the entire gene to be examined is recorded through the entire result table generator based on the discrimination data on whether the nucleotide polymorphism of the single nucleotide polymorphism site identified in the step (c) step;
(f) constructing a reference report database by storing information on the report form format, extracting the results from the entire result table created in the step (d) through the report result file creator, Generating a final result file for outputting a test report after comparing with a test report format and outputting a test report describing whether or not a base mutation of a single nucleotide polymorphism site of the genes to be tested is described using the generated final result file through a report writer , When the single nucleotide polymorphic site of the genes to be tested is judged to be a mutant nucleotide in the step (c) ', the nutrient necessary for ingesting to improve or prevent the disease associated with the gene mutated through the test report Record food information in a report.
The method according to claim 3 or 4, wherein the gene to be tested in step (a) or (a) is one or more genes selected from the group consisting of the following genes:
ACAT (Acetyl-Coenzyme-A-acetyltransferase),
AHCY (S-adenosylhomocysteinehydrolase),
BHMT (Betaine &lt; RTI ID = 0.0 &gt; omocysteinemethytransferase)
Cystathionine-beta-synthase (CBS),
COMT (Catechol-O-methyltransferase),
MAOA (Monoamineoxidase A),
Methylenetetrahydrofolatereductase (MTHFR),
MTR (Methioninesynthase),
MTRR (Methioninesynthasereductase),
SHMT (Serine hydroxymethyltransferase),
VDR (VitaminDreceptor),
NOS (NitricOxidesynthase),
SUOX (Sulfiteoxidase),
TS (Thymidylate synthase),
GST_T1 (Glutathione S-transferase theta 1), and
GST_M1 (Glutathione S-transferase Mu 1).
The method according to claim 3 or 4, wherein the single nucleotide polymorphic site of the genes to be tested is at least one selected from the group consisting of the following single nucleotide polymorphisms: ACAT-rs3741049 (SEQ ID NO: 1), AHCY-rs819147 (SEQ ID No. 2), BHMT-rs651852 (SEQ ID No. 3), BHMT-rs58580 (SEQ ID No. 4), CBS-rs234706 (SEQ ID No. 5), CBS- rs1801181 , MTHR-rs1801131 (SEQ ID NO: 11), MTR-rs1805087 (SEQ ID NO: 12), MTRR-rs1801394 (SEQ ID NO: 9), COMT-rs4818 (SEQ ID NO: 13), VDR-rs1799983 (SEQ ID NO: 14), SHMT-rs1979277 (SEQ ID NO: 15), VDR-rs731236 SUOX-rs7731115 (SEQ ID NO: 19), TS-rs16430 (SEQ ID NO: 20).
4. The method according to claim 3, wherein the base sequence comprising a single nucleotide polymorphic site of the gene to be tested, which is stored in the reference gene database of step (b), comprises three nucleotides constituting one codon at a single nucleotide polymorphism site, Wherein the nucleotide sequence is a nucleotide sequence in which any nucleotide sequence is added to the 3 nucleotide 3'-direction upstream (up-stream) and 5'-direction downstream (down-stream).
4. The method according to claim 3, wherein the determination of whether or not the single nucleotide polymorphic site of the gene to be inspected in the gene base sequence comparator of step (b) is a base mutation is performed by sorting the nucleotide sequence to be analyzed and the nucleotide sequence stored in the boundary sequence database Adding an arbitrary nucleotide sequence before and after three nucleotides next to the border sequence end, and outputting the nucleotide sequence with a unique number attached thereto.
9. The method according to claim 8, wherein the determination of whether or not a single nucleotide polymorphism site of the subject gene in the gene base sequence comparator of step (b) is a base mutation is performed by comparing the base sequence output with the unique number, Number of the polymorphism site of the gene to be tested, and performing sequence discrimination to discriminate whether the polymorphism site of the single nucleotide polymorphism of the gene to be tested is a base mutation.
A system for providing nutrient or food information that requires ingestion to improve or prevent a disease associated with a base-mutated gene after performing information on base mutation by performing gene base sequence analysis on a newborn baby,
The system includes a gene sequence analyzing unit 10, a gene mutation discriminating unit 20, and a test report preparing unit 40,
The gene sequence analyzer 10 includes a gene sequence analyzer 11 for determining the nucleotide sequence of the DNA of a test subject from a biological sample of a newborn baby, a gene sequence sequence input unit 12 for inputting the determined nucleotide sequence of the DNA, And a gene base sequence converting unit (13) for converting the base sequence of the inputted DNA into a suitable file format,
The gene mutation discriminator 20 comprises a gene base sequence file input unit 21 for inputting a file of a base sequence to be analyzed, a reference gene database storing a nucleotide sequence information including a single nucleotide polymorphism site of the genes to be tested (22), a boundary sequence database (23) for storing nucleotide sequence information in a 3'-direction upstream region or a 5'-direction downstream region based on a single nucleotide polymorphism site of the gene to be tested, A nucleotide sequence comparison unit for comparing the nucleotide sequence stored in the border sequence database unit and the nucleotide sequence of the single nucleotide polymorphic site stored in the reference gene database unit to determine whether the nucleotide sequence of the single nucleotide polymorphic site of the gene to be tested is a base mutation 24), the base mutation determination data obtained by the gene base sequence comparison unit And on the basis of the results include the entire table creation unit 25 for creating a full-result table mutated whether the record of all of the inspection target gene,
The report creating unit 40 extracts a result from the created result report table 41, compares the result with the report form format from the reference report database 41, A report result file creating unit 42 for generating a final result file for outputting a test report, a base mutation site of the single nucleotide polymorphism site of the genes to be tested is described using the generated final result file, (43) for outputting a report describing the nutrient or food information required for ingesting to improve or prevent the disease associated with the gene mutated in the test report when the polymorphic site base is judged to be a mutant base &Lt; / RTI &gt;
A system for providing nutrient or food information that requires ingestion to improve or prevent a disease associated with a base-mutated gene after performing information on base mutation by performing gene base sequence analysis on a newborn baby,
The system includes a gene sequence analysis and gene variation discrimination unit 30 and a report writing unit 40,
The gene sequence analysis and gene mutation discrimination unit 30 is an oligonucleotide probe capable of binding to a sequence containing a single nucleotide polymorphism (SNP) base of the genes to be tested, which specifically binds to a mutation base of the SNP A DNA base nucleic acid obtained from a biological sample of a newborn using a wild type base probe that specifically binds to the wild type base of the SNP and an oligonucleotide primer capable of amplifying the sequence containing the SNP base, A real-time PCR reaction unit 31 for performing real-time PCR on a subject, a real-time PCR result analysis unit 32 for analyzing a real-time PCR result to confirm whether a single nucleotide polymorphic site of the subject gene is a base mutation, Based on the discrimination data on the base mutation obtained from the division, The variation whether the entire record full results total result to create a table includes a table producing unit 33,
The report creating unit 40 extracts a result from the created result report table 41, compares the result with the report form format from the reference report database 41, A report result file creating unit 42 for generating a final result file for outputting a test report, a base mutation site of the single nucleotide polymorphism site of the genes to be tested is described using the generated final result file, (43) for outputting a report describing the nutrient or food information required for ingesting to improve or prevent the disease associated with the gene mutated in the test report when the polymorphic site base is judged to be a mutant base &Lt; / RTI &gt;
12. The system according to claim 10 or 11, wherein the gene to be tested is at least one gene selected from the group consisting of the following genes:
ACAT (Acetyl-Coenzyme-A-acetyltransferase),
AHCY (S-adenosylhomocysteinehydrolase),
BHMT (Betaine &lt; RTI ID = 0.0 &gt; omocysteinemethytransferase)
Cystathionine-beta-synthase (CBS),
COMT (Catechol-O-methyltransferase),
MAOA (Monoamineoxidase A),
Methylenetetrahydrofolatereductase (MTHFR),
MTR (Methioninesynthase),
MTRR (Methioninesynthasereductase),
SHMT (Serine hydroxymethyltransferase),
VDR (VitaminDreceptor),
NOS (NitricOxidesynthase),
SUOX (Sulfiteoxidase),
TS (Thymidylate synthase),
GST_T1 (Glutathione S-transferase theta 1), and
GST_M1 (Glutathione S-transferase Mu 1).
12. The system according to claim 10 or 11, wherein the single nucleotide polymorphic site of the genes to be tested is at least one selected from the group consisting of the following single nucleotide polymorphisms: ACAT-rs3741049 (SEQ ID NO: 1), AHCY-rs819147 (SEQ ID No. 2), BHMT-rs651852 (SEQ ID No. 3), BHMT-rs58580 (SEQ ID No. 4), CBS-rs234706 (SEQ ID No. 5), CBS- rs1801181 , MTHR-rs1801131 (SEQ ID NO: 11), MTR-rs1805087 (SEQ ID NO: 12), MTRR-rs1801394 (SEQ ID NO: 9), COMT-rs4818 (SEQ ID NO: 13), VDR-rs1799983 (SEQ ID NO: 14), SHMT-rs1979277 (SEQ ID NO: 15), VDR-rs731236 SUOX-rs7731115 (SEQ ID NO: 19), TS-rs16430 (SEQ ID NO: 20).
11. The method according to claim 10, wherein the base sequence comprising a single nucleotide polymorphic site of the gene to be tested stored in the reference gene database (22) comprises three nucleotides constituting one codon at a single nucleotide polymorphism site, Wherein the nucleotide sequence is a nucleotide sequence in which any nucleotide sequence is added to 3 nucleotides in the 3 'direction upstream (up-stream) and 5' direction downstream (down-stream).
11. The method according to claim 10, wherein the determination of whether or not the single nucleotide polymorphism site of the subject gene in the gene base sequence comparison unit (24) is a base mutation is performed by sorting the nucleotide sequence to be analyzed and the nucleotide sequence stored in the boundary sequence database Comprising the step of adding an arbitrary nucleotide sequence before and after three nucleotides following the sequence end and outputting the nucleotide sequence with a unique number attached thereto.
16. The method according to claim 15, wherein the determination of whether or not the single nucleotide polymorphic site of the subject gene in the gene base sequence comparison unit (24) is a base mutation is performed by comparing the base sequence output with the unique number, And performing sequence alignment to discriminate whether a single nucleotide polymorphic site of the gene to be tested is a base mutation or not.
A computer-readable recording medium on which a program for executing the method according to any one of claims 1 to 9 is recorded.

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