JP2004239766A - Test method using dna microarrays - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To make a subject surely identificable and specificable when testing health condition by using DNA microarrays. <P>SOLUTION: The test method is practiced by reading (step S1) a hybridization pattern of the DNA microarrays including a first DNA probe group (area B) which can be utilized for identifying the subject and a second DNA probe group (area A) which can be utilized for testing health condition of the subject, identifying (steps S3 to S7) the subject by analyzing a pattern corresponding to the first DNA probe group from the hybridization pattern which has been read and by generating (steps S8 to S10) test information by analyzing a pattern corresponding to the second DNA probe group from the hybridization pattern which has been read. <P>COPYRIGHT: (C)2004,JPO&NCIPI

Description

[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a testing technique using a so-called DNA microarray for testing a health condition by testing a gene from a sample such as blood.
[0002]
[Prior art]
In a sample test using the subject's blood, saliva, urine, etc., enter the sample number for each container containing the sample, except for those that give simple results on the spot. After recording the correspondence so that it can be understood, the analysis is performed by the test device or the sample is sent to the test facility.
[0003]
In the case of performing a health checkup for the purpose of preventing a disease by the above-mentioned specimen test or when observing the course of the disease, comparison with past test results is important or necessary. At this time, when performing a medical examination in a company or an examination for a patient at a hospital, the examinee is managed by an identification number (ID number) or the like. It is relatively easy to see the results. However, if the identification number is incorrectly input when searching for a subject, the test result of another subject will be referred to.
[0004]
On the other hand, if a person undergoes a personal health checkup or receives a test by mail or courier, the identification number of the subject is already registered for the second and subsequent tests. Often. In this case, if the subject correctly remembers his / her own identification number or has a card or the like on which the identification number is written, the subject is identified and specified, and the past test results are referred to. It is easy. However, if the subject does not correctly remember the identification number or loses the card or the like on which the identification number is written, it becomes difficult to search past test records of the subject.
[0005]
Further, when trying to identify and identify the subject from the name and the date of birth, the same name and date of birth may be the same person, and it is not sufficient to reliably identify the subject. When the address and the telephone number are used, they may be changed. Therefore, there is a problem in reliability in identifying the subject. In addition, if the subject is present, there is a possibility that fingerprints, voiceprints, irises, retinal patterns, and the like can be used to identify and specify the subject. However, in the case of a sample alone, it is not possible to identify and specify by these methods.
[0006]
[Patent Document 1]
JP 2001-147231 A
[Problems to be solved by the invention]
As described above, it is difficult to reliably identify and identify the subject by the conventional method, and in many cases, past test data cannot be searched.
[0008]
Recently, it has become possible to use a DNA microarray (also referred to as a DNA chip) to diagnose some cancers and determine liver function as one of the sample testing methods. In the future, it is expected that tests using such a DNA microarray, such as diagnosis of various diseases and selection of a treatment method, will become possible. However, even in an inspection using a DNA microarray, management is performed by writing a number or a barcode on the DNA microarray itself by engraving or the like. Alternatively, it has been proposed that a DNA microarray incorporates an IC memory to store and manage the name, gender, number, and the like of a subject (see Patent Document 1). However, no method has been proposed for reliably identifying and specifying a subject corresponding to the DNA microarray.
[0009]
The present invention has been made in view of the above-described problem, and it is an object of the present invention to reliably identify and specify a subject when performing a health test using a DNA microarray.
[0010]
[Means for Solving the Problems]
An inspection method using the DNA microarray according to the present invention for achieving the above object,
Reading to read a hybridization pattern in a DNA microarray including a first DNA probe group that can be used to identify the subject and a second DNA probe group that can be used to test the health condition of the subject Process and
An identification step of analyzing a pattern corresponding to the first DNA probe group from the hybridization pattern read in the reading step to identify a subject;
Generating a test information by analyzing a pattern corresponding to the second DNA probe group from the hybridization pattern read in the reading step.
[0011]
BEST MODE FOR CARRYING OUT THE INVENTION
Hereinafter, preferred embodiments of the present invention will be described with reference to the accompanying drawings.
[0012]
FIG. 1 shows a block diagram of an inspection system using a DNA microarray in the present embodiment. The output of a barcode reader 2, the input / output of a DNA microarray reader 3, and the input / output of a storage device 4 such as a hard disk are connected to a system control unit 1 that controls the entire system.
[0013]
The DNA microarray 5 is subjected to the following reaction in advance. DNA is extracted with a DNA extractor from the blood collected from the subject, and the extracted DNA is subjected to a hybridization reaction with the DNA microarray 5 in a reaction device.
[0014]
The DNA microarray 5 is composed of tens to hundreds of thousands of DNA probes arranged at high density on a solid surface such as a glass plate of about 1 inch square. By performing a hybridization reaction with sample DNA using the DNA microarray 5, it is characterized in that many genes can be tested at once. Further, these DNA probes are regularly arranged in a matrix, and the feature is that the address (for example, the number of rows and the number of columns) of each DNA probe can be easily taken out as information. Known genes to be tested include gene polymorphisms of individuals as well as disease-related genes.
[0015]
FIG. 2 shows a DNA microarray 5 of the present embodiment. In the drawing, DNA probes having different sequences are bound to the regions indicated by ○. A region A in FIG. 2 is provided with a DNA probe group used for testing the health condition of a disease or the like, which is the original test purpose of the DNA microarray 5, and forms a test DNA probe sequence portion. . In the region A, only a DNA probe for testing a disease to be tested may be arranged, or if there is room, DNA probes for a plurality of diseases are arranged, and You may make it detect only a DNA probe.
[0016]
On the other hand, a region B in FIG. 2 is a portion where DNA probe groups for identifying a subject are arranged. In the present embodiment, approximately 500 types of DNA probes for the major histocompatibility complex (MHC) gene are used as the DNA probes for identification arranged in the region B. Then, the subject is identified from a hybridization pattern image obtained by reacting the DNA probe group in the region B with the DNA of the subject.
[0017]
The MHC gene is a region where genes of the immune system are most concentrated in the human genome, and its nucleotide sequence has recently been clarified (Nature volume 401, p921-923, 1999) and has attracted attention. This sequence contains a gene involved in the determination of conformity / incompatibility in bone marrow transplantation, organ transplantation and the like. At present, the determination of conformity / incompatibility in organ transplantation and bone marrow transplantation is performed by testing using leukocytes, but testing using leukocytes is time-consuming and has a small amount of information. Is expected to become mainstream. There are three types of MHC (HLA antigen in the case of human) as class I antigens, HLA-A, B and C, and three types of class II antigens as HLA-DR, DQ and DP.
[0018]
Each individual receives a total of 12 antigens, one from each of their parents, which is the "type" of that individual. On the other hand, at present, about 1000 types of genes including HLA-A, HLA-B, HLA-C, HLA-DR, HLA-DQ, and HLA-DP have been identified. Newer MHC genes are being elucidated one after another, and the number is expected to increase further in the future. Since only 12 genes are selected from among 1000 or more genes, it is considered extremely rare that a combination of each type with another person is matched. In fact, in the case of bone marrow transplantation and organ transplantation, the above-mentioned combinations of types rarely match. This indicates that the pattern of the MHC gene is rich in variations, and can be considered as a gene group suitable for individual identification. Also, this group of genes does not change with age. In the present embodiment, utilizing such a situation, an individual is identified using a DNA probe for 500 of the above 1,000 or more genes.
[0019]
A region C in FIG. 2 is a portion on which a barcode is described, and a barcode indicating the type of the DNA microarray 5 and a manufacturing number by which each of them can be identified is recorded. The barcode may be printed directly on the DNA microarray 5, or may be printed and pasted on paper or the like.
[0020]
In the present embodiment, the portion where the DNA probes for identifying the subject are arranged and the portion where the DNA probes used for examining a health condition such as a disease are clearly separated, but for each probe, If they are managed by address, there is no problem even if both are mixed.
[0021]
Now, the DNA microarray 5 after the above-mentioned hybridization reaction is as shown in FIG. 3, for example. In the figure, the region indicated by ● emits fluorescence with a probe that has formed a hybrid with the DNA of the subject. The pattern formed by ● is a hybridization pattern. In the portion where the DNA probes for identifying the subject are arranged (region B), the result of the hybridization reaction is binary, and either the hybridization reaction is performed or not. That is, it is composed of two types, that is, whether or not it emits fluorescence (● and ○). On the other hand, although not shown in FIG. 3, in a portion (region A) where DNA probes used for testing the health state of a disease or the like, which is the original test purpose of the DNA microarray 5, there is also an intermediate between the two.
[0022]
FIG. 4 is a flowchart illustrating a processing procedure in the inspection system using the DNA microarray 5 of the present embodiment. First, in step S1, the system control unit 1 of the inspection system causes the barcode reader 2 to read the barcode described in the area C (FIG. 2) of the DNA microarray 5. The hybridization pattern is read by the DNA microarray reader 3.
[0023]
The barcode in the region C of the DNA microarray 5 is a code for identifying the DNA microarray 5, as described above. In step S2, the system control unit 1 determines the type of the DNA microarray 5 from the barcode reading result. Thus, it is possible to determine which disease the DNA microarray 5 to be tested is for. When a DNA microarray 5 having a different combination of DNA probes for identifying a subject in the region B is used, it is necessary to put that information in a barcode. In this case, the individual is identified based on the type of the DNA microarray and the pattern of the region B. In the present embodiment, information is described in a barcode on the DNA microarray 5 and the information is read by the barcode reader 2. However, numbers and characters are described instead of the barcode, and the information is read by a scanner or the like. You may make it recognize.
[0024]
If it is determined that the DNA microarray 5 is the DNA microarray 5 of the present embodiment, the hybridization pattern image for the region B from the DNA microarray reader 3 is processed and digitized in step S3. As described above, in region B, approximately 500 types of DNA probes for the MHC gene are arranged. The digitization is performed according to which DNA probe on the DNA microarray 5 has hybridized with the DNA of the subject. As described above, the DNA probes on the DNA microarray 5 are regularly arranged in a matrix, and each DNA probe can be specified by an address (for example, a position of a certain number of rows and a certain number of columns). Hereinafter, the code obtained by such digitization is referred to as a personal identification code.
[0025]
Next, in step S4, the CPU of the inspection system compares the personal identification code obtained in step S3 with the numerical value of the hybridization pattern image already registered in the inspection result database in the storage device 4, that is, the personal identification code. . The test result database has a data structure as shown in FIG. 5C, and a personal identification code 521 obtained by digitizing a hybridization pattern, corresponding subject information 522, and test result information 523 are registered in association with each other. Is done. If the same code does not exist, it is determined that the subject is a new subject, and the process proceeds to step S5. In step S5, the subject information is obtained from the production number of the DNA microarray 5 in the barcode read in step S1 (described later with reference to FIGS. 5A and 5B). Then, in step S6, the numerical value (personal identification code 521) corresponding to the hybridization pattern of the area B obtained in step S3 and the subject information 522 (name, gender, date of birth, etc. of the subject) are stored in the storage device. 4, and the process proceeds to step S8.
[0026]
In the present embodiment, when a test request is received, the correspondence between the subject (test subject information) and the sample number is registered in the storage device 4. FIG. 5A shows this registration state, in which the subject information 501 and the sample number 502 are registered in the test request report 500 in association with each other. At the time of the test, the correspondence between the registered sample number and the serial number of the DNA microarray 5 used for the test is registered in the storage device 4 as test process information 510 as preprocessing. This state is shown in FIG. The serial number 512 of the DNA microarray is registered in correspondence with the sample number 511. Therefore, in the above step S5, the corresponding sample number can be specified from the production number of the DNA microarray read from the barcode in the region C, and the subject information is obtained from this sample number.
[0027]
On the other hand, if the same numerical value is found in step S4, it is determined that the subject has been examined before and the process proceeds to step S7. In step S7, the past inspection result of the subject is read from the inspection result database in the storage device 4. If the test results other than the DNA microarray are also registered in the test result database, those results may be read at this time.
[0028]
Next, a test for a disease which is an original purpose of the DNA microarray 5 is performed. In step S8, the hybridization pattern image in the region A (FIG. 3) where the DNA probe for the test disease is arranged is processed. Then, in step S9, the positivity of each disease to be tested is calculated and registered in the test result database in the storage device 4. In the present embodiment, the positivity for each disease is calculated, but information such as the degree of cure of the disease and the selection of a treatment method will be obtained in accordance with the type of test.
[0029]
In step S10, the subject information, the current test result, and the past test result, if any, are displayed on a monitor (not shown), and / or printed by a printer (not shown). Regardless of whether the examinee only looks at the results or the doctor looks at the results and makes a diagnosis, the past test results are important in preventing and monitoring the disease.
[0030]
In this embodiment, about 500 types of DNA probes for the MHC gene are used, but the number can be reduced in consideration of other information used for identifying the subject. For example, the name and the date of birth of the subject can also be used to identify the subject, and about 200 types of DNA probes for the MHC gene can be arranged on the DNA microarray.
[0031]
In this embodiment, a DNA probe for the MHC gene is used, but a group of genes called single nucleotide polymorphism (SNPs) can also be used as a group of genes suitable for personal identification. This group of genes can be added to a DNA microarray carrying the MHC gene for the purpose of adding further information.
[0032]
As described above, the DNA microarray of the present embodiment can be used to examine the health condition of the subject, with the first DNA probe group (region B) that can be used to identify the subject. A second DNA probe group (region A). Therefore, it is possible to reliably identify and specify the subject and to perform a health condition test.
[0033]
Further, according to the present embodiment, since the first DNA probe group is composed of the probes for the genes of the major histocompatibility antigens, the probability of identifying and specifying the subject becomes extremely high and is stable. The subject can be identified.
[0034]
Further, according to the present embodiment, there is further provided a probe identification display (region C) for identifying a probe configuration of at least one of the first and second DNA probe groups. For example, if the probe identification display identifies the configuration of the second DNA probe group, it is possible to use a plurality of different types of second DNA probe groups (region A) corresponding to a plurality of types of test purposes. It becomes possible. As a result, necessary inspections can be reliably performed.
[0035]
Further, according to the present embodiment, the identification information (manufacturing number) for identifying the DNA microarray itself is included. By using this identification display, for example, even if the subject to be tested for the first time is not registered, correspondence with the subject can be surely taken.
[0036]
Further, according to the test system of the above embodiment, the first DNA probe group (region B) that can be used to identify the subject and the second DNA probe that can be used to test the health of the subject. The hybridization pattern in the DNA microarray (5) including the DNA probe group (region A) is read (DNA microarray reader 3, S1), and the pattern corresponding to the first DNA probe group is determined from the read hybridization pattern. The subject is analyzed to identify the subject (S3), and a pattern corresponding to the second DNA probe group is analyzed from the read hybridization pattern to generate test information (S8, S9).
[0037]
As described above, the test system reads the hybridization pattern of the DNA microarray, identifies the subject by referring to the information stored in the storage device 4, and tests the necessary health condition. For this reason, it is possible to reliably identify the subject to be inspected and execute the necessary inspection without performing any troublesome work by the inspector. Further, the inspection result can be stored in a storage device.
[0038]
Further, the inspection system of the present embodiment stores the subject and past test results (storage device 4), and reads out the past test results of the identified subject. As a result, it is possible to easily know the health condition in consideration of past changes. For example, when receiving a test at a hospital, if a person using a DNA microarray at the same test institution at the time of a medical checkup in a company, the subject can be easily identified and past test results can be called up. Therefore, it can be used for diagnosis in comparison with the present results.
[0039]
As described above, according to the test system of the present embodiment, it is possible to reliably determine whether or not the subject has undergone a health condition test using a DNA microarray in the past, and may have undergone the test. In this case, past test results can be presented together with the current test results.
[0040]
Further, the DNA microarray has a first identification (for example, a barcode in the area C) indicating the probe configuration of the first probe group (area B), and reads the hybridization pattern and the first identification (S1, bar). The code reader 2, the DNA microarray reader 3) analyzes the hybridization pattern of the first DNA probe group based on the configuration of the first DNA probe group recognized based on the first identification display.
[0041]
The DNA microarray has a second identification indicating the probe configuration of the second probe, reads the hybridization pattern and the second identification, and recognizes the second DNA probe based on the second identification. The hybridization pattern of the second DNA probe group is analyzed on the basis of the above structure. Since the examination of the health condition of the subject is performed according to the identification result, the required test can be reliably performed without the troublesome work of the examiner.
[0042]
In addition, the DNA microarray has an identification to identify itself, and the subject can be identified based on the identification.
[0043]
【The invention's effect】
As described above, according to the present invention, it is possible to reliably identify and specify a subject when performing a health test using a DNA microarray.
[Brief description of the drawings]
FIG. 1 is a block configuration diagram of an inspection system using a DNA microarray according to an embodiment.
FIG. 2 is a schematic diagram of a DNA microarray used in the present embodiment.
FIG. 3 is a schematic diagram of an example of a hybridization pattern.
FIG. 4 is a flowchart illustrating a processing procedure in the inspection system according to the embodiment.
FIG. 5 is a diagram illustrating a data configuration example of registration data according to the embodiment;

Claims (1)

Reading to read a hybridization pattern in a DNA microarray including a first DNA probe group that can be used to identify the subject and a second DNA probe group that can be used to test the health condition of the subject Process and
An identification step of analyzing a pattern corresponding to the first DNA probe group from the hybridization pattern read in the reading step to identify a subject;
A generating step of analyzing a pattern corresponding to the second DNA probe group from the hybridization pattern read in the reading step to generate test information, the test method using a DNA microarray.

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