KR102120914B1 - Marker for determining front face - Google Patents

Abstract

The present invention relates to a marker composition for face identification, comprising a polynucleotide selected from the group consisting of polynucleotides composed of SEQ ID NOs: 1-7 and a combination thereof, or comprising a polynucleotide complementary thereto; a composition for face identification, comprising a preparation capable of detecting or amplifying the marker composition for face identification; a kit for face identification, comprising the composition for face identification; a microarray for face identification, comprising the marker composition for face identification; and a method for providing information for face identification. The marker composition for frontal face identification provided in the present invention may be used to derive genetic influences of diseases associated with facial phenotypes, and also can be widely utilized in crime investigations.

Description

Marker for face recognition {MARKER FOR DETERMINING FRONT FACE}

The present invention relates to a marker for front face identification, and more specifically, the present invention includes polynucleotides selected from the group consisting of nucleotides of SEQ ID NOs: 1 to 7 and combinations thereof, or polynucleotides complementary thereto. Includes a marker composition for face discrimination, a face discrimination composition comprising an agent capable of detecting or amplifying the face discrimination marker composition, a kit for face discrimination including the face discrimination composition, and a marker composition for face discrimination The present invention relates to a microarray for face identification and a method for providing information for face identification.

As interest in quality of life increases along with the improvement of living standards, preferences for proactive health management such as health status measurement and proper exercise management are increasing. The most important of the various information necessary for such management can be said to be information such as the constitution of the subject and the current state of health. Since the current health status of the subject is continuously changed according to the surrounding environment and living environment of the subject, it is practically difficult to perform health management using this as a variable, but since the constitution of the subject is rarely changed, it is necessary for health management. It is necessary to develop a method to use.

In this regard, Sasang Medicine suggests that it is effective to differently treat the same disease or symptom according to the constitution, and divides the constitution of a person into four according to the deviation of the genital organs. In order to discriminate constitutions based on Sasang Medicine, a method of finding and confirming each constitutional disease is used through the Sasang Constitutional Discrimination Program (QSSCCII) using a questionnaire certified by the Sasang Constitutional Medicine Association. However, such a conventional method often relies on the subjective judgment of the diagnostician, so there is a limit to reliability, and thus studies for determining constitution based on more objective facts have been actively conducted.

The face phenotype is one of the most prominent phenotypes representing differences between individuals. Although it is certain that it is controlled by genetic characteristics, the mechanism of action of genes for facial phenotype determination remains unknown. In addition, studies on the relationship between the genetic risk of the disease and the genetic characteristics of the face phenotype are also insufficient.

Of the facial phenotypes, facial morphology is classified as an important feature in forensic medicine. Facial anomalies in the face form account for more than half of congenital anomalies, leading to social maladjustment of patients. In forensic science, genetic information is considered important evidence that provides data on personal identification and external characteristics such as iris and hair color. Recently, high-resolution 3D imaging technology that uses face morphology as a statistical value has been combined with DNA information to open up new possibilities.

Facial morphology is determined by genetic factors rather than environmental factors. The face-building process is an evolutionarily conserved precise process associated with cell migration, interaction, diffusion and differentiation of various tissue cells. Studies using human subjects and animal models with congenital skull anomalies have identified genetic factors affecting facial formation. For example, multiple signaling pathways have been reported to be important factors during embryonic skull morphogenesis, including bone morphogenetic protein, sonic hedgehog, fibrous explosive growth factor, growth hormone receptor, and Wnt/β-catenin pathway.

Furthermore, a recent genome-wide association study (GWAS) was conducted to discover that the genetic variant of the PAX3 locus was related to the shape of the nose, confirming the association of the PAX3 locus in European subjects, and affecting facial morphology. Four new genomes were identified in the genes PRDM16, TP63, C5orf50, and COL17A1. In addition, to determine the phenotype of the nose, a technique using rs2193054, an SNP present in the SOX9 gene, was developed (Korean Patent No. 10-1761801). However, these studies have been conducted on Europeans whose genetic traits differ from Asians, including Koreans, and to date, studies on Asians have been insufficient.

On the other hand, montages in criminal investigations are used when photographs of criminals to be arranged are not available. The current method used to create a montage finds the characteristics and similarities of the criminal based on the memory of the people who witnessed the criminal's face, and resembles similar parts such as contours, eyes, nose, mouth, ears, chin, eyebrows, and hair. Choose, synthesize, and replicate. This basic photo is shown to the eyewitness again, and the correction is repeated until a match is made to the image of the criminal who has the eyewitness. However, there was a possibility that the memory of the eyewitness could be distorted, so the montage created in the current way often did not match the face of the criminal who was arrested. Accordingly, there is a need for a montage to be prepared based on more objective facts, such as the arrest of a criminal by suspect DNA analysis.

Under these backgrounds, the present inventors performed a full profile genome-wide association study (GWAS) on the face morphological phenotype viewed from the front, and additional verification analysis to analyze the face profile, eye profile, and eye tail length through replication analysis. A single nucleotide polymorphism (SNP) derived from five genes (OSR1-WDR35, HOXD-MTX2, WDR27, SOX9, and DHX35 genes) that have been established to have a correlation with nose width was discovered, and the present invention was completed.

One object of the present invention is to provide a marker composition for face discrimination comprising a polynucleotide selected from one or more polynucleotide groups consisting of the nucleotide sequence of SEQ ID NOs: 1 to 7 or a polynucleotide complementary thereto.

Another object of the present invention is to provide a composition for face identification comprising an agent capable of detecting or amplifying the composition.

Another object of the present invention is to provide a face recognition kit comprising the composition.

Another object of the present invention is to provide a microarray for face identification comprising the marker composition.

Another object of the present invention is to provide a method for providing information for face identification.

Each description and embodiment disclosed in the present invention can be applied to each other description and embodiment. That is, all combinations of the various elements disclosed in the present invention fall within the scope of the present invention. In addition, the scope of the present invention is not limited by the specific descriptions described below.

One embodiment of the present invention for achieving the above object is a marker composition for face identification comprising a polynucleotide selected from one or more polynucleotide group consisting of the nucleotide sequence of SEQ ID NO: 1 to 7 or a polynucleotide complementary thereto to provide.

The term "polynucleotide consisting of the nucleotide sequence of SEQ ID NOs: 1 to 7" of the present invention is a polymorphic sequence including a polymorphic region of a gene involved in phenotype for a face, and a polymorphic sequence is a polynucleotide sequence. It means a sequence comprising a polymorphic site containing SNP. The polynucleotide sequence may be DNA or RNA.

The term "polymorphism" of the present invention means a case where two or more alleles exist in one locus, and among polymorphic sites, only a single base is different from a single base polymorphism ( It is called single nucleotide polymorphism (SNP). As a specific example, a polymorphic marker has two or more alleles showing a frequency of occurrence of 1% or more, more preferably 5% or 10% or more, in a selected population.

The term "allele" of the present invention refers to several types of a gene that exist at the same locus of a homologous chromosome. Alleles are also used to indicate polymorphism, for example, SNPs have two types of alleles.

In the present invention, the polynucleotide consisting of the nucleotide sequence of SEQ ID NO: 1 may include rs7567283, which is SNP present in the OSR1-WDR35 gene associated with the frontal facial contour, and SEQ ID NO: 2 relates to the curvature of the upper eyelid SRS present in the HOXD-MTX2 gene may include rs970797, and SEQ ID NO: 3 may include rs3736712, SNP present in the WDR27 gene related to the length of the eye tail, and SEQ ID NO: 4 related to the nose sub-width It may include the SNP present in the DHX35 gene, rs2206437, and SEQ ID NOs: 5 to 7 include s9910003, rs1859979, and rs9915190, SNPs present in the SOX9 gene related to lateral nasal angle, nasal length, nasal tip protrusion, and nasal contour. can do. In addition, the marker for face identification provided by the present invention may further include a polynucleotide consisting of the nucleotide sequence of SEQ ID NO: 8, which includes SRS rs2193054, which is the SNP present in the SOX9 gene, known as the nose phenotype gene.

The 175th base sequence of rs7567283, which is the SNP included in SEQ ID NO: 1 may be C or T, and the 141th base sequence of rs970797, which is the SNP included in SEQ ID NO: 2, may be C or A, and the sequence The 141st nucleotide sequence of rs3736712, the SNP included in SEQ ID NO: 3 may be T or C, and the 141st nucleotide sequence of rs2206437, SNP included in SEQ ID NO: 4 may be A or T, and SEQ ID NO: 5 The 141st base sequence of rs9910003, which is SNP included in, may be C or T, and the 141th base sequence of rs1859979, which is SNP included in SEQ ID NO: 6, may be T or C, included in SEQ ID NO:7 The 141st base sequence of rs9915190, which is an SNP, may be C or A, and the 141st base sequence of rs2193054 included in SEQ ID NO: 8 may be G or C.

The term "face discrimination" of the present invention is based on a phenotype for frontal face contour, curvature of the upper eyelid, eye tail length, nose sub-width, nose tip protrusion, nose depth, side nose area, side nose lip angle, side nose angle By means of analyzing the face by means.

Specifically, as a result of determining the face phenotype in one embodiment of the present invention, the OSR1-WDR35 genetic region (rs7567283) is expressed as en-ex-go [(A) enR-exR-goR] in relation to the frontal facial contour. It was confirmed to be related to the right face angle (P = 2.75Х10 ^-8 ), and the HOXD-MTX2 genetic region (rs970797) was related to the curvature of the upper eyelid. That is, the tangential angle of the left eye el3 (P = 7.40Х10 ^-9 ) and the tangential angle of the right eye er3 [(A) Tan_er3] (P = 3.97Х10 ^-9 ), and the WDR27 genetic region (rs3736712) was associated with the eye. It was associated with tail length (psR-exR) (P=8.44Х10 ^-10 ). In addition, the rs2193054 of SOX9 is nose-shaped with lateral nose angle [(A) n-prn-sn)] (P = 6.17 Х 10 ^-17 ) and nose tip protrusion [(H) prn-sn] (P = 5.34 Х 10 ^-9 ), and it was confirmed that rs2206437 of DHX35 is associated with the nose sub-width (sbalR-sbalL) (P = 1.61Х10 ^-9 ) (FIG. 3 ).

In addition, multiple signals of the SOX9 locus were identified by confirming the locational relevance of the GWAS found in one embodiment of the present invention. These four signals appeared in similarly related patterns for the five nasal phenotypes, and the five characteristics were the nasal tip protrusion [(H) prn-sn], the nose depth [(H) n-prn], and the lateral nasal region. There are [(AR) n-prn-sn], lateral nose lip angle [(A) prn-sn], and lateral nose angle [(A) n-prn-sn]. Signaling SNPs were rs2193054, rs9910003, rs1859979 and rs9915190 located upstream of about 91, 238, 688 and 974kb, respectively, of the SOX9 transcription initiation site, and through these results, facial contour, eye contour, eye tail length, nose width and A single base polymorphism derived from five genes (OSR1-WDR35, HOXD-MTX2, WDR27, SOX9, and DHX35 genes) having established associations was discovered to confirm the association between facial phenotypes. It can be seen that discrimination or prediction may be possible for a phenotype (FIG. 4).

Another embodiment of the present invention provides a composition for face identification comprising an agent capable of detecting or amplifying the marker composition for face identification.

The term "an agent capable of detecting or amplifying a marker" of the present invention means an agent capable of specifically recognizing or amplifying the SNP contained in the marker for face discrimination, or specifically, amplifying the SNP. It may be a probe capable of specifically binding to a polymorphic site containing SNP, a polynucleotide containing the SNP marker, or a primer capable of specifically amplifying a complementary polynucleotide thereof.

The term "probe" of the present invention means a nucleic acid fragment such as RNA or DNA corresponding to a few bases to hundreds of bases in short, capable of achieving specific binding with mRNA, and is labeled The presence or absence of a specific mRNA can be confirmed. The probe may be manufactured in the form of an oligonucleotide probe, a single stranded DNA probe, a double stranded DNA probe, or an RNA probe.

The probe used to recognize and bind to the SNP marker in the present invention includes a sequence complementary to a polynucleotide sequence comprising SNP, but is not limited thereto, and may be in the form of DNA, RNA or DNA-RNA hybrids. . In addition, a fluorescent labeling factor, a radiolabeling factor, etc. may be additionally attached to the 5'or 3'end of the probe in order to be visually recognizable.

The term "primer" of the present invention is a base sequence having a short free 3'terminal hydroxyl group (free 3'hydroxyl group) can form a complementary template (template) and base pair (base pair) and start for template strand copying A short sequence that functions as a point. The primers used for amplifying SNP markers in the present invention are molded under appropriate conditions in suitable buffers (e.g., four different nucleoside triphosphates and polymers such as DNA, RNA polymerases or reverse transcriptases) and suitable temperatures. It may be a single-stranded oligonucleotide that can serve as a starting point for the synthesis of the indicated DNA, and the appropriate length of the primer may vary depending on the purpose of use, but can be usually used in a size of 15 to 30 nucleotides. The primer sequence need not be completely complementary to the polynucleotide containing the SNP marker or a complementary polynucleotide thereof, but can be used if it is sufficiently complementary to hybridize.

In addition, the primers can be modified, e.g. methylation, encapsulation, substitution of nucleotides or modification between nucleotides, e.g. uncharged linkages (e.g. methyl phosphonate, phosphotriester, phosphoroamidate, Carbamate, etc.) or charged linkers (eg, phosphorothioate, phosphorodithioate, etc.).

Another embodiment of the present invention provides a kit for discriminating faces comprising the composition. Specifically, the kit is not limited thereto, but may be an RT-PCR (Reverse Transcription Polymerase Chain Reaction) kit, a DNA analysis (eg, DNA chip) kit.

The kit of the present invention can determine the face phenotype by confirming the base of SNP provided by the present invention through amplification using the above composition, or by checking the expression level of mRNA. As a specific example, the kit provided in the present invention may be a kit including essential elements necessary for performing RT-PCR.

For example, RT-PCR kits, in addition to each primer pair specific for the SNP, RT-PCR kits include test tubes or other suitable containers, reaction buffers (pH and magnesium concentrations vary), deoxynucleotides (dNTPs) , Taq-polymerase and enzymes such as reverse transcriptase, DNase, RNAse inhibitor, DEPC-water (DEPC-water), sterilized water, and the like. In addition, it may include a primer pair specific to the gene used as a quantitative control.

As another example, the kit of the present invention may be a DNA chip kit for face identification including essential elements necessary to perform a DNA chip.

The term "DNA chip" of the present invention means one of the DNA microarrays that can identify each base of hundreds of thousands of DNA at once.

The DNA chip kit is a flat solid support plate, typically a nucleic acid species attached to a glass surface that is not larger than a microscope slide in a gridded array, in which nucleic acids are regularly arranged on the chip surface, DNA It is a tool that enables multiple parallel analysis by generating multiple hybridization reactions between nucleic acids on a chip and complementary nucleic acids contained in a solution treated on a chip surface.

Another embodiment of the present invention provides a microarray for face identification comprising the marker composition.

The microarray may include DNA or RNA polynucleotides. The microarray is composed of a conventional microarray, except that the polynucleotide of the present invention is included in the probe polynucleotide.

Methods for preparing microarrays by immobilizing probe polynucleotides on a substrate are well known in the art. The probe polynucleotide means a polynucleotide capable of hybridizing, and means an oligonucleotide capable of specifically binding to a complementary strand of a nucleic acid. The probe of the present invention is an allele-specific probe, in which a polymorphic site is present in a nucleic acid fragment derived from two members of the same species, and hybridizes to a DNA fragment derived from one member, but not to a fragment derived from another member. . In this case, the hybridization conditions show a significant difference in the hybridization intensity between alleles, and must be sufficiently strict to hybridize to only one of the alleles. This can lead to good hybridization differences between different allelic forms. The probe of the present invention can be used in a method for determining a face phenotype by detecting an allele. The determination methods include detection methods based on hybridization of nucleic acids, such as Southern blots, and may be provided in a form pre-bonded to a substrate of a DNA chip in a method using a DNA chip. The hybridization can usually be carried out under stringent conditions, for example a salt concentration of 1M or less and a temperature of 25°C or higher. For example, conditions of 5× SSPE (750 mM NaCl, 50 mM Na Phosphate, 5 mM EDTA, pH 7.4) and 25-30° C. may be suitable for allele specific probe hybridization.

The process of immobilizing the probe polynucleotide associated with the face identification of the present invention on a substrate can also be easily performed using this conventional technique. In addition, hybridization of nucleic acids on microarrays and detection of hybridization results are well known in the art. The detection is, for example, by labeling a nucleic acid sample with a labeling substance capable of generating a detectable signal comprising a fluorescent substance such as Cy3 and Cy5, then hybridizing on a microarray and generating from the labeling substance. The hybridization result can be detected by detecting the signal to be performed.

Another embodiment of the present invention is a polymorphic site comprising (a) a polynucleotide consisting of a nucleotide sequence of SEQ ID NOs: 1 to 7 from DNA of a sample isolated from an individual or an SNP selected from one or more polynucleotide groups complementary thereto. (Polymorphic site) amplifying; And (b) determining a base of the amplified polymorphic site. At this time, the DNA of the isolated sample can be obtained from a sample separated from an individual.

The term "individual" of the present invention means a person who is an object to determine a face phenotype, and by using the separated sample obtained from the person, the base of the polymorphic site containing the SNP is analyzed to determine the face phenotype. Can be. The sample may be a sample such as hair, urine, blood, various body fluids, separated tissue, isolated cells, or saliva, but is not particularly limited thereto.

The step of amplifying the polymorphic site of the SNP from the DNA of step (a) can be any method known to those skilled in the art. For example, it can be obtained by amplifying and purifying the target nucleic acid through PCR. Other ligase chain reactions (LCR) (Wu and Wallace, Genomics 4, 560 (1989), Landegren et al., Science 241, 1077 (1988)), transcription amplification (Kwoh et al., Proc. Natl. Acad. Sci. USA 86, 1173 (1989)) and autologous sequence replication (Guatelli et al., Proc. Natl. Acad. Sci. USA 87, 1874 (1990)) and nucleic acid based sequence amplification (NASBA) can be used.

Determining the base of the amplified polymorphic site in step (b) of the above method is sequence analysis, hybridization by microarray, allele specific PCR, dynamic allele hybridization technique (dynamic allele- specifichybridization, DASH), PCR extension analysis, PCR-SSCP, PCR-RFLP analysis or TaqMan technique, SNPlex platform (Applied Biosystems), mass spectrometry (e.g. Sequenom's MassARRAY system), minisequencing method, Bio -Plex system (BioRad), CEQ and SNPstream system (Beckman), Molecular Inversion Probe array technology (e.g., Affymetrix GeneChip), and BeadArray Technologies (e.g., Illumina GoldenGate and Infinium analysis) However, it is not particularly limited. Alleles can be identified in the polynucleotide containing the SNP by the above methods or other methods available to those skilled in the art to which the present invention pertains. Determining the base of such a mutation site can preferably be performed through a DNA chip.

The TaqMan method includes (1) designing and manufacturing a primer and a TaqMan probe to amplify a desired DNA fragment; (2) labeling probes of different alleles with FAM dye and VIC dye (Applied Biosystems); (3) using the DNA as a template, and performing PCR using the primers and probes; (4) after the PCR reaction is completed, analyzing and confirming the TaqMan assay plate with a nucleic acid analyzer; And (5) determining the base of the polynucleotides of step (1) from the analysis results.

The sequencing analysis may use a conventional method for sequencing, and may be performed using an automated genetic analyzer. In addition, allele specific PCR refers to a PCR method for amplifying a DNA fragment in which the mutation is located with a primer set including a primer designed with the base at which the mutation site is located as the 3'end. The principle of the method is, for example, when a specific base is substituted from A to G, a primer comprising A as a 3'end base and a reverse primer capable of amplifying a DNA fragment of a suitable size are designed and PCR When performing the reaction, when the base of the mutation site is A, the amplification reaction is normally performed to observe the band at the desired position, and when the base is substituted with G, the primer may complementarily bind to the template DNA, This is because the amplification reaction is not properly performed because the 3'end does not complement. DASH can be performed by a conventional method, preferably by a method such as Prince.

Meanwhile, PCR extension analysis first amplifies a DNA fragment containing a base in which a single-nucleotide polymorphism is located with a primer pair, and then deactivates it by dephosphorylating all nucleotides added to the reaction, and a specific extension primer, dNTP mixture , By performing a primer extension reaction by adding didioxynucleotide, reaction buffer and DNA polymerase. At this time, the extension primer uses the 5'direction of the base where the mutation site is located as the 3'end, and a nucleic acid having the same base as the didioxynucleotide is excluded from the dNTP mixture. It is selected from one of the base types indicated. For example, when there is a substitution from A to G, when a mixture of dGTP, dCTP and TTP and ddATP are added to the reaction, the primer at the base where the substitution occurs is extended by a DNA polymerase, and after several bases, A The primer extension reaction is terminated by ddATP at the position where the base first appears. If the substitution does not occur, the extension reaction is terminated at that position, and thus the length of the extended primer can be compared to determine the type of base representing the variation.

At this time, as a detection method, when the extension primer or didioxynucleotide is fluorescently labeled, the mutation may be detected by detecting fluorescence using a gene analyzer (eg, Model 3700 of ABI) used for general sequencing. When using a non-labeled extension primer and didioxynucleotide, genetic variation of the SNP can be detected by measuring molecular weight using a matrixassisted laser desorption ionization-time of flight (MALDI-TOF) technique.

If the marker composition for front face discrimination provided by the present invention is used, it will be able to derive the genetic influence of diseases related to facial morphological phenotype and be widely used in criminal investigations.

1 is a schematic diagram showing face points used for facial features. Participants took pictures from the front and contour, and 23 front and 7 side face points were extracted. Facial phenotypes such as distance, angle and area were measured based on the facial data collection software itself. A represents a point in the right eye region, B represents a point in the left eye region, C represents a point in the front region, and D represents a point in the side.
2A-2G are plots showing the positional relationship for five new positions. The association of individual SNPs in the found GWAS is represented by log10 (P) for the chromosome base pair position. The y-axis on the right represents the estimated recombination rate from the HapMap CHB and JPT populations. The P value is derived from the discovery phase. Purple circles and diamonds represent the results of discovery and meta-analysis (step 1 + step 2), respectively. In the meta-analysis (step 1 + step 2), seven signal plots for five new SNPs showing significant P values across the genome are described. 2A is a plot showing the association of rs7567283 to the right face angle of of en-ex-go[(A) enR-exR-goR], and FIG. 2B is rs970797 to the tangent angle of er3 [(A) Tan_er3]. This is a plot showing the association, FIG. 2C is a plot showing the association of rs970797 to the tangent angle of el3 [(A) Tan_el3], and FIG. 2D is a plot showing the association of rs3736712 to the tail length (psR-exR), and FIG. 2e is a plot showing the association of rs2193054 to the lateral nasal angle [(A) n-prn-sn], and FIG. 2f is a plot showing the association of rs2193054 to the nasal tip protrusion [(H) prn-sn]. 2g is a plot showing the association of rs2206437 to the nose sub-width (sbalR-sbalL).
3 is a schematic diagram showing associated facial features for five new SNPs. Facial features and five new SNPs associated with them were presented in the front, side and eye images of the face. ① is rs7567283 (OSR1-WDR35) and right face angle, ② is rs970797 (HOXD1-MTX2) and left and right curvature of the upper eyelid, ③ is rs3736712 (WDR27) and right eye tail length, ④ is rs2193054 (SOX9) and nose The shape (angle and height), ⑤ represents rs2206437 (DHX35) and nose sub-width.
4 is a plot showing SOX9 location and associated signals in the genetic environment in the vicinity of SOX9. The five panels show multiple signals. Five nose features; Nostril depth [(H) n-prn], protruding nose tip [(H) prn-sn], lateral nose area [(AR) n-prn-sn], lateral nose lip angle [(A) prn-sn], For the side nose angle ((A) n-prn-sn)], ① at the SOX9 position is rs9915190, ② is rs1859979, ③ is rs9910003, ④ is rs2193054. These are denoted by -log10 (P) for the base pair position of chromosome 17 (Mb) and all P values are from the discovery phase. The sixth panel shows genes and regulatory regions. The gray box represents the approximate boundary of the transformation breakpoint cluster, and the black box represents fine removal. (a) shows Sp4, (b) shows F1, (c) shows Pierre Robin sequence (PRS) breakpoint cluster, (d) shows distal breakpoint cluster, (e) shows proximal breakpoint cluster, and (f) shows Sp2. The last panel shows LD blocks based on the HapMap database (HapMap Phase II JPT + CHB, hg18).

Hereinafter, the present invention will be described in more detail through the following examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.

Example 1. Study participants

For the Korean Genomics and Epidemiology Study (KoGES), GWAS (Phase 1) discovery participants were recruited from two regions in Korea (Ansan and Anseong) from 2009 to 2012. The criteria to include participants in this study used face images and genome-wide genotyping data. Exclusion criteria were cancer history, gender mismatch, hidden family relevance, low genotyping rate (<95%), and sample contamination. A total of 5643 individuals (2648 men and 2995 women) met the requirements and selected them for the Discovery GWAS analysis (Phase 1).

As a part of the Korea Constitution Multicenter Study (KCMS) project, the follow-up replication analysis (step 2) was 1,926 (687 males and 1,239 females) who were 20 years of age or older and collected from 19 oriental hospitals from 2007 to 2012. ).

To validate multiple correlated signals at the SOX9 site, another set of reader clones recruited for the Constitutional Multilateral Study (KCMS) from 2011 to 2012 was used. After applying the inclusion and exclusion criteria mentioned above, 1940 individuals (587 males and 1353 females) were used to confirm the association between nose and multiple variations within the SOX9 locus.

Example 2. Facial features

Participants took pictures from both the front and the side without makeup. It was photographed using a digital camera (DSLR Nikon D90: Nikon AF 50-mm F1.8D lens, 3216 Х 2136 pixels) and complied with the following standard conditions. That is, while the hair is worn on the headband and turned back, the center point of the ball and the two points connecting the contour of the face and the upper ear (for example, the points obsR and obsL in FIG. 1) are positioned at the same level, and the ruler is It was placed about 10 mm below the chin to convert the pixels to millimeters.

Using the OpenCV (Open Source Computer Vision Library), a self-developed program in Visual Studio C++ detects and analyzes faces, eyes, noses, mouths, and contours to automatically extract facial feature points from front and side images. Given an input image, Adaboost-based detectors sequentially detect faces, eyes, noses, and mouths to reduce the region of interest (ROI) step by step. The facial feature points in each ROI were found in the facial contour obtained through histogram-based image segmentation. The location of the extracted points was confirmed by the operator and the same extraction procedure for facial feature points was applied to both the search and verification sets. The accuracy of automatic land marking was 98.8% on average, and data was excluded if there were inaccurate landmarks.

As can be seen in Table 1 and Figure 1, the facial characteristics analyzed in the study were described by the distance, distance ratio, angle, area and eye curvature of the 23 front and 7 side face points.

For linear regression analysis, 15 variables severely out of the normal distribution (upper forehead slope depth ((H) tr-m), over-eye protrusion [(H) on], forehead protrusion depth (m-mtro), left eyelid Average curvature[(AC) el1-el7], maximum curvature of left eyelid[(MC) el1-el7], average curvature of right eyelid[(AC) er1-er7], maximum curvature of right eyelid[(MC) er1-er7) , Side nose length (n-sn), nose tip height [(V) prn-sn, nose tip protrusion [(H) prn-sn, side nose region [(AR) n-prn-sn], side nose lip angle [(A) prn-sn], lateral nose angle [(A) n-prn-sn-], upper right lip thickness [(V) cphR-sto], upper left lip thickness [(V) cphL-sto]] Was log-transformed. Outliers were removed from each facial feature.

Example 3. Genotyping determination analysis

In the GWAS (Stage 1) study group, DNA genotype was performed using Affymetrix Genome-Wide Human SNP Array 5.0 (Affymetrix, Santa Clara, CA, USA). Of the 500,568 SNPs in the Affymetrix SNP array, 311,944 SNPs were excluded after excluding high-genotyping SNPs (>5%), low MAF SNPs (<0.05), and SNPs out of Hardy-Wineberg equilibrium (P<0.0001) GWAS analysis was performed on the subjects.

LD pruning was performed and 128 sentinel SNPs were selected for the follow-up investigation of SNPs meeting the implicit threshold (P <5Х10 ^-6 ) for association with facial features. Genotyping of 1926 samples for verification (step 2) was performed using Applied Biosystems QuantStudio 12K Flex Real-Time PCR System. For the control of genotype quality, SNPs with low crystallinity (<95%), low MAF (<0.01) and poor genotype clustering are excluded. Subjects with high genotype loss rates (>5%) were also excluded from the analysis.

The genotypes of the three variants (rs9915190, rs1859979 and rs2193054) within the SOX9 locus were determined using unlabeled oligonucleotide probes (UOPs) on 1940 polymorphic nucleotides (SOX9 replication set). An aliquot of the polymerase chain reaction amplification water containing the SNP site was diluted in a solution containing 1 mM UOP, 5 mM SYTO-9 (Invitrogen, Carlsbad, CA, USA), 12.5 mM EDTA and 10 mM Tris (pH 8.0). The DNA of the UOP sample was sequentially treated with denaturation (95° C. 5 seconds), annealing (60° C. 1 minute) and gradually increasing to 74° C. at a rate of 1° C./s. Fluorescence emission was read using a Light Cycler 480 device (Roche, Indianapolis, IN, USA). The genotype was determined from three melting patterns of UOP (main homozygous, heterozygous and minor homozygous).

Example 4. Statistical analysis

GWAS was performed to detect deformations related to facial features such as front and side images of the eyes, nose and contours. Age, gender, and BMI using PLINK version 1.09 through linear regression analysis in additional models. P values found for the GWAS (Step 1) was 5.0Х10 ^-6. Quantitative-quartile plots for facial features consisted of the distribution of observed P values versus the theoretical distribution of expected P values. LocusZoom was used to create a regional association plot for the 1 Mb genomic region around the peak SNP.

In the follow-up analysis (Phase 2), multiple linear regression analyzes were performed to determine the association with 117 SNPs, age, gender, and BMI of 1926 participants using PLINK v1.09 to determine their association with corresponding facial characteristics.

All meta-analysis calculations were implemented in PLCH and METAL, and assumed a fixed effect of determining heterogeneity between studies using Cochran's Q test. The SNP of the binding assay was considered significant when the P value was below 5.0Х10 ^-8 (traditional genome-wide significance level).

Conditional analysis was performed to identify SNPs of the SOX9 locus independently associated with nasal traits in stage 1 subjects. Multiple regression analyzes of each SOX9 SNP were performed for each nose by adjusting age, gender, BMI and other SOX9 SNPs (or coordinating three different SOX9 SNPs together). In addition, several linear regression analyzes were performed using R version 3.0.2 to verify multiple association signals for nasal characteristics in different independent replicate sets, including 1940 participants (SOX9 replicate set).

All meta-analysis calculations were implemented in PLCH and METAL, and assumed a fixed effect of determining heterogeneity between studies using Cochran's Q test. The SNP of the binding assay was considered significant when the P value was below 5.0Х10 ^-8 (traditional genome-wide significance level).

For eQTL analysis, databases from GTExPortal and BRAINEAC were used along with additional data from the paper. HaploReg was used to summarize functional annotations such as chromatin structure, methylation, protein motif and transcription factor binding, and functional variant scores were calculated using RegulomeDB (Schadt EE et al. Mapping the genetic architecture of gene expression in human liver. PLoS Biol. 2008;6(5):e107., Westra HJ et al.Systematic identification of trans eQTLs as putative drivers of known disease associations.Nat Genet. 2013;45(10):1238-43., Fairfax BP et al Innate immune activity conditions the effect of regulatory variants upon monocyte gene expression.Science. 2014; 343(6175):1246949).

Example 5. Facial properties and heritability analysis

For a comprehensive study of facial morphology, as can be seen in Table 1, the individual subject's front face, including 17 faces, 10 foreheads, 15 eyes, 30 upper eyelids, 11 noses, and 2 mouths, and A total of 85 facial variables were selected from both side photographs (FIG. 1).

As can be seen in FIG. 1, the facial features are distinguished by distance, distance ratio, angle, area, and curvature (eyelid) from 23 front and 7 side face points, and facial features are developed using software developed in-house. Automatically extracted from each picture.

First, the correlation between body mass index (BMI) and facial features was analyzed. The correlation was greatest in the face width characteristics including face width including face base width, bottom face width, top face width and middle face width (r=0.355-0.487). In addition, the correlation between gender, age, and facial features was analyzed. The correlation of sex ratio was highest in the nasal region (r=-0.542) and the upper facial region (r=-0.516), and the age correlation was er7 or el7 (r=-0.306 to -0.326) tangential angle and eyelids. It was found to be the highest in eye characteristics, such as niche (r=-0.301 to -0.312). As expected, a significant correlation was observed for similar traits under the criteria of a P-value threshold adjusted to Bonferroni for 1Х10 ^-5 significance. The correlation coefficient (r) between facial width characteristics including facial base width, lower facial width, upper facial width and middle face width ranged from 0.643 to 0.928. Of the nasal traits, the nasal contour was correlated with the nose depth (r=0.573) and the tip of the nose (r=0.771).

In addition, the GCTA program was used to estimate the narrow-sense hereditary for facial features, and the areas with the highest heritability were the tip of the nose (0.417), the lateral nose lip angle (0.365), and the upper lip thickness (right: 0.299, left: 0.344).

Example 6. GWAS discovery

GWAS (step 1, n=5643) and cloning analysis (step 2, n=1926) were performed on 85 different facial characteristics. A total of 311,944 single nucleotide polymorphisms (SNPs) were examined in a linear regression model as independent variables of facial features controlled by age, sex and BMI as covariates. GWAS results for each facial feature are also indicated by the -log10 (P) value for the chromosome location in the Manhattan plot. As a result of performing GWAS (step 1) on 5 facial characteristics, a genetic association was found showing a significant level (P <5Х10 ^-8 ) of the whole genome for 7 traits, 7 of 85 facial characteristics Has 2 eye-related features [eye tail length (psR-exR) and tangential angle of el3 ((A) Tan_el3)] and 5 nose-related features Nose depth ((H) n-prn], nose tip protrusion [ (H) prn-sn], side nose region [(AR) n-prn-sn], side nose lip angle [(A) prn-sn], side nose angle [(A) n-prn-sn)] Related to this, the discovery GWAS showed a genetic association at the genome-wide significance level (P <5Х10 ^-8 ). The SOX9, TBX3-MED13L and VPS13B genetic regions met the overall genomic significance level for nasal related properties, and the WDR27 and HOXD-MTX2 genetic regions met the genomic overall significance level for eye shape (Figure 1).

Example 7. Follow-up research and meta-analysis

To perform a verification analysis (step 2) on an additional 1926 samples, among the 128 SNPs selected based on the implicit significance level (P <5Х10 ^-6 ) in GWAS analysis, 117 SNPs that were successfully genotyped For the verification analysis was performed. As a result, 21 GWAS associations by 2 SNPs (2 faces, 1 forehead, 1 eye, 4 eyelids, and 13 noses) were verified (P <0.05).

As a result of meta-analysis (step 1+2), as shown in Table 2, the five genetic regions are rs7567283 (OSR1-WDR35 locus), rs970797 (HOXD-MTX2 locus), rs3736712 (WDR27 locus), rs2193054 (SOX9 locus) ) And rs2206437 (DHX35 genetic region), it was confirmed that the 5 genetic regions reached a significant level throughout the genome. In addition, as can be seen in FIGS. 2A-2G, the results of these five genetic regions and their associations are depicted in the regional association plots of FIGS. 2A-2G.

As can be seen in FIG. 3 based on the meta-analysis, the OSR1-WDR35 genetic region (rs7567283) is a right face angle expressed as en-ex-go [(A) enR-exR-goR] in relation to the frontal facial contour. It was confirmed to be associated with (P = 2.75Х10 ^-8 ). The HOXD-MTX2 genetic region (rs970797) was associated with the curvature of the upper eyelid. That is, it was related to the tangent angle of the left eye el3 (P = 7.40Х10 ^-9 ) and the tangent angle of the right eye er3 [(A) Tan_er3] (P = 3.97Х10 ^-9 ). The WDR27 genetic region (rs3736712) was associated with the length of the eye tail (psR-exR) (P=8.44Х10 ^-10 ). The rs2193054 of SOX9 showed the strongest signal in this study, the lateral nasal angle [(A) n-prn-sn)] (P = 6.17 Х 10 ^-17 ) and nose tip protrusion [(H) prn- sn](P = 5.34 Х 10 ^-9 ). DHX35's rs2206437 was associated with nasal sub-width (sbalR-sbalL) (P = 1.61Х10 ^-9 ).

In addition, in the linear regression model (R2 of R2-covariate of SNP), the difference in phenotype explained by SNP (s)(%) obtained by R2 fraction of related SNP was analyzed. Consequently, the difference in phenotype described by the associated SNP was lower than 1% in all SNPs.

The locus identified in this study showed multiple associations between the analyzed facial traits. As can be seen in Table 2, only the traits satisfying the significance level of the entire genome according to the P value are shown. If the criteria were applied less stringently (i.e., P <1 Х 10 ^-4 ), it was confirmed that the number of suggestive traits in the found GWAS increased, and most of the implicit associations face similar to the five new variants identified in this study. It showed characteristics.

Example 8. Multiple signals at SOX9 locus

As can be seen in Figure 4, the SOX9 locus showed multiple signals, as can be seen in the figure of the positional association of the discovered GWAS. These four signals appeared in similarly related patterns for the five nasal phenotypes, and the five features were the nasal tip protrusion [(H) prn-sn], the nostril depth [(H) n-prn], and the lateral nasal region. There are [(AR) n-prn-sn], lateral nose lip angle [(A) prn-sn], and lateral nose angle [(A) n-prn-sn]. Signaling SNPs were rs2193054, rs9910003, rs1859979, and rs9915190 located approximately 91, 238, 688, and 974kb upstream of the SOX9 transcription initiation site, respectively. Both rs2193054 (91 kb) and rs1859979 (688 kb) met the importance of the whole genome. On the other hand, the two SNPs of rs9910003 (238kb) and rs9915190 (974kb) showed a rather weak association.

These four variants were tested for independence of binding signals by examining pair-linked chain imbalance (LD) and conditional linkage analysis. The four SOX9 SNPs did not detect LD in both the Phase 1 and 1000 Genomes populations, with the exception of the weak LD detected between rs2193054 and rs9910003 (0.19 in the Phase 1 population, 0.08-0.25 in the 1000 Genomes database). The association of rs9910003 persisted with other variations, but did not persist after adjustment to rs2193054. Thus, as can be seen in Table 3 and Figure 4, these SNPs (rs2193054, rs1859979 and rs9915190) were further genetically analyzed to verify their association using a 1940 Stage 2 sample. These three SNPs went beyond the importance of the entire genome after meta-analysis, and further studies of these variants by HaploReg revealed promoters and enhancer histone macros, DNase hypersensitivity regions and motifs that changed in their sequence.

Example 9. Verification analysis of facial feature GWAS genetic region

As can be seen in Table 4, a verification analysis was performed on the GWAS genetic region related to faces reported in previous papers. A total of 41 lead SNPs were selected for this analysis. The Affymetrix Genome-Wide Human SNP Array 5.0 genotyping platform did not include these 41 SNPs except rs6555969 (C5orf50), so 41 lead SNPs using LDlink (https://analysis tools.nci.nih.gov/) Surrogate SNP was extracted. LDlink) After filtering X-chromosome SNPs and GWAS QC-failed SNPs under the criteria of r ² > 0.6, 63 surrogate SNPs from 13 lead SNPs were selected to investigate their association with relevant facial features investigated in this study. . As shown in Table 4, lead SNPs per one lead SNP indicating the highest LD (r ² ) value among surrogate SNPs were identified.

rs4648379 is was related to the nose width and nose above the existing looking surrogate SNP rs4648478 (r ² = 0.61) are associated with the side nose angle [(A) n-prn- sn] In the verification analysis (P = 5.70 Х 10 ^{- 6} ). In the present invention, since there were 11 characteristics related to the nose, the significance level of verification analysis was set to P = 4.5 Х 10 ^-3 through Bonferroni correction. Thus, SNP rs4648379 appears to be reproduced in the present invention. Likewise, rs2045323 was reported to be related to three nasal phenotypes (nostral slope, nasal protrusion and nasal tip angle), nasal sub-width (sbalR-sbalL) (surrogate SNP rs4315762, r ² = 0.68, P = 4.84 Х 10 ^-6 ).

Another SNP rs1852985 was previously shown to be related to the nostril width, and the association with the nostril angle [(A) prn-n] (rs1284964, r ² = 0.85, P = 2.28Х10 ^-5 ) was verified, and it was associated with the nose width. It was reported that rs2424399 verified the association with the nose sub-width (sbalR-sbalL) (rs6082475, r ² = 1.0, P = 7.28Х10 ^-4 ).

In addition, of the 23 lead SNPs that have been identified for association with nose size from a large-scale cohort (n> 70,000) target study (using self-reporting information for nose size), 8 lead SNPs were added for verification analysis of our sample targets. Was selected as. As a result of analyzing whether the characteristics of the nose are related to 40 surrogate SNPs for 8 lead SNPs, as shown in Table 4, two SNPs (rs767764-nostril angle and rs6101567-front nose length) It was verified in the present invention.

Consequently, the inventors found that the OSR1-WDR35 genetic region (rs7567283) is associated with the frontal facial contour, the HOXD-MTX2 genetic region (rs970797) is associated with the curvature of the upper eyelid, and the WDR27 genetic region (rs3736712) is associated with the eye tail length. Related, the rs2193054 of SOX9 is nose-shaped and is related to the lateral nose angle and nose tip protrusion, rs9910003, rs1859979 and rs9915190 are related to the side nose angle, nose length, nose tip protrusion and nose contour, and the DHX35's rs2206437 It was confirmed that it was related to the width of the lower nose.

From the above description, those skilled in the art to which the present invention pertains will appreciate that the present invention may be implemented in other specific forms without changing its technical spirit or essential features. In this regard, it should be understood that the embodiments described above are illustrative in all respects and not restrictive. The scope of the present invention should be construed as including all changes or modifications derived from the meaning and scope of the following claims rather than the above detailed description and equivalent concepts thereof.

<110> Korea Institute of Oriental Medicine <120> MARKER FOR DETERMINING FRONT FACE <130> KPA190399-KR <160> 8 <170> KopatentIn 2.0 <210> 1 <211> 355 <212> DNA <213> Artificial Sequence <220> <223> rs7567283 <220> <221> variation <222> (175) <223> y= c or t <400> 1 cctaactgtt ctctatttaa cagcaattac tgagtccttg ctatgtctca agaactattc 60 taagtgctgt acatgcattt gctcatttaa ttttaatgac aaccctttaa ggtaagtaca 120 attacatccc cattttacag aatgaactaa ggcacagaag aattaaataa attgyccaag 180 gtctgtgctc tatttatctg ttactgcata ataaacacct caaatttagt gacataaaac 240 agcaactgtt ttattatgct catgaattct gaaggtcaag cagagtaggg gtatcttctt 300 tctgctccat gatagttgca tctcagctag gaggactgga ctgactaggc ggtga 355 <210> 2 <211> 321 <212> DNA <213> Artificial Sequence <220> <223> rs970797 <220> <221> variation <222> (141) <223> m= c or a <400> 2 ttacattttg aaaaaatacc atgatgtgca aatgtgcata ccctattcag ccaacatatc 60 atagatactg tatagtaaca tctgggaata ttaaactttg cctttactgg caacccaatt 120 ggcatcttga atttacagtg magatgtttt atactgatgt gttttggaaa tctttgaagt 180 attctcaaga cagtattctg aggtttctgc agtggtccac ttgagccttt tgaagttccc 240 tatacaatag gatacataca tatattttcc aaaacatgtt ttagtgggaa aagaagaaaa 300 gttcaagttg gcggtataat a 321 <210> 3 <211> 321 <212> DNA <213> Artificial Sequence <220> <223> rs3736712 <220> <221> variation <222> (141) <223> y= t or c <400> 3 gccatcatag aaacactata aagttaagag ggctttatag acacttaggc tgctataaaa 60 aattatccca tttttatatt caagtcaata tgttttttca agtctaaaac agtgtacagt 120 atagaaaagg gcaatgaaga yagtctctta ttttagtgat aatcttctgt cctgataact 180 tattaagtgg aggggaatgc aagtttttaa aaaatacttt gatgttttta tttttattga 240 aaaaaatgtt agagacagca tctccctctt gcccaagctc aactcttggg ctcctgcaat 300 cttcccaccc cagcctcctg a 321 <210> 4 <211> 321 <212> DNA <213> Artificial Sequence <220> <223> rs2206437 <220> <221> variation <222> (141) <223> w= a or t <400> 4 gctccctact acttaatctc acttgagcaa gaaaatattc ctgtgaagtg ggtagggctg 60 aacttattcc cattttacag atgattaaac tgaataagct ttggaaccat ctcctttgga 120 agcaaagtaa ctcactatgg wctaaacact ttgagaaaag agagaagaaa attgagatga 180 attcatgctt tgcctcaatt ccctgtatct ttcatgttaa attaccttgc ttcatgttat 240 tgctgcaaat ttggctttgt tagtgcagac ctgacctgga tctgtctata tttctgcata 300 gagagatgac cttaatgtat t 321 <210> 5 <211> 321 <212> DNA <213> Artificial Sequence <220> <223> rs9910003 <220> <221> variation <222> (141) <223> y= c or t <400> 5 tgaaaatata aaccccatgc agtgaccaag tggtaagaag ttaagtgaga gtaaagaaat 60 tggggcagct cagggcaccg gagatctagg gaggagaaaa aaaacacatc aagaaaacta 120 aaagaagaac taaacaattg yccaagacct attttaacca tttcacaagt ttgcagacta 180 ctctgccata gggaaaagtc catggtcaac acttctggaa gagcaaaagc cctagattac 240 ccacatccca agctactttc agcaaacaac tgagtagagt caatgaaaag tcaccacagt 300 ccctctagga atggtaacat g 321 <210> 6 <211> 321 <212> DNA <213> Artificial Sequence <220> <223> rs1859979 <220> <221> variation <222> (141) <223> y= t or c <400> 6 gttaccagct ttgacacaca gccagaacac ctgggaaggc acacccagat catctttcat 60 tagtttcctt ttatttgagg catatcttaa gggtacatgt ccatgcatac atacacttgt 120 gtgtctgtgt gtgtaggtaa yagtgctatg aaaatctggt taatatctgg ggttacagtt 180 attcttccat ggagttttga tacaagtgag atagtctaga ctctcatact aagatatttc 240 ttaaatatga cttcactctt acctaacaag ccaaaagaat atttctgagt gttaggcata 300 tggggatttc cagttaccca c 321 <210> 7 <211> 321 <212> DNA <213> Artificial Sequence <220> <223> rs9915190 <220> <221> variation <222> (141) <223> m= c or a <400> 7 agtaagaaca gatgggctac taaggcaaaa ggtctccatg caaatcatat caagaaagac 60 caaaaccaag gaaaggatag ccatcgtaga tccatgattg tttcagtctg ccaaaataaa 120 aggcttttca atggtttatc mcagatgaca gctgatttct aaagaagtag ccggattttt 180 ttttctatat ctctgcacac aaagtgaaca cagttcatag gtaaagaaca aagcacactt 240 gcttgtagca atgatacaaa cttaaggggt ccatttagag aattcttatt ttgaatgtga 300 ttaattgcat ggaaccagaa t 321 <210> 8 <211> 321 <212> DNA <213> Artificial Sequence <220> <223> rs2193054 <220> <221> variation <222> (141) <223> s= g or c <400> 8 aatctccaga gagagcaata gaagcccagc ttgagggaaa tgactggacc ttgattactt 60 aggataaaaa gagatcaatt tatggtagga ctatctattt atgtctgcac attcatcagg 120 tttgcctagg aaaggagtct sagaaaatgt gttggaattg ggcacttctg atgtctatcc 180 tattccttgt cttggttgat aacactttct ccagtcccca gatctcattt taggaaatga 240 gacttgttat caggcatcct agagcctcca tatttttctg agtctttctg tgtctgccgg 300 caccattgac gttgttacta t 321

Claims (13)

Combination of polynucleotides consisting of the nucleotide sequence of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6 and SEQ ID NO: 7 or a marker composition for face identification comprising a complementary polynucleotide .
According to claim 1, wherein the composition is a marker composition for face identification, which further comprises a polynucleotide composed of the nucleotide sequence of SEQ ID NO: 8 or a polynucleotide complementary thereto.
According to claim 1, wherein the polynucleotide consisting of the nucleotide sequence of SEQ ID NO: 1 is related to the front face contour, marker composition for face identification.
According to claim 1, wherein the polynucleotide consisting of the nucleotide sequence of SEQ ID NO: 2 is related to the curvature of the upper eyelid, a marker composition for face identification.
According to claim 1, wherein the polynucleotide consisting of the nucleotide sequence of SEQ ID NO: 3 is related to the length of the eye tail, the marker composition for face identification.
According to claim 1, wherein the polynucleotide consisting of the nucleotide sequence of SEQ ID NO: 4 is related to the sub-width of the nose, the marker composition for face identification.
According to claim 1, wherein the polynucleotide consisting of the nucleotide sequence of SEQ ID NOs: 5 to 7 is associated with lateral nose tip protrusion, nose depth, lateral nose region, lateral nose lip angle, lateral nose angle, respectively Marker composition.
A composition for face identification comprising an agent capable of detecting or amplifying the marker composition for face identification according to any one of claims 1 to 7.
A face discrimination kit comprising the composition for face discrimination of claim 8.
The kit of claim 9, wherein the kit is an RT-PCT kit or a DNA chip kit.
A microarray for face discrimination comprising the marker composition for face discrimination according to any one of claims 1 to 7.
(a) contained in a combination of polynucleotides consisting of the nucleotide sequence of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6 and SEQ ID NO: 7 from DNA of a sample isolated from an individual Amplifying a polymorphic site comprising SNP; And
(b) determining the base of the amplified polymorphic site, the method of providing information for face identification.
The method of claim 12, wherein the polymorphic site further comprises an SNP contained in a polynucleotide composed of the nucleotide sequence of SEQ ID NO: 8.

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