WO2022075747A1 - Marqueurs génétiques polymorphes liés à l'élasticité et à la résistance à la traction de cheveux humains et leur utilisation - Google Patents

Marqueurs génétiques polymorphes liés à l'élasticité et à la résistance à la traction de cheveux humains et leur utilisation Download PDF

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WO2022075747A1
WO2022075747A1 PCT/KR2021/013709 KR2021013709W WO2022075747A1 WO 2022075747 A1 WO2022075747 A1 WO 2022075747A1 KR 2021013709 W KR2021013709 W KR 2021013709W WO 2022075747 A1 WO2022075747 A1 WO 2022075747A1
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snp
elasticity
hair
tensile strength
low
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Korean (ko)
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권오상
김종일
온정윤
손호영
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서울대학교 산학협력단
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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6813—Hybridisation assays
    • C12Q1/6827—Hybridisation assays for detection of mutation or polymorphism

Definitions

  • the present invention relates to a genetic polymorphic marker related to human hair elasticity and tensile strength, and uses thereof.
  • GWAS genome-wide association study
  • SNP single nucleotide polymorphism
  • Whole genome association analysis refers to a method of statistically analyzing associations with diseases by searching for the genotypes of about 500,000 to 2 million SNPs.
  • various genetic mutations have been discovered worldwide by this method, and attempts have been made to identify susceptibility genes to diseases using GWAS, but the decisive factor has not yet been identified.
  • the present inventors performed GWAS analysis in detecting a variant using the same sample size to confirm the genotype related to the tensile strength and elasticity of individual hair. As a result, significant SNPs were identified, The invention was completed.
  • the present inventors selected a specific gene having a significant correlation with human hair elasticity and tensile strength and a single nucleotide polymorphism (SNP) marker of the corresponding gene, and using the same, the elasticity of human hair Alternatively, the present invention was completed by developing a SNP marker composition for diagnosis or prediction of tensile strength.
  • SNP single nucleotide polymorphism
  • Another object of the present invention is to provide a composition for diagnosis or prediction of elasticity or tensile strength of human hair.
  • Another object of the present invention is to provide a kit for diagnosing or predicting the elasticity or tensile strength of human hair.
  • the present invention provides a SNP marker composition for diagnosing or predicting elasticity or tensile strength of human hair, comprising at least one SNP selected from the group consisting of the following first SNPs to 135th SNPs:
  • the present invention provides a composition for diagnosing or predicting elasticity or tensile strength of human hair, comprising, as an active ingredient, an agent for detecting or amplifying one or more SNPs selected from the group consisting of the first SNP to the 135th SNP. .
  • the present invention provides a use for diagnosing or predicting the elasticity or tensile strength of human hair of a composition
  • a composition comprising as an active ingredient an agent for detecting or amplifying one or more SNPs selected from the group consisting of the first SNP to the 135th SNP. .
  • the agent for detecting the SNP may be a probe capable of detecting one or more SNPs selected from the group consisting of the first SNP to the 135th SNP, but is not limited thereto.
  • the agent amplifying the SNP may be a primer set capable of detecting one or more SNPs selected from the group consisting of the first SNP to the 135th SNP, but is not limited thereto. .
  • the present invention provides a kit for diagnosing or predicting elasticity or tensile strength of human hair, comprising the composition.
  • the kit may be an RT-PCR kit or a microarray chip kit, but is not limited thereto.
  • the hair when one or more SNPs selected from the group consisting of the first SNPs to the 135th SNPs are identified from a nucleic acid sample isolated from an individual, the hair is diagnosed as having low elasticity and low tensile strength, or hair with low elasticity and low tensile strength. It provides an information providing method for diagnosing or predicting the elasticity or tensile strength of hair, including the step of predicting that hair will occur.
  • one or more SNPs selected from the group consisting of the first SNPs to the 135th SNPs are identified from a nucleic acid sample isolated from an individual, it is diagnosed as hair with low elasticity and low tensile strength, or with low elasticity and low tensile strength. It provides a method for diagnosing or predicting hair elasticity or tensile strength, comprising the step of predicting hair growth.
  • the SNP is sequencing, exome sequencing, microarray hybridization, allele specific PCR, dynamic allele hybridization technique ( dynamic allele-specific hybridization), PCR extension analysis, and Taqman technique, but may be identified by one or more methods selected from the group consisting of, but is not limited thereto.
  • the prediction method, prediction kit and prediction model of low-elasticity and low-tensile strength hair using the single nucleotide polymorphism marker of the present invention can predict individuals with low-elasticity and low tensile strength hair with high accuracy in advance for each individual. It works. Furthermore, based on the information obtained through the prediction method, prediction kit, and prediction model of the present invention, personalized medical devices, medicines and cosmetics, active ingredients, etc. that can improve or maintain the strength and elasticity of low-elasticity and low-tensile strength hair It is expected that it can be applied to the development of
  • ROC receiver operating characteristic
  • the present inventors confirmed that a specific gene and thousands of single nucleotide polymorphisms (SNPs) present on the gene are associated with low elasticity and low tensile strength hair.
  • SNPs single nucleotide polymorphisms
  • the present invention in order to increase the accuracy of diagnosis or prediction, there is a history that can affect the elasticity or tensile strength of the hair, such as having damaged the scalp or performing a perm, dyeing, etc. on the hair within the last 3 months Those with or suffering from diseases were excluded from the study subjects, and SNPs associated with low elasticity and low tensile strength hair were obtained by analyzing the genes of the selected study subjects (see Examples 1 and 2).
  • association analysis using the SNP markers of the test group/control group was performed to detect the genotype associated with low elasticity and low tensile strength hair, and compared with the normal control group, individuals with low elasticity and low tensile strength hair 135 SNPs observed in a statistically significant number were selected (see Example 3).
  • polynucleotide or “nucleic acid” refers to deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) in the form of single or double strands. Unless otherwise limited, known analogs of natural nucleotides that hybridize to nucleic acids in a manner analogous to naturally occurring nucleotides are also included.
  • DNA consists of four bases: adenine (A), guanine (G), cytosine (C), and thymine (T), and RNA consists of uracil (U) instead of thymine (Uracil, U).
  • A forms a hydrogen bond with T or U
  • C forms a hydrogen bond with the base G, and the relationship between these bases is called 'complementary'.
  • complementary means that a targeting moiety in a nucleic acid molecule is sufficient to selectively hybridize to a target (eg, an EDN gene) under certain hybridization or annealing conditions, specifically physiological conditions (in a cell). It means complementary, which may have one or more mismatched nucleotide sequences, and has a meaning encompassing both substantially complementary and perfectly complementary, and more specifically means completely complementary.
  • 'c.' means a mutation in the protein coding region
  • '(base position) single nucleotide
  • symbol > single nucleotide
  • 'polymorphism' refers to the occurrence of two or more alternative sequences or alleles (or alleles) within a genetically determined population
  • 'single nucleotide polymorphism (SNP)' refers to one polymorphism of the base.
  • a single base (A, T, C, or G) in the genome refers to the diversity of DNA sequences that occur between members of a species or between chromosomes of an individual.
  • 'mRNA messenger RNA or messenger RNA
  • RNA messenger RNA or messenger RNA
  • 'mRNA is an RNA that serves as a blueprint for polypeptide synthesis (protein translation, translation) by transferring the genetic information of the base sequence of a specific gene to the ribosome during protein synthesis.
  • protein translation, translation protein translation, translation
  • the term “marker” refers to a nucleotide sequence used as a reference point when identifying genetically unspecifiedly related loci.
  • the term also applies to nucleic acid sequences complementary to marker sequences, such as nucleic acids used as primer sets capable of amplifying the marker sequence.
  • the location on the genetic map of a genetic marker is referred to as a genetic locus.
  • the term “gene marker” may be used interchangeably with terms such as a DNA marker, a biomarker, and a molecular marker.
  • the marker can be usefully used because it can rapidly distinguish traits without being affected by the cultivation environment or growth period of crops.
  • a genetic marker is a method of indicating polymorphism between individuals by targeting differences in the nucleotide sequence of DNA, which is the essence of genetic phenomena. (Restriction Fragment Length Polymorphism) probes or SCAR (Sequence Characterized Amplified Region) markers are being used.
  • allele means that one gene present at the same locus of a homologous chromosome has different traits.
  • the term “elasticity” or “elasticity” is a characteristic of hair that the hair tries to support at a right angle from the scalp surface, and is related to 'k (Stiffness)', which is the modulus of elasticity in Hooke's law, It is different from the F elastic force, which is a restoring force that acts in the opposite direction to gravity to keep the hair at a right angle from the scalp surface.
  • the proximal part (about 3 cm) of the occipital hairs of 401 study subjects was obtained, and the cross-sectional area of the hair was measured using a laser scanning micrometer (LSM-6200).
  • LSM-6200 laser scanning micrometer
  • the sample, which has measured the cross-sectional area, is fixed at both ends of the hair with a clamp, mounted on a flexible Miniature Tensile Tester (MTT-175) machine, the pulling force is increased at both ends until the hair sample is cut, and the force at the time of cutting is increased. measured.
  • the term “elasticity and tensile strength” of hair as used herein is determined by a method of measuring the tensile length, stress, and tensile force of the hair by pulling the hair based on the force measured at this time, and the force per unit area of the hair It is expressed in units of (gmf/sq micron).
  • low elasticity and low tensile strength hair refers to hair whose values measured by the above method are below the cut-off point that can distinguish the lower 15% (lower 59 people based on 401 people). was defined as The cut value suggested in the present invention was 0.0285 (gmf/sq micron).
  • the low elasticity and low tensile strength hair is lower 50%, lower 40%, lower 35%, lower 30%, lower 25%, lower 20%, lower 15%, lower 10%, lower 9%, lower 8%, lower 7%, lower 6%, lower 5%, lower 4%, lower 3%, lower 2%, or lower 1% may refer to hair having power per unit area of hair, but It is not limited.
  • the low elasticity and low tensile strength hair has a strength per unit area of 0.05 (gmf / sq micron) or less, 0.03 (gmf / sq micron) or less, 0.028 ( gmf / sq micron) or less, or about 0.0285 (gmf / sq micron) or less sq micron) or less, but is not limited thereto.
  • diagnosis refers to determining a subject's susceptibility to a particular disease or condition, determining whether a subject currently has a particular disease or disorder, It is a concept that includes both determining the prognosis of an affected subject, or therametrics (eg, monitoring the condition of an object to provide information on treatment efficacy).
  • the present invention can provide a marker composition for diagnosing or predicting elasticity or tensile strength of human hair comprising one or more SNPs selected from the group consisting of the following first SNPs to 135th SNPs:
  • the present invention provides a composition for diagnosing or predicting low elasticity and low tensile strength hair, comprising as an active ingredient an agent for detecting or amplifying one or more SNPs selected from the group consisting of the first to 135th SNPs.
  • the composition for diagnosis or prediction of elasticity or tensile strength of human hair may be a composition for diagnosis or prediction of low elasticity and low tensile strength hair, but is not limited thereto.
  • the above-mentioned first SNP to 135 SNP may be located on the base sequence of SEQ ID NO: 1 to SEQ ID NO: 135, respectively.
  • the base corresponding to the SNP position according to the present invention is represented by r, and based on the SNP position, the sequence 100 nt in the 5' direction, the 3' direction The sequence 100 nt is indicated.
  • the nucleotide sequence of SEQ ID NO: 1 indicates the SNP position as r, and the nucleotide sequence of 100 nt in length is indicated on both sides based on this, and a total length of 201 nt is indicated.
  • the nucleotide sequence of SEQ ID NO: 1 to SEQ ID NO: 135 is used for the purpose of specifying the position of the SNP in an individual, particularly a human, and therefore, the length of the nucleotide sequence of SEQ ID NO: 1 to SEQ ID NO: 135 is in the indicated range.
  • the present invention is not limited by the
  • rs_IDs of the first to 135th SNPs are not searched on genebank dbSNP, they can be interpreted as follows according to the order of description:
  • the second SNP, 6:147531955:CATT:C is number 6
  • the 147531955th base on the chromosome may refer to a SNP mutated from CATT to the minor allele C.
  • the 30th SNP, 10:52789962:G:GT may refer to a SNP in which the 52789962th base on chromosome 10 is mutated from G to the minor allele GT.
  • the term “detection” means measuring and confirming the presence or absence of a target substance (SNP in the present invention), or measuring and confirming a change in the presence level of a target substance am. Therefore, the “agent” according to the present invention is an agent capable of specifically binding to and recognizing the site containing the SNP according to the present invention or amplifying the site containing the SNP, specifically, at the site containing the SNP. It may be a set of primers capable of specifically amplifying a probe capable of specifically binding, a polynucleotide including a region including the SNP, or a polynucleotide complementary thereto.
  • primer is a short single-stranded oligonucleotide that serves as a starting point of DNA synthesis.
  • a primer binds specifically to a polynucleotide as a template under suitable buffer and temperature conditions, and DNA polymerase adds a nucleoside triphosphate having a base complementary to the template DNA to the primer to link it. is synthesized
  • a primer generally consists of a sequence of 15 to 30 bases, and the melting temperature (Tm) at which it binds to the template strand varies depending on the base composition and length.
  • the sequence of the primer does not need to have a completely complementary sequence to a partial nucleotide sequence of the template, and it is sufficient if it hybridizes with the template and has sufficient complementarity within a range capable of performing an intrinsic function of the primer. Therefore, in the present invention, the primer set as the detection agent according to the present invention can be easily designed with reference to the nucleotide sequence of the cDNA or genomic DNA of the SNP site.
  • a primer for detecting SNP does not need to have a sequence that is perfectly complementary to each gene sequence, and if it has a length and complementarity suitable for the purpose of measuring the amount of mRNA by amplifying a specific section of mRNA or cDNA through DNA synthesis Suffice.
  • the primers for the amplification reaction are composed of a set (pair) that complementarily binds to the template (or sense) and the opposite side (antisense) of both ends of a specific section of the mRNA to be amplified.
  • the term “probe” refers to RNA having a length of several to hundreds of base pairs that can specifically bind to mRNA, cDNA (complementary DNA), DNA, etc. of a specific gene. Alternatively, it refers to a polynucleotide fragment such as DNA, and is labeled so that the presence or absence, expression level, etc. of the target mRNA or cDNA to be bound to can be checked. Probe selection and hybridization conditions can be appropriately selected according to techniques known in the art. The probe may be used in a diagnostic method for detecting an allele (or allele, allele).
  • the diagnostic methods include detection methods based on hybridization of nucleic acids, such as Southern blot, and may be provided in a form previously bound to a substrate of a DNA chip in a method using a DNA chip.
  • the primer or probe may be chemically synthesized using a phosphoramidite solid support synthesis method or other well-known methods.
  • the primer or probe can be variously modified according to methods known in the art within the range that does not interfere with hybridization with the polynucleotide to be detected.
  • modifications include methylation, encapsulation, substitution of one or more homologues of natural nucleotides, and modifications between nucleotides, such as uncharged linkages such as methyl phosphonates, phosphoesters, phosphoroamidates, carbamates, etc. ) or charged linkages (eg, phosphorothioate, phosphorodithioate, etc.), and binding of a labeling material using fluorescence or enzymes.
  • uncharged linkages such as methyl phosphonates, phosphoesters, phosphoroamidates, carbamates, etc.
  • charged linkages eg, phosphorothioate, phosphorodithioate, etc.
  • the probe may further have a reporter conjugated to its 5' end.
  • the reporter is FAM (6-carboxyfluorescein), Texas red (texas red), fluorescein (fluorescein), fluorescein chlorotriazinyl (fluorescein chlorotriazinyl), HEX (2',4',5',7'-tetrachloro -6-carboxy-4,7-dichlorofluorescein), rhodamine green, rhodamine red, tetramethylrhodamine, fluorescein isothiocyanate (FITC), oregon green, Alexa alexa fluor, JOE (6-Carboxy-4',5'-Dichloro-2',7'-Dimethoxyfluorescein), ROX (6-Carboxyl-X-Rhodamine), TET (Tetrachloro-Fluorescein), TRITC ( It may be any one or more selected from the group consisting of
  • the probe may further have a quencher conjugated to its 3' end.
  • the quencher is TAMRA, BHQ (black hole quencher) 1, BHQ2, BHQ3, NFQ (nonfluorescent quencher), dabcyl, Eclipse, DDQ (deep dark quencher), Blackberry Quencher (Blackberry Quencher), Iowa black (Iowa black) ) may be any one or more selected from the group consisting of, but any known material that can be used as a quencher in the art may be used.
  • the present invention may provide a kit for diagnosing or predicting elasticity or tensile strength of human hair comprising the composition according to the present invention.
  • the kit confirms the SNP marker through amplification or by confirming the presence of a specific allele, for example, a minor allele in the SNP marker, to diagnose low elasticity, low tensile strength hair or predict the risk of occurrence.
  • the kit may be an RT-PCR kit or a microarray chip kit, but is not limited thereto.
  • the RT-PCR kit may include each primer set capable of amplifying a nucleic acid comprising the SNP site, in addition to a test tube or other suitable container, reaction buffer, deoxynucleotides (dNTPs), Taq-polymerization enzymes and enzymes such as reverse transcriptase, DNase, RNAse inhibitors, DEPC-water, sterile water, and the like.
  • dNTPs deoxynucleotides
  • Taq-polymerization enzymes and enzymes such as reverse transcriptase, DNase, RNAse inhibitors, DEPC-water, sterile water, and the like.
  • a primer set specific for a gene used as a quantitative control may be included together.
  • the microarray chip kit may include a microarray having a substrate on which a nucleic acid including the SNP site is immobilized.
  • the microarray may be composed of a conventional microarray except that the polynucleotide, primer set, or probe of the present invention is included.
  • Hybridization of nucleic acids on microarrays and detection of hybridization results are well known in the art.
  • a nucleic acid sample is labeled with a fluorescent material, for example, a label capable of generating a detectable signal including a material such as Cy3 and Cy5, and then hybridized on a microarray and the labeling material
  • a hybridization result can be detected by detecting a signal generated from
  • the hair is diagnosed as having low elasticity and low tensile strength, or hair with low elasticity and low tensile strength. It is possible to provide an information providing method for diagnosing or predicting the elasticity or tensile strength of hair, including the step of predicting that hair will occur.
  • the prediction and diagnosis of the risk of low elasticity and low tensile strength hair of the SNP marker according to the present invention was determined by measuring the frequency of each marker.
  • significance is characterized by having a p-value of less than 0.05, less than 0.01, less than 0.001, less than 0.0001, less than 0.00001, less than 0.000001, less than 0.0000001, or less than 0.00000001, but is not limited thereto.
  • the base of the SNP site according to the present invention when the base of the SNP site according to the present invention is a minor allele by confirming the gene of the individual, the frequency of the normal control group and the test group having low elasticity and low tensile strength hair (case) Among the values, it is judged as the phenotype of the group with a high frequency value, and if the base of the SNP site is a major allele, the group with a low frequency value among the frequency values of the normal control group and the test group with low elasticity and low tensile strength hair It can be judged by the phenotype.
  • the term “subject” or “subject” refers to a subject for diagnosing or predicting hair elasticity or tensile strength.
  • sample can be used without limitation as long as it is collected from an individual or subject to diagnose or predict the elasticity or tensile strength of hair, for example, cells or tissues obtained by biopsy, blood, whole blood, It may be serum, plasma, saliva, cerebrospinal fluid, various secretions, urine, feces, and the like. Preferably, it may be selected from the group consisting of blood, plasma, serum, saliva, nasal fluid, sputum, ascites, vaginal secretion and urine, and preferably blood, plasma or serum.
  • the sample may be pretreated prior to use for detection or diagnosis. For example, it may include homogenization, filtration, distillation, extraction, concentration, inactivation of interfering components, addition of reagents, and the like.
  • the SNP is sequencing, exome sequencing, microarray hybridization, allele specific PCR, dynamic allele hybridization technique (dynamic allele-) specific hybridization), PCR extension analysis, and Taqman technique may be identified by one or more methods selected from the group consisting of, but not limited thereto.
  • 15 SNP markers among the above-mentioned 135 markers are reselected to give a risk score, and the genotype is detected for each individual, and according to the frequency of each SNP marker secured, low elasticity, low tensile strength
  • the risk of hair was also calculated. Sensitivity and specificity were calculated according to the calculated risk reference value, and the high ROC and AUC values were obtained based on this. Using the data obtained as described above, the risk of low-elasticity, low-tensile strength hair was quantified to construct a model that could predict the risk of occurrence (see Example 4).
  • the present invention includes calculating the risk score of one or more SNPs selected from the group consisting of the following single nucleotide polymorphisms (SNPs) from a sample isolated from an individual,
  • SNPs single nucleotide polymorphisms
  • an information providing method for diagnosing or predicting low-elasticity and low-tensile-strength hair characterized in that the higher the sum of the calculated risk scores is greater than 0, the higher the probability of low-elasticity-low-tensile-strength hair:
  • the risk score is +2.14;
  • the risk score is +2.06;
  • the risk score is +1.23;
  • the risk score is +1.49;
  • the risk score is +2.08;
  • the risk score is +1.84;
  • the risk score is +2.08;
  • the risk score is +1.13;
  • the risk score is +1.64;
  • the risk score is +1.02.
  • the present invention includes the step of deriving the risk of low-elasticity and low-tensile-strength hair from the sample isolated from the subject by Equation 1 below, and the greater the derived risk is greater than 0, the higher the probability of occurrence of low-elasticity and low-tensile strength hair It provides an information providing method for diagnosing or predicting low elasticity and low tensile strength hair, characterized in that it is predicted to be high:
  • R n is a risk score corresponding to the minor allele of the nth SNP is the minor allele of Table A below,
  • F n is the frequency value of the minor allele of the nth SNP
  • n is one or more integers selected from the group consisting of 1 to 15 integers;
  • the risk is derived by identifying one or a combination of two or more of the 15 selected SNP markers of the present invention. According to the frequency of a minor allele in each SNP site of an individual, the risk can be calculated by summing all the risk scores of the corresponding SNP markers shown in Table 2 above.
  • Equation 1 when n is 1 and the frequency value is 2, that is, when the frequency of the base C at the SNP position corresponding to the 101st base in the nucleotide sequence of SEQ ID NO: 1 in the subject is 2, again
  • the frequency of the 2329141th base (rs11831183) of chromosome 12 of an individual when the frequency of the 2329141th base (rs11831183) of chromosome 12 of an individual is 2, the risk increases by 2.14 ⁇ 2, and when the frequency of the base T of the marker is 1, the risk increases by 2.14 ⁇ 1 do.
  • the 112, 225, 799 bases of chromosome 12 are all C, the risk does not increase.
  • the risk is determined by checking the base and frequency value of the SNP position corresponding to the 101st base within any one or more of the base sequences of SEQ ID NO: 1 to SEQ ID NO: 15, and summing all the values multiplied by the assigned risk score. is derived As such, the summation of risk scores derived from one or more SNPs is expressed as sigma ( ⁇ ) in Equation 1 above.
  • the risk may be to determine the predicted sensitivity and specificity according to Table B below according to the risk (LELTR) derived by Equation 1:
  • low elasticity and low tensile strength hair can be predicted with a sensitivity of 91.53% and a specificity of 74.85% at the risk standard of 3.21.
  • sensitivity refers to a sample or patient whose final clinical pathological diagnosis is low-elasticity and low-tensile-strength hair. percentage predicted to be
  • the term “specificity” means that there is no risk of low elasticity and low tensile strength hair through the information providing method or method according to the present invention for a sample or patient whose final clinical pathological diagnosis is normal, that is, normal is the predicted proportion.
  • the SNP is sequencing, exome sequencing, microarray hybridization, allele specific PCR, dynamic allele hybridization technique (dynamic allele-) specific hybridization), PCR extension analysis, and Taqman technique may be identified by one or more methods selected from the group consisting of, but not limited to.
  • the low elasticity and low tensile strength hair may be for Koreans, but is not limited thereto.
  • the present invention provides a kit for diagnosing or predicting low elastic and low tensile strength hair comprising an agent for detecting or amplifying one or more SNPs selected from the group consisting of the following single nucleotide polymorphisms (SNPs) as an active ingredient,
  • SNPs single nucleotide polymorphisms
  • the kit quantifies the risk of low-elasticity, low-tensile strength hair according to Equation 1, and the higher the value is greater than 0, the higher the probability of occurrence of low-elasticity low-tensile strength hair.
  • the “agent” according to the present invention is an agent capable of specifically binding to and recognizing a region containing a SNP according to the present invention or amplifying a region containing the SNP, specifically, specific to the region containing the SNP. It may be a set of primers capable of specifically amplifying a probe capable of binding positively, a polynucleotide including a region including the SNP, or a polynucleotide complementary thereto, and the detailed description is described above. As it is the same as bar, it is omitted.
  • the kit may be an RT-PCR kit or a microarray chip kit, but is not limited thereto.
  • the present invention predicts that the higher the risk (LELTR) of low-elasticity and low-tensile-strength hair calculated by Equation 1, the higher the probability of occurrence of low-elasticity and low tensile strength hair, and the risk derived by Equation 1 (LELTR) ) according to Table 3 above, it provides a low-elasticity, low-tensile-strength hair risk diagnosis or prediction model, characterized in that it has a predictive sensitivity and specificity.
  • the term “predictive model” refers to a specific mathematical model obtained by applying a prediction method to collected data. In the examples described herein, such data is based on whether the base of the SNP position according to the present invention from a sample of an individual, more specifically a nucleic acid sample, is a minor allele or a majority allele, and the risk score and frequency assigned to the minor allele. It consists of the sum of the products of values.
  • the present inventors collected blood to secure genes from 401 women who visited the Department of Dermatology, Seoul National University Hospital.
  • the tensile strength of hair obtained from the parietal region of the volunteer's scalp was measured with a machine (MTT-175), and individuals whose tensile strength was in the lower 15% were classified as a test group, and those that did not were classified as a control group.
  • gDNA Only gDNA whose OD260/280 value of 1.7 or higher, concentration of 10 ng/ ⁇ l or higher, and intact gDNA band confirmed on 1X TAE (Tris-acetate-EDTA) 1% agarose gel by extracting gDNA from the blood of the study subject is used for subsequent analysis. was used.
  • genotyping geno-typing was performed on gDNA samples isolated from the blood of study subjects using the Affymetrix Axiom KORV1.1 chip (Ref 550769). The analysis was performed through the processes of gDNA amplification, DNA fragmentation, quality control, hybridization, staining, and scanning.
  • a scanned image was obtained using the GeneTitan MC (Affymetrix) system and the Gene Chip Command Console Software (AGCC), and a .cel file was obtained based on this.
  • Affymetrix Gene Chip Command Console Software
  • genotypes for 827,783 SNPs were obtained.
  • additional SNPs were obtained through the imputation method (NARD + 1KGp3 reference by Eagle v2.4.1 phasing, InfoScore > 0.9 filtering).
  • quality control (QC) for SNPs was performed as follows:
  • SNPs single nucleotide polymorphisms
  • association analysis using SNP markers of the test group/control group was performed.
  • association analysis a chi-squared test was performed using the PLINK whole genome data analysis program, and the significance level was confirmed through the p-value.
  • SNPs with a p-value of 0.01 or less related to low-elasticity and low-tensile-strength hair that is, a statistically significant number of SNPs observed in patients with low-elasticity and low-tensile-strength hair compared to the normal control group, were selected.
  • information such as a chromosome position, a nucleotide sequence, a frequency, a significance level, etc.
  • rs_id refers to rs-ID, a unique marker assigned to a single nucleotide polymorphism (SNP) registered with the National Center for Biotechnology Information (NCBI) that accumulates genetic information of living organisms.
  • SNP single nucleotide polymorphism
  • the prediction method, prediction kit and prediction model of low-elasticity and low-tensile strength hair using the single nucleotide polymorphism marker of the present invention can predict individuals with low-elasticity and low tensile strength hair with high accuracy in advance for each individual. It works. Furthermore, based on the information obtained through the prediction method, prediction kit, and prediction model of the present invention, personalized medical devices, medicines and cosmetics, active ingredients, etc. that can improve or maintain the strength and elasticity of low-elasticity and low-tensile strength hair It is expected that it can be applied to the development of

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Abstract

La présente invention concerne un modèle de prédiction de l'élasticité et de la résistance à la traction des cheveux sur la base de marqueurs génétiques polymorphes, etc., la présente invention ayant pour effet d'être capable, pour des individus respectifs, de prédire à l'avance et avec une grande précision un individu ayant des cheveux à faible élasticité et à faible résistance à la traction. En outre, sur la base des informations obtenues par un procédé de prédiction, un kit de prédiction et un modèle de prédiction de la présente invention, cette dernière devrait trouver une application dans le développement de dispositifs médicaux personnalisés, de produits pharmaceutiques et cosmétiques, et d'ingrédients actifs, etc., capables d'améliorer ou de maintenir dans un état actuel la résistance et l'élasticité de cheveux à faible élasticité et à faible résistance à la traction.
PCT/KR2021/013709 2020-10-07 2021-10-06 Marqueurs génétiques polymorphes liés à l'élasticité et à la résistance à la traction de cheveux humains et leur utilisation WO2022075747A1 (fr)

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KR1020200129071A KR102374865B1 (ko) 2020-10-07 2020-10-07 인체 모발 탄력 인장강도 관련 유전자 다형성 마커 및 이의 용도

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Citations (4)

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Publication number Priority date Publication date Assignee Title
US20120329726A1 (en) * 2009-10-05 2012-12-27 Kao Corporation Hair Shape Susceptibility Gene
KR20170050212A (ko) * 2015-10-30 2017-05-11 (주)아모레퍼시픽 모발 탄력 측정 방법
JP2019041758A (ja) * 2017-08-29 2019-03-22 株式会社エバージーン 髪質を判定する方法
KR20200005779A (ko) * 2018-07-09 2020-01-17 (주) 메디젠휴먼케어 단일염기다형성을 이용한 탈모 표현형 예측 방법

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JP6757924B2 (ja) * 2015-08-24 2020-09-23 国立大学法人 東京大学 オキシトシン感受性予測マーカー

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US20120329726A1 (en) * 2009-10-05 2012-12-27 Kao Corporation Hair Shape Susceptibility Gene
KR20170050212A (ko) * 2015-10-30 2017-05-11 (주)아모레퍼시픽 모발 탄력 측정 방법
JP2019041758A (ja) * 2017-08-29 2019-03-22 株式会社エバージーン 髪質を判定する方法
KR20200005779A (ko) * 2018-07-09 2020-01-17 (주) 메디젠휴먼케어 단일염기다형성을 이용한 탈모 표현형 예측 방법

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