Genetic polymorphic markers for determining type of skin pigmentation and use thereof

Abstract

The present invention relates to a composition for diagnosing skin pigmentation, comprising a probe capable of detecting a gene polymorphism marker having significant association with the degree of skin pigmentation or a preparation capable of amplifying it; a kit or microarray for diagnosing skin pigmentation of a skin type, comprising the composition for diagnosing skin pigmentation of the skin type; and a method for providing information on the degree of skin pigmentation using the gene polymorphism marker or a combination of markers.

Description

Technology Field

[0001] The present invention relates to a composition for diagnosing skin pigmentation, comprising a gene polymorphism marker having significant association with the degree of skin pigmentation, a probe capable of detecting the same, or a preparation capable of amplifying it; a kit or microarray for diagnosing skin pigmentation of a skin type, comprising the composition for diagnosing skin pigmentation of the skin type; and a method for providing information on the degree of skin pigmentation using the gene polymorphism marker or a combination of markers. Background Technology

[0003] Changes in skin pigmentation can be influenced by environmental factors as well as factors such as age, sex, and genetic variation. According to many recent genome-wide studies (GWAS), genetic variations located within genes functionally linked to the biological pathways of pigmentation are significantly associated with skin pigmentation. However, since most existing GWAS studies have focused on Europeans and there are few studies on Asian populations, the understanding of genetic variations associated with skin pigmentation in Asians is limited.

[0004] The skin is the outermost layer of the human body and performs various functions such as responding to the external environment to protect the body from harmful substances, sensing other sensations, and regulating body temperature; the proper functioning of the skin is essential for protecting the body from disease and maintaining attractiveness.

[0005] Skin pigmentation types are classified into those that determine skin color in the absence of external environmental stimuli and irritant skin pigmentation such as freckles and facial pigment spots (Shekar et al., J Invest Dermatol. 2005, 125: 1119-1129, Del Bino et al., Int J Mol Sci. 2018;19(9):2668), and the level of pigmentation varies significantly depending on race and individual. To identify genetic factors involved in traits related to skin pigmentation, studies on numerous candidate genes, including BNC2, UGT1A8, IRF4, and POMC, were conducted on European and American populations (Jacobs et al., Hum Genet. 2013, 132: 147-158; Nan et al., Int J Cancer. 2009; 125: 909-917; Praetorius C et al., Cell. 2013; 155: 1022-1033). Furthermore, due to the genetic complexity of traits related to skin pigmentation, whole-genome analysis studies were conducted to identify hundreds or thousands of loci, revealing that numerous genes such as MC1R, SLC24A5, SLC45A2, and BNC2 are associated with traits related to skin pigmentation.

[0006] Most existing GWAS studies have focused on Europeans, and there are few studies on Asians, so the understanding of genetic variations associated with skin pigmentation in Asians is low. Therefore, additional research on diverse populations is needed to discover new genetic variations or identify causative genes that regulate skin pigmentation.

[0008] Against this backdrop, the inventors identified genetic characteristics determining individual skin traits to establish scientific skin classification criteria and developed personalized active ingredients based on these criteria. As a result of their diligent efforts to contribute to the development of customized cosmetics for different skin characteristics through various product segmentations, they identified a method for diagnosing the presence of pigmentation by selecting specific single nucleotide polymorphism (SNP) markers that have a significant correlation with skin pigmentation, thereby completing the present invention. The problem to be solved

[0010] One objective of the present invention is to provide a single nucleotide polymorphism (SNP) marker for diagnosing skin pigmentation.

[0011] Another objective of the present invention is to provide a composition for diagnosing skin pigmentation, comprising a probe capable of detecting a single nucleotide polymorphism (SNP) marker for diagnosing skin pigmentation or a preparation capable of amplifying it.

[0012] Another objective of the present invention is to provide a kit or microarray for diagnosing skin pigmentation comprising the above-mentioned composition for diagnosing skin pigmentation.

[0013] Another objective of the present invention is to provide a method for providing information on whether skin pigmentation is present, comprising the step of identifying a polymorphic site of the single nucleotide polymorphism marker. means of solving the problem

[0015] Each description and embodiment disclosed in the present invention may 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. Furthermore, the scope of the present invention should not be considered limited by the specific descriptions provided below.

[0017] As one embodiment for achieving the objective of the present invention, the present invention provides a single nucleotide polymorphism (SNP) marker for diagnosing skin pigmentation.

[0018] In another aspect, the present invention provides a composition for diagnosing skin pigmentation, comprising a probe capable of detecting a single nucleotide polymorphism (SNP) marker for diagnosing skin pigmentation or a preparation capable of amplifying it.

[0019] The skin type of an individual can be distinguished based on the presence or absence of the above-mentioned skin pigmentation.

[0020] In the present invention, the term "polymorphism" refers to a case where two or more alleles exist at a single gene locus, and among polymorphic regions, a case where only a single nucleotide differs from person to person is called a single nucleotide polymorphism (SNP). A preferred polymorphism marker has two or more alleles that exhibit an occurrence frequency of 1% or more, more specifically 10% or 20% or more, in a selected population. A "gene polymorphism marker" generally refers to a case where two or more alleles are observed at the same gene location (nucleotide), and generally, depending on the individual, there exist cases of major allele / major allele, major allele / minor allele, or minor allele / minor allele. In the present invention, the term may be used interchangeably with "polymorphic marker" and may refer to the bases and base regions of a sub-allele, or may be defined together with the chromosome number and base position, but is not limited thereto.

[0021] In the present invention, the term "allele" refers to multiple types of a single gene located at the same locus on homologous chromosomes. Alleles are also used to indicate polymorphism; for example, an SNP has two types of alleles. Additionally, it refers to a combination of two or more bases that have the same chromosome number and base position, and said bases include a major allele that occurs frequently in individuals of a specific population and a minor allele that occurs less frequently than said major allele.

[0022] Specifically, the gene polymorphism markers of the present invention are associated with skin pigmentation. When one possesses one or more minor alleles among two alleles, skin pigmentation can be said to be significant compared to individuals possessing major alleles. That is, in the case of major alleles / minor alleles or minor alleles / minor alleles, it can be seen that the skin characteristics exhibit a higher or lower degree of skin pigmentation compared to the case of possessing major alleles / major alleles.

[0023] In the present invention, the term "rs_id" refers to an rs-ID, which is an independent marker assigned to all initially registered SNPs by NCBI, which began accumulating SNP information in 1998. The rs_id listed in such a table refers to the SNP marker, which is a polymorphic marker of the present invention.

[0024] In the present invention, the term "skin type" refers to the skin type of an individual to be measured or diagnosed. Skin types that can be measured by the SNP of the present invention are included without limitation, but specifically may be pigmentation. Since the single nucleotide polymorphism marker of the present invention enables accurate measurement of skin type, it can also provide information on the changed skin type of the skin in contact with the active ingredient, and thus may enable the provision of personalized cosmetics, but is not limited thereto.

[0025] The above skin pigmentation is also related to whitening and may include, but is not limited to, a diagnostic marker for determining whether a skin type is whitening skin that tans easily due to high pigmentation or white skin that does not tan easily due to low pigmentation.

[0026] Furthermore, for the purposes of the present invention, the term "skin pigmentation" refers to the observation that the color of a part of an individual's skin changes to black or brown compared to the overall color. That is, it refers to the result of measuring the proportion of areas observed to be black or brown, which are relatively darker than the surrounding skin color, and a reduction in pigmentation can induce a skin whitening effect.

[0027] Specifically, the single nucleotide polymorphism marker may be one or more single nucleotide polymorphism markers selected from the single nucleotide polymorphism markers shown in Tables 1 to 3. The single nucleotide polymorphism markers shown in Tables 1 to 3 may be used to determine whether there is an association with the degree of skin pigmentation.

[0028] The determination of whether the single nucleotide polymorphism markers of the present invention can diagnose skin type was made by measuring the frequency of each marker. Such significance is characterized by, but is not limited to, p-values ​​such as 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 0.000000001. Specifically, the p-value may be less than 0.01, more specifically, the p-value may be less than 0.001, and even more specifically, less than 0.0001, but is not limited thereto.

[0030] The single nucleotide polymorphism (SNP) markers of the present invention may be one or more selected from the markers shown in Tables 1 to 3, but are not limited thereto. The single nucleotide polymorphism (SNP) markers may be one or more, and may be used in combinations of a number capable of determining pigmentation, such as two or more, three or more, four or more, etc., but are not limited thereto.

[0031] The above marker may be the SNP itself, a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the SNP location, or a polynucleotide consisting of sequences complementary thereto, but is not limited thereto.

[0032] Specifically, as one specific example, the single nucleotide polymorphism marker may be one or more selected from the markers listed in Table 1, but is not limited thereto.

[0033] The selected markers among those shown in Table 1 can be explained as follows.

[0034] For example, if the SNP ID is rs1710447, the Chr.Position (GRCh ver. 37) is listed as "5:149192846" and the Allele is initiated as A>G, this indicates that the 149192846th base of human chromosome 5 is A or G, and the base located to the right of the ">" in the allele may indicate the major allele and the base located to the left may indicate the minor allele.

[0035] In one specific example, the marker selected from Table 1 is a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149192846th base of human chromosome 5, wherein the 149192846th base of human chromosome 5 is A or G (rs17110447); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149191111th base of human chromosome 5, wherein the 149191111th base of human chromosome 5 is C or T (rs4235745); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149195389th base of human chromosome 5, wherein the 149195389th base of human chromosome 5 is T or C (rs251467); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149196682nd base of human chromosome 5, wherein the 149196682nd base of human chromosome 5 is T or G (rs109077); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149200603rd base of human chromosome 5, wherein the 149200603rd base of human chromosome 5 is T or C (rs32587); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149194923rd base of human chromosome 5, wherein the 149194923rd base of human chromosome 5 is T or C (rs109075); A polynucleotide comprising 5 to 100 consecutive DNA sequences including the 149202206th base of human chromosome 5, wherein the 149202206th base of human chromosome 5 is C or G (rs28282); a polynucleotide comprising 5 to 100 consecutive DNA sequences including the 149194485th base of human chromosome 5, wherein the 149194485th base of human chromosome 5 is C or T (rs251468); a polynucleotide comprising 5 to 100 consecutive DNA sequences including the 149195603rd base of human chromosome 5, wherein the 149195603rd base of human chromosome 5 is C or G (rs251466);A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149196090th base of human chromosome 5, wherein the 149196090th base of human chromosome 5 is A or C (rs251465); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149196234th base of human chromosome 5, wherein the 149196234th base of human chromosome 5 is G or C (rs251464); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149205630th base of human chromosome 5, wherein the 149205630th base of human chromosome 5 is G or T (rs32581); A polynucleotide comprising 5 to 100 consecutive DNA sequences including the 149210848th base of human chromosome 5, wherein the 149210848th base of human chromosome 5 is C or T (rs32579); a polynucleotide comprising 5 to 100 consecutive DNA sequences including the 149211868th base of human chromosome 5, wherein the 149211868th base of human chromosome 5 is G or A (rs32578); a polynucleotide comprising 5 to 100 consecutive DNA sequences including the 149209546th base of human chromosome 5, wherein the 149209546th base of human chromosome 5 is C or T (rs32580); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149212430th base of human chromosome 5, wherein the 149212430th base of human chromosome 5 is G or A (rs45520937); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149216304th base of human chromosome 5, wherein the 149216304th base of human chromosome 5 is C or T (rs45543631); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149226633rd base of human chromosome 5, wherein the 149226633rd base of human chromosome 5 is G or A (rs75739000);A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149216256th base of human chromosome 5, wherein the 149216256th base of human chromosome 5 is C or T (rs45588534); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149228648th base of human chromosome 5, wherein the 149228648th base of human chromosome 5 is C or T (rs26124); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149213456th base of human chromosome 5, wherein the 149213456th base of human chromosome 5 is A or G (rs32576); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149204852nd base of human chromosome 5, wherein the 149204852nd base of human chromosome 5 is C or G (rs17110586); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149218886th base of human chromosome 5, wherein the 149218886th base of human chromosome 5 is C or A (rs32574); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149215213th base of human chromosome 5, wherein the 149215213th base of human chromosome 5 is C or G (rs32575); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149229822nd base of human chromosome 5, wherein the 149229822nd base of human chromosome 5 is G or T (rs6579761); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149231519th base of human chromosome 5, wherein the 149231519th base of human chromosome 5 is C or T (rs26122); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149233110th base of human chromosome 5, wherein the 149233110th base of human chromosome 5 is C or A (rs7712296);A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149233186th base of human chromosome 5, wherein the 149233186th base of human chromosome 5 is C or T (rs17653703); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149216987th base of human chromosome 5, wherein the 149216987th base of human chromosome 5 is A or G (rs10783180); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149199148th base of human chromosome 5, wherein the 149199148th base of human chromosome 5 is G or A (rs251459); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149231830th base of human chromosome 5, wherein the 149231830th base of human chromosome 5 is A or G (rs26121); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149195125th base of human chromosome 5, wherein the 149195125th base of human chromosome 5 is T or G (rs109076); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149232525th base of human chromosome 5, wherein the 149232525th base of human chromosome 5 is A or G (rs888853); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149197230th base of human chromosome 5, wherein the 149197230th base of human chromosome 5 is T or C (rs251460); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149232308th base of human chromosome 5, wherein the 149232308th base of human chromosome 5 is G or A (rs2341294); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149196329th base of human chromosome 5, wherein the 149196329th base of human chromosome 5 is G or A (rs251463);A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149230952nd base of human chromosome 5, wherein the 149230952nd base of human chromosome 5 is A or G (rs1549188); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149230745th base of human chromosome 5, wherein the 149230745th base of human chromosome 5 is T or C (rs1549186); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149230787th base of human chromosome 5, wherein the 149230787th base of human chromosome 5 is C or T (rs1549187); A polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149231786th base of human chromosome 5, wherein the 149231786th base of human chromosome 5 is G or A (rs1107344); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149234235th base of human chromosome 5, wherein the 149234235th base of human chromosome 5 is C or A (rs393499); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149234236th base of human chromosome 5, wherein the 149234236th base of human chromosome 5 is A or T (rs439598); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149159174th base of human chromosome 5, wherein the 149159174th base of human chromosome 5 is G or A (rs55926576); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149190810th base of human chromosome 5, wherein the 149190810th base of human chromosome 5 is C or T (rs79489540); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149190810th base of human chromosome 5, wherein the 149194785th base of human chromosome 5 is G or A (rs80069564);A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149191547th base of human chromosome 5, wherein the 149191547th base of human chromosome 5 is C or T (rs78814834); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149193133rd base of human chromosome 5, wherein the 149193133rd base of human chromosome 5 is C or T (rs77655035); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149195726th base of human chromosome 5, wherein the 149195726th base of human chromosome 5 is C or T (rs17110463); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149196638th base of human chromosome 5, wherein the 149196638th base of human chromosome 5 is C or T (rs4705385); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149196916th base of human chromosome 5, wherein the 149196916th base of human chromosome 5 is A or G (rs112183859); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149192166th base of human chromosome 5, wherein the 149192166th base of human chromosome 5 is T or C (rs4705384); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149197747th base of human chromosome 5, wherein the 149197747th base of human chromosome 5 is C or G (rs17600568); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149199467th base of human chromosome 5, wherein the 149199467th base of human chromosome 5 is C or T (rs79435714); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149197609th base of human chromosome 5, wherein the 149197609th base of human chromosome 5 is T or C (rs76390604);A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149197815th base of human chromosome 5, wherein the 149197815th base of human chromosome 5 is T or C (rs10491360); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149200932nd base of human chromosome 5, wherein the 149200932nd base of human chromosome 5 is G or A (rs2003602); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149190799th base of human chromosome 5, wherein the 149190799th base of human chromosome 5 is G or A (rs79694606); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149190248th base of human chromosome 5, wherein the 149190248th base of human chromosome 5 is C or G (rs75548653); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149203782nd base of human chromosome 5, wherein the 149203782nd base of human chromosome 5 is A or G (rs17653577); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149205992nd base of human chromosome 5, wherein the 149205992nd base of human chromosome 5 is G or A (rs741582); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149201956th base of human chromosome 5, wherein the 149201956th base of human chromosome 5 is C or G (rs1078325); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149208516th base of human chromosome 5, wherein the 149208516th base of human chromosome 5 is G or T (rs76994147); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149206531st base of human chromosome 5, wherein the 149206531st base of human chromosome 5 is G or A (rs45560442);A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149227540th base of human chromosome 5, where the 149227540th base is T or C (rs76174857); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149204461st base of human chromosome 5, where the 149204461st base is C or T (rs62382344); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149192744th base of human chromosome 5, where the 149192744th base is G or T (rs67393352); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149189449th base of human chromosome 5, wherein the 149189449th base of human chromosome 5 is G or C (rs11948432); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149205417th base of human chromosome 5, wherein the 149205417th base of human chromosome 5 is C or A (rs32582); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149196564th base of human chromosome 5, wherein the 149196564th base of human chromosome 5 is C or T (rs71586143); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149200402nd base of human chromosome 5, wherein the 149200402nd base of human chromosome 5 is A or G (rs17462080); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149199656th base of human chromosome 5, wherein the 149199656th base of human chromosome 5 is C or T (rs7729592); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149196513th base of human chromosome 5, wherein the 149196513th base of human chromosome 5 is A or G (rs251462);A polynucleotide comprising 5 to 100 consecutive DNA sequences including the 149199889th base of human chromosome 5, wherein the 149199889th base of human chromosome 5 is G or A (rs32589); a polynucleotide comprising 5 to 100 consecutive DNA sequences including the 149200920th base of human chromosome 5, wherein the 149200920th base of human chromosome 5 is A or G (rs32586); a polynucleotide comprising 5 to 100 consecutive DNA sequences including the 149202168th base of human chromosome 5, wherein the 149202168th base of human chromosome 5 is A or G (rs32585); A polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149200043rd base of human chromosome 5, wherein the 149200043rd base of human chromosome 5 is T or C (rs32588); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149203993rd base of human chromosome 5, wherein the 149203993rd base of human chromosome 5 is A or G (rs32584); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149187322nd base of human chromosome 5, wherein the 149187322nd base of human chromosome 5 is G or A (rs73267734); A polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149204444th base of human chromosome 5, wherein the 149204444th base of human chromosome 5 is C or T (rs32583); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149178996th base of human chromosome 5, wherein the 149178996th base of human chromosome 5 is T or C (rs76861039); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149178996th base of human chromosome 5, wherein the 149179725th base of human chromosome 5 is T or C (rs17461842);A polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149185923rd base of human chromosome 5, wherein the 149185923rd base of human chromosome 5 is C or A (rs75321435); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149187212th base of human chromosome 5, wherein the 149187212th base of human chromosome 5 is C or T (rs80262653); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149187212th base of human chromosome 5, wherein the 149187640th base of human chromosome 5 is G or A (rs75294071); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149183256th base of human chromosome 5, wherein the 149183256th base of human chromosome 5 is G or T (rs75465608); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149234701st base of human chromosome 5, wherein the 149234701st base of human chromosome 5 is G or A (rs4705386); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149236008th base of human chromosome 5, wherein the 149236008th base of human chromosome 5 is G or A (rs76295025); A polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149164366th base of human chromosome 5, wherein the 149164366th base of human chromosome 5 is G or A (rs74340302); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149230730th base of human chromosome 5, wherein the 149230730th base of human chromosome 5 is C or T (rs25846); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149186478th base of human chromosome 5, wherein the 149186478th base of human chromosome 5 is A or T (rs4705383);A polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149162451st base of human chromosome 5, wherein the 149162451st base of human chromosome 5 is G or A (rs62382308); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149162294th base of human chromosome 5, wherein the 149162294th base of human chromosome 5 is G or A (rs72830233); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149212471st base of human chromosome 5, wherein the 149212471st base of human chromosome 5 is G or A (rs17572019); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149179741st base of human chromosome 5, wherein the 149179741st base of human chromosome 5 is C or A (rs72830248); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149159862nd base of human chromosome 5, wherein the 149159862nd base of human chromosome 5 is C or G (rs62382307); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149184905th base of human chromosome 5, wherein the 149184905th base of human chromosome 5 is G or T (rs759814); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149159107th base of human chromosome 5, wherein the 149159107th base of human chromosome 5 is A or G (rs56160216); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149211392nd base of human chromosome 5, wherein the 149211392nd base of human chromosome 5 is C or G (rs13178617); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149182832nd base of human chromosome 5, wherein the 149182832nd base of human chromosome 5 is G or C (rs55650980);A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 149208768th base of human chromosome 5, where the 149208768th base is A or G (rs10491361); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 16795790th base of human chromosome 9, where the 16795790th base is A or C (rs16935073); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 16795241st base of human chromosome 9, where the 16795241st base is T or C (rs10810635); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 16,794,418th base of human chromosome 9, where the 16,794,418th base is C or A (rs12376135); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 16,806,521st base of human chromosome 9, where the 16,806,521st base is T or C (rs12351269); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 16,801,450th base of human chromosome 9, where the 16,801,450th base is G or T (rs4455968); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 16808172nd base of human chromosome 9, wherein the 16808172nd base of human chromosome 9 is C or G (rs10122901); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 16806694th base of human chromosome 9, wherein the 16806694th base of human chromosome 9 is G or C (rs10121347); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 16801743rd base of human chromosome 9, wherein the 16801743rd base of human chromosome 9 is C or A (rs4523356);A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 16801120th base of human chromosome 9, wherein the 16801120th base of human chromosome 9 is A or C (rs10962609); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 16788274th base of human chromosome 9, wherein the 16788274th base of human chromosome 9 is A or G (rs12378588); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 16788253rd base of human chromosome 9, wherein the 16788253rd base of human chromosome 9 is T or C (rs12341542); A polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 16,790,074th base of human chromosome 9, where the 16,790,074th base is T or G (rs10115109); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 16,790,968th base of human chromosome 9, where the 16,790,968th base is G or C (rs2183407); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 16,788,363rd base of human chromosome 9, where the 16,788,363rd base is A or G (rs12378598); A polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 16,790,960th base of human chromosome 9, where the 16,790,960th base is A or G (rs2183406); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 16,799,844th base of human chromosome 9, where the 16,799,844th base is C or T (rs10119811); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 16,793,202nd base of human chromosome 9, where the 16,793,202nd base is T or C (rs12341168);A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 16,793,104th base of human chromosome 9, where the 16,793,104th base is A or G (rs10120562); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 16,792,350th base of human chromosome 9, where the 16,792,350th base is A or C (rs10119731); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 16,796,252nd base of human chromosome 9, where the 16,796,252nd base is T or G (rs10962601); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 16,792,675th base of human chromosome 9, where the 16,792,675th base is G or C (rs10125996); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 16,791,865th base of human chromosome 9, where the 16,791,865th base is C or T (rs12380481); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 16,787,767th base of human chromosome 9, where the 16,787,767th base is T or C (rs73410488); A polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 16,788,327th base of human chromosome 9, where the 16,788,327th base is A or G (rs10756814); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 16,788,333rd base of human chromosome 9, where the 16,788,333rd base is T or C (rs74645810); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 16,788,336th base of human chromosome 9, where the 16,788,336th base is A or G (rs76233908);A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 16,788,308th base of human chromosome 9, where the 16,788,308th base is C or T (rs10756813); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 16,788,328th base of human chromosome 9, where the 16,788,328th base is G or A (rs76211545); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 16,815,861st base of human chromosome 9, where the 16,815,861st base is A or G (rs10962619); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 16825110th base of human chromosome 9, wherein the 16825110th base of human chromosome 9 is C or T (rs7043062); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 16789652nd base of human chromosome 9, wherein the 16789652nd base of human chromosome 9 is T or C (rs4961496); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 16795159th base of human chromosome 9, wherein the 16795159th base of human chromosome 9 is A or G (rs10962598); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 16812810th base of human chromosome 9, wherein the 16812810th base of human chromosome 9 is T or C (rs10962618); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 16789024th base of human chromosome 9, wherein the 16789024th base of human chromosome 9 is T or C (rs10810632); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 16789436th base of human chromosome 9, wherein the 16789436th base of human chromosome 9 is A or G (rs6475082);A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 16820923rd base of human chromosome 9, wherein the 16820923rd base of human chromosome 9 is C or G (rs10962622); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 16795588th base of human chromosome 9, wherein the 16795588th base of human chromosome 9 is A or T (rs16935071); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 16795211th base of human chromosome 9, wherein the 16795211th base of human chromosome 9 is G or C (rs57542309); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 16,824,921st base of human chromosome 9, where the 16,824,921st base is C or G (rs10810640); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 16,788,367th base of human chromosome 9, where the 16,788,367th base is C or T (rs10810631); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 11,956,8133rd base of human chromosome 10, where the 11,956,8133rd base is G or A (rs17096846); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119570121st base of human chromosome 10, wherein the 119570121st base of human chromosome 10 is A or T (rs1925258); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119569921st base of human chromosome 10, wherein the 119569921st base of human chromosome 10 is G or A (rs1925257); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119570915th base of human chromosome 10, wherein the 119570915th base of human chromosome 10 is G or T (rs55927713);A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119571832nd base of human chromosome 10, wherein the 119571832nd base of human chromosome 10 is G or A (rs17096850); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119572168th base of human chromosome 10, wherein the 119572168th base of human chromosome 10 is C or A (rs4751640); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119547342nd base of human chromosome 10, wherein the 119547342nd base of human chromosome 10 is C or T (rs4752110); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119561946th base of human chromosome 10, wherein the 119561946th base of human chromosome 10 is C or T (rs61865966); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119570716th base of human chromosome 10, wherein the 119570716th base of human chromosome 10 is C or A (rs28605039); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119563422nd base of human chromosome 10, wherein the 119563422nd base of human chromosome 10 is T or A (rs61865967); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119544822nd base of human chromosome 10, wherein the 119544822nd base of human chromosome 10 is A or G (rs7098480); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119544385th base of human chromosome 10, wherein the 119544385th base of human chromosome 10 is C or T (rs9804204); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119547279th base of human chromosome 10, wherein the 119547279th base of human chromosome 10 is G or T (rs2025562);A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119544027th base of human chromosome 10, wherein the 119544027th base of human chromosome 10 is G or T (rs10749248); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119545571st base of human chromosome 10, wherein the 119545571st base of human chromosome 10 is G or A (rs10749249); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119547081st base of human chromosome 10, wherein the 119547081st base of human chromosome 10 is T or C (rs10749250); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119547669th base of human chromosome 10, wherein the 119547669th base of human chromosome 10 is A or G (rs72829865); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119545287th base of human chromosome 10, wherein the 119545287th base of human chromosome 10 is T or G (rs7099175); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119545401st base of human chromosome 10, wherein the 119545401st base of human chromosome 10 is G or A (rs10787792); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119545101st base of human chromosome 10, wherein the 119545101st base of human chromosome 10 is T or C (rs1925285); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119545375th base of human chromosome 10, wherein the 119545375th base of human chromosome 10 is A or T (rs10787791); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119545741st base of human chromosome 10, wherein the 119545741st base of human chromosome 10 is T or G (rs4752106);A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119545762nd base of human chromosome 10, wherein the 119545762nd base of human chromosome 10 is T or C (rs4752107); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119546979th base of human chromosome 10, wherein the 119546979th base of human chromosome 10 is T or C (rs2025561); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119545238th base of human chromosome 10, wherein the 119545238th base of human chromosome 10 is T or C (rs7098850); A polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119546034th base of human chromosome 10, wherein the 119546034th base of human chromosome 10 is A or T (rs4752109); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119546496th base of human chromosome 10, wherein the 119546496th base of human chromosome 10 is G or T (rs2031458); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119546323rd base of human chromosome 10, wherein the 119546323rd base of human chromosome 10 is A or G (rs10787794); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119552651st base of human chromosome 10, wherein the 119552651st base of human chromosome 10 is G or A (rs55723754); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119566093rd base of human chromosome 10, wherein the 119566093rd base of human chromosome 10 is C or T (rs11198114); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119564143rd base of human chromosome 10, wherein the 119564143rd base of human chromosome 10 is C or T (rs11198112);A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119563401st base of human chromosome 10, wherein the 119563401st base of human chromosome 10 is T or C (rs10444110); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119565538th base of human chromosome 10, wherein the 119565538th base of human chromosome 10 is C or A (rs10444039); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119561969th base of human chromosome 10, wherein the 119561969th base of human chromosome 10 is C or T (rs7070575); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119573178th base of human chromosome 10, wherein the 119573178th base of human chromosome 10 is C or T (rs7098111); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119572403rd base of human chromosome 10, wherein the 119572403rd base of human chromosome 10 is C or T (rs35563099); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119587425th base of human chromosome 10, wherein the 119587425th base of human chromosome 10 is G or A (rs4751641); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119584730th base of human chromosome 10, wherein the 119584730th base of human chromosome 10 is C or T (rs61865972); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119599727th base of human chromosome 10, wherein the 119599727th base of human chromosome 10 is A or G (rs61866015); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119575974th base of human chromosome 10, wherein the 119575974th base of human chromosome 10 is C or T (rs1806957);A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119576317th base of human chromosome 10, wherein the 119576317th base of human chromosome 10 is G or C (rs555269109); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119576318th base of human chromosome 10, wherein the 119576318th base of human chromosome 10 is G or T (rs532411111); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119576319th base of human chromosome 10, wherein the 119576319th base of human chromosome 10 is C or G (rs4994045); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119584861st base of human chromosome 10, where the 119584861st base of said chromosome 10 is A or G (rs6585463); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119562387th base of said chromosome 10, where the 119562387th base of said chromosome 10 is C or T (rs12146158); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119572476th base of said chromosome 10, where the 119572476th base of said chromosome 10 is C or A (rs74317863); A polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119577677th base of human chromosome 10, where the 119577677th base of human chromosome 10 is G or A (rs34878973); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119601436th base of human chromosome 10, where the 119601436th base of human chromosome 10 is T or G (rs7098136); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119575798th base of human chromosome 10, where the 119575798th base of human chromosome 10 is C or T (rs12773211);A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119601939th base of human chromosome 10, wherein the 119601939th base of human chromosome 10 is G or C (rs7916406); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119602316th base of human chromosome 10, wherein the 119602316th base of human chromosome 10 is G or A (rs61866016); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119602424th base of human chromosome 10, wherein the 119602424th base of human chromosome 10 is G or T (rs61866017); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119601743rd base of human chromosome 10, wherein the 119601743rd base of human chromosome 10 is G or A (rs12250372); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119586963rd base of human chromosome 10, wherein the 119586963rd base of human chromosome 10 is C or T (rs4752118); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119586186th base of human chromosome 10, wherein the 119586186th base of human chromosome 10 is A or T (rs10749252); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119586231st base of human chromosome 10, wherein the 119586231st base of human chromosome 10 is C or T (rs7085292); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119586178th base of human chromosome 10, wherein the 119586178th base of human chromosome 10 is C or T (rs4752117); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119587158th base of human chromosome 10, wherein the 119587158th base of human chromosome 10 is G or A (rs10749253);A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119591330th base of human chromosome 10, wherein the 119591330th base of human chromosome 10 is G or A (rs10886151); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119586980th base of human chromosome 10, wherein the 119586980th base of human chromosome 10 is A or G (rs4752119); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119586462nd base of human chromosome 10, wherein the 119586462nd base of human chromosome 10 is C or A (rs4431946); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119592083rd base of human chromosome 10, wherein the 119592083rd base of human chromosome 10 is C or T (rs1925264); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119595140th base of human chromosome 10, wherein the 119595140th base of human chromosome 10 is G or A (rs11498896); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 119582802nd base of human chromosome 10, wherein the 119582802nd base of human chromosome 10 is C or T (rs4752116); A polynucleotide comprising 5 to 100 consecutive DNA sequences including the 119591168th base of human chromosome 10, wherein the 119591168th base of human chromosome 10 is C or A (rs11198135); a polynucleotide comprising 5 to 100 consecutive DNA sequences including the 119581527th base of human chromosome 10, wherein the 119581527th base of human chromosome 10 is G or A (rs10886148); a polynucleotide comprising 5 to 100 consecutive DNA sequences including the 89985940th base of human chromosome 16, wherein the 89985940th base of human chromosome 16 is G or A (rs2228479);A polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 89986760th base of human chromosome 16, wherein the 89986760th base of human chromosome 16 is A or G (rs3212369); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 89987201st base of human chromosome 16, wherein the 89987201st base of human chromosome 16 is A or G (rs3212371); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 89986608th base of human chromosome 16, wherein the 89986608th base of human chromosome 16 is A or G (rs2228478); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 89985177th base of human chromosome 16, wherein the 89985177th base of human chromosome 16 is T or C (rs3212359); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 89985441st base of human chromosome 16, wherein the 89985441st base of human chromosome 16 is T or A (rs3212363); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 89986025th base of human chromosome 16, wherein the 89986025th base of human chromosome 16 is T or C (rs33932559); A polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 89986154th base of human chromosome 16, where the 89986154th base is A or G (rs885479); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 89985222nd base of human chromosome 16, where the 89985222nd base is A or G (rs3212361); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 200473658th base of human chromosome 2, where the 200473658th base is C or T (rs12693889);A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200475044th base of human chromosome 2, wherein the 200475044th base of human chromosome 2 is C or G (rs755276); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200492565th base of human chromosome 2, wherein the 200492565th base of human chromosome 2 is A or G (rs1901150); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200492076th base of human chromosome 2, wherein the 200492076th base of human chromosome 2 is A or C (rs4673381); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200484107th base of human chromosome 2, wherein the 200484107th base of human chromosome 2 is A or G (rs1823487); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200478921st base of human chromosome 2, wherein the 200478921st base of human chromosome 2 is T or G (rs1450566); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200491198th base of human chromosome 2, wherein the 200491198th base of human chromosome 2 is G or C (rs62180586); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200491299th base of human chromosome 2, wherein the 200491299th base of human chromosome 2 is G or A (rs13419888); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200477380th base of human chromosome 2, wherein the 200477380th base of human chromosome 2 is A or T (rs1450571); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200477504th base of human chromosome 2, wherein the 200477504th base of human chromosome 2 is C or T (rs10563018);A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200477506th base of human chromosome 2, where the 200477506th base is A or C (rs56112313); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200484696th base of human chromosome 2, where the 200484696th base is A or G (rs2034486); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200484696th base of human chromosome 2, where the 200485100th base of human chromosome 2 is T or C (rs7591758); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200487486th base of human chromosome 2, wherein the 200487486th base of human chromosome 2 is C or A (rs1868723); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200491726th base of human chromosome 2, wherein the 200491726th base of human chromosome 2 is A or C (rs7597643); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200491726th base of human chromosome 2, wherein the 200491877th base of human chromosome 2 is A or G (rs4675732); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200484452nd base of human chromosome 2, wherein the 200484452nd base of human chromosome 2 is T or G (rs2034484); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200491187th base of human chromosome 2, wherein the 200491187th base of human chromosome 2 is A or G (rs13394614); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200479539th base of human chromosome 2, wherein the 200479539th base of human chromosome 2 is A or T (rs4675721);A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200488306th base of human chromosome 2, wherein the 200488306th base of human chromosome 2 is T or C (rs6435022); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200488785th base of human chromosome 2, wherein the 200488785th base of human chromosome 2 is T or C (rs1450565); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200488905th base of human chromosome 2, wherein the 200488905th base of human chromosome 2 is A or G (rs1450564); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200489109th base of human chromosome 2, wherein the 200489109th base of human chromosome 2 is G or A (rs1450563); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200484657th base of human chromosome 2, wherein the 200484657th base of human chromosome 2 is C or G (rs2167215); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200484657th base of human chromosome 2, wherein the 200481019th base of human chromosome 2 is A or T (rs1376134); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200486976th base of human chromosome 2, wherein the 200486976th base of human chromosome 2 is T or G (rs983677); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200487539th base of human chromosome 2, wherein the 200487539th base of human chromosome 2 is G or C (rs1868724); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200489964th base of human chromosome 2, wherein the 200489964th base of human chromosome 2 is C or G (rs10206526);A polynucleotide comprising 5 to 100 consecutive DNA sequences including the 200490260th base of human chromosome 2, wherein the 200490260th base of human chromosome 2 is A or G (rs986750); a polynucleotide comprising 5 to 100 consecutive DNA sequences including the 200491038th base of human chromosome 2, wherein the 200491038th base of human chromosome 2 is A or G (rs12467197); a polynucleotide comprising 5 to 100 consecutive DNA sequences including the 200482025th base of human chromosome 2, wherein the 200482025th base of human chromosome 2 is A or G (rs6730854); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200482231st base of human chromosome 2, wherein the 200482231st base of human chromosome 2 is G or A (rs6759297); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200482513th base of human chromosome 2, wherein the 200482513th base of human chromosome 2 is C or T (rs1450567); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200480777th base of human chromosome 2, wherein the 200480777th base of human chromosome 2 is T or C (rs1376133); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200481498th base of human chromosome 2, wherein the 200481498th base of human chromosome 2 is C or G (rs2122532); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200481506th base of human chromosome 2, wherein the 200481506th base of human chromosome 2 is A or T (rs2122533); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200495743rd base of human chromosome 2, wherein the 200495743rd base of human chromosome 2 is A or C (rs4675733);A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200482881st base of human chromosome 2, wherein the 200482881st base of human chromosome 2 is A or T (rs4507037); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200499444th base of human chromosome 2, wherein the 200499444th base of human chromosome 2 is G or A (rs12693894); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200499255th base of human chromosome 2, wherein the 200499255th base of human chromosome 2 is T or A (rs12052634); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200491272nd base of human chromosome 2, wherein the 200491272nd base of human chromosome 2 is A or G (rs13394647); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200474888th base of human chromosome 2, wherein the 200474888th base of human chromosome 2 is C or A (rs768637); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200478354th base of human chromosome 2, wherein the 200478354th base of human chromosome 2 is G or C (rs4675720); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200484686th base of human chromosome 2, wherein the 200484686th base of human chromosome 2 is C or T (rs2034485); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200485648th base of human chromosome 2, wherein the 200485648th base of human chromosome 2 is T or C (rs6743286); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200498327th base of human chromosome 2, wherein the 200498327th base of human chromosome 2 is C or T (rs78394027);A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200501964th base of human chromosome 2, wherein the 200501964th base of human chromosome 2 is C or G (rs7562843); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200499206th base of human chromosome 2, wherein the 200499206th base of human chromosome 2 is C or G (rs12053334); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200500431st base of human chromosome 2, wherein the 200500431st base of human chromosome 2 is C or T (rs4624324); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200500296th base of human chromosome 2, wherein the 200500296th base of human chromosome 2 is T or C (rs12477506); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200506846th base of human chromosome 2, wherein the 200506846th base of human chromosome 2 is C or T (rs28890501); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200492529th base of human chromosome 2, wherein the 200492529th base of human chromosome 2 is A or C (rs1901151); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200501467th base of human chromosome 2, wherein the 200501467th base of human chromosome 2 is T or A (rs57791827); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200505203rd base of human chromosome 2, wherein the 200505203rd base of human chromosome 2 is T or G (rs4673384); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200494912th base of human chromosome 2, wherein the 200494912th base of human chromosome 2 is A or G (rs7609357);A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200496036th base of human chromosome 2, wherein the 200496036th base of human chromosome 2 is T or C (rs4673383); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200497907th base of human chromosome 2, wherein the 200497907th base of human chromosome 2 is T or G (rs1450561); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200499399th base of human chromosome 2, wherein the 200499399th base of human chromosome 2 is A or G (rs11691837); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200501134th base of human chromosome 2, wherein the 200501134th base of human chromosome 2 is T or C (rs10191530); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200499157th base of human chromosome 2, wherein the 200499157th base of human chromosome 2 is A or G (rs12053332); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200498080th base of human chromosome 2, wherein the 200498080th base of human chromosome 2 is A or G (rs1450559); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200490231st base of human chromosome 2, wherein the 200490231st base of human chromosome 2 is C or A (rs60315704); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200497975th base of human chromosome 2, wherein the 200497975th base of human chromosome 2 is G or A (rs1450560); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200501827th base of human chromosome 2, wherein the 200501827th base of human chromosome 2 is T or C (rs10194512);A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200489315th base of human chromosome 2, wherein the 200489315th base of human chromosome 2 is G or A (rs17590093); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200497286th base of human chromosome 2, wherein the 200497286th base of human chromosome 2 is G or T (rs7578193); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200494182nd base of human chromosome 2, wherein the 200494182nd base of human chromosome 2 is G or A (rs1450562); A polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 200497711th base of human chromosome 2, which is A or G (rs4675735); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 200496814th base of human chromosome 2, which is A or T (rs4675734); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 200509555th base of human chromosome 2, which is G or A (rs149819797); A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200509556th base of human chromosome 2, wherein the 200509556th base of human chromosome 2 is C or T (rs145839112); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200495510th base of human chromosome 2, wherein the 200495510th base of human chromosome 2 is A or G (rs77833142); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200510641st base of human chromosome 2, wherein the 200510641st base of human chromosome 2 is A or C (rs78251380);A polynucleotide composed of 5 to 100 consecutive DNA sequences including the 200510941st base of human chromosome 2, where the 200510941st base is T or G (rs80333946); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 3548231st base of human chromosome 19, where the 3548231st base is A or G (rs2240751); a polynucleotide composed of 5 to 100 consecutive DNA sequences including the 3542983rd base of human chromosome 19, where the 3542983rd base is C or T (rs12608592); A polynucleotide comprising 5 to 100 consecutive DNA sequences including the 3540539th base of human chromosome 19, wherein the 3540539th base is G or C (rs12984831); and one or more polynucleotides selected from the group consisting of the 3540539th base and their complementary polynucleotides, but not limited thereto. The markers described above are merely examples in Table 1 and may be selected from chromosomes at other locations in the same manner as described above.

[0036] As another embodiment, one or more of the single nucleotide polymorphism (SNP) markers shown in Table 2, as in Table 1, may be selected, but are not limited thereto.

[0037] As another embodiment, one or more of the single nucleotide polymorphism (SNP) markers shown in Table 3, as in Table 1, may be selected, but are not limited thereto.

[0038] The single nucleotide polymorphism markers shown in Tables 2 and 3 may be interpreted and selected as described above, but are not limited thereto.

[0040] In the present invention, the alleles have the same chromosome number in each individual, and among them, there exist a major allele and a minor allele of an SNP, and as the base of the polymorphic region of the polymorphic marker increases by one to the minor allele, the major allele may decrease by one, and as the major allele increases by one, the minor allele may decrease by one. However, the range in which the minor allele and the major allele may increase or decrease may be within three types: i) major allele / major allele, ii) major allele / minor allele, and iii) minor allele / minor allele, and the alleles may decrease or increase within the range of the three types, but are not limited thereto.

[0041] In addition, the marker in the present invention is a marker capable of determining the degree of change in the phenotype (pigmentation) as the number of major alleles increases one by one, based on the base of the polymorphic region of the polymorphic marker of the individual. For example, among the markers shown in Table 1, if the 149192846th base of chromosome 5 of the individual is the minority allele A (rs17110447), the effect size is negative (-), so it can be determined that pigmentation is decreasing, and if the 16795241st base of chromosome 9 of the individual is the minority allele C (rs10810635), the effect size is positive (+), so it can be determined that pigmentation is increasing, but is not limited thereto.

[0042] Specifically, the above single nucleotide polymorphism marker may, but is not limited to, increase pigmentation when it contains one or more of the following bases that are major alleles:

[0043] The 16,795,790th base of human chromosome 9 is A; the 16,795,241st base of human chromosome 9 is T; the 16,794,418th base of human chromosome 9 is C; the 16,806,521st base of human chromosome 9 is T; the 16,801,450th base of human chromosome 9 is G; the 16,808,172nd base of human chromosome 9 is C; the 16,806,694th base of human chromosome 9 is G; the 16,801,743rd base of human chromosome 9 is C; the 16,801,120th base of human chromosome 9 is A; the 16,788,274th base of human chromosome 9 is A; the 16,788,253rd base of human chromosome 9 is T; the 16,790,074th base of human chromosome 9 is T; The 16,790,968th base of human chromosome 9 is G; the 16,788,363rd base of human chromosome 9 is A; the 16,790,960th base of human chromosome 9 is A; the 16,799,844th base of human chromosome 9 is C; the 16,793,202nd base of human chromosome 9 is T; the 16,793,104th base of human chromosome 9 is A; the 16,792,350th base of human chromosome 9 is A; the 16,796,252nd base of human chromosome 9 is T; the 16,792,675th base of human chromosome 9 is G; the 16,791,865th base of human chromosome 9 is C; the 16,787,767th base of human chromosome 9 is T; the 11,956,8133rd base of human chromosome 10 is G; The 119570121st base of human chromosome 10 is A; the 119569921st base of human chromosome 10 is G; the 119570915th base of human chromosome 10 is G; the 119571832nd base of human chromosome 10 is G; the 119572168th base of human chromosome 10 is C; the 119547342nd base of human chromosome 10 is C; the 119561946th base of human chromosome 10 is C; the 119570716th base of human chromosome 10 is C;The 119563422nd base of human chromosome 10 is T; the 119544822nd base of human chromosome 10 is A; the 119544385th base of human chromosome 10 is C; the 119547279th base of human chromosome 10 is G; the 119544027th base of human chromosome 10 is G; the 119545571st base of human chromosome 10 is G; the 119547081st base of human chromosome 10 is T; the 119547669th base of human chromosome 10 is A; the 119545287th base of human chromosome 10 is T; the 119545401st base of human chromosome 10 is G; the 119545101st base of human chromosome 10 is T; The 119545375th base of human chromosome 10 is A; the 119545741st base of human chromosome 10 is T; the 119545762nd base of human chromosome 10 is T; the 119546979th base of human chromosome 10 is T; the 119545238th base of human chromosome 10 is T; the 119546034th base of human chromosome 10 is A; the 119546496th base of human chromosome 10 is G; the 119546323rd base of human chromosome 10 is A; the 119552651st base of human chromosome 10 is G; the 119566093rd base of human chromosome 10 is C; the 89985940th base of human chromosome 16 is G; The 89986760th base of human chromosome 16 is A; the 89987201st base of human chromosome 16 is A; the 89986608th base of human chromosome 16 is A; the 89985177th base of human chromosome 16 is T; the 89985441st base of human chromosome 16 is T; the 89986025th base of human chromosome 16 is T; the 89986154th base of human chromosome 16 is A; the 89985222nd base of human chromosome 16 is A; the 200473658th base of human chromosome 2 is C;The 200475044th base of human chromosome 2 is C; the 200492565th base of human chromosome 2 is A; the 200492076th base of human chromosome 2 is A; the 200484107th base of human chromosome 2 is A; the 200478921st base of human chromosome 2 is T; the 200491198th base of human chromosome 2 is G; the 200491299th base of human chromosome 2 is G; the 200477380th base of human chromosome 2 is A; the 200477504th base of human chromosome 2 is C; the 200477506th base of human chromosome 2 is A; the 200484696th base of human chromosome 2 is A; The 200485100th base of human chromosome 2 is T; the 200487486th base of human chromosome 2 is C; the 200491726th base of human chromosome 2 is A; the 200491877th base of human chromosome 2 is A; the 200484452nd base of human chromosome 2 is T; the 200491187th base of human chromosome 2 is A; the 200479539th base of human chromosome 2 is A; the 200488306th base of human chromosome 2 is T; the 200488785th base of human chromosome 2 is T; the 200488905th base of human chromosome 2 is A; the 200489109th base of human chromosome 2 is G; The 200484657th base of human chromosome 2 is C; the 200481019th base of human chromosome 2 is A; the 200486976th base of human chromosome 2 is T; the 200487539th base of human chromosome 2 is G; the 200489964th base of human chromosome 2 is C; the 200490260th base of human chromosome 2 is A; the 200491038th base of human chromosome 2 is A; the 200482025th base of human chromosome 2 is A; the 200482231st base of human chromosome 2 is G; the 200482513th base of human chromosome 2 is C;The 200480777th base of human chromosome 2 is T; the 200481498th base of human chromosome 2 is C; the 200481506th base of human chromosome 2 is A; the 200495743rd base of human chromosome 2 is A; the 200482881st base of human chromosome 2 is A; the 200499444th base of human chromosome 2 is G; the 200499255th base of human chromosome 2 is T; the 200491272nd base of human chromosome 2 is A; the 200474888th base of human chromosome 2 is C; the 200478354th base of human chromosome 2 is G; the 200484686th base of human chromosome 2 is C; The 200485648th base of human chromosome 2 is T; the 200498327th base of human chromosome 2 is C; the 200501964th base of human chromosome 2 is C; the 200499206th base of human chromosome 2 is C; the 200500431st base of human chromosome 2 is C; the 200500296th base of human chromosome 2 is T; the 200506846th base of human chromosome 2 is C; the 200492529th base of human chromosome 2 is A; the 200501467th base of human chromosome 2 is T; the 200505203rd base of human chromosome 2 is T; the 200494912 A of human chromosome 2; The 200496036th base of human chromosome 2 is T; the 200497907th base of human chromosome 2 is T; the 200499399th base of human chromosome 2 is A; the 200501134th base of human chromosome 2 is T; the 200499157th base of human chromosome 2 is A; the 200498080th base of human chromosome 2 is A; the 200490231st base of human chromosome 2 is C; the 200497975th base of human chromosome 2 is G; the 200501827th base of human chromosome 2 is T; the 200489315th base of human chromosome 2 is G;The 200497286th base of human chromosome 2 is G; the 200494182nd base of human chromosome 2 is G; the 200497711th base of human chromosome 2 is A; the 200496814th base of human chromosome 2 is A; the 200509555th base of human chromosome 2 is G; the 200509556th base of human chromosome 2 is C; the 200495510th base of human chromosome 2 is A; the 200510641st base of human chromosome 2 is A; and the 200510941st base of human chromosome 2 is T.;

[0044] In addition, the above single nucleotide polymorphism marker may reduce pigmentation when it contains one or more of the following bases that are major alleles, but is not limited thereto:

[0045] The 149192846th base of human chromosome 5 is A; the 149191111th base of human chromosome 5 is C; the 149195389th base of human chromosome 5 is T; the 149196682nd base of human chromosome 5 is T; the 149200603rd base of human chromosome 5 is T; the 149194923rd base of human chromosome 5 is T; the 149202206th base of human chromosome 5 is C; the 149194485th base of human chromosome 5 is C; the 149195603rd base of human chromosome 5 is C; the 149196090th base of human chromosome 5 is A; the 149196234th base of human chromosome 5 is G; The 149205630th base of human chromosome 5 is G; the 149210848th base of human chromosome 5 is C; the 149211868th base of human chromosome 5 is G; the 149209546th base of human chromosome 5 is C; the 149212430th base of human chromosome 5 is G; the 149216304th base of human chromosome 5 is C; the 149226633rd base of human chromosome 5 is G; the 149216256th base of human chromosome 5 is C; the 149228648th base of human chromosome 5 is C; the 149213456th base of human chromosome 5 is A; the 149204852nd base of human chromosome 5 is C; The 149218886th base of human chromosome 5 is C; the 149215213th base of human chromosome 5 is C; the 149229822nd base of human chromosome 5 is G; the 149231519th base of human chromosome 5 is C; the 149233110th base of human chromosome 5 is C; the 149233186th base of human chromosome 5 is C; the 149216987th base of human chromosome 5 is A; the 149199148th base of human chromosome 5 is G; the 149231830th base of human chromosome 5 is A; the 149195125th base of human chromosome 5 is T;The 149232525th base of human chromosome 5 is A; the 149197230th base of human chromosome 5 is T; the 149232308th base of human chromosome 5 is G; the 149196329th base of human chromosome 5 is G; the 149230952nd base of human chromosome 5 is A; the 149230745th base of human chromosome 5 is T; the 149230787th base of human chromosome 5 is C; the 149231786th base of human chromosome 5 is G; the 149234235th base of human chromosome 5 is C; the 149234236th base of human chromosome 5 is A; the 149159174th base of human chromosome 5 is G; The 149190810th base of human chromosome 5 is C; the 149194785th base of human chromosome 5 is G; the 149191547th base of human chromosome 5 is C; the 149193133rd base of human chromosome 5 is C; the 149195726th base of human chromosome 5 is C; the 149196638th base of human chromosome 5 is C; the 149196916th base of human chromosome 5 is A; the 149192166th base of human chromosome 5 is T; the 149197747th base of human chromosome 5 is C; the 149199467th base of human chromosome 5 is C; the 149197609th base of human chromosome 5 is T; The 149197815th base of human chromosome 5 is T; the 149200932nd base of human chromosome 5 is G; the 149190799th base of human chromosome 5 is G; the 149190248th base of human chromosome 5 is C; the 149203782nd base of human chromosome 5 is A; the 149205992nd base of human chromosome 5 is G; the 149201956th base of human chromosome 5 is C; the 149208516th base of human chromosome 5 is G; the 149206531st base of human chromosome 5 is G; the 149227540th base of human chromosome 5 is T;The 149204461st base of human chromosome 5 is C; the 149192744th base of human chromosome 5 is G; the 149189449th base of human chromosome 5 is G; the 149205417th base of human chromosome 5 is C; the 149196564th base of human chromosome 5 is C; the 149200402nd base of human chromosome 5 is A; the 149199656th base of human chromosome 5 is C; the 149196513th base of human chromosome 5 is A; the 149199889th base of human chromosome 5 is G; the 149200920th base of human chromosome 5 is A; the 149202168th base of human chromosome 5 is A; The 149200043rd base of human chromosome 5 is T; the 149203993rd base of human chromosome 5 is A; the 149187322nd base of human chromosome 5 is G; the 149204444th base of human chromosome 5 is C; the 149178996th base of human chromosome 5 is T; the 149179725th base of human chromosome 5 is T; the 149185923rd base of human chromosome 5 is C; the 149187212th base of human chromosome 5 is C; the 149187640th base of human chromosome 5 is G; the 149183256th base of human chromosome 5 is G; the 149234701st base of human chromosome 5 is G; The 149236008th base of human chromosome 5 is G; the 149164366th base of human chromosome 5 is G; the 149230730th base of human chromosome 5 is C; the 149186478th base of human chromosome 5 is A; the 149162451st base of human chromosome 5 is G; the 149162294th base of human chromosome 5 is G; the 149212471st base of human chromosome 5 is G; the 149179741st base of human chromosome 5 is C; the 149159862nd base of human chromosome 5 is C; the 149184905th base of human chromosome 5 is G;The 149159107th base of human chromosome 5 is A; the 149211392nd base of human chromosome 5 is C; the 149182832nd base of human chromosome 5 is G; the 149208768th base of human chromosome 5 is A; the 16788327th base of human chromosome 9 is A; the 16788333rd base of human chromosome 9 is T; the 16788336th base of human chromosome 9 is A; the 16788308th base of human chromosome 9 is C; the 16788328th base of human chromosome 9 is G; the 16815861st base of human chromosome 9 is A; the 16825110th base of human chromosome 9 is C; the 16789652nd base of human chromosome 9 is T; The 16,795,159th base of human chromosome 9 is A; the 16,812,810th base of human chromosome 9 is T; the 16,789,024th base of human chromosome 9 is T; the 16,789,436th base of human chromosome 9 is A; the 16,820,923rd base of human chromosome 9 is C; the 16,795,588th base of human chromosome 9 is A; the 16,795,211th base of human chromosome 9 is G; the 16,824,921st base of human chromosome 9 is C; the 16,788,367th base of human chromosome 9 is C; the 11,956,4143rd base of human chromosome 10 is C; the 11,956,3401st base of human chromosome 10 is T; the 11,956,5538th base of human chromosome 10 is C; The 119561969th base of human chromosome 10 is C; the 119573178th base of human chromosome 10 is C; the 119572403rd base of human chromosome 10 is C; the 119587425th base of human chromosome 10 is G; the 119584730th base of human chromosome 10 is C; the 119599727th base of human chromosome 10 is A; the 119575974th base of human chromosome 10 is C; the 119576317th base of human chromosome 10 is G;The 119576318th base of human chromosome 10 is G; the 119576319th base of human chromosome 10 is C; the 119584861st base of human chromosome 10 is A; the 119562387th base of human chromosome 10 is C; the 119572476th base of human chromosome 10 is C; the 119577677th base of human chromosome 10 is G; the 119601436th base of human chromosome 10 is T; the 119575798th base of human chromosome 10 is C; the 119601939th base of human chromosome 10 is G; the 119602316th base of human chromosome 10 is G; the 119602424th base of human chromosome 10 is G; The 119601743rd base of human chromosome 10 is G; the 119586963rd base of human chromosome 10 is C; the 119586186th base of human chromosome 10 is A; the 119586231st base of human chromosome 10 is C; the 119586178th base of human chromosome 10 is C; the 119587158th base of human chromosome 10 is G; the 119591330th base of human chromosome 10 is G; the 119586980th base of human chromosome 10 is A; the 119586462nd base of human chromosome 10 is C; the 119592083rd base of human chromosome 10 is C; the 119595140th base of human chromosome 10 is G; The 119582802nd base of human chromosome 10 is C; the 119591168th base of human chromosome 10 is C; the 119581527th base of human chromosome 10 is G; the 3548231st base of human chromosome 19 is A; the 3542983rd base of human chromosome 19 is C; and the 3540539th base of human chromosome 19 is G.;

[0046] The above bases are listed in Table 1 only as an example and are not specifically described, but markers involved in pigmentation can also be derived in the same way through Tables 2 and 3.

[0048] In addition, the marker in the present invention is a marker capable of determining the degree of change in the phenotype (pigmentation) as the number of minor alleles increases one by one at the base of the polymorphic region of the polymorphic marker of the individual. For example, among the markers shown in Table 1, if the 149192846th base of chromosome 5 of the individual is the minor allele G (rs17110447), the effect size is negative (-), so it can be determined that pigmentation is decreasing, and if the 16795241st base of chromosome 9 of the individual is the minor allele C (rs10810635), the effect size is positive (+), so it can be determined that pigmentation is increasing, but is not limited thereto.

[0049] Specifically, the above single nucleotide polymorphism marker may, but is not limited to, increase pigmentation when it contains one or more of the following bases which are minor alleles:

[0050] The 16,795,790th base of human chromosome 9 is C; the 16,795,241st base of human chromosome 9 is C; the 16,794,418th base of human chromosome 9 is A; the 16,806,521st base of human chromosome 9 is C; the 16,801,450th base of human chromosome 9 is T; the 16,808,172nd base of human chromosome 9 is G; the 16,806,694th base of human chromosome 9 is C; the 16,801,743rd base of human chromosome 9 is A; the 16,801,120th base of human chromosome 9 is C; the 16,788,274th base of human chromosome 9 is G; the 16,788,253rd base of human chromosome 9 is C; the 16,790,074th base of human chromosome 9 is G; The 16,790,968th base of human chromosome 9 is C; the 16,788,363rd base of human chromosome 9 is G; the 16,790,960th base of human chromosome 9 is G; the 16,799,844th base of human chromosome 9 is T; the 16,793,202nd base of human chromosome 9 is C; the 16,793,104th base of human chromosome 9 is G; the 16,792,350th base of human chromosome 9 is C; the 16,796,252nd base of human chromosome 9 is G; the 16,792,675th base of human chromosome 9 is C; the 16,791,865th base of human chromosome 9 is T; the 16,787,767th base of human chromosome 9 is C; the 11,956,8133rd base of human chromosome 10 is A; The 119570121st base of human chromosome 10 is T; the 119569921st base of human chromosome 10 is A; the 119570915th base of human chromosome 10 is T; the 119571832nd base of human chromosome 10 is A; the 119572168th base of human chromosome 10 is A; the 119547342nd base of human chromosome 10 is T; the 119561946th base of human chromosome 10 is T; the 119570716th base of human chromosome 10 is A;The 119563422nd base of human chromosome 10 is A; the 119544822nd base of human chromosome 10 is G; the 119544385th base of human chromosome 10 is T; the 119547279th base of human chromosome 10 is T; the 119544027th base of human chromosome 10 is T; the 119545571st base of human chromosome 10 is A; the 119547081st base of human chromosome 10 is C; the 119547669th base of human chromosome 10 is G; the 119545287th base of human chromosome 10 is G; the 119545401st base of human chromosome 10 is A; the 119545101st base of human chromosome 10 is C; The 119545375th base of human chromosome 10 is T; the 119545741st base of human chromosome 10 is G; the 119545762nd base of human chromosome 10 is C; the 119546979th base of human chromosome 10 is C; the 119545238th base of human chromosome 10 is C; the 119546034th base of human chromosome 10 is T; the 119546496th base of human chromosome 10 is T; the 119546323rd base of human chromosome 10 is G; the 119552651st base of human chromosome 10 is A; the 119566093rd base of human chromosome 10 is T; the 89985940th base of human chromosome 16 is A; The 89986760th base of human chromosome 16 is G; the 89987201st base of human chromosome 16 is G; the 89986608th base of human chromosome 16 is G; the 89985177th base of human chromosome 16 is C; the 89985441st base of human chromosome 16 is A; the 89986025th base of human chromosome 16 is C; the 89986154th base of human chromosome 16 is G; the 89985222nd base of human chromosome 16 is G; the 200473658th base of human chromosome 2 is T;The 200475044th base of human chromosome 2 is G; the 200492565th base of human chromosome 2 is G; the 200492076th base of human chromosome 2 is C; the 200484107th base of human chromosome 2 is G; the 200478921st base of human chromosome 2 is G; the 200491198th base of human chromosome 2 is C; the 200491299th base of human chromosome 2 is A; the 200477380th base of human chromosome 2 is T; the 200477504th base of human chromosome 2 is T; the 200477506th base of human chromosome 2 is C; the 200484696th base of human chromosome 2 is G; The 200485100th base of human chromosome 2 is C; the 200487486th base of human chromosome 2 is A; the 200491726th base of human chromosome 2 is C; the 200491877th base of human chromosome 2 is G; the 200484452nd base of human chromosome 2 is G; the 200491187th base of human chromosome 2 is G; the 200479539th base of human chromosome 2 is T; the 200488306th base of human chromosome 2 is C; the 200488785th base of human chromosome 2 is C; the 200488905th base of human chromosome 2 is G; the 200489109th base of human chromosome 2 is A; The 200484657th base of human chromosome 2 is G; the 200481019th base of human chromosome 2 is T; the 200486976th base of human chromosome 2 is G; the 200487539th base of human chromosome 2 is C; the 200489964th base of human chromosome 2 is G; the 200490260th base of human chromosome 2 is G; the 200491038th base of human chromosome 2 is G; the 200482025th base of human chromosome 2 is G; the 200482231st base of human chromosome 2 is A; the 200482513th base of human chromosome 2 is T;The 200480777th base of human chromosome 2 is C; the 200481498th base of human chromosome 2 is G; the 200481506th base of human chromosome 2 is T; the 200495743rd base of human chromosome 2 is C; the 200482881st base of human chromosome 2 is T; the 200499444th base of human chromosome 2 is A; the 200499255th base of human chromosome 2 is A; the 200491272nd base of human chromosome 2 is G; the 200474888th base of human chromosome 2 is A; the 200478354th base of human chromosome 2 is C; the 200484686th base of human chromosome 2 is T; The 200485648th base of human chromosome 2 is C; the 200498327th base of human chromosome 2 is T; the 200501964th base of human chromosome 2 is G; the 200499206th base of human chromosome 2 is G; the 200500431st base of human chromosome 2 is T; the 200500296th base of human chromosome 2 is C; the 200506846th base of human chromosome 2 is T; the 200492529th base of human chromosome 2 is C; the 200501467th base of human chromosome 2 is A; the 200505203rd base of human chromosome 2 is G; the 200494912 G of human chromosome 2; The 200496036th base of human chromosome 2 is C; the 200497907th base of human chromosome 2 is G; the 200499399th base of human chromosome 2 is G; the 200501134th base of human chromosome 2 is C; the 200499157th base of human chromosome 2 is G; the 200498080th base of human chromosome 2 is G; the 200490231st base of human chromosome 2 is A; the 200497975th base of human chromosome 2 is A; the 200501827th base of human chromosome 2 is C; the 200489315th base of human chromosome 2 is A;The 200497286th base of human chromosome 2 is T; the 200494182nd base of human chromosome 2 is A; the 200497711th base of human chromosome 2 is G; the 200496814th base of human chromosome 2 is T; the 200509555th base of human chromosome 2 is A; the 200509556th base of human chromosome 2 is T; the 200495510th base of human chromosome 2 is G; the 200510641st base of human chromosome 2 is C; and the 200510941st base of human chromosome 2 is G.;

[0051] In addition, the above single nucleotide polymorphism marker may reduce pigmentation when it contains one or more of the following bases that are minor alleles, but is not limited thereto:

[0052] The 149192846th base of human chromosome 5 is G; the 149191111th base of human chromosome 5 is T; the 149195389th base of human chromosome 5 is C; the 149196682nd base of human chromosome 5 is G; the 149200603rd base of human chromosome 5 is C; the 149194923rd base of human chromosome 5 is C; the 149202206th base of human chromosome 5 is G; the 149194485th base of human chromosome 5 is T; the 149195603rd base of human chromosome 5 is G; the 149196090th base of human chromosome 5 is C; the 149196234th base of human chromosome 5 is C; The 149205630th base of human chromosome 5 is T; the 149210848th base of human chromosome 5 is T; the 149211868th base of human chromosome 5 is A; the 149209546th base of human chromosome 5 is T; the 149212430th base of human chromosome 5 is A; the 149216304th base of human chromosome 5 is T; the 149226633rd base of human chromosome 5 is A; the 149216256th base of human chromosome 5 is T; the 149228648th base of human chromosome 5 is T; the 149213456th base of human chromosome 5 is G; the 149204852nd base of human chromosome 5 is G; The 149218886th base of human chromosome 5 is A; the 149215213th base of human chromosome 5 is G; the 149229822nd base of human chromosome 5 is T; the 149231519th base of human chromosome 5 is T; the 149233110th base of human chromosome 5 is A; the 149233186th base of human chromosome 5 is T; the 149216987th base of human chromosome 5 is G; the 149199148th base of human chromosome 5 is A; the 149231830th base of human chromosome 5 is G; the 149195125th base of human chromosome 5 is G;The 149232525th base of human chromosome 5 is G; the 149197230th base of human chromosome 5 is C; the 149232308th base of human chromosome 5 is A; the 149196329th base of human chromosome 5 is A; the 149230952nd base of human chromosome 5 is G; the 149230745th base of human chromosome 5 is C; the 149230787th base of human chromosome 5 is T; the 149231786th base of human chromosome 5 is A; the 149234235th base of human chromosome 5 is A; the 149234236th base of human chromosome 5 is T; the 149159174th base of human chromosome 5 is A; The 149190810th base of human chromosome 5 is T; the 149194785th base of human chromosome 5 is A; the 149191547th base of human chromosome 5 is T; the 149193133rd base of human chromosome 5 is T; the 149195726th base of human chromosome 5 is T; the 149196638th base of human chromosome 5 is T; the 149196916th base of human chromosome 5 is G; the 149192166th base of human chromosome 5 is C; the 149197747th base of human chromosome 5 is G; the 149199467th base of human chromosome 5 is T; the 149197609th base of human chromosome 5 is C; The 149197815th base of human chromosome 5 is C; the 149200932nd base of human chromosome 5 is A; the 149190799th base of human chromosome 5 is A; the 149190248th base of human chromosome 5 is G; the 149203782nd base of human chromosome 5 is G; the 149205992nd base of human chromosome 5 is A; the 149201956th base of human chromosome 5 is G; the 149208516th base of human chromosome 5 is T; the 149206531st base of human chromosome 5 is A; the 149227540th base of human chromosome 5 is C;The 149204461st base of human chromosome 5 is T; the 149192744th base of human chromosome 5 is T; the 149189449th base of human chromosome 5 is C; the 149205417th base of human chromosome 5 is A; the 149196564th base of human chromosome 5 is T; the 149200402nd base of human chromosome 5 is G; the 149199656th base of human chromosome 5 is T; the 149196513th base of human chromosome 5 is G; the 149199889th base of human chromosome 5 is A; the 149200920th base of human chromosome 5 is G; the 149202168th base of human chromosome 5 is G; The 149200043rd base of human chromosome 5 is C; the 149203993rd base of human chromosome 5 is G; the 149187322nd base of human chromosome 5 is A; the 149204444th base of human chromosome 5 is T; the 149178996th base of human chromosome 5 is C; the 149179725th base of human chromosome 5 is C; the 149185923rd base of human chromosome 5 is A; the 149187212th base of human chromosome 5 is T; the 149187640th base of human chromosome 5 is A; the 149183256th base of human chromosome 5 is T; the 149234701st base of human chromosome 5 is A; The 149236008th base of human chromosome 5 is A; the 149164366th base of human chromosome 5 is A; the 149230730th base of human chromosome 5 is T; the 149186478th base of human chromosome 5 is T; the 149162451st base of human chromosome 5 is A; the 149162294th base of human chromosome 5 is A; the 149212471st base of human chromosome 5 is A; the 149179741st base of human chromosome 5 is A; the 149159862nd base of human chromosome 5 is G; the 149184905th base of human chromosome 5 is T;The 149159107th base of human chromosome 5 is G; the 149211392nd base of human chromosome 5 is G; the 149182832nd base of human chromosome 5 is C; the 149208768th base of human chromosome 5 is G; the 16788327th base of human chromosome 9 is G; the 16788333rd base of human chromosome 9 is C; the 16788336th base of human chromosome 9 is G; the 16788308th base of human chromosome 9 is T; the 16788328th base of human chromosome 9 is A; the 16815861st base of human chromosome 9 is G; the 16825110th base of human chromosome 9 is T; the 16789652nd base of human chromosome 9 is C; The 16,795,159th base of human chromosome 9 is G; the 16,812,810th base of human chromosome 9 is C; the 16,789,024th base of human chromosome 9 is C; the 16,789,436th base of human chromosome 9 is G; the 16,820,923rd base of human chromosome 9 is G; the 16,795,588th base of human chromosome 9 is T; the 16,795,211th base of human chromosome 9 is C; the 16,824,921st base of human chromosome 9 is G; the 16,788,367th base of human chromosome 9 is T; the 11,956,4143rd base of human chromosome 10 is T; the 11,956,3401st base of human chromosome 10 is C; the 11,956,5538th base of human chromosome 10 is A; The 119561969th base of human chromosome 10 is T; the 119573178th base of human chromosome 10 is T; the 119572403rd base of human chromosome 10 is T; the 119587425th base of human chromosome 10 is A; the 119584730th base of human chromosome 10 is T; the 119599727th base of human chromosome 10 is G; the 119575974th base of human chromosome 10 is T; the 119576317th base of human chromosome 10 is C;The 119576318th base of human chromosome 10 is T; the 119576319th base of human chromosome 10 is G; the 119584861st base of human chromosome 10 is G; the 119562387th base of human chromosome 10 is T; the 119572476th base of human chromosome 10 is A; the 119577677th base of human chromosome 10 is A; the 119601436th base of human chromosome 10 is G; the 119575798th base of human chromosome 10 is T; the 119601939th base of human chromosome 10 is C; the 119602316th base of human chromosome 10 is A; the 119602424th base of human chromosome 10 is T; The 119601743rd base of human chromosome 10 is A; the 119586963rd base of human chromosome 10 is T; the 119586186th base of human chromosome 10 is T; the 119586231st base of human chromosome 10 is T; the 119586178th base of human chromosome 10 is T; the 119587158th base of human chromosome 10 is A; the 119591330th base of human chromosome 10 is A; the 119586980th base of human chromosome 10 is G; the 119586462nd base of human chromosome 10 is A; the 119592083rd base of human chromosome 10 is T; the 119595140th base of human chromosome 10 is A; The 119582802nd base of human chromosome 10 is T; the 119591168th base of human chromosome 10 is A; the 119581527th base of human chromosome 10 is A; the 3548231st base of human chromosome 19 is G; the 3542983rd base of human chromosome 19 is T; and the 3540539th base of human chromosome 19 is C.;

[0053] The above bases are listed in Table 1 only as an example and are not specifically described, but markers involved in pigmentation can also be derived in the same way through Tables 2 and 3.

[0055] In the present invention, the term "probe capable of detecting a marker for diagnosing skin type pigmentation" refers to a composition capable of diagnosing skin pigmentation by specifically confirming it through a hybridization reaction with a polymorphic region of the gene as described above, and the specific method of such gene analysis is not particularly limited and may be based on any gene detection method known in the technical field to which this invention belongs.

[0056] In the present invention, the term "preparation capable of amplifying a marker for diagnosing skin type pigmentation" refers to a composition capable of diagnosing skin pigmentation by confirming a polymorphic region of the gene as described above through amplification, and specifically refers to a primer capable of specifically amplifying a polynucleotide of the marker for diagnosing skin type pigmentation.

[0057] The primer used for the amplification of the polymorphic marker above refers to a single-stranded oligonucleotide capable of acting as a starting point for template-directed DNA synthesis under appropriate conditions in an appropriate buffer (e.g., four different nucleoside triphosphates and a polymerizer such as DNA, RNA polymerase, or reverse transcriptase) and at an appropriate temperature. The appropriate length of the primer may vary depending on the purpose of use, but is typically 15 to 30 nucleotides. Shorter primer molecules generally require lower temperatures to form a stable hybrid with the template. The primer sequence does not need to be perfectly complementary to the template, but must be sufficiently complementary to hybridize with the template.

[0058] In the present invention, the term "primer" refers to a short sequence having a short free 3' hydroxyl group, capable of forming base pairs with a complementary template, and functioning as a starting point for template strand replication. The primer can initiate DNA synthesis in the presence of reagents for a polymerization reaction (i.e., DNA polymerase or reverse transcriptase) and four different nucleoside triphosphates at an appropriate buffer solution and temperature. Skin type can be predicted by performing PCR amplification and determining whether a desired product is produced. PCR conditions and the lengths of sense and antisense primers can be modified based on those known in the art.

[0059] The probes or primers of the present invention may be chemically synthesized using the phosphoramidite solid support method or other widely known methods. These nucleic acid sequences may also be modified using many means known in the art. Non-limiting examples of such modifications include methylation, "capping," substitution with one or more homologues of the natural nucleotide, and modification between nucleotides, for example, modification to an uncharged linkage (e.g., methyl phosphonate, phosphotriester, phosphoroamidate, carbamate, etc.) or a charged linkage (e.g., phosphorothioate, phosphorodithioate, etc.).

[0061] In another aspect, the present invention provides a kit for diagnosing pigmentation of a skin type comprising the above-described composition for diagnosing skin pigmentation. The kit may be an RT-PCR kit or a DNA chip kit, but is not limited thereto.

[0062] The kit of the present invention can diagnose skin type by confirming SNP polymorphism markers, which are skin type diagnostic markers, through amplification, or by confirming the expression level of SNP polymorphism markers and the mRNA expression level. As a specific example, the kit for measuring the mRNA expression level of skin type diagnostic markers in the present invention may be a kit containing essential elements necessary for performing RT-PCR. In addition to each primer pair specific to the gene of the skin type diagnostic marker, the RT-PCR kit may include a test tube or other suitable container, a reaction buffer (with varying pH and magnesium concentration), deoxyribonucleotides (dNTPs), enzymes such as Taq-polymerase and reverse transcriptase, DNase, RNAse inhibitors, DEPC-water, sterile water, etc. It may also include a primer pair specific to the gene used as a quantitative control. Furthermore, specifically, the kit of the present invention may be a skin type diagnostic kit containing essential elements necessary for performing DNA chip analysis. A DNA chip kit is a tool that enables large-scale parallel analysis by attaching nucleic acid species in a gridded array to a glass surface, typically a flat solid support plate, which is not larger than a microscope slide, and in which nucleic acids are arranged uniformly on the chip surface, causing multiple hybridization reactions to occur between the nucleic acids on the DNA chip and the complementary nucleic acids contained in the solution treated on the chip surface.

[0064] In another aspect, the present invention provides a microarray for diagnosing pigmentation of a skin type comprising the above-mentioned composition for diagnosing skin pigmentation.

[0065] The microarray may comprise DNA or RNA polynucleotides. The microarray is composed of a conventional microarray, except that the probe polynucleotides contain the polynucleotides of the present invention.

[0066] A method for manufacturing a microarray by immobilizing a probe polynucleotide on a substrate is well known in the art. The probe polynucleotide refers to a polynucleotide capable of hybridization, meaning an oligonucleotide capable of sequence-specific binding to the complementary strand of nucleic acid. The probe of the present invention is an allele-specific probe in which a polymorphic site exists among nucleic acid fragments derived from two members of the same species, so that it hybridizes to a DNA fragment derived from one member but not to a fragment derived from the other member. In this case, the hybridization conditions must be sufficiently strict to ensure that hybridization occurs only with one of the alleles, showing a significant difference in hybridization intensity between the alleles. By doing so, a good difference in hybridization between different allele forms can be induced. The probe of the present invention can be used for detecting alleles and for skin type diagnosis methods, etc. Such diagnostic methods include detection methods based on nucleic acid hybridization, such as Southern Blot, and may be provided in a form pre-bound to the substrate of a DNA chip in a method using a DNA chip. The hybridization mentioned above can usually be performed under strict conditions, for example, a salt concentration of 1 M or less and a temperature of 25°C or higher. For example, conditions of 5x SSPE (750 mM NaCl, 50 mM Na₂Phosphate, 5 mM EDTA, pH 7.4) and 25–30°C may be suitable for allele-specific probe hybridization.

[0067] The process of immobilizing the probe polynucleotide associated with skin diagnosis of the present invention onto a substrate can also be easily manufactured using such prior art. Furthermore, the hybridization of nucleic acids on microarrays and the detection of hybridization results are well known in the art. Such detection can be achieved, for example, by labeling a nucleic acid sample with a labeling material capable of generating a detectable signal, such as a fluorescent substance like Cy3 and Cy5, then hybridizing it on a microarray, and detecting the signal generated from the labeling material to detect the hybridization result.

[0069] In another aspect, the present invention provides a method for providing information on whether skin pigmentation is present, comprising: (a) amplifying or hybridizing a polymorphic region of the single nucleotide polymorphism marker in DNA obtained from a sample isolated from an individual; and (b) identifying the base of the amplified or hybridized polymorphic region of step (a).

[0070] The term "subject" in the present invention refers to a subject for diagnosing the presence or absence of skin pigmentation. DNA may be obtained from samples such as hair, urine, blood, various body fluids, isolated tissues, isolated cells, or saliva from the specimen, but is not limited thereto.

[0071] The method for obtaining genomic DNA in step (a) above may use any method known to those skilled in the art.

[0072] The step of amplifying the polymorphic site of the single nucleotide polymorphism marker from the DNA obtained in step (a) above or hybridizing it with a probe may be performed using any method known to those skilled in the art. For example, the target nucleic acid can be obtained by amplifying it via PCR and purifying it. Other methods may include ligase chain reaction (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)), self-maintaining sequence replication (Guatelli et al., Proc. Natl. Acad. Sci. USA 87, 1874 (1990)), and nucleic acid-based sequence amplification (NASBA).

[0073] Determining the bases of the polymorphic region in step (b) of the above method includes, but is not limited to, sequencing analysis, microarray hybridization, allele-specific PCR, dynamic allele-specific hybridization (DASH), PCR extension analysis, SSCP, PCR-RFLP analysis or TaqMan technique, SNPlex platform (Applied Biosystems), mass spectrometry (e.g., Sequenom’s MassARRAY system), mini-sequencing 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 methods). One or more alleles in a polymorphic marker, including microsatellites, SNPs, or other types of polymorphic markers, can be identified by the above methods or other methods available to those skilled in the art to which the present invention pertains. Determining the bases of such polymorphic sites can specifically be performed using an SNP chip.

[0074] The above method may additionally determine, but is not limited to, that pigmentation increases or decreases when (c) the bases of the amplified or hybridized polymorphic region contain one or more bases that are minor alleles according to the single nucleotide polymorphism marker. Additionally, it may additionally determine, but is not limited to, that pigmentation increases or decreases when (c) the bases of the amplified or hybridized polymorphic region contain one or more bases that are major alleles according to the single nucleotide polymorphism marker.

[0075] In the present invention, the term "SNP chip" refers to a DNA microarray capable of identifying each base of hundreds of thousands of SNPs at once.

[0076] The TaqMan method comprises: (1) a step of designing and constructing primers and TaqMan probes to amplify a desired DNA fragment; (2) a step of labeling probes of different alleles with FAM dye and VIC dye (Applied Biosystems); (3) a step of performing PCR using the above primers and probes with the above DNA as a template; (4) a step of analyzing and verifying the TaqMan analysis plate with a nucleic acid analyzer after the above PCR reaction is completed; and (5) a step of determining the genotypes of the polynucleotides of step (1) from the analysis results.

[0077] In the above, sequencing analysis may be performed using conventional methods for determining base sequences or using an automated gene analyzer. Additionally, allele-specific PCR refers to a PCR method that amplifies a DNA fragment at the location of an SNP using a primer set designed with the base at the SNP location as the 3' end. The principle of the above method utilizes the fact that, for example, when a specific base is substituted from A to G, if a PCR reaction is performed by designing a primer containing A as the 3' end base and a reverse primer capable of amplifying a DNA fragment of appropriate size, the amplification reaction proceeds normally and a band at the desired location is observed when the base at the SNP location is A; however, when the base is substituted to G, the primer can bind complementarily to the template DNA, but the 3' end side cannot bind complementarily, so the amplification reaction is not properly performed. DASH can be performed using conventional methods, and specifically, it can be performed by the method of Prince et al.

[0078] Meanwhile, PCR extension analysis is performed by first amplifying a DNA fragment containing the base where the single nucleotide polymorphism is located using a primer pair, then inactivating all nucleotides added to the reaction by dephosphorylating them, and finally adding an SNP-specific extension primer, a dNTP mixture, a dideoxynucleotide, a reaction buffer, and DNA polymerase to perform a primer extension reaction. At this time, the extension primer takes the base immediately adjacent to the 5' direction of the base where the SNP is located as its 3' end, nucleic acids having the same base as the dideoxynucleotide are excluded from the dNTP mixture, and the dideoxynucleotide is selected from one of the base types representing the SNP. For example, in the case of a substitution from A to G, if a mixture of dGTP, dCTP, and TTP and ddATP are added to the reaction, the primer at the base where the substitution occurred is extended by DNA polymerase, and after a few bases, the primer extension reaction is terminated by ddATP at the location where the A base first appears. If the above substitution does not occur, the extension reaction terminates at that location, so the type of base representing the SNP can be determined by comparing the lengths of the extended primers.

[0079] In this case, as a detection method, when an extension primer or dideoxynucleotide is fluorescently labeled, the SNP can be detected by detecting fluorescence using a gene analyzer used for general base sequence determination (e.g., ABI’s Model 3700, etc.), and when unlabeled extension primers and dideoxynucleotides are used, the SNP can be detected by measuring the molecular weight using the MALDI-TOF (matrix assisted laser desorption ionization-time of flight) technique. Effects of the invention

[0081] Through the genetic polymorphism markers of the present invention that have significant association with the degree of skin pigmentation, information regarding an individual's degree of skin pigmentation can be provided, and furthermore, customized ingredients or products capable of alleviating the degree of skin pigmentation can be developed based on the information of the genetic polymorphism markers observed in the individual. Specific details for implementing the invention

[0083] The present invention will be described in more detail below through examples. These examples are merely illustrative of the present invention and should not be interpreted as limiting the scope of the present invention.

[0085] The aim was to identify genomic regions (genetic variations) in Korean women that show differences in the degree (numerical value) of facial skin pigmentation according to genetic information. To identify genomic regions (genetic variations) associated with pigmentation, the present invention utilized a microarray genotyping chip (product of Illumina) capable of screening at the whole-genome level without pre-selecting candidate genes.

[0086] In this invention, an image-based specialized skin diagnostic device (PIE Janus3) was utilized to evaluate the degree of pigmentation, and the results were used after correction for age and principal component values ​​to minimize external effects that could influence the degree of skin pigmentation (numerical value).

[0087] Linear regression analysis was used to confirm the association between genomic regions (gene mutations) and the degree of skin pigmentation (numerical values), and the significance of the correlation and the genetic effect were quantified.

[0089] Example 1: Classification of skin characteristics and gene extraction

[0090] To derive genetic polymorphism markers capable of explaining the general degree of skin pigmentation, healthy Korean women aged 20 to 70 were recruited. Furthermore, for skin measurement, all subjects washed their faces with cleanser or soap and waited for 30 minutes without applying any products to allow the skin to adapt to the measurement environment before evaluating the degree of skin pigmentation. An image-based specialized skin diagnostic device (PIE Janus3) was utilized for the evaluation (measurements and analyses were performed according to the device manufacturer's manual).

[0091] The degree of skin pigmentation in a typical individual (possessing a major allele / major allele) refers to the average facial pigmentation measured on 17,019 subjects in whom two alleles were observed at the same gene location (base), and the value was derived as the ratio of areas observed to be relatively dark or brown compared to the surrounding skin color within the analysis area.

[0093] Gene collection was performed through saliva collection, and to ensure effective gene collection, all subjects were prohibited from consuming any food, including water, starting 30 minutes prior to collection.

[0095] Among the above subjects, those who: ① are pregnant, breastfeeding, or planning to become pregnant within 6 months; ② have used a steroid-containing topical agent for the treatment of a skin disease for more than 1 month; ③ have not passed 6 months since participating in the same study; ④ have sensitive or hypersensitive skin; ⑤ have skin abnormalities such as moles, acne, erythema, or telangiectasia on the test site; ⑥ have used the same or similar cosmetic or pharmaceutical product on the test site within 3 months of the start of the study; ⑦ have received or plan to receive a procedure (dermabrasion, Botox, or other skin care) on the test site within 6 months; ⑧ have a chronic wasting disease (asthma, diabetes, hypertension, etc.); ⑨ have atopic dermatitis; or ⑩ are otherwise deemed difficult to participate in by the principal investigator were excluded from the study.

[0097] Example 2: Genotype analysis according to skin characteristics

[0098] For gene analysis, human genomic DNA was extracted from saliva using the QIAmp mini prep kit (QIAGEN), and its quality was verified by absorbance (OD 260 / 280) or band testing using a 1x TAE 1% agarose gel at 1.7, concentration 50 ng / ul, and gene analysis was performed only on samples that passed the quality test.

[0099] Genetic analysis was conducted using an Illumina microarray genotyping chip; specifically, the genes of the subjects were analyzed using the same company's global screening array product.

[0100] The Illumina microarray genotyping chip gene analysis experiment was conducted according to the provided manual, and the processes of genomic DNA amplification, DNA fragmentation, precipitation, hybridization, staining, washing, coating, and scanning were performed using the provided reagents.

[0101] The microarray genotyping chip from the experiment was scanned using iScan Control Software (Illumina), and once the scan was complete, an idat file was automatically generated, and data quality control (sample call rate 98%, marker call rate 98%) and genetic information verification were performed using GenomeStudio (Illumina).

[0102] In this experiment, only data that passed data quality control after genetic analysis was used.

[0104] Example 3: Derivation of Genetic Polymorphism Markers Significantly Associated with Skin Pigmentation Degree Using Genotype Analysis by Skin Type

[0105] To derive gene polymorphism markers that are significantly associated with the degree of skin pigmentation, linear regression analysis using gene polymorphism markers of the subjects was performed, and PLINK v 1.90 and SNP & Variation suite (Golden Helix, Inc., Bozeman, Montana, USA) were used for the analysis.

[0106] Imputation analysis was performed using the Beagle v 5.1 program to obtain information on additional genetic polymorphism markers using the genetic polymorphism markers identified through experiments. For this analysis, reference data was obtained from the 1000 Genomes project, an international open genome data database.

[0107] Imputation is a statistical technique that infers unanalyzed genetic polymorphism marker information based on genetic polymorphism marker information obtained through experiments.

[0108] For quality control of the genetic polymorphism markers to be analyzed, each genetic polymorphism marker was used only if it exceeded the minor allele frequency or 0.01 and the Hardy-Weinberg equilibrium or 0.000001 criteria.

[0109] The significance of gene polymorphism markers associated with the degree of skin pigmentation was evaluated using linear regression analysis F-statistics, and the criterion was set at P-value < 0.0001.

[0110] To minimize external effects that may affect the degree of skin pigmentation and to derive the effects based on genetic information, the degree of skin pigmentation can be corrected using age or BMI information or lifestyle information (drinking, smoking, dietary habits, sleep habits, etc.) and utilized in the analysis (e.g., performing linear regression analysis).

[0111] A large number of gene polymorphism markers associated with the degree of skin pigmentation were identified, and it was confirmed that these gene polymorphism markers are mainly located on chromosomes 2, 5, 9, 10, 16, and 19 of the human genome.

[0113] A list of SNP markers significantly associated with skin pigmentation is shown in Tables 1 to 3 below.

[0115]

[0116]

[0117]

[0118]

[0119]

[0120]

[0121]

[0122]

[0123]

[0124]

[0125]

[0126]

[0127]

[0128]

[0129]

[0130]

[0131]

[0132]

[0133]

[0134]

[0135]

[0136]

[0137]

[0138]

[0139]

[0140]

[0141]

[0142]

[0143]

[0144]

[0145]

[0146]

[0147]

[0148]

[0149]

[0150]

[0151]

[0152]

[0153]

[0154]

[0155]

[0156]

[0157]

[0158]

[0159]

[0160]

[0161]

[0162]

[0163]

[0164]

[0165]

[0166]

[0167]

[0168]

[0169]

[0170]

[0171]

[0172]

[0173]

[0174]

[0175]

[0176]

[0177]

[0178]

[0179]

[0180]

[0181]

[0182]

[0183]

[0184]

[0185]

[0186]

[0187]

[0188]

[0189]

[0190]

[0191]

[0192]

[0193]

[0194]

[0195]

[0196]

[0197]

[0198]

[0199]

[0200]

[0201]

[0202]

[0203]

[0204]

[0205]

[0206]

[0207]

[0208]

[0209]

[0210]

[0211]

[0212]

[0213]

[0214]

[0215]

[0216]

[0217]

[0218]

[0219]

[0220]

[0221]

[0222]

[0223]

[0224]

[0225]

[0226]

[0227]

[0228]

[0229]

[0230]

[0231]

[0232]

[0233]

[0234]

[0235]

[0236]

[0237]

[0238]

[0239]

[0240]

[0241]

[0242]

[0243]

[0244]

[0245]

[0246]

[0247]

[0248]

[0249]

[0250]

[0251]

[0252]

[0253]

[0254]

[0255]

[0256]

[0257]

[0258]

[0259]

[0260]

[0261]

[0262]

[0263]

[0264]

[0265]

[0266]

[0267]

[0268]

[0269]

[0270]

[0271]

[0272]

[0273]

[0274]

[0275]

[0276]

[0277]

[0278]

[0279]

[0280]

[0281]

[0282]

[0283]

[0284]

[0285]

[0286]

[0287]

[0288]

[0289]

[0290]

[0291]

[0292]

[0293]

[0294]

[0295]

[0296]

[0297]

[0298]

[0299]

[0300]

[0301]

[0302]

[0303]

[0304]

[0305]

[0306]

[0307]

[0308]

[0309]

[0310]

[0311]

[0312]

[0313]

[0314]

[0315]

[0316]

[0317]

[0318]

[0319]

[0320]

[0321]

[0322]

[0323]

[0324]

[0325]

[0326]

[0327]

[0328]

[0329]

[0330]

[0331]

[0332]

[0333]

[0334]

[0335]

[0336]

[0337]

[0338] 1) National Institutes of Health (NIH) ID; sequences can be verified on the relevant website.

[0339] 2) Meaning of (major allele) or (minor allele)

[0340] 3) minor allele frequency = (2mm + Mm) / 2(MM + Mm + mm)

[0341] 4) Statistical significance of phenotypic differences among the three genotypes (M / M, M / m, m / m) (M: major allele, m: minor allele)

[0342] 5) Degree of change in phenotype (pigmentation) as the number of minor alleles increases one by one (-: decrease in pigmentation, +: increase in pigmentation), degree of pigmentation = ratio of the area of ​​pigmentation to the total area, provided that intensity weighting and threshold values ​​are applied to the pigmented area, use of commercially available device (Janus3, PIE, Korea)

[0343] 6) Analysis using Beagle v5.1

[0345] As a result, gene variants associated primarily with skin pigmentation were identified in a total of seven genomic regions.

[0346] Among the many gene variants, the gene variants showing the highest association significance representing each genomic region are as follows.

[0347] [BNC2 at 9p22 (rs16935073; P-value = 4.02Х10 -35 ), PPARGC1B at 5q32 (rs26127; P-value = 6.40Х10 -59 ), 10q26 (rs11198143; P-value = 9.24Х10 -41 ),

[0348] FANCA at 16q24 (rs12921383; P-value = 1.07Х10 -43 ), 2q33 (rs4675687; P-value = 2.90Х10 -22 ), and MFSD12 at 19p13 (rs2240751; P-value = 2.12Х10 -10 ), 11q22 (rs4794701; P-value = 7.29Х10 -21 )]

[0350] From the foregoing description, those skilled in the art to which the present invention pertains will understand that the present invention may be implemented in other specific forms without altering its technical concept or essential features. In this regard, the embodiments described above should be understood as illustrative in all respects and not restrictive. The scope of the present invention should be interpreted as including all modifications or variations derived from the meaning and scope of the claims set forth below and their equivalents, rather than from the detailed description above.

Claims

Claim 1 A composition for diagnosing skin pigmentation, comprising a probe capable of detecting or a preparation capable of amplifying a single nucleotide polymorphism (SNP) marker for diagnosing skin pigmentation, wherein the single nucleotide polymorphism marker for diagnosing skin pigmentation comprises rs72829879. Claim 2 A composition according to claim 1, wherein the single nucleotide polymorphism marker for diagnosing skin pigmentation additionally comprises rs251465 or rs7024720. Claim 3 A composition according to claim 1, wherein the single nucleotide polymorphism marker for diagnosing skin pigmentation further comprises a polynucleotide corresponding to the single nucleotide polymorphism marker rs72829879; and one or more polynucleotides selected from the group consisting of polynucleotides complementary thereto. Claim 4 A composition according to claim 2, wherein the single nucleotide polymorphism marker for diagnosing skin pigmentation further comprises one or more polynucleotides selected from the group consisting of a polynucleotide corresponding to a single nucleotide polymorphism marker rs251465 or rs7024720; and polynucleotides complementary thereof. Claim 5 A kit for diagnosing skin pigmentation comprising a composition of any one of claims 1 to 4. Claim 6 In paragraph 5, the above kit is a kit for diagnosing skin pigmentation, which is an RT-PCR kit or a DNA chip kit. Claim 7 A microarray for diagnosing skin pigmentation, comprising a single nucleotide polymorphism (SNP) marker for diagnosing skin pigmentation according to claim 1. Claim 8 (a) a step of amplifying or hybridizing with a probe a polymorphic region of a single nucleotide polymorphism marker for diagnosing skin pigmentation according to claim 1 in DNA obtained from a sample isolated from an individual; and (b) a step of identifying the base of the amplified or hybridized polymorphic region of step (a), comprising a method for providing information on whether skin pigmentation is present. Claim 9 A method for providing information on whether skin pigmentation is present, wherein, in paragraph 8, the sample is hair, urine, blood, various body fluids, isolated tissue, isolated cell, or saliva. Claim 10 A method for providing information on whether skin pigmentation is present, wherein, in claim 8, the amplification and identification of the polymorphic region are performed using an SNP chip.

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